CZ20002893A3 - Glucocorticoid-selective anti-inflammatory agents - Google Patents

Abstract

Compounds of formula (I) are effective for partially or completely antagonizing, repressing, agonizing or modulating glucocorticoid receptors and treating immune, autoimmune and inflammatory diseases in mammals. Pharmaceutical compositions containing compounds of formula (I) and methods of inhibiting immune or autoimmune diseases in mammals are also described.

Description

GLUCOCORTICOPHYPIC SELECTIVE ANTI-INFLAMMATORY AGENTS

Technical field

The present invention relates to glucocorticoid-selective benzopyrano[3,4]quinolines receptors that are effective in treating immune and autoimmune diseases, pharmaceutical compositions containing these compounds, and methods of inhibiting inflammation, inflammatory diseases, immune and autoimmune diseases in mammals.

State of the art

Intracellular receptors (IRs) are a class of structurally related proteins involved in the regulation of gene expression. Steroid hormone receptors are a subgroup of this large family, whose natural ligands are typically endogenous steroids such as estradiol, progesterone, and cortisol. Artificial ligands for these receptors play important roles in human health, and of these receptors, the glucocorticoid receptor (GR) plays an essential role in regulating human physiology and immune responses. Steroids that interact with the GR have been shown to be potent anti-inflammatory agents. Despite this utility, steroidal GR ligands are not selective. It is believed that side effects associated with chronic dosing are the result of cross-reactivity with other steroid receptors such as estrogen, progesterone, androgen, and mineralocorticoid receptors, which have somewhat homologous ligand binding regions.

Selective GR modulators (e.g., repressors, agonists, partial agonists, and antagonists) of the present disclosure can be used to affect basic life-sustaining systems of the body, including carbohydrate, protein, and lipid metabolism, and the functions of the cardiovascular, hepatic, central nervous, immune, skeletal muscle, and other organs and tissues. Given the known state of the art, GR modulators have proven effective in the treatment of inflammation, tissue rejection, autoimmunity, various malignancies such as leukemias and lymphomas, Cushing's disease, acute adrenal insufficiency, congenital adrenal hyperplasia, rheumatic fever, polyarteritis nodosa, granulomatous polyarteritis, myeloid cell line inhibition, immune proliferation/apoptosis, HP A axis suppression and regulation, hypercortisolemia, modulation of Th1/Th2 cytokine balance, chronic kidney disease, stroke and spinal cord injury, hypercalcemia, hyperglycemia, adrenal insufficiency, chronic primary adrenal insufficiency, secondary adrenal insufficiency, congenital adrenal hyperplasia, cerebral edema, thrombocytopenia and Little's syndrome.

GR modulators are particularly effective in disease states including systemic inflammation, e.g., inflammatory bowel disease, systemic lupus erythematosus, polyarteritis nodosa, Wegener's granulomatosis, giant cell arteritis, rheumatoid arthritis, osteoarthritis, hay fever, allergic rhinitis, urticaria, angioneurotic edema, chronic obstructive pulmonary disease, asthma, tendonitis, bursitis, Crohn's disease, ulcerative colitis, autoimmune chronic active hepatitis, organ transplantation, hepatitis, and cirrhosis. GR active compounds have also been used as immunostimulants and repressors and as agents for wound healing and tissue repair.

GR modulators have also found use in various local diseases such as inflammatory alopecia areata, panniculitis, psoriasis, discoid lupus erythematosus, inflamed cysts, atopic dermatitis, pyoderma gangrenosum, pemphigus vulgaris, bullous pemphigoid, systemic lupus erythematosus, dermatomyositis, herpes gestationis, eosinophilic fasciitis, relapsing polychondritis, inflammatory vasculitis, sarcoidosis, Sweet's disease, reactive leprosy type 1, capillary hemangioma, contact dermatitis, atopic dermatitis, lichen planus, exfoliative dermatitis, erythema nodosum, acne, hirsutism, toxic epidermal necrolysis, erythema multiforme, cutaneous T-cell lymphoma.

Selective glucocorticoid receptor antagonists have been sought unsuccessfully for decades. These agents could potentially find application in a variety of disease states associated with human immunodeficiency virus (HIV), cell apoptosis, and cancer, including, but not limited to, Kaposi's sarcoma, activation and modulation of the immune system, desensitization of inflammatory responses, IL-1 expression, antiretroviral therapy, production of natural killer cells, lymphocytic leukemia, and treatment of retinitis pigmentosa. Cognitive and behavioral processes are also sensitive to glucocorticoid therapy, where antagonists could potentially be effective in treating processes such as cognitive performance, memory and learning, depression, addiction, mood disorders, chronic fatigue syndrome, schizophrenia, stroke, sleep disorders, and anxiety.

The essence of the invention

In one embodiment of the present invention, the compounds of formula I are:

or pharmaceutically acceptable salts or prodrugs thereof, wherein the substituent R 1 is -Li-Ra, wherein Li is selected from (1) a covalent bond, (2) -O-, (3) -S(0) _t -, wherein the index t is 0, 1 or 2, (4) -C(X)-, (5) -NR ₇ -, wherein the substituent R ? is selected from (a) hydrogen, (b) aryl, (c) cycloalkyl having three to twelve carbon atoms, (d) alkanoyl, where the alkyl portion has one to twelve carbon atoms, (e) alkoxycarbonyl, where the alkyl portion has one to twelve carbon atoms, (t) alkoxycarbonyl, where the alkyl portion has one to twelve carbon atoms and is substituted with 1 or 2 aryl groups, (g) alkyl having one to twelve carbon atoms, (h) alkyl having one to twelve carbon atoms substituted with 1 or 2 substituents independently selected from (i) aryl and (ii) cycloalkyl having three to twelve carbon atoms, (i) alkenyl having three to twelve carbon atoms, with the proviso that the carbon of the carbon-carbon double bond is not directly attached to the nitrogen, (j) alkynyl having three to twelve carbon atoms, with the proviso that the carbon of the carbon-carbon triple bond is not directly attached to the nitrogen (6) -NR _x C(X)NR9-, where X is O or S and Rs and Rg are independently selected from >

• · 9 · φ ·φ · 4 ·· ·

9* 9 4 4 · 4 · 4 4 4

444 44 4 444 44 44 4 • 444 «4444 *··> ·· 44 44 44 44 (a) hydrogen, (b) aryl, (c) cycloalkyl having three to twelve carbon atoms, (d) alkyl having one to twelve carbon atoms, (e) alkyl having one to twelve carbon atoms substituted with 1 or 2 substituents independently selected from aryl or cycloalkyl having three to twelve carbon atoms, (f) alkenyl having three to twelve carbon atoms, with the proviso that the carbon of the carbon-carbon double bond is not directly attached to the nitrogen (g) alkynyl having three to twelve carbon atoms, with the proviso that the carbon of the carbon-carbon triple bond is not directly attached to the nitrogen (7) -X'C(X)-, where X is as defined above and X' is O or S, (8) -C(X)X'-, (9) -X'C(X)X'where X and X' are as defined above and X is O or S, with the proviso that if X is O, then at least one of X' or X is O, (10) -NR ₈ C(X)-, (11) -C(X)NRs-, (12) -NR ₈ C(X)X'-, (13) -X'C(X)NR ₈ -, (14) -SOsNR,-, (15) -NRsSOj-, and (16) -NR8SO ₂ NR ₉ where (6) - (16) are drawn with their right ends attached to a substituent Ra that is selected from (1) -OH, (2) -OG, where G is a protecting group -OH, (3) -SH, (4) -CO2R20, where the substituent R ₂₀ is hydrogen or an alkyl having one to twelve carbon atoms, (5) alkoxycarbonyl, (6) -CN, (7) halogen, • ·♦··· · ····· · · « • · * · · · « · ···· »· ·· «« «· ·« (8) haloalkoxy groups having one to twelve carbon atoms, (9) perfluoroalkoxy groups having one to twelve carbon atoms, (10) -CHO, (11) -NR7R7, where the substituent R7 is as defined above and the substituent Rr is selected from (a) hydrogen atom, (b) aryl, (c) cycloalkyl having three to twelve carbon atoms, (d) alkanoyl, where the alkyl portion has one to twelve carbon atoms, (e) alkoxycarbonyl, where the alkyl portion has one to twelve carbon atoms (f) alkoxycarbonyl, where the alkyl portion has one to twelve carbon atoms and is substituted with 1 or 2 aryl groups, (g) alkyl having one to twelve carbon atoms, (h) alkyl having one to twelve carbon atoms substituted with 1 or 2 substituents independently selected from (i) aryl and (ii) cycloalkyl having three to twelve carbon atoms, (i) alkenyl having three to twelve carbon atoms, with the proviso that the carbon of the carbon-carbon double bond is not directly attached to the nitrogen (j) alkynyl having three to twelve carbon atoms, with the proviso that the carbon of the carbon-carbon triple bond is not directly attached to the nitrogen (12) -C(X) _NR8R9 , (13) -OSO2R11, where R11 is selected from (a) aryl, (b) cycloalkyl having three to twelve carbon atoms, (c) alkyl having one to twelve carbon atoms, (d) alkyl having one to twelve carbon atoms substituted with 1, 2, 3 or 4 halogen substituents and (e) perfluoroalkyl having one to twelve carbon atoms, (14) alkyl having one to twelve carbon atoms, (15) alkenyl having two to twelve carbon atoms, with the proviso that the carbon of the carbon-carbon double bond is not directly attached to Li if Li is other than a covalent bond, • · · · ···· ···« • · ♦ · · · · · · 4 · • ··· · » · ··· · · « · · * · · · 9 9 9 9

9999 99 99 99 99 99 (16) alkynyl having two to twelve carbon atoms, with the proviso that the carbon of the carbon-carbon triple bond is not directly attached to Li if Li is other than a covalent bond, wherein (14), (15) and (16) may be optionally substituted with 1, 2 or 3 substituents independently selected from (a) an alkoxy group having one to twelve carbon atoms, (b) -OH, with the proviso that two -OH groups are not attached to the same carbon atom, (c) -SH, (d) a thioalkoxy group having one to twelve carbon atoms, with the proviso that two -SH groups are not attached to the same carbon atom, (e) -CN, (í) halogen, (g) -CHO, (h) -NO ₂ , (i) a haloalkoxy group having one to twelve carbon atoms, (j) perfluoroalkoxy groups having one to twelve carbon atoms, (k) -NR7R7·, (l) =nnr ₇ r ₇ ·, (m) -NR7NR7 R7 , where the substituents R ₇ and R7 are as defined above and the substituent R ₇ is selected from (i) hydrogen, (ii) aryl, (iii) cycloalkyl having three to twelve carbon atoms, (iv) alkanoyl, where the alkyl portion has one to twelve carbon atoms, (v) alkoxycarbonyl, where the alkyl portion has one to twelve carbon atoms, (vii) alkoxycarbonyl, where the alkyl portion has one to twelve carbon atoms substituted with 1 or 2 ayl groups, (vii) alkyl having one to twelve carbon atoms, (viii) alkyl having one to twelve carbon atoms substituted with 1 or substituents independently selected from aryl or cycloalkyl having three to twelve carbon atoms,

9

Β ··· · · * Β·· · · · · « \ · ········ ··«· ·· ·* «Β »» ··

(n) (ix) alkenyl having three to twelve carbon atoms, with the proviso that the carbon-carbon double bond is not directly attached to the nitrogen, and (x) alkynyl having three to twelve carbon atoms, with the proviso that the carbon-carbon triple bond is not directly attached to the nitrogen, -CO2R10, where R10 is selected from (θ) (i) aryl, (ii) aryl substituted with 1, 2 or 3 alkyls having one to twelve carbon substituents, (iii) cycloalkyl having three to twelve carbon atoms, (iv) alkyl having one to twelve carbon atoms, and (v) alkyl having one to twelve carbon atoms substituted with aryl or cycloalkyl having three to twelve carbon atoms, -C(X)NRgR ₉ , (P) =N-ORi ₀ , (q) =NRio, (r) -S(OXR ₁₀ , (s) -X'C(X)R ₁₀ , (t) (=X), and (at) -axis ₂ r„,

(17) cycloalkyl having three to twelve carbon atoms, (18) cycloalkenyl having four to twelve carbon atoms, with the proviso that the carbon of the carbon-carbon double bond is not directly attached to Li, wherein Li is other than a covalent bond, wherein (17) and (18) may be optionally substituted with 1, 2, 3 or 4 substituents independently selected from (a) alkyl having one to twelve carbon atoms, (b) aryl, (c) alkoxy having one to twelve carbon atoms, (d) halogen, (e) alkoxycarbonyl, wherein the alkyl has one to twelve carbon atoms, and (f) -OH, with the proviso that two • « ·♦· * · are not attached to the same carbon atom

-OH groups, (19) perfluoroalkyl having one to twelve carbon atoms, (20) aryl, and (21) heterocycles, wherein (20) and (21) may be optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from (a) alkyl having one to twelve carbon atoms, (b) alkanoyloxy group where the alkyl moiety has one to twelve carbon atoms, (c) alkoxycarbonyl where the alkyl moiety has one to twelve carbon atoms, (d) alkoxy groups having one to twelve carbon atoms, (e) halogen, (f) -OH, with the proviso that no two -OH groups are attached to the same carbon atom, (g) thioalkoxy groups having one to twelve carbon atoms, (h) perfluoroalkyl having one to twelve carbon atoms, (i) -NR ₇ R ₇ , (j) -CO ₂ R ₁₀ , (k) -OSO ₂ Rn, and (0 (=x);

the substituents R ₂ , R ₃ and R 4 are independently a hydrogen atom or a substituent R g or the substituents R 1 and R ₂ together are -X*-Y*-Z*-, where X* is -O- or -CH ₂ -, Y* is -C(O)- or (C(R ₁₂ )(R ₁₃ )) _v -, where the substituents R ₂ and R ₃ are independently a hydrogen atom or an alkyl having one to twelve carbon atoms and the index v is 1, 2 or 3 and Z* is selected from -CH ₂ -, -CH ₂ S(O)t-, -CH ₂ O-, -CH ₂ NR ₇ -, -NR ₇ - and -O-;

L ₂ is selected from (1) a covalent bond, (2) alkylene having one to twelve carbon atoms, (3) alkylene having one to twelve carbon atoms substituted with 1 or 2 substituents independently selected from « «

(a) spiroalkyl having three to eight carbon atoms, (b) spiroalkenyl having five or eight carbon atoms, (c) oxo, (d) halogen, and (e) -OH, with the proviso that no two -OH groups are attached to the same carbon atom, (4) alkynylene having two to twelve carbon atoms, (5) (6) (7) (8)

-NR7-, -C(X)-, -O-, and -S(O\-; and _R5 is selected from (1) halogen, (2) hydrogen, (3) -C(= _NR7 ) _OR10 , (4) -CN, with the proviso that if _R5 is (1), (2) or (3) then _L2 is a covalent bond, (5) alkyl having one to twelve carbon atoms, (6) alkynyl having up to twelve carbon atoms, with the proviso that the carbon of the carbon-carbon triple bond is not directly attached to L3 if L3 is other than a covalent bond, (7) cycloalkyl having three to twelve carbon atoms, (8) heterocycle, (9) aryl wherein (5) - (9) may be optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from (a) -OH, with the proviso that two -OH groups are not attached to the same carbon atom, (b) -SH, with the proviso that two • ** * · Ί» * * • · * · « « « t • · * · · · 9 * · * • * * W · · * <» * * ·· * ·

-SH groups, (c) -CN, (d) halogen, (e) -CHO, (0 -no ₂ , (g) haloalkoxy groups having one to twelve carbon atoms, (h) perfluoroalkoxy groups having one to twelve carbon atoms, (i) -NRs-Rs»·, where the substituents R ₈ and R 9 are selected from (i) a hydrogen atom, (ii) alkanoyl, where the alkyl portion has one to twelve carbon atoms, (iii) alkoxycarbonyl, where the alkyl portion has one to twelve carbon atoms, (iv) alkoxycarbonyl, where the alkyl portion has one to twelve carbon atoms and is substituted with 1 or 2 phenyl substituents, (v) cycloalkyl having three to twelve carbon atoms, (vii) alkyl having one to twelve carbon atoms, (vii) alkyl having one to twelve carbon atoms substituted with 1, 2 or 3 substituents independently selected from alkoxy groups having one to twelve carbon atoms, cycloalkyl having three to twelve carbon atoms, aryl and alkoxycarbonyl, where the alkyl group has one to twelve carbon atoms, (viii) alkenyl having three to twelve carbon atoms, with the proviso that the carbon of the carbon-carbon double bond is not directly attached to the nitrogen, (ix) alkynyl having three to twelve carbon atoms, with the proviso that the carbon of the carbon-carbon triple bond is not directly attached to the nitrogen, (x) -C(O)NRxRy, where the substituents Rx and Ry are independently selected from hydrogen and alkyl having one to twelve carbon atoms, (xi) alkoxy groups having one to twelve carbon atoms, (xii) aryl, and (xiii) aryl substituted with 1, 2, 3,4 or 5 substituents independently selected from alkyl having one to twelve carbon atoms, alkanoyloxy groups where the alkyl portion has one to twelve carbon atoms, alkoxycarbonyl where the alkyl portion has one to twelve carbon atoms, alkoxy groups having one to twelve carbon atoms, halogen,

-OH with the proviso that two -OH groups are not attached to the same carbon atom, thioalkoxy groups having one to twelve carbon atoms, perfluoroalkyl having one to twelve carbon atoms,

-NR7R7',

-CO2R10,

-OSO2R11, (—X) or the substituents Rs· and R9· together with the nitrogen atom to which they are attached form a ring selected from (i) aziridine, (ii) azetidine, (iii) pyrrolidine, (iv) piperidine, (v) pyrazine, (vii) morpholine, (vii) phthalimide, (viii) thiomorpholine, and (ix) thiomorpholine sulfone wherein (i) - (ix) may be optionally substituted with 1, 2 or 3 alkyls having one to twelve carbon substituents,

0) =NNR ₈ R ₉ ·, (k) -NR ₇ NRsR9', (l) -CO ₂ R ₈ , (m) -C(X)NR8-R9, (n) =N-OR ₈ , (o) =NR ₈ , (p) -SÍOXRw, (q) -X'C(X)R«, « · * *♦ · ♦ 0 · * 0 *0 0 • · 0 · 0 0 * 0 00« • · * * * 0 0 0 · · 0 * 0« 0 • 0·· » · · · · 12 ** *'*' ** ^Μ ω m (s) -0-(CH ₂ )qZ-R 10, where the substituent R ₁₀ is defined above, the index q is 1, 2 or 3 and Z is O or -S(O)t-, (t) -OC(X)NR ₈ R ₉ , (u) -OSO ₂ R _h , (v) alkanoyloxy groups, where the alkyl group has one to twelve carbon atoms, (w) -LbRío, where L _B is selected from (i) a covalent bond, (ii) -O-, (iii) -S(O)t-, and (iv) -C(X)-, and the substituent R30 is selected from (i) alkyl having one to twelve carbon atoms, (ii) alkenyl having one to twelve carbon atoms, with the proviso that the carbon of the carbon-carbon double bond is not directly attached to Lb if Lb is other than a covalent bond, (iii) alkynyl having one to twelve carbon atoms, with the proviso that the carbon of the carbon-carbon triple bond is not directly attached to L _B if L _B is other than a covalent bond, where (i), (ii) and (iii) may be optionally substituted with cycloalkyl having three to twelve carbon atoms,

-OH with the proviso that no two -OH groups are attached to the same carbon atom, a carbon atom, a halogen, an alkoxy group having one to twelve carbon atoms, a thioalkoxy group having one to twelve carbon atoms,

-NRsRg,

-O-(CH ₂ ) _q -Z-R 10 , alkoxycarbonyl, where the alkyl group has one to twelve carbon atoms, alkanoyloxy groups, where the alkyl group has one to twelve carbon atoms,

Φφ ·» ·* φφ φφ ·· * φ · φ φφφφ φφφφ φ « φ ··»♦ ι φ « * • ΦΦΦ · * φ ΦΦΦ · φ · « φ φ ΦΦΦ «φφφφ φφφφ φφ ·· φφφφφ φφ

-NR7SO2-(alkyl having one to twelve carbon atoms),

-OSO ₂ -(alkyl having one to twelve carbon atoms), aryl, and heterocycles, (iv) aryl, (v) aryl substituted with 1, 2, 3, 4 or 5 substituents independently selected from alkyl having one to twelve carbon atoms, halogen,

-NO2, and -OH, with the proviso that no two -OH groups are attached to the same carbon atom, (vi) heterocycles, and (vii) heterocycles substituted with 1, 2, 3, 4, or 5 substituents independently selected from alkyl having one to twelve carbon atoms, halogen,

-NO2, and -OH with the proviso that two -OH groups are not attached to the same carbon atom, (x) -X'C(X)XRio, (y) -NHC(O)NHNH ₂ , (z) alkenyl having two carbon atoms, (aa) -C(=NR ₇ )ORio, and (bb) -NR7(X)NRsR9-,

with the proviso that when R5 is (9), then _L3 is other than -NR7- or -O-, wherein the carbon-carbon double bond has the Z or E configuration and the substituents _R19 , R20 and R21 are independently selected from (a) hydrogen, « · *488 4 4 8 8

9 4 9 4 8 4

89· 4 4 9 4844

9 4 9 4

- _A 44 8 4 99 ·· · · • 9 4 · ·· 84 (b) halogen, (c) alkoxycarbonyl, where the alkyl group has one to twelve carbon atoms, (d) alkyl having one to twelve carbon atoms, and (e) alkyl having one to twelve carbon atoms substituted with (i) alkoxy having one to twelve carbon atoms, (ii) -OH, with the proviso that two -OH groups are not attached to the same carbon atom, (iii) -SH, with the proviso that two -SH groups are not attached to the same carbon atom, (iv) -CN, (v) halogen, (vi) -CHO, (vii) -NO ₂ , (viii) haloalkoxy groups having one to twelve carbon atoms, (ix) perfluoroalkoxy groups having one to twelve carbon atoms, (x) -NR^Ry, (xi) =NNR ₈ -R ₉ -, (xii) -NRýNRs-Rr, (xiii) -CO2R10, (XÍV) -C(X)NR8-R9, (xv) =N-ORm, (xvi) =NRio, (xvii) -S(0)tRio, (xviii) -X'C(X)Rio, (xix) (=X), (xx) -0-(CH ₂ ) _q -Z-Rio, (xxi) -OC(X)NR8R ₉ , (xxii) -L _b R ₃ o, (xxiii) alkanoyloxy groups, where the alkyl group has one or twelve carbon atoms, (xxiv) -OSO ₂ Rh, and • 4 4 4 »4 · • ·*· 4 4

4 4 4 44

44 • 4 · 4 » 4 4 4

4 4 4 4

4 4 (χχν) -NR ₇ (X)NRg R ₉ or the substituents R ₂ o and R ₂ i together are selected from (a) cycloalkyl having three to twelve carbon atoms, (b) cycloalkenyl having four to twelve carbon atoms, and '22

R-23 (c) (allen), wherein R ₂₂ and R ₂₃ are independently hydrogen or alkyl having one to twelve carbon atoms, and (11) cycloalkenyl having four to twelve carbon atoms, wherein together the cycloalkenyl group or the ring formed by R ₂₀ and R ₂₁ may be substituted with one or two substituents independently selected from (a) alkoxy having one to twelve carbon atoms, (b) -OH, with the proviso that two -OH groups are not attached to the same carbon atom, (c) -SH, with the proviso that two -SH groups are not attached to the same carbon atom, (d) -CN, (e) halogen, (f) -CHO, (g) -no ₂ , (h) haloalkoxy having one to twelve carbon atoms, (i) perfluoroalkoxy having one to twelve carbon atoms, (j) -NRgRsr, (k) =nnr ₈ r ₉ ·, (l) -nr ₇ nr ₈ r ₉ , (m) -CO ₂ R ₁₀ , (n) -C(X)NRsR ₉ -, (o) =N-ORio, (p) =nr ₁₀ , (q) -S(O)tR ₁₀ , (r) -X'C(X)R ₁₀ , (s) (=X),

Φ· Φ· Φ<* *· ·· ΦΦ • Φ Φ « Φ Φ Φ < · ♦ « « β·· Φ Φ φ Φ φ φ φ φ • ΦΦ« φ · Φ ·ΦΦ ♦ Φ · Φ Φ

Φ Φ · » Φ Φ Φ Φ Φ

Φ·ΦΦ ΦΦ «Φ »Φ ΦΦ Φ-Φ

(t) -O-(CH ₂ ) _q -ZR ₁₀ , (at) -OC(X)NRsR ₉ , (in) -LbR30, (w) alkanoyloxy groups, where the alkyl group has one to twelve carbon atoms, (x) -OSO ₂ Rn, and (y) -NR ₇ (X)NR 5 R ₉ ;

the substituent R<5 is a hydrogen atom or an alkyl having one to twelve carbon atoms; or

-L2-R5 and R6 together are selected from (1) -o, (2) , where δ is 1, 2, 3 or 4 and A is selected from (a) _-CH2- , (b) -O-, (c) -S(0) _t , and (d) _-NR7- , and

Rome.

(3) , wherein the carbon-carbon double bond may have an E or Z configuration and the substituents R ₂ 6 and R ₂ 6 are independently selected from (a) hydrogen, (b) alkenyl having three to twelve carbon atoms, (c) aryl, (d) heterocycles, (e) alkyl having one to twelve carbon atoms, (f) cycloalkyl having three to twelve carbon atoms, (g) cycloalkenyl having four to twelve carbon atoms, and (h) cycloalkenyl having four to twelve carbon atoms, wherein (a) - (f) may be optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from (i) alkoxy having one to twelve carbon atoms, (ii) -OH, with the proviso that there are no ·· ·♦ ♦♦ ·« ·· ·* • «« · · ·· « · » # · • · · · · · * ♦ · · * • ♦·· · » · *·· * t »· » • · · ♦ ♦ · · · · «·*· *· ·* ♦♦ ·« *· two -OH groups attached, (iii) -SH, with the proviso that two -SH groups are not attached to the same carbon atom, (iv) -CN, (v) halogen, (vii) -CHO, (vii) -NO2, (viii) haloalkoxy groups having one to twelve carbon atoms, (ix) perfluoroalkoxy groups having one to twelve carbon atoms, (x) -NR ₈ R ₉ , (xi) =NNR ₈ -R ₉ ·, (xii) -NR ₇ NR ₈ R ₉ , (xiii) -C0 ₂ Rio, (xiv) -C(X)NR ₈ R ₉ , (xv) =N-ORio, (xvi) =NRio, (xvii) -S(0)tRio, (xviii) -X'C(X)R ₁₀ , (xix) (=X), (xx) -O-(CH ₂ ) _q -ZR ₁₀ , (xxi) -OC(X)NR 8 R ₉ , (xxii) -L _b R ₃ o , (xxiii) alkanoyloxy groups, where the alkyl group has one to twelve carbon atoms, (xxiv) -OSO ₂ R n , and (xxv) -NR ₇ (X)NR ₈ R ₉ ;

the substituents R ₁₆ and R 18 are independently hydrogen or alkyl having one to six carbon atoms; or the substituents R ₁₆ and R 18 together are alkenyl having two carbon atoms;

the dashed line represents an optionally present double bond, with the proviso that if the substituents R ₁₆ and R ₁₇ together are alkenyl having two carbon atoms, then the double bond is not present;

φ * φ · φ · φ φ • φ φ φ φ φ φ φ φ φ· φφ ·*

ΦΦ • · φ · · φφφ φ φ φφφ φ » φ φ φ φφφφ φφ *« • · φ φ φ φ φ φφφ φ φ φφ

Υ is selected from carbon, nitrogen and N+^O');

the substituent R _n is absent or is hydrogen or alkyl having one to six carbon atoms, with the proviso that if a double bond is present and Y is nitrogen or N ⁺ (=O), then the substituent R 17 is absent; and the substituents R ₈ and R ₈ are independently hydrogen or alkyl having one to six carbon atoms; or the substituents R ₈ and R ₈ - together are a cycloheteroalkyl ring or a cycloalkyl ring having three to eight carbon atoms.

In another embodiment of the invention, compounds of formula II are described.

or pharmaceutically acceptable salts or prodrugs thereof, wherein the substituents R 1 , R ₂ , R 3 , R 4 , R 5 , R 6 and L ₂ are as defined above.

In another embodiment of the invention, compounds of formula III are provided.

or pharmaceutically acceptable salts or prodrugs thereof, wherein the substituents R 1 , R ₂ , R ₃ , R 4 , R ₅ , R ₆ and L ₂ are as defined above.

In another embodiment of the invention, compounds of formula IV are described.

0» 00

0 0 0 • 0 0

000

0

Λ· 0* ·*

0 0 · · 0« 0 • 00 0 »«0 0 • · 0 0··· 0 · · 0 0 0 »000

00 00 00 or their pharmaceutically acceptable salts or prodrugs, wherein

Y is nitrogen or N ⁺ (=O ) and the substituents R 1 , R 5 , R 6 and L 2 are as defined above.

In another embodiment of the invention, compounds of formula V are described.

or pharmaceutically acceptable salts or prodrugs thereof, wherein the substituents R 1 , R 5 and L ₂ are as defined above.

the substituents R ₁₆ and R ₁₇ are independently hydrogen or alkyl having one to six carbon atoms; and the substituents R ₁₈ and R ₁₈ are independently hydrogen or alkyl having one to six hydrogen atoms; or the substituents R ₁₈ and R ₁₈ together are a cycloheteroalkyl ring or a cycloalkyl ring having three to eight carbon atoms;

• 0 * 0

000 · 0

0 ·

0 0

0 0 « 0 0

In another embodiment of the invention, methods of selectively partially antagonizing, agonizing, or modulating glucocorticoid receptors are described.

In another embodiment of the invention, methods of treating a disease comprising administering an effective amount of a compound of formula I are described.

In yet another embodiment of the invention, pharmaceutical compositions comprising compounds of formula I are described.

Compounds of the present invention include, but are not limited to,

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano[3,4-f]quinoline-1H[1]benzopyrano[3,4-f|quinoline,

2.5-dihydro-10-methoxy-2,2,4-trimethyl-5-(2-propenyl)-1Η-[1]benzopyrano[3,4-f|quinoline,

2.5-Dihydro-2,2,4,N-tetramethyl-5-(2-propenyl)-1Η-[1]benzopyrano[3,4-f]quinoline-10-amine, methyl 2,5-dihydro-2,2,4-trimethyl-5-(2-propenyl)-1H-[1]benzopyrano[3,4-f]quinoline-10carboxylate,

10-ethenyl-2,5-dihydro-2,2,4-trimethyl-5-(2-propenyl)-1H-[1]benzopyrano[3,4-f}quinoline,

10-ethyne 1-2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-(2-propenyl)-1H-[1]benzopyrano[3,4f]quinoline,

2.5-Dihydro-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano[3,4-flquinolin-10-ol,

10-(difluoromethoxy)-2,5-dihydro-2,2,4-trimethyl-5-(2-propenyl)-1H-[1]benzopyrano[3,4fquinoline,

10-ethoxy-2,5-dihydro-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano[3,4-f|quinoline,

2,5-dihydro-2,2,4-trimethyl-5-phenyl-1H-[l]benzopyrano[3,4-f]quinoline-10-acetate (ester), 5-(3-bromo-5-methylpheny 1 )-2,5-dihydro-10-methoxy-2,2,4-trimethyl- 1Η-[ 1 ]benzopyrano[3,4f]quinoline, acetate 3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolin-5-yl)phenol, (ester),

3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolin-5-yl)-phenol, • 9 9 9

9 9 9 •w «η *· • · « · · · » · · · • ··· · · # • · · ·

9999 99 99 *

··· **»

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[[3-(methylthio)methoxy]phenyl]-1H[ 1 ]benzopyrano[3,4-f|quinoline, [3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolin-5-yl)-phenyl]dimethylcarbamate,

5-[3-(2-furanyl)-5-methylphenyl]-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline,

2.5-dihydro-10-methoxy-2,2,4-trimethyl-5-[3-methyl-5-(1-morpholinyl)phenyl]-1H[1]benzopyrano[3,4-f]quinoline,

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(phenylmethylene)-1H-[1]benzopyrano[3,4fquinoline,

5-(3,5-dichlorophenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline,

5-butyl-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4-f|quinoline,

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[3-(trifluoromethyl)phenyl]-1H-[1]benzopyrano[3,4fquinoline,

2.5-Dihydro-10-methoxy-5-(4-methoxyphenyl)-2,2,4-dimethyl-1H-[1]benzopyrano[3,4fquinoline,

5-(3-Chlorophenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[l]benzopyrano[3,4-f]quinoline, 2,5 -dihydro-10-methoxy-2,2,4-trimethyl-5-(3-methylphenyl)-1H-[1Jbenzopyrano[3,4-f]quinoline, (±) 2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-phenyl-1H-[l]benzopyrano[3,4-f]quinoline, (±)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-phenyl-1H-[l]benzopyrano[3,4-f]quinoline, 5-(3,5-dimethylphenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline,

5-(4-chlorophenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline,

5-(3,4-dimethylphenyl)-2,5-dihydro-10-methoxy-2,2,4-dimethyl-1H-[1]benzopyrano[3,4fquinoline,

5-(4-Fluorophenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline, 5-[3,5-bis(trifluoromethyl)phenyl]-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline, (-)-5-(3,5-dichlorophenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[l]benzopyrano[3,4fjquinoline, «« Φ· ft φ · Φ φ * Φ

Φ »·· « Φ

ΙΦΦΦ ΦΦ φφ ΦΦ I Φ Φ Φ * φ · · • ♦ · ΦΦ ♦* «φ • · φ * φφ »♦ (+)-5-(3,5-dichlorophenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-lH-[l]benzopyrano[3,4-quinoline,

5-(3,5-difluorophenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4f]quinoline,

2.5-Dihydro-10-methoxy-2,2,4,N-tetramethyl-N-phenyl-1H-[1]benzopyrano[3,4-f]quinoline-5amine, (-)2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-(2-propenyl)-1H-[1]benzopyrano[3,4-f]quinoline, (+)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-(2-propenyl)-1H-[1Jbenzopyrano[3,4fquinoline,

2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline,

4-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolin-5-yl)-N,Ndimethylbenzenamine,

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(5-methoxy-2-thienyl)-1H-[1]benzopyrano[3,4fquinoline,

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(5-propyl-2-ithienyl)-1H-[1]benzopyrano[3,4fquinoline,

2.5-Dihydro-10,methoxy-2,2,4-trimethyl-5-[4-(1-morpholinyl)phenyl]-1H-[1]benzopyrano[3,4fquinoline,

-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolin-5-y1)-3,3dimethyl-2-butanone,

2.5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline-5-carbonitrile,

-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolin-5-yl)-2propanone, methyl-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolin-5-acetate,

2-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4-f]quinolin-5-yl)-1 phenylethanone,

5-[2-(chloromethyl)-2-propene 1 ]-2,5-dihydro-10-methoxy-2,2,4-trimethyl- 1H[ 1 jbenzopyrano [3,4-f]quinoline,

2.5-dihydro-10-methoxy-2,2,4-trimethyl-(-methylene-1Η-[1]benzopyrano[3,4-f]quinoline-5propanol, acetate (ester),

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(4-methylphenyl)-1H-[1]benzopyrano[3,4fjquinoline, • ·** «a a aaa a a a a a • aaa « a · a · ··♦· ·· ·* ·· '· ·*

5-(3-fluoro-4-methylphenyl)-2 ₃ 5-dihydro-10-methoxy-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4f]quinoline,

5-(3-Bromophenyl)-2,5-dihydro-10-methoxy-2,2 ₅ 4-trimethyl-1H-ri]benzopyrano[3,4-fJquinoline,

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(phenylniethyl)-1H-[1]benzopyrano[3,4-f]quinoline,

2.5-dihydro-10-methoxy-2 ₃ 2 ₃ 4-trimethyl-5-propyl-1H-[1]benzopyrano[ _3s 4-f]equinoline ₃ 5-(4-fluorophenyl)-2,5-dihydro-10-methoxy-2 ₃ 2 _; 4-trimethyl 1-1Η-[1]benzopyrano[3,4-f]quinoline, 5-(3-fluorophenyl)-2,5-dihydro-10-methoxy-2 ₅ 2,4-trimethyl-1H-[1]benzopyrano[3 ₅ 4-f]equinoline,

2.5-Dihydro-10-methoxy-2,2,4,5-tetramethyl-1H-[1]benzopyrano[3 ₅ 4-f]quinoline ₅

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(1-methylethyl)-1H-[1]benzopyrano[3,4f|quinoline,

2 _J 5-dihydro-10,methoxy-2,2,4-trimethyl-5-(2-methylpropyl)-1H-[1]benzopyrano[3 _! 4f]quinoline,

5-ethyl-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-fquinoline, 2,5-dihydro-10-methoxy-2 ₃ 2 ₃ 4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline-5-carboximidic acid ethyl ester,

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-(-methylene 1H-[1]benzopyrano[3,4-f]quinoline-5propanol,

2.5-dihydro-10-methoxy-2,2,4,N,N-pentamethyl-1H-[1]benzopyrano[3.4-1]equinoline-5-acetamide,

2.5-dihydro-10-methoxy-2 ₅ 2,4,N ₅ N-pentamethyl-1H-[1]benzopyrano[3,4-flquinoline-5ethanamine,

N-cyclopropyl-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[ _3J 4-f]quinoline-5acetamide,

2.5- dihydro-10-methoxy-2 ₃ 2,4-trimethyl-5-(2-propynyl)-1Η-[ 1 ]benzopyrano[3,4-phenylquinoline,

5-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4-1]quinolin-5-yl-2(5H)furanone,

5-(3-butene 1)-2,5-dihydro-10-methoxy-2,2,4-trimethylbyl-1Η-[1]benzopyrano[3,4-quinoline,

2.5-Dihydro-10-methoxy-2 _J 2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline-5-propanol, 10-ethyl-2 ₃ 5-dihydro-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano[3,4-f|quinoline, 2 ₃ 5-dihydro-2,2 ₃ 4 ₃ 10-tetramethyl-5-phenyl-lH-[l]benzopyrano[3,4-f]equinoline ₃ 5-(3,5-dichlorophenyl)-10-ethyl-2 ₃ 5-dihydro-2,2 ₃ 4-trimethyl-lH-[l]benzopyrano[3 ₃ 4-f]quinoline, 5-(3,5-dichlorophenyl)-2,5-dihydro-2,2 ₅ 4 ₃ N-tetramethyl-1H-[l]benzopyrano[3,4-f]quinoline-10amine, fr· ·· • · · · • · • · ···· ·· ··· · · • ·

5-(3,5-dichlorophenyl)-2,5-dihydro-2,2,4-trimethyl-N-(2-propenyl)-1H-[1]benzopyrano[3,4fquinolin-10-amine,

2.5-Dihydro-2,2,4-trimethyl-5-phenyl-10-(2-propynyloxy)-1H-[ljbenzopyrano[3,4-fquinoline,

2.5-Dihydro-2,2,4-trimethyl-5-phenyl-10-(2-propenyloxy)-1H-[1]benzopyrano[3,4-fquinoline,

2.5-dihydro-2,2,4-trimethyl-5-(2-propenyl)-1Η-[1]benzopyrano[3,4-quinoline-10-methanol,

2.5-Dihydro-2,2,4-trimethyl-5-(2-propenyl)-1H-[1-benzopyrano[3,4-quinoline-10-carboxylic acid,

5-(3,5-dichlorophenyl)-10-ethoxy-2,5-dihydro- _2,2s 4-trimethyl-1H-[1]benzopyrano[3,4f]quinoline,

5-(3,5-dichlorophenyl)-2,5-dihydro-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4-f]quinolin-10-ol,

5-(3,5-Dichlorophenyl)-2,5-dihydro-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-quinolin-10yl]methylcarbonate,

2.5-Dihydro-2,2,4-trimethyl-5-(2-propenyl)-1H-[1]benzopyrano[3,4-fquinolin-10-ol, 10-(bromodifluoromethoxy)-2,5-dihydro-2,2,4-trimethyl-5-(2-propenyl)-1H[ 1 ]benzopyrano[3,4-fquinolin-10-ol, [3 -(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-quinolin-5-yl)phenyl]methylcarbonate,

2.5-Dihydro-10-methoxy-5-(3-methoxyphenyl)-2,2,4-trimethyl-1H-[ljbenzopyrano[3,4fjquinoline,

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[3-(2-propenyloxy)phenyl]-1H-[1]benzopyrano[3,4fquinoline,

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[3-(phenylmethoxy)phenyl)-1H-[ljbenzopyrano[3,4fquinoline,

5-[3-(cyclopropylmethoxy)phenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H[1]benzopyrano[3,4-fJquinoline,

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[3-[2-(1-piperidinyl)ethoxy)phenyl]-1H[1]benzopyrano[3,4-f]quinoline,

-(3-hexyloxyphenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1jbenzopyrano[3,4fquinoline,

5-(3-(2,4-dinitrophenoxy)phenyl]-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H[ljbenzopyrano[3,4-fj quinoline,

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[3-(2~propynyloxy)phenyl]-1H~ [ 1 ]benzopyrano[3,4-f]equinoline, »·· · · • ·· ·

3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4f]quinolin-5-yl)phenol 4-methylbenzenesulfonate (ester),

4-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1Η-[1]benzopyrano(3,4-f]equinolin-5yl)phenol acetate (ester),

4-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]equinolin-5-yl)-phenol,

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[[4-(methylthio)methoxy]phenyl]-1H[ 1 ]benzopyrano[3,4-f]quinoline, [4-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f!quinolin-5yl)phenyl]dimethylcarbamate,

2.5-Dihydro-1Q-methoxy-2,2,4-trimethyl-5-[4-(phenylmethoxy)phenyl)-1Η-[1]benzopyrano[3,4flquinoline,

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[3-(methoxymethoxy)phenyl]-1H[1]benzopyrano[3,4-f]quinoline, ((2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-fJquinolin-5-yl)phenyl]lmorpholinecarboxylate,

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[3-[(methylsulfonyl)methoxy]phenyl]-1H[1]benzopyrano[3,4-f]quinoline,

O-(3-(2,5-dihydro-1Q-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f)quinolin-5yl)phenyl]ester,

2.5-dihydro-10-methoxy-2,2,4-trimethyl-5-[3-(methylthio)phenyl]-1H-[1]benzopyrano[3,4f]quinoline,

O-(3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano(3,4-f]quinolin-5yl)phenyl)methylcarbonothioate, [3-2,5-dihydro-10-methoxy-2,2,4-trimethyl]-1H-[1]benzopyrano[3,4-f]quinolin-5yl)phenyl]trifluoromethanesulfonate,

5-(3-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)phenyl]-2,5-dihydro-10-methoxy-2,2,4-trimethyl1H-[1Jbenzopyrano[3,4-f]quinoline, ethyl 3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolin-5yl)benzoate,

-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano(3,4-f]quinolin-5-yl)benzoic acid,

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[3-methyl-5-(2-propenyl)phenyl]-1H[1]benzopyrano[3,4-quinoline, • · • ·

1-(3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano(3,4-f]quinolin-5-yl)-5methylphenylethanone,

3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-fJquinolin-5-yl)-5-trimethylbenzenemethanol,

5-[3-(2-furanyl)phenyl]-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline,

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[3-methyl-5-(1H-pyrrolidin-1-yl)phenyl]-1H[1]benzopyrano(3,4-quinoline,

3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline-5-methyl)5,N-dimethylbenzenamine,

3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolin-5-yl)-5methyl-N-(2-propenyl)benzamide,

3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolin-5-yl)-N-(2methoxyethyl)-5-methylbenzenamine,

3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolin-5-yl)-N-(2propenyl)benzenamine,

N'-[3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-fJquinolin-5-yl)-5methylphenyl]-N,N-dimethylurea,

N -[3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4-fJquinolin-5yl)phenyl)benzenemethanamine,

5-((3,5-dichlorophenyl)methylene]-2,5-dihydro-10-methoxy-2,2,4,trimethyl-1H[1]benzopyrano[3,4-quinoline,

5-[(4-chlorophenyl)methylene]-2,5-dihydro-10-methoxy-2.2 ₅ 4-trimethyl-1H-[1]benzopyrano[3,4fquinoline,

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[[3-(trifluoromethyl)-phenyl-methylene-1H-[1-benzopyrano[3,4-quinoline,

5-((2,6-difluorophenyl)methyleneJ-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H[1Jbenzopyrano[3,4-quinoline,

5-((2-Chlorophenyl)methylene-2,5-dihydro-1H-methoxy-2,2,4-trimethyl-1H-[1H-benzopyrano[3,4]quinoline,

5-((2,6-dichlorophenyl)methylene]-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H[ 1 Jbenzopyrano[3,4-fJquinoline, . ··· · · Β Β·Β Β · Β Β • Β Β · · · · · ······ ·· ·· ·* *

5-[(2-Fluorophenyl)methylene]-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4f]quinoline,

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[(4,5-dihydro-4,4-dimethyl-2-oxazolyl)methylene]1H-[1]benzopyrano[3,4-f]quinoline,

2.5-dihydro-10-methoxy-2,2,4-trimethyl-5-(2-pyridinylmethylene)-1H-[1]benzopyrano[3,4f]quinoline,

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(2-thienyl)-1H-[1]benzopyrano[3,4-f]quinoline,

2.5-Dihydro-9,10-dimethoxy-2,2,4-trimethyl-5-(2-propenyl)-1H-[l]benzopyrano[3,4fquinoline,

5-(2-cyclohexen-1-yl)-2,5-dihydro-9,10-dimethoxy-2,2,4-trimethyl-1H-[1Jbenzopyrano[3,4fquinoline,

2.5-Dihydro-10-methoxy-5-(3-methyl-3-butenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4f]quinoline,

2.5-Dihydro-10-methoxy-5-(5,5-dimethyl-3-cyclohexenyl)-2,2,4-trimethyl-1H[ 1 jbenzopyrano [3,4-f] quinoline, rel (5R,2'R) 2,5-dihydro-10-methoxy-5-(2-oxo-3 -tetrahydropyranyl)-2,2,4-trimethyl-1H[ ]benzopyrano[3,4-f]quinoline, anti(5R,2'5)2,5-dihydro-10-methoxy-5-(2-oxo-3-tetrahydropyranyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline,

2.5-dihydro-10-methoxy-5-(3-cyclopentenyl)-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4f]quinoline,

2.5-dihydro-10-methoxy-5-(3-cyclohexenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4f]quinoline,

2.5-dihydro-10-methoxy-5-(3-butenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline,

2.5-dihydro-10-methoxy-5-(1-ethenyl-1-cyclohexyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4f]quinoline,

2.5-dihydro-10-methoxy-5-(4,4-dimethyl-3-cyclohexenyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline,

2.5-dihydro-10-methoxy-5-(1-methylene-2-cyclohexyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline,

2.5-Dihydro-10-methoxy-5-(l-oxo-2-cyclohexyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4f]quinoline, • φ φ φ

2.5-dihydro-10-methoxy-5-(3-cyclooctenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4f]quinoline,

2.5-Dihydro-10-methoxy-5-(3-cycloheptenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fjquinoline,

2.5-dihydro-10-methoxy-5-(1-cyclohexenylmethyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4f]quinoline,

2.5-dihydro-10-methoxy-5-(3,3-dimethyl-6-cyclohexenyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline,

2.5-Dihydro-10-methoxy-5-(2-bromo-3-propenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4f]quinoline, rel(5R,3'R) 2,5-dihydro-10-methoxy-5-(1-hydroxymethyl-3-cyclohexenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline, rel(5R,3'S) 2,5-dihydro-10-methoxy-5-(1-hydroxymethyl-3-cyclohexenyl)-2,2,4-trimethyl1H-[1]benzopyrano[3,4-f]quinoline,

2.5-dihydro-10-methoxy-5-(3-hydroxymethyl-3-cyclohexenyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline,

2.5-Dihydro-10-methoxy-5-(3-indolyl)-2;2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline, rei (5S,3'S) 2,5-dihydro-10-methoxy-5-(1-methyl-3-cyclohexenyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline, rel (5R,3'S) 2,5-dihydro-10-methoxy-5-(l-methyl-3-cyclohexenyl)-2,2,4-trimethyl-1H[ 1 ] benzopyrano [3,4-f]quinoline, (-) (5S,3'S) 2,5-dihydro-10-methoxy-5-(l -methyl-3-cyclohexenyl)-2,2,4-trimethyl-1H[ 1 ]benzopyrano[3,4-f]quinoline, (-) (5S, 3'R) 2,5-dihydro-10-methoxy-5-(1-hydroxymethyl-3-cyclohexenyl)-2,2,4-trimethyl1 H-[ 1 ]benzopyrano[3,4-f]quinoline, (+) (5R, 3'S) 2,5-dihydro-10-methoxy-5-( 1-hydroxymethyl-3-cyclohexenyl)-2,2,4-trimethyl 1 H-[ 1 ]benzopyrano[3,4-f]quinoline, (-)-(5S, 3'R) 2,5-dihydro-10-methoxy-5-(1-methyl-3-cyclohexenyl)-2,2,4-trimethyl-1H[ 1 ]benzopyrano[3,4-f]quinoline, (+)-(5R, 3'S) 2,5-dihydro-10-methoxy-5-(1-methyl-3-cyclohexenyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline,

2.5-Dihydro-10-methoxy-5-(1-chloromethyl-3-cyclohexenyl)-2,2,4-trimethyl-1H[ 1 ]benzopyrano [3,4-f] quinoline, • · • · · · · rel (5R, 3'R) 2,5-dihydro-10-methoxy-5-(1-methoxymethyl-3-cyclohexenyl)-2,2,4-trimethyl-1H[ 1 ]benzopyrano[3,4-f]quinoline, rel (5R, 3'R) 2,5-dihydro-10-methoxy-5-(1-methylthiomethyl-3-cyclohexenyl)-2,2,4trimethyl-1 H-[ 1 ]benzopyrano[3,4-f]quinoline, rel (5R, 3'S) 2,5-dihydro-10-methoxy-5-(1-acetoxymethyl-3-cyclohexenyl)-2,2,4-trimethyl1 H-[ 1 ]benzopyrano[3,4-fquinoline, rel (5R, 3'R) 2,5-dihydro-10-methoxy-5-(1-acetoxymethyl-3-cyclohexenyl)-2,2,4-trimethyl1 H-[ 1 ]benzopyrano[3,4-f]quinoline, rel (5R, 3'R) 2,5-dihydro-10-methoxy-5-(l-methoxymethyl-3-cyclohexenyl)-2,2,4-trimethyl1 Η- [ 1Jbenzopyrano[3,4-f]quinoline, rel (5R, 3'R) 2,5-dihydro-10-methoxy-5-(l-(N,N-dimethylamino)methyl-3-cyclohexenyl2,2,4-trimethyl-1 H-[ 1 ]benzopyrano[3,4-f]quinoline, rel (5R, 3'S) 2,5-dihydro-10-methoxy-5-(l-methylthiomethyl-3-cyclohexenyl)-2,2,4-trimethyl-1 Η- [ 1 ]benzopyrano [3,4-f] quinoline, rel (5R, 3'R) 2,5-dihydro-10-methoxy-5-(1-(N-morpholino)methyl-3-cyclohexenyl)-2,2,4trimethyl-1 H-[ 1 Jbenzopyrano [3,4-f] quinoline, rel (5R, 3'R) 2,5-dihydro-10-methoxy-5-(l-(N-methyl-N-methylsulfonylamino)methyl-3-cyclohexenyl)-2,2,4-trimethyl-1H-[l]benzopyrano[3,4-f]quinoline, rel (5R, 3'S) 2,5-dihydro-10-methoxy-5-(l-(N,N-dimethylamino)methyl-3-cyclohexenyl)-2,2,4-trimethyl-1H-[ 1 Jbenzopyrano [3,4-f]quinoline, rel (5R, 3'R) 2,5-dihydro-10-methoxy-5-(1-(N-methylamino)methyl-3-cyclohexenyl)-2,2,4trimethyl-1 Η- [ 1 Jbenzopyrano [3,4-f]quinoline,

2.5-dihydro-10-methoxy-5-(2-methyl-3-propenyl)-2,2,4-trimethyl-1H-[1Jbenzopyrano[3,4f]quinoline,

2.5-Dihydro-10-methoxy-5-(1,3-butadiene-2-yl)-2,2,4-trimethyl-1H-[1Jbenzopyrano[3,4fjquinoline,

2.5-dihydro-10-methoxy-5-(2-carbomethoxy-3-propenyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline,

2.5-dihydro-10-methoxy-5-(1,2-dihydroxy-3-propyl)-2,2,4-trimethyl-1H-[1Jbenzopyrano[3,4f]quinoline,

2,5-dihydro-10-methoxy-5-(1,2-epoxy-3-propenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fjquinoline,

2,5-dihydro-10-methoxy-5-( 1 -(N-phthalimido)-3-propyl-2,2,4-trimethyl-1H[ 1 ]benzopyrano[3,4-fquinoline, • · · · ·

2,5-dihydro-10-methoxy-5-(1-amino-3-propyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline,

2.5-Dihydro-10-methoxy-5-(1-(hydrazinocarbonylamino)-3-propyl)-2,2,4-trimethyl-1H[ 1 ]benzopyrano[3,4-f]quinoline, (E)-2,5-dihydro-10-methoxy-5-(2-carbomethoxy-1 -ethenyl)-2,2,4-trimethyl-1H[ 1 ]benzopyrano[3,4-f]quinoline, (Z)-2,5-dihydro-10-methoxy-5-(1-propenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4f]quinoline, (E) 2,5-dihydro-10-methoxy-5-(3-(N,N-dimethylaminocarbonyloxy-1-propenyl)-2,2,4rimethyl-1Η-[ 1 ]benzopyrano[3,4-f]quinoline, (E)-2,5 -dihydro-10-methoxy-5-(3 -methoxymethoxy-1 -propenyl)-2,2,4-trimethyl-1H[ 1 ]benzopyrano[3,4-f]quinoline,

2.5-Dihydro-10-methoxy-5-(3-hydroxy-3-propenyl)-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4jquinoline, methyl 2-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-jquinolin-5yl)acetyl hydroxamate,

2-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolin-5yl)acetaldehyde,

2.5-Dihydro-10-methoxy-5-(2-cyclohexylideneylethyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-fJquinoline,

2.5-Dihydro-10-methoxy-5-(2-cyclopentylideneylethyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-fJquinoline,

2.5-Dihydro-10-methoxy-5-(2-cycloheptylideneylethyl)-2,2,4-trimethyl-1H[ 1 Jbenzopyrano [3,4-f]quinoline,

2.5-Dihydro-10-methoxy-5-(3-methyl-2-butenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fJquinoline, trans 2,5-dihydro-10-methoxy-5-(2-penten-1-yl)-2,2,4-trimethyl-1H-[1jbenzopyrano[3,4fJquinoline,

2.5-Dihydro-10-methoxy-5-(1,1-difluoro-1-propen-3-yl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline, (E) methyl 2-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolin-5yl) 2-butenoate, (E) 2,5-dihydro-10-methoxy-5-(4-hydroxy-2-buten-1 -yl)-2,2,4-trimethyl-1H[ 1 ]benzopyrano [3,4-f]quinoline, (E) 2,5-dihydro-10-methoxy-5-(4-(N,N-dimethylaminocarbonyloxy)-2-buten-1-yl)-2,2,4-trimethyl-1H[1] ]benzopyrano[3,4-f]quinoline, (E) 2,5-dihydro-10-methoxy-5-(4-(N-methylaminocarbonyloxy)-2-buten-1-yl)-2,2,4trimethyl-1 Η- [ 1 ]benzopyrano[3,4-f]quinoline, (2,5-dihydro-10-methoxy-5-(2-butenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f)quinoline,

2.5-dihydro-10-methoxy-5-(2-hydroxyethyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4f]quinoline,

2.5-dihydro-10-methoxy-5-(2-(N-benzylcarbonyloxyethyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline,

2.5-dihydro-10-methoxy-5-(2-(N-morpholinocarbonyloxyethyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline,

2.5-dihydro-10-methoxy-5-(2-(N-(2-methoxyethyl)aminocarbonyloxyethyl)-2,2,4-trimethyl1H-[1]benzopyrano[3,4-f]quinoline,

2.5-Dihydro-10-methoxy-5-(2-(N-methylaminocarbonyloxy)ethyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline,

2.5-dihydro-10-methoxy-5-(2-(N,N-dimethylaminocarbonyloxyethyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline,

2.5-dihydro-10-methoxy-5-(2-methoxymethoxyethyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline,

2.5-dihydro-10-methoxy-5-(2,2-dimethylthoxycarbonylamino)methyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline,

2.5-Dihydro-10-methoxy-5-(aminomethyl 1 )-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline,

2.5-dihydro-10-methoxy-5-(ethoxycarbonylamino)methyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline,

2.5-dihydro-10-methoxy-5-(carboethoxy)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline,

2.5-dihydro-10-methoxy-5-(cyclopentyl)-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4-f]quinoline,

2.5-dihydro-10-methoxy-5-(1-methylpropane-1,2-dienyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline,

2.5-dihydro-10-methoxy-5-(3,4,5-trifluorophenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4f]quinoline,

2.5-Dihydro-10-methoxy-5-(cyclohexyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline,

2.5-dihydro-10-methoxy-5-(2-pyridyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline,

2.5-Dihydro-10-methoxy-5-(3-pyridyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline,

2.5- dihydro-10-methoxy-5-(4-pyridyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline, (10-chloro-9-hydroxy-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro[ 1 ]benzopyrano[3,4f]quinoline,

10-chloro-9-hydroxy-5-phenyl-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4-f]quinoline,

10-chloro-9-hydroxy-5-(3-trifluoromethylpheny 1-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-f]quinoline,

10-chloro-9-hydroxy-5-(3,5-dimethylphenyl)-2,2,4-trimethyl-1H-2,5-dihydro[ 1 ]benzopyrano[3,4-f]quinoline, rel-(5S, 3'R)-9-hydroxyl0-methoxy-5-[1-hydroxymethyl-3-cyclohexenyl]-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano [3,4-f]quinoline, (-) 2,5(5)-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(3 S -cyclopentenyl)-1H[ 1 ] benzopyrano [3,4-f] quinoline, (-) 2,5(5)-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(3 R -cyclopentenyl)-1H[ 1 ] benzopyrano [3,4-f] quinoline,

10-chloro-9-hydroxy-5-(3,5-dichlorophenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4f]quinoline, (+)-(5R,3'S) 2,5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(3-cyclopentenyl)-1H[1]benzopyrano[3,4-f]quinoline, (+)-(5R,3'R)2,5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(3-cyclopentenyl)-1H[1]benzopyrano[3,4-f]quinoline,

10-chloro-9-hydroxy-5-[3,4-difluorophenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4fquinoline,

9-10-methylenedioxy-5-phenyl-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4-f]quinoline,

5-(3-propenyl)-9-chloro-10-ethenyl-2,2,4-trimethyl-2,5-dihydro-1H-[1]benzopyrano[3,4fquinoline,

9-chloro-10-methoxy-5-phenyl-2,2,4-trimethyl-2,5-dihydro-1H-[1]benzopyrano[3,4-f]quinoline,

• · • · • · · · ♦* ··

5-(3-propenyl)-9-chloro-10-difluoromethoxy-2,2,4-trimethyl-2,5-dihydro-1H[1]benzopyrano[3,4-f]quinoline,

9-chloro-10-difluoromethoxy-5-phenyl-2,2,4-trimethyl-2,5-dihydro-1H-[1]benzopyrano[3,4f]quinoline,

8-fluoro-10-methoxy-5-phenyl-2,2,4-trimethyl-2,5-dihydro-lH-[l]benzopyrano[3,4-f]quinoline, 5-(3-propenyl)-8-fluoro-10-methoxy-2,2,4-trimethyl-2,5-dihydro-lH-[l]benzopyrano[3,4f]quinoline, (10-methoxy-9-fluoro-5-(3-propene) ~2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4f]quinoline,

10-Methoxy-9-hydroxy-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4f]quinoline, (+/-) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cyclohexenyl)-1H[1]benzopyrano[3,4-f]quinoline, (+/-) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(l -methylcyclohexen-3-yl)-1H[ 1 Jbenzopyrano [3,4-f]quinoline, (-) (5S, 3'S)-9-hydroxy-5-[l-methyl-3-cyclohexenyl]-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H- [ 1 ]benzopyrano[3,4-f]quinoline, (+) (5R,3'R)-9-hydroxy-5-[l-methyl-3-cyclohexenyl]-10-methoxy-2,2,4-trimethyl-2,5dihydro-1H-[l ]benzopyrano[3,4-f]quinoline, (+) (5R,3'S)-9-hydroxy-5-[l -methyl-3-cyclohexenyl]-1H 0-Methoxy-2,2,4-trimethyl-2,5dihydro-1 H-[ 1 ]benzopyrano[3,4-f]quinoline, (-) (5S,3'R)-9-hydroxy-5-[l-methyl-3-cyclohexenyl]-10-methoxy-2,2,4-trimethyl-2,5dihydro-1 Η-[ 1 ]benzopyrano[3,4-f]quinoline, rel (5S,3 (R)-9-hydroxy-5-[1-hydroxymethyl-3 -cyclohexenyl]-10-methoxy-2,2,4-trimethyl2,5-dihydro-1 H-[ 1 ]benzopyrano[3,4-f]quinoline, (+/-) (5S,3'R) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-( 1 -methylcyclohexen-3yl)-1 H-[ 1 Jbenzopyrano[3,4-f]quinoline, rel (5S,3'R)-9-hydroxy-5-[1-methoxymethyl-3-cyclohexenyl]-10-methoxy-2,2,4-trimethyl2.5-dihydro-1H-[1]benzopyrano[3,4-f]quinoline,

2.5-Dihydro-9-hydroxy-10-methoxy-5-propyl-2,2,4-trimethyl-1H-[1]benzopyrano[3,4f]quinoline, (-) (5S,3'S) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cycloheptenyl)-1H[ 1 ]benzopyrano[3,4-f]quinoline, ·· • · · • * * • · · • · ·

9 • · · • · · • · · • ·· · ·· (-) (5S,3'R) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cycloheptenyl)-1H[ 1 ]benzopyrano[3,4-f]quinoline,

2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano[3,4fquinoline,

2.5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3,5-difluorophenyl)-1H[1]benzopyrano[3,4-f]quinoline,

2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3,4,5-trifluorophenyl)-1H[1]benzopyrano[3,4-f)quinoline,

-butyl-2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4f]quinoline, (-) (5S,3'S)2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cyclopentenyl)-1H[1]benzopyrano[3,4-f]quinoline, (-)(5S,3'R)2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cyclopentenyl)-1H[1]benzopyrano[3,4-f]quinoline,

2.5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-[3,4-difluorophenyl)-1H[1]benzopyrano[3,4-f]quinoline,

2.5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(4-fluorophenyl)-1H-[1]benzopyrano[3,4f]quinoline,

2.5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-trifluoromethylphenyl)-1H[1]benzopyrano[3,4-f]quinoline,

2.5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-5-bistrifluoromethylphenyl)-1H[1]benzopyrano[3,4-f]quinoline,

2.5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-trifluoromethyl-4-chlorophenyl)-1H[1]benzopyrano[3,4-f]quinoline,

2.5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2-methylpropyl)-1H[1]benzopyrano[3,4-f]quinoline,

2.5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-fluoro-4-chlorophenyl)-1H[1]benzopyrano[3,4-f]quinoline,

2.5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-butenyl)-1 Η-[ 1 ]benzopyrano[3,4f]quinoline,

2.5- dihydro-9-hydroxy-10-methoxy-5-(phenylmethyl)-2,2,4-trimethyl-1 H-[l]benzopyrano[3,4f]quinoline, (-) (5S,3'R) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-[l-ethyl-3-cyclohexenyl]1 Η- [ 1 ]benzopyrano[3,4-f]quinoline, ) * ··· (-) (S) 5-cyclopentyl-2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-triniethyl-1H[ 1 ]benzopyrano[3,4-f]quinoline, (+) (R) 5-cyclopentyl-2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-1H[ 1 ]benzopyrano[3,4-f]quinoline,

2.5-Dihydro-9-hydroxy-10-methoxy-5-(3-propynyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline,

2.5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2-propyl)-1H-[1]benzopyrano(3,4f]quinoline,

2.5- dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(5-methoxy-2-thienyl)-1H[ 1 ]benzopyrano[3,4-f]quinoline, (±) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2,3,4,5,6-pentafluorophenyl)-1H[ 1 ]benzopyrano [3,4-f]quinoline, (+/-) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5(S)-(3(S)-lhydroxymethylcyclopenten-3-yl)-1 H-[ 1 ]benzopyrano[3,4-f)quinoline, (+/) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5(S)-(3(S)-l) methyl carboxylate cyclopenten-3 -yl)-1 Η- [ 1 jbenzopyrano [3,4-f]quinoline, (-) (5S,3'S) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cyclohexenyl)-1H[l]benzopyrano[3,4-f]quinoline, (-) (5S,3'R) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cyclohexenyl)-1H[1]benzopyrano[3,4-f]quinoline,

2.5- dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2-thienyl)-1H-[1]benzopyrano[3,4f]quinoline, (±) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2-methylphenyl)-1H[1]benzopyrano[3,4-f]quinoline,

2.5- dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2-acetoxymethyl-3-propenyl)-1H[ 1 ]benzopyrano[3,4-f]quinoline, (+) (5R,3'S) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-[1-ethyl-3-cyclohexenyl]1 Η- [ 1 jbenzopyrano[3,4-f]quinoline,

2.5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-cyclohexyl-1H-[l]benzopyrano[3,4fjquinoline,

2.5.5-trihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline,

2.5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2-hydroxymethyl-3-propenyl)-1H[ 1 ]benzopyrano[3,4-f]quinoline,

ΦΦ φφ » φ · « φ φ ’ methyl 2-[2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-1 H-[l]benzopyrano[3,4-f]-5quinolines 1 jacetate, (Z) (2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2-butenyl)-lH[1 ]benzopyrano[3,4-f]quinoline,

2.5-Dihydro-9-hydroxyl0-methoxy-2,2,4-trimethyl-5-(3-methyl-2-butenyl)-1H[1]benzopyrano[3,4-f]quinoline, (+) (5S,3'S) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cyclohexenyl)-1H[1]benzopyrano [3,4-f]quinoline, (+) (5R,3'R) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cyclohexenyl)-1H[ 1 ]benzopyrano[3,4-f]quinoline, (+) (5R,3'S) 2,5(R)-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cyclopentenyl)-1H[ 1 ]benzopyrano[3,4-f]quinoline, (+) (5R,3'R)2,5(R)-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cyclopentenyl)-1H[ 1 ]benzopyrano[3,4-f]quinoline, rel-(5S)-9-hydroxy-5-[(3R-(l) -methoxycarbonylcyclohexen-3-yl]-10-methoxy-2,2,4trimethyl-2,5-dihydro-1H-[1]benzopyrano[3,4-f]quinoline,

2.5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2-methyl-3-propenyl)-1H[1]benzopyrano[3,4-f]quinoline,

9.10-dimethoxy-5-(3-propenyl~2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4f]quinoline,

9.10-dimethoxy-5-[3-cyclohexenyl]-methoxy-2,2,4-trimethyl-2,5-dihydro-1H[1]benzopyrano[3,4-f]quinoline,

10-methoxy-9-ethoxy-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4f]quinoline,

10-methoxy-9-(3-propenyloxy)-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-f]quinoline,

10-methoxy-9-(3-propynyloxy)-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-f]quinoline,

2.5-dihydro-9-acetoxy-10-methoxy-2,2,4-trimethyl-5-(2-propenyl)-1H-[1]benzopyrano[3,4t]quinoline,

2.5-Dihydro-9-(4-N,N-dimethylamino-4-oxo-butanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2propenyl)-1H-[1]benzopyrano[3,4-f]quinoline,

7-Bromo-5-[3-cyclohexenyl)-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H-[1]benzopyrano[3,4f]quinoline,

449 • 4 φ« ♦ 8 4

8 4

444 » 4 4 » · ·

89

10-methoxy-7-bromo-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4fquinoline,

7-bromo-5-[1-methyl-3-cyclohexenyl]-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H[l]benzopyrano[3,4-f]quinoline,

10-Methoxy-9-bromo-5-(3-propene 1 )-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4fquinoline,

7.9-dibromo-10-methoxy-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4f]quinoline,

7.9-dibromo-5-(cyclohexen-3-yl)-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H[1]benzopyrano[3,4-f]quinoline,

7.9-Dibromo-5-[1-methyl-3-cyclohexenyl]-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H[1Jbenzopyrano[3,4-f]quinoline,

10-methoxy-7-(2-ethenyl)-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-f]quinoline,

10-methoxy-7-methyl-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4fquinoline,

10-Methoxy-7-acetyl-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[l]benzopyrano[3,4f]quinoline, (+/-) 2,5-dihydro-9-methyl-10-methoxy-2,2,4-trimethyl-5-(1-methylcyclohexen-3-yl)-1H[l]benzopyrano[3,4-f]quinoline,

10-methoxy-7-methyl-9-methyl-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-f]quinoline,

10-chloro-5-(3-propenyl)-2,2,4-trimethyl-2,5-dihydro-1H-[1]benzopyrano[3,4-f]quinoline, (+/-) 2,5-dihydro-10-chloro-2,2,4-trimethyl-5-phenyl-1H-[l]benzopyrano[3,4-f]quinoline,

2.5-Dihydro-10-methoxy-5-(3-(N-methyl-N-(carbomethoxymethyl)aminocarbonyloxy)phenyl)2,2,4-trimethyl-1H-[1Jbenzopyrano[3,4-f]quinoline,

2.5- dihydro-10-methoxy-5-(3-(N-methyl-N-(N-methylcarbonyl)aminocarbonyloxy)phenyl)2,2,4-trimethyl-1Η-[1]benzopyrano[3,4-f]quinoline,

2.5-Dihydro-10-methoxy-5-(3-(N-methylaminocarbonyloxy)phenyl)-2,2,4-trimethyl-1H[ 1 Jbenzopyrano [3,4-fquinoline,

2.5- dihydro-10-methoxy-5-(3-(2-hydroxyethyl)phenyl)-2,2,4-trimethyl-1H[ 1 ]benzopyrano[3,4-fquinoline, «· ** • · · · • ··· • ♦ ···« ·· «« *· • · · • · · • ··<

« <í

2.5-dihydro-10-methoxy-5-(3-(2-methanesulfonyloxyethyl)phenyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline,

2.5-Dihydro-10-methoxy-5-(3-(2-methylthioethyl)phenyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline,

2.5-Dihydro-10-methoxy-5-(3-(2-(N,N-dimethylaminocarbonyloxy)ethyl)phenyl)-2,2,4trimethyl-1H-[1]benzopyrano[3,4-f]quinoline,

2.5-Dihydro-10-methoxy-5-(3-(2-(N,N-dimethylaminoethyl)phenyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline,

2.5-dihydro-10-methoxy-5-cyclopropyl-2,2,4-trimethyl-1H-[l]benzopyrano[3,4-f]quinoline,

2.5-Dihydro-10-methoxy-5-ethenyl-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline, trans

,

2.5-Dihydro-10-methoxy-5-(2-methylpropenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4f]quinoline, trans 2,5-dihydro-10-methoxy-5-(1-cyclohexenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4f]quinoline,

2.5-dihydro-10-(2-furanyl~5-(3-propenyl~2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline,

2.5-dihydro-10-cyano-5-(3-propenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f|quinoline,

2.5-dihydro-10-carboxy-5-(3-propenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline,

2.5-Dihydro-10-(2-hydroxymethyl)-5-(3-propenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4f]quinoline,

2.5-dihydro-10-formyl-5-(3-propenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline,

2.5-dihydro-10-aminomethyl-5-(3-propenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4f]quinoline,

2.5-dihydro-10-methoxymethyl-5-(3,-propenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4f|quinoline,

2.5-dihydro-10-ethenyl-5-phenyl-2,2,4-trimethyl-1H-[l]benzopyrano[3,4-f]quinoline,

2.5-Dihydro-10-ethynyl-5-phenyl-2,2,4-trimethyl-1H-[l]benzopyrano[3,4-f]quinoline, methyl 2,5-dihydro-5-phenyl-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline-10-carboxylate, *· φ · · • · ··*·

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• · • · ·» • · ·

• 99 9 •

10-methoxy-5-(1-methylpropylidene)-2,5-dihydro-5-phenyl-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline,

10-methoxy-5-(1-butylidene)-2,5-dihydro-5-phenyl-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4fj quinoline,

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-3-oxide-5-phenyl-1H-[1]benzopyrano[3,4-quinazoline,

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-phenyl-1H-[1jbenzopyrano[3,4-quinazoline,

2.5-Dihydro-10-methoxy-2,2-[spiro(tetrahydro-4-pyranyl)j-4-methyl-5-allyl-1H[1]benzopyrano[3,4-quinoline,

2.5-Dihydro-10-methoxy-2,2-[spiro(hexyl)j-5-allyl-1H-[ljbenzopyrano[3,4-fquinoline,

2.5-Dihydro-10-methoxy-2,2-diethyl-4-methyl-5-allyl-1H-[1jbenzopyrano[3,4-quinoline,

2.5-Dihydro-10-methoxy-2,2,3,4-tetramethyl-5-allyl-1H-[1]benzopyrano[3,4-quinoline,

2.5-dihydro-10-methoxy-2,2-dimethyl-4-ethyl-5-allyl-1H-[1]benzopyrano[3,4-f]quinoline,

2.5- dihydro-10-methoxy-2,2,3-trimethyl-5-allyl-1H-[1jbenzopyrano[3,4-fquinoline, Z-5-(benzylidenyl)-9-hydroxy-10-methoxy-2,2,4-trimethyl-1H-2,5-dihydro[1jbenzopyrano[3,4-fquinoline,

Z-5-(2,5-difluorobenzylideneyl)-9-hydroxy-10-methoxy-2,2,4-trimethyl-1H-2,5-dihydrojlbenzopyrano[3,4-fquinoline,

Z-5-(3-fluorobenzylideneyl)-10-chloro-9-hydroxy-2,2,4-trimethyl-2,5-dihydro-1H[1]benzopyrano[3,4-quinoline,

Z-10-chloro-9-hydroxy-5-(2-picolinylideneyl)-2,2,4-trimethyl-2,5-dihydro-1H[1]benzopyrano[3,4-quinoline,

Z-9-hydroxy-10-methoxy-5-(2-picolinylideneyl)-2,2,4-trimethyl-2,5-dihydro-1H[ 1 j benzopyrano [3,4-fj quinoline,

9-hydroxy-10-methoxy-5-(3,5-difluorophenyl)enthylidene-2,5-dihydro-5-phenyl-2,2,4-trimethyl1H-[1jbenzopyrano[3,4-quinoline,

9-hydroxy-10-methoxy-5-[3,4-difluorophenyl jmethylidene-2,5-dihydro-5-phenyl-2,2,4-trimethyl1 H-[ 1 jbenzopyrano[3,4-fjquinoline, (Z) 9-hydroxy-10-methoxy-5-((4-fluorophenyl)methylene)-2,2,4-trimethyl-1 H-2,5-dihydro[ 1 jbenzopyrano[3,4-quinoline, (Z)-9-hydroxy-10-rnethoxy-5-([2,3-difluorophenyl]methylene)-2,2,4-trimethyl-1H-2,5-dihydro[ 1 jbenzopyrano[3,4-quinoline,

Z-5-(3-Fluorobenzylideneyl)-10-methoxy-9-hydroxy-2,2,4-trimethyl-2,5-dihydro-1H[1]benzopyrano[3,4-fquinoline, rel (5S,3'R)-9-hydroxy-5-(1-methoxymethyl-3-cyclohexenyl)-10-chloro-2,2,4-triethyl-2,5dihydro-1H-[1]benzopyrano[3,4-fquinoline,

9-hydroxy-10-methoxy-5-ethyl-2,2,4-trimethyl-2,5-dihydro-1H-[ 1Jbenzopyrano[3,4fjquinoline, (+/-) 2,5-dihydro-9-cyanomethoxy-10-methoxy-2,2,4-trimethyl-5-allyl-1H[ 1Jbenzopyrano[3,4-f]quinoline,

2.5-Dihydro-9-(4-N,N-diethylamino-4-oxo-butanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2-propenyl)-1H-[1jbenzopyrano[3,4-fquinoline,

2.5-Dihydro-9-(4-N-piperidino-4-oxo-butanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2propenyl)-1H-[1Jbenzopyrano[3,4-fJquinoline,

2.5-Dihydro-9-(4-N-morpholino-4-oxo-butanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2propenyl)-1H-[1]benzopyrano[3,4-fquinoline,

2.5-Dihydro-9-(4-N,N-dimethylamino-4-oxo-butanoyloxy)-10-methoxy-2,2,4-trimethyl-5(3,4,5-trifluorophenyl)-1H-[1Jbenzopyrano[3,4-quinoline,

2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-5-difluorophenylmethyl)-1H[ 1 Jbenzopyrano [3,4-fquinoline,

2.5-Dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(2-thienyl)-1H-[1]benzopyrano[3,4fjquinoline,

2.5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-cyclopentyl-1H-[1Jbenzopyrano[3,4f]quinoline,

2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-((2-fluorophenyl)methyl)-1H[1]benzopyrano[3,4-quinoline,

2.5-Dihydro-9-hydroxymethyl-10-methoxy-2,2,4-trimethyl-5-allyl-1H-[1]benzopyrano[3,4fquinoline,

2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(1-pentenyl)-1H-[1Jbenzopyrano[3,4fj quinoline,

2.5-Dihydro-9-methylcarboxylate-10-methoxy-2,2,4-trimethyl-5-aUyl-1H-[1Jbenzopyrano[3,4]quinoline,

2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-allyl-1H-[ 1Jbenzopyrano[3,4fquinoline, (-) (5S, 3'S) 2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-(cyclopenten-3-yl)-1H[ 1Jbenzopyrano[3,4fquinoline, (-) (5S, 3'S) 2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-(cyclohexen-3-yl)-1H[ 1 Jbenzopyrano[3,4-fquinoline, • · • · * · ·

9 ♦ • · • · (-) (5S, 3'R) 2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-(cyclohexen-3-yl)-1H[ 1 ]benzopyrano[3,4-f|quinoline, (-) (5S, 3'R) 2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-(cyclopenten-3-yl)-1H[ 1 ] benzopyrano[3,4-f]quinoline,

2.5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3(Z)-pentenyl)-1H[1]benzopyrano[3,4-f]quinoline,

2.5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-acetoxyphenyl)-1H[1]benzopyrano[3,4-f]quinoline,

10-difluoromethoxy-5-[[3-(methylthio)methoxy]phenyl]-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-f]quinoline,

2.5-dihydro-7-bromo-9-hydroxy-10-chloro-2,2,4-trimethyl-5-allyl-1H-[1]benzopyrano[3,4fjquinoline,

2.5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-hydroxyphenyl)-1H[1]benzopyrano[3,4-f]quinoline,

2.5- dihydro-9-methylthiomethoxy-10-methoxy-2,2,4-trimethyl-5-(3(methylthio)methoxyphenyl)-1 Η- [ 1 ]benzopyrano [3,4-f] quinoline,

2.5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-(methylthiomethoxy)phenyl)~ 1H[1]benzopyrano[3,4-f]quinoline,

9-hydroxy-10-chloro-5-(phenylmethylene)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4f]quinoline,

2.5- dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-([2-N,N-dimethylcarbamoyloxy]phenyl)1H-[1]benzopyrano[3,4-f]quinoline,

2,5-dihydro-9-Ν,Ν-dimethylcarbamoyloxy-10-methoxy-2,2,4-trimethyl-5-((2-N,N dimethylcarbamoyloxy] phenyl)-1 Η- [1] benzopyrano [3,4-f] quinoline,

2.5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-ethyl-1H-[1]benzopyrano[3,4-f]quinoline,

2.5-Dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-isopropyl-1H-[1]benzopyrano[3,4fquinoline,

9-hydroxy-10-methoxy-5-(phenylmethylene)-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-f]quinoline,

2.5- dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-butyl-1H-[1]benzopyrano[3,4-f]quinoline,

2.5- dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(1-thiazol-2-yl)-1H[1]benzopyrano[3,4-f]quinoline,

2.5-Dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(2-methylpropyl)-1H-[1Jbenzopyrano[3,4fjquinoline,

2.5-Dihydro-9-hydroxymethyl-10-chloro-2,2,4-trimethyl-5-allyl-1H-[1Jbenzopyrano[3,4fJ quinoline,

2.5- dihydro-9-hydroxy-10-chloro-2,4-trimethyl-5-propyl-1H-[ 1 ]benzopyrano[3,4-fjquinoline, 9-hydroxy-10-methoxy-5-([3-fluorophenylJmethylene)-2,2,4-trimethyl-1H-2,5-dihydro[ 1Jbenzopyrano[3,4-f]quinoline,

9-hydroxy-10-chloro-5-([2-pyridyl]methylene)-2,2,4-trimethyl-1H-2,5-dihydro[ 1 Jbenzopyrano [3,4-fJquinoline, rel-(5S)-9-hydroxy-5-[(3S)-(1-hydroxymethyl)cyclohexen-3-ylJ-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H-[ Jbenzopyrano[3,4-tJquinoline, rel-(5S)-9-hydroxy-5-[(3S)-(1-methoxycarbonyl)cyclohexen-3-yl]-10-methoxy-2,2,4trimethyl-2,5-dihydro-1H-[l]benzopyrano[3,4-tJquinoline,

2.5- dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3,5-dichlorophenyl)-1H[ 1 Jbenzopyrano [3,4-fJ quinoline, (-) (5S,3'S) 2,5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(1-methylcyclohexen-3-yl)1 H-[ 1 Jbenzopyrano [3,4-fJ quinoline, (-) (5S,3'R) 2,5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(1-methylcyclohexen-3-yl)1 H-[ 1 ]benzopyrano[3,4-fjquinoline, (+) (5R,3'S) 2,5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(1-methylcyclohexen-3-yl)1 Η- [ 1 ] benzopyrano [3,4-f] quinoline, (+) (5R,3'R) 2,5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(l-methylcyclohexen-3-yl)1 Η- [ 1 ] benzopyrano [3,4-fJ quinoline, (+/-) 2,5-dihydro-9-(4-N,N-dimethylamino-4-oxo-butanoyloxy)-10-chloro-2,2,4-trimethyl-5allyl-1 H-[ 1 Jbenzopyrano[3,4-fJquinoline, (-) 2,5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-cyclopentyl-1 H-[ 1 Jbenzopyrano[3,4fJquinoline,

2.5- dihydro-9-(4-N,N-dimethylamino-4-oxo-butanoyloxy-10-methoxy-2,2,4-trimethyl-5-(lmethylethyl)-1 Η- [ 1 ] benzopyrano [3,4-f] quinoline,

2.5-Dihydro-9-(4-N,N-dimethylamino-4-oxo-butanoyloxy)-10-methoxy-5-(phenylmethyl)2,2,4-trimethyl-1H-[1Jbenzopyrano[3,4-f]quinoline,

2.5-Dihydro-9-(4-N,N-dimethylamino-4-oxo-butanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2thienyl)-1 Η- [ 1J benzopyrano [3,4-fJ quinoline, • ·

···· · · · · «·

2.5- dihydro-9-(4-N,N-dimethylaminobutanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2propenyl)-1 Η- [1] benzopyrano [3,4-f] quinoline,

9-(2-ethoxy-2-oxo-ethylannnocarbonyl)-oxy-10-methoxy-5-(3-propenyl)-2,2,4-trimethyl-1H2.5-dihydro-[1]benzopyrano[3,4-f]quinoline, (+/-) 2,5-dihydro-9-(3-acetamido-propanoyloxy-10-methoxy-2,2,4-trimethyl-5-allyl-1H[1 ] benzopyrano [3,4-f] quinoline, (+/-) 2,5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-benzyl-1 H-[ 1 ]benzopyrano[3,4f] quinoline,

9-hydroxy-10-methoxy-5-(phenylmethylene)-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-f]quinoline,

9-(dimethylaminothiocarbonyl)-oxy-10-methoxy-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5dihydro-] 1 ]benzopyrano[3,4-f]quinoline, (+/-) 2,5-dihydro-9-(N-carbamoyl-2-aminoacetoxy-10-methoxy-2,2,4-trimethyl-5-allyl-1H[ 1 ]benzopyrano[3,4-f]quinoline, (+/-) 2,5-dihydro-9-(4-ethoxy-4-oxo-butoxy)-10-methoxy-2,2,4-trimethyl-5-allyl-1H[ 1 ]benzopyrano[3,4-f]quinoline, (+/-) 2,5-dihydro-9-(4-oxo-pentanoyloxy-10-methoxy-2,2,4-trimethyl-5-allyl-1H[1]benzopyrano[3,4-f]quinoline,

2,5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(3,4,5-trifluorophenyl)-1H[1]benzopyrano[3,4-f]quinoline,

2.5-dihydro-9-methylthiomethoxy-10-methoxy-2,2,4-trimethyl-5-allyl-1H[1]benzopyrano[3,4-f]quinoline,

2.5-Dihydro-9-(4-N,N-diethylamino-4-oxo-pentanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2propeny1)-1H-[l]benzopyrano[3,4-f]quinoline,

2.5- dihydro-9-(4-N,N-dimethylamino-4-oxo-pentanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2propenyl)-1 Η- [ 1 ] benzopyrano [3,4-f] quinoline,

2.5-Dihydro-9-(4-N-piperidino-4-oxo-pentanoyloxy-10-methoxy-2,2,4-trimethyl-5-(2propenyl)-1Η-[1Jbenzopyrano[3,4-f]quinoline,

2.5- dihydro-9-(4-N-morpholino-4-oxo-pentanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2propenyl)-1 Η- [ 1 ] benzopyrano [3,4-f] quinoline, (-) 2,5-dihydro-9-(4-N,N-dimethylamino-4-oxo-butanoyloxy)-10-methoxy-2,2,4-trimethyl5(S)-(3(S)-1-cyclopenten-3-yl)-1H-[1jbenzopyrano[3,4-f]quinoline,

10-Methoxy-9-(allylaminocarbonyl)oxy-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro[ 1 ]benzopyrano[3,4-f]quinoline, •4 44 44 44 44 • 4 · 4 4 444·

4 4 44 4 4 44 · • 444 44 4 444 44 44 · 4 444 44444

4444 44 44 44 4· 44

10-methoxy-9-(cyclohexylaminocarbonyl)-oxy-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5dihydro-[1]benzopyrano[3,4-f]quinoline,

2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-thienyl)-1H-[1]benzopyrano[3,4f]quinoline, and

2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(4-(fluorophenyl)methyl)-1H[ 1 ]benzopyrano[3,4-quinoline,

Detailed description of the invention

Definition of terms

The term alkanoyl, as described herein, refers to an alkyl group attached to the parent molecular moiety through a carbonyl group.

The term alkanoyloxy, as described herein, refers to an alkanoyl group attached to the parent molecular moiety through an oxygen atom.

The term alkenyl, as described herein, refers to a monovalent branched or unbranched hydrocarbon group having two to twelve carbon atoms derived from a hydrocarbon having at least one carbon-carbon double bond.

The term alkoxy, as described herein, refers to an alkyl group attached to the parent molecular group through an oxygen atom.

The term alkoxycarbonyl, as described herein, refers to an ester group, i.e., an alkoxy group attached to the parent molecular moiety through a carbonyl group.

The term alkyl, as described herein, refers to a monovalent branched or unbranched chain having one to twelve carbon atoms derived from a saturated hydrocarbon.

The term alkylene, as described herein, refers to a branched or unbranched chain having one to twelve carbon atoms derived from an alkane.

The term alkynyl, as described herein, refers to a monovalent branched or unbranched hydrocarbon chain having two to twelve carbon atoms with at least one carbon-carbon triple bond.

The term alkynylene, as described herein, refers to a divalent branched or unbranched chain having two to twelve carbon atoms derived from an alkyne.

The term amino, as described herein, refers to -NH 2 .

The term aryl, as described herein, refers to a monocyclic or bicyclic carbocyclic ring system having one or two aromatic rings. Aryl Group • φ φ φ

it can also be fused to a cyclohexane, cyclohexene, cyclopentane or cyclopentene ring.

The term carboxy, as described herein, refers to -CO2H.

The term cycloalkenyl, as described herein, refers to a monovalent group derived from a cyclic or bicyclic hydrocarbon having three to twelve carbon atoms that has at least one carbon-carbon double bond.

The term cycloalkyl, as described herein, refers to a monovalent group having three to twelve carbon atoms derived from a saturated cyclic or bicyclic hydrocarbon.

The term halogen, as described herein, refers to F, Cl, Br, or I.

The term "heterocycle" as used herein refers to a 4-membered, 5-membered, 6-membered or 7-membered ring containing one, two or three heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur. 4-membered and 5-membered rings have 0-2 double bonds and 6-membered and 7-membered rings have 0-3 double bonds. The term heterocycle also includes bicyclic, tricyclic and tetracyclic groups in which any of the above heterocyclic rings is fused to one or two rings independently selected from aryl, cyclohexane, cyclohexene, cyclopentane, cyclopentene rings or other monocyclic heterocyclic rings. Heterocycles include zvcridinyl, benzimidazolyl, benzofuryl, benzithiazolyl, benzothienyl, benzoxazolyl, biotinyl, cinnolinyl, dihydrouryl, dihydroindolyl, dihydropyranyl, dihydrothienyl, dithiazolyl, furyl, homopiperidyl, imidazolidyl, imidazolinyl, imidazolyl, indolyl, isoquinolyl, isothiazolidinyl, isothiazolyl, isoxazolidinyl, isoxazolyl, morpholinyl, oxadiazolyl, oxazolidinyl, oxazolyl, pipidinyl, piperidinyl, pyranyl, pyrazolidinyl, pyrazinyl, pyrazolyl, pyrazolinyl, pyridazinyl, pyridyl, pyrimidinyl, pyrimidyl, pyrrolidinyl, pyrrolinyl, pyrrolyl, quinolinyl, quinoxaloyl, tetrahydrofuryl, tetrahydroisoquinolyl, tetrahydroquinolyl, tetrazolyl, thiadiazolyl, thiazolidinyl, thiazolyl, thienyl, thiomorpholinyl, triazolyl, etc.

Heterocycles also include bridged bicyclic groups, where monocyclic heterocyclic groups are bridged by an alkylene group such as

’ * ’ etc.

Heterocycles also include compounds of the formula • · · ·>

G>

\· <?

, where X is selected from -CH ₂ -, -CH ₂ O- and -O- and Y is selected from -C(O)- and (C(R) ₂ ) _v -, where the substituent R is hydrogen or alkyl having one to four carbon atoms and the index v is 1-3. These heterocycles include 1,3-benzodioxolyl, 1,4-benzodioxanyl, and the like.

The term heterocycloalkyl, as described herein, refers to non-aromatic partially saturated or fully saturated 4- to 8-membered rings having one or two heteroatoms independently selected from oxygen, nitrogen, and sulfur, in which the nitrogen or sulfur heteroatoms may optionally be oxidized and the nitrogen heteroatom may optionally be quaternized.

The term N-protected amino group, as described herein, refers to groups that are introduced to protect the amino group from unwanted reactions during synthetic steps. Commonly used N-protecting groups are published in Greene, Protective Groups In Organic Synthesis (John Wiley & Sons, New York (1981)). Preferred N-protecting groups include formyl, acetyl, benzoyl, pivaloyl, t-butylacetyl, phenylsulfonyl, benzyl, t-butyloxycarbonyl (Boc) and benzyloxycarbonyl (Cbz).

The term O-protected carboxy group, as described herein, refers to esters or amides protecting the carboxyl group introduced to protect or block the carboxylic acid group during reactions involving other functional groups or sites of compounds. Carboxy protecting groups are published in Greene, Protective Groups In Organic Synthesis (1981). Furthermore, carboxy protecting groups can be used as prodrugs, whereby they can be readily cleaved in vivo, e.g., by enzymatic hydrolysis to release the biologically active parent compound. Such groups are well known to those skilled in the art, as they are widely used in the protection of carboxyl groups in the penicillin and cephalosporin ranges as described in U.S. Patent Nos. 3,840,556 and 3,719,667.

The term oxo, as described herein, refers to (=0).

The term "pharmaceutically acceptable prodrugs" as used herein refers to those prodrugs of the compounds of the present invention which are within the scope of sound medical judgment suitable for use in contact with human and lower animal tissue without causing toxicity, irritation, allergic reactions, etc., commensurate with a reasonable benefit/risk ratio, and effective for their intended use, as well as zwitterion forms of the compounds of the present invention, where possible. Prodrugs of the present invention may be readily transformable in vivo to the parent compound of the above formula, e.g. by hydrolysis in blood. Full details can be found in T. Higuchi and V. Stella, Pro-drugs as

• 0 0 · 0 0 0 0

0 0 0 0 0 0 0 0 0 00 47

Novel Delivery Systems, Vol. 14 of the A.C.S. Symposium Series and in Edward B. Roche, ed., Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press, 1987, both incorporated herein by reference.

The term "pharmaceutically acceptable salt" as used herein refers to those salts which, within the scope of sound medical judgment, are suitable for use in contact with human or lower animal tissues without toxicity, irritation, allergic reactions, etc., and are commensurate with a reasonable benefit/risk ratio. Pharmaceutically acceptable salts are well known in the art, e.g., S. M. Berge, et al., describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 66: 1-19 (1977). The salts may be prepared in situ during the final isolation and purification of the compounds of the invention or separately by reacting the free base with a suitable organic acid. Examples of acid addition salts include acetate, adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, butyrate, borate, camphor, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, fumarate, glucoheptonate, glycerophosphate, hemisulfate, heptanoate, hexanoate, hydrogen chloride, hydrogen bromide, hydrogen iodide, 2-hydroxyethanesulfonate, lactobionate, lactate, laurate, lauryl, sulfate, malate, maleate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, tartrate, thiocyanate, toluenesulfonate, undecanoate, and valerate. Pharmaceutically acceptable salts include, but are not limited to, alkali metal or alkaline earth metal cations, such as lithium, sodium, potassium, calcium, magnesium or aluminum salts, and the like, and non-toxic quaternary ammonium salts and amine cations including ammonia, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, diethylamine, ethylamine, and the like.

The compounds of the present invention may exist as stereoisomers where asymmetric or chiral centers are present. These compounds are designated by the symbols “R” and “S” depending on the configuration of the substituents on the chiral carbon atom. The present invention contemplates various stereoisomers and mixtures thereof. Stereoisomers include enantiomers and diastereomers, and mixtures of enantiomers or diastereomers, and mixtures of enantiomers are designated as (±). Individual stereoisomers of the compounds of the present invention may be prepared synthetically from commercially available starting materials containing asymmetric or chiral centers or by preparation of a racemic mixture followed by resolution into the enantiomers, techniques within the skill of the art. These methods of resolution into enantiomers are such as: (1) attachment of a mixture of enantiomers to a chiral « * « φ φ φ · φ φφφ φ · φφφφ φφ φ φ· • φ φ φ • φ φ · φ φ φ · φ φ φ φ φ· φφ auxiliary group, separation of the resulting mixture of diastereomers by recrystallization or chromatography and liberation of the optically pure product from the auxiliary group or (2) direct separation of the mixture of optical enantiomers on chiral chromatographic columns.

Geometric isomers may also occur in the compounds of the present invention. The present invention contemplates various geometric isomers and mixtures thereof formed by the arrangement of substituents around a carbon-carbon double bond or by the arrangement of substituents around a carbocyclic ring. The substituents around a carbon-carbon double bond are designated as Z and E configurations, with the term “Z” representing substituents on the same side of the carbon-carbon double bond and the term “E” representing substituents that are on opposite sides of the carbon-carbon double bond. The arrangement of substituents around a carbocyclic ring is designated as cis and trans, with the term “cis” representing substituents on the same side of the ring plane and the term “trans” representing substituents that are on opposite sides of the ring plane. Mixtures of compounds where the substituents are arranged on both sides of the ring plane, i.e. on the same and opposite sides, are designated cis/trans.

Methods for studies of radioligand binding to the human cytosolic glucocorticoid and progesterone receptor

The procedure described in Anal. Biochem. 1970, 37, 244-252, incorporated herein by reference, was used. Cytosol preparations of human glucocorticoid receptor isoform-α [GRX] and human progesterone receptor isoform-A [PRA] were obtained from Ligand Pharmaceuticals (San Diego, CA). Both receptor cDNAs were cloned into baculovirus expression vectors and expressed in insect-derived SF21 cells. [ ³ H]-dexamethasone (Dex, specific activity 82-86 Ci/mmol) and [ ³ H]-progesterone (Prog, specific activity 97-102 Ci/mmol) were purchased from Amersham Life Sciences (Arlington Heights, IL). MAFC NOB Multiscreen plates with type C glass fiber were purchased from Millipore (Burlington, MA). Hydroxyapatite Bio-Gel HTP gel was from Bio-Rad Laboratories (Hercules, CA). Tris(hydroxymethyl)aminomethane (Tris), ethylenediaminetetraacetic acid (EDTA), glycerol, dithiothreitol (DTT), and sodium molybdate were from Sigma Chemicals (St. Louis, MO). Scintillation fluid was from Packard Instrument (Meriden, CT).

Stock solutions (32 mM) of compounds were prepared in dimethyl sulfoxide (DMSO) and 50X solutions of test compound were prepared from a 32 mM solution with a 20:20 mixture of DMSO/ethanol. The 50X solution was then diluted with binding buffer containing 10 mM Tri00 * 0 0 0

0 0 0

0 0 ♦

0 0 0

0 00

0 • 0 00 • 0 0 0

0 0 0 • 0 0·0

HCl, 1.5 mM EDTA, 10% glycerol, 1 mM DTT, 20 mM sodium molybdate, pH 7.5 at 4° C. 1% DMSO/ethanol was used in binding assays.

GRX and PRA binding reactions were performed in Millipore Multiscreen plates. For GR binding assays, [ ³ H]-Dex (-35,000 dpm (~0.9 nM)), GRX cytosol (-35 pg protein), test compound, and binding buffer were mixed to a total volume of 200 μΐ and incubated at 4°C overnight on a plate shaker. Specific binding was defined as the difference between [ ³ H]Prog binding in the absence and presence of 3 μΜ unlabeled Prog.

After overnight incubation, 50 μΐ of hydroxyapatite slurry (25% w/v) was added to each tube and the plates were incubated for 10 minutes at °C on a plate shaker. The plates were aspirated using a Millipore vacuum system and each tube was rinsed with 300 μΐ of ice-cold binding buffer. A 250 μΐ aliquot of Packard Microscint-20 was added to each tube and the tubes were shaken at room temperature for 20 minutes. The amount of radioactivity was determined by a plate reader.

Determination of inhibition constant (Ki)

The concentrations of test compounds that inhibited 50% of specific binding (IC50) were determined by Hill analysis of competition binding experiments. The Ki of test compounds was determined using the Cheng-Prusoff equation K1=IC50/(1+[L*]/[Kl]), where L* is the radioligand concentration and Kl is the radioligand dissociation constant determined by saturation analysis. For GRX, Kl was -1.5 nM and for PRA, Kl was -4.5 nM. The inhibitory potency of the compounds of the invention and their selectivity for GR and PR receptors are shown in Table 1

ΦΦ ΦΦ φ · φ φ • · · · φ φ φ · φ φ φ φ φ ΦΦ φ · φ φ φ · * φ φ φ φ φφφ φ φ φ φ·· · φ φ

ΦΦ ΦΦ φ φ φ φ φ φ φ · φ φ φφφ φ φ φ φ φ φ φ

Table 1

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0* > «0 « > 0 0 <

» 0 0 » 0 0 « ♦· • 0

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• · * 0 000

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ΦΦ ·· • φ φ φ φ φ · φ · · φ φ · φφφφ φφ • φ «· φ φ φ · φ φ φ · φ φ φφφ φ φ φ • Φ φφ

Φ· φφ φ φ φ φ φ φ φ · φ φ φ · φ φ φ · φ φ φφ

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9 9 9 • · 9 99

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··« · • ··♦ » »

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Φ· • * · • · · φφφ φ φ φφ φφ ·» φ φ φ « φ · · φ φ φ φφφ φ φ φ φφ φ*

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• ♦ · · * ·· · • ·· · · Β Β · • · · · · · ♦ · Β • Β Β · Β Β β ·· · · · · Β ·

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The present invention also provides pharmaceutical compositions comprising the compounds of the present invention formulated together with one or more non-toxic pharmaceutically acceptable carriers. The pharmaceutical compositions may be specially formulated for oral administration in solid or liquid forms, for parenteral injection, or for rectal administration.

The pharmaceutical compositions of the present invention may be administered to humans or other mammals orally, rectally, parenterally, intracystically, intravaginally, intraperitoneally, topically (powders, ointments or drops), buccally or as an oral or nasal spray. The term "parenterally" as used herein refers to routes of administration that include intravenous, intramuscular, intraperitoneal, intrastemal, subcutaneous and intraarticular injection and infusion.

Pharmaceutical preparations of the present invention for parenteral injection comprise pharmaceutically acceptable sterile aqueous or non-aqueous solutions, dispersions, suspensions or emulsions, as well as sterile powders for reconstitution into sterile injectable solutions or dispersions immediately prior to use. Examples of suitable aqueous and non-aqueous carriers, diluents, solvents or vehicles include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, etc.), and suitable mixtures thereof, vegetable oils (such as olive oil) and injectable organic esters such as ethyl oleate. Intrinsic fluidity can be maintained, for example, by the use of coating agents such as lecithin, by the maintenance of the desired particle size in the case of dispersions and by the use of surfactants. Conversely, reduced particle size can maintain biological activity.

These preparations may also contain adjuvants such as preservatives, detergents, emulsifiers and dispersants. Prevention against the action of microorganisms may be achieved by the inclusion of various antibacterial and antifungal agents such as paraben, chlorobutanol, phenol, sorbic acid, etc. It may also be desirable to include isotonic

0 • 00 0 0 • 0

• ♦ • · 0 0 0 0 agents, such as sugars, sodium chloride, etc. Prolonged absorption of injectable pharmaceutical forms can be brought about by the inclusion of agents, such as aluminum monostearate and gelatin, which delay absorption.

To prolong the effect of a drug, it is often desirable to delay the absorption of the drug when it is injected subcutaneously or intramuscularly. This can be achieved by using liquid suspensions of crystalline or amorphous substances with poor water solubility. The rate of absorption of the drug, then, depends on its rate of dissolution, which may depend on the crystal size and crystalline form. Alternatively, slower absorption of a parenterally administered drug form is achieved by dissolving or suspending the drug in an oil vehicle.

Injectable depot forms are made by forming microencapsulated matrices of the drug in biodegradable polymers, such as polylactide-polyglycolide, poly(orthoesters) and poly(anhydrides). The rate of drug release can be controlled depending on the ratio of drug to polymer and the origin of the individual polymers used. Depot injectable formulations are also prepared by entrapping the drug in liposomes or microemulsions, which are compatible with body tissues.

Injectable formulations may be sterilized, for example, by filtration through a bacterial-retaining filter or by incorporating sterilizing agents in the form of sterile solid preparations which may be dissolved or dispersed in sterile water or other sterile injectable media immediately prior to use.

Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such dosage forms, the active compound is mixed with at least one inert, pharmaceutically acceptable excipient or carrier, such as sodium citrate or dicalcium phosphate, and/or a) fillers or extenders such as starch, lactose, sucrose, glucose, mannitol and orthosilicic acid, b) binders such as carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose and acacia, c) wetting agents such as glycerol, d) disintegrating agents such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates and calcium carbonate, e) solution inhibitors such as paraffin, f) absorption accelerators such as quaternary ammonium compounds, g) detergents such as cetyl alcohol and glycerol monostearate, h) adsorbents such as, for example, kaolin and bentonite kaolin and (i) lubricants such as, for example, talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate and mixtures thereof. In the case of capsules, tablets and pills, the dosage forms may also contain a buffering agent.

99

9 9 9

9 9 ·

9 9 9

9 9 9

9 9 9

9 · • ♦·♦ 9 9

99 9 9

9 9 9

9 9 9 · · *· • · ·

9 9

Solid preparations of a similar type can also be used as fillers in lightly filled and densely filled gelatin capsules using such excipients as lactose or milk sugar, as well as polyethylene glycols of high relative molecular weight, etc.

Solid dosage forms, such as tablets, dragees, capsules, pills and granules, can be prepared with coatings and shells, such as enteric coatings and other coatings well known in the pharmaceutical formulation art. Solid dosage forms can optionally contain opacifying agents and can also be free of such preparations that release the active ingredients only or preferentially in a certain part of the intestinal tract, optionally to some extent delayed. Examples of encapsulating preparations that can be used include polymeric substances and waxes.

The active compounds may also be in microencapsulated form with one or more of the above-mentioned excipients.

Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active compounds, liquid dosage forms may contain inert diluents commonly used in the art, e.g., such as water or other solvents, solubilizing agents and emulsifiers, such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (especially cottonseed, peanut, corn, germ, olive, castor and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and sorbitan fatty acid esters and mixtures thereof.

In comparison to inert diluents, oral preparations may also include adjuvants, such as detergents, emulsifying and suspending agents, sweetening agents, flavoring agents, and fragrance-releasing agents.

Suspensions, in addition to the active compounds, may contain suspending agents such as, for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth, and mixtures thereof.

Formulations for rectal or vaginal administration are preferably suppositories, which may be prepared by mixing the compounds of the invention with suitable, non-irritating excipients or carriers, such as cocoa butter, polyethylene glycols or wax suppositories, which are solid at room temperature but liquid at body temperature and therefore melt in the rectum or vaginal cavity to release the active compound.

φ 'φφ φ φ ♦ φφφ φ φ · · · • φ φ φ φφφφφ φφφφ φφ φφ φφ ♦* ··

The compositions of the present invention may also be administered in the form of liposomes. As is known in the art, liposomes are generally derived from phospholipids or other lipid substances. Liposomes are formed by monolamellar or multilamellar hydrated liquid crystals which are dispersed in an aqueous medium. Any non-toxic, physiologically acceptable and metabolizable lipid capable of forming liposomes may be used. The present compositions in liposomal form may contain, depending on the compound of the present invention, stabilizing agents, preservatives, excipients, etc. Preferred lipids are phospholipids and phosphatidylcholines (lecithins), both natural and synthetic. Methods for forming liposomes are known in the art. See, e.g., Prescott, Ed., Methods in Cell Biology, Volume XIV, Academic Press, New York, N.Y. (1976), 33 et seq., which is incorporated herein by reference.

Dosage forms for topical administration of the compounds of this invention further include powders, sprays, ointments, inhalants. The active ingredient is admixed under sterile conditions with a pharmaceutically acceptable carrier and any necessary preservatives or buffers as appropriate. Ophthalmic formulations, ear drops, eye ointments, powders and solutions are also contemplated within the scope of the present invention.

The actual dosage levels of the active ingredients in the pharmaceutical compositions of the present invention may vary to provide an amount of the active compound(s) effective to achieve the desired therapeutic response for the individual patient, composition, and route of administration. The selected dosage level will depend on the activity of the individual compound, the route of administration, the severity of the condition being treated, and the condition and prior medical history of the patient being treated. However, it is known in the art to start with lower doses of the compound than are required to achieve the desired therapeutic effect and gradually increase the dosage level until the desired effect is achieved.

A general dosage level administered orally to a mammalian patient is from about 1 to 50 mg, more preferably from about 5 to 20 mg, of active compound per kilogram of body weight per day. If desired, the effective daily dosage may be divided into several doses for administration, e.g., from two to four separate doses per day.

The abbreviations used in the description of the diagrams and examples are as follows:

BF ₃ OEt ₂ for the complex of boron trifluoride and diethyl ether;

DMF for N,Y-dimethylformamide;

DMSO for dimethyl sulfoxide; and

THF for tetrahydrofuran.

ΦΦ ΦΦ φ φ φ φ φ φ φ φ φ φ φ φφφ φ φ φ φ φ φ φ φ

ΦΦΦΦΦΦ φ·

Φ φ φ φ φ φ φ φ φφ φ φ φ ΦΦ φ ΦΦ

Synthesis method

The compounds and methods of the present invention will be better understood in connection with the following schemes, which illustrate methods by which the compounds of the invention may be prepared.

The syntheses of compounds of the present invention are described in Schemes 1-21.

OMe

OMe

OMe

B(0H) ₂

As shown in the examples in Scheme 1, resorcinol dimethyl ether is metalated with a strong base such as n-butyllithium or sec-butyllithium, reacted with a trialkoxyborate such as trimethyl- or triisopropylborate, and hydrolyzed with an acid such as 2M HCl to give the boronic acid derivative 1A. Reaction of compound 1A with methyl-(5-nitro-2-bromobenzoate) in the presence of a (palladium) catalyst such as tetrakis(triphenylphosphine)palladium complex or dichlorobis(triphenylphosphine)palladium complex gives biphenyl IB. Demethylation of compound IB is achieved with reagents such as BBr3 to give hydroxylactone IC, which is reacted with an alkylating agent such as methyl iodide to give compound ID. Conversion of compound ID to amine IE is achieved using hydrogen gas and a (palladium) catalyst such as 10% palladium on charcoal. Compound IE is converted to quinoline IF by a Skraup ring annulation reaction. Introduction of functionalization at the C5 position of compound IF to give compound 1 is achieved by addition of organometallic reagents such as phenyllithium to the C5 carbonyl to give compound 1G, • · • 4 followed by deoxygenation with Lewis acids such as BF ₃ OEt ₃ and reducing agents such as triethylmonosilane to give compound 1.

Scheme 2

A more preferred method for obtaining the compounds of the invention is shown in Scheme 2. Compound 1F is converted to methyl acetal 2B, via hemiacetal 2A, using a two-step procedure involving conversion of compound 1F to 2A using reagents such as diisobutylaluminum hydride in an aprotic solvent such as dichloromethane followed by acid-catalyzed acetal formation with acids such as p-toluenesulfonic acid monohydrate and alcohols such as methanol to obtain compound 2B, which is then reacted with a nucleophile such as allyltrimethylsilane in the presence of a Lewis acid such as a mixture of boron trifluoride and diethyl ether to prepare C5 allyl analogs, e.g., Example 2. The Lewis acid/methyl acetal complex is also condensed with organomagnesium chlorides, bromides, or iodides to obtain the compound of the invention, e.g., Example 11.

• · • · • * ·· ·♦ ·· • · · · · · • ♦ · · ·

Ml · · · · · • · · · · ·· ·♦ ··

Scheme 3

3C: R=S0zCF ₃

3: R=NHMe 4: R=CC>2Me 5: R=CH=CH ₂ 6: R=CsCH

As shown in Scheme 3, the C10 position is subjected to the same reduction/Skraup reaction conditions as described in Scheme 1 to give hydroxyquinoline 3B. Compound 3B is converted to the triflate derivative 3C with reagents such as trifluoromethanesulfonic anhydride, then derivatized at the C5 position as described in Schemes 1 and 2 to give analogs such as 3D. In coupling reactions mediated by catalysts (palladium) for amines, carbonylations, Stille coupling reactions and modified Sonagashiro reactions, functionalized triflates at the C10 position were used to obtain aminomethyl, carbomethoxy, vinyl and acetylenic derivatives of compound 3D such as the allyl substituted at the C5 position in Examples 11, 4, 5 and 6.

• 0 00

0 · · • 0 « «

• 0 0 *

0000 00

000 0 0 »00 0 0 · 00 00

7Β: R=TBS 9; R=Et

7: R=H 10: R=C(O)Me

As shown in Scheme 4, reaction of compound 3B with tert-butyldimethylsilyl ether (TBS) and a base such as imidazole, triethylamine or diisopropylethylamine and functionalization at the C5 position as described in Schemes 1-3 provides silane 7B. Removal of the silane group with reagents such as tetra(n-butylammonium fluoride) in THF to provide phenol 7 and reaction with R-X or RC(O)X, where R is an alkyl group and X is a leaving group such as halogen, provides alkoxy or carboxy compounds such as Examples 9 and 10. Haloalkoxy analogs are prepared from compound 3B by nucleophilic displacement using a polyhalogenated alkylating agent such as CF2HCl to provide compound 8A followed by functionalization at the C5 position of compound 8A as described in Schemes 1-3 to provide compound 8.

• « 9 9

9 9 • 9 9 9 • 9 9 «

» · »

Scheme 5 ·· ·-* • · · · ♦ * · • ··· • · ···· ·* ·« « » · • · ·

9 • »

12: R=C(O)CH ₃ 13: R=H 14: R=CH2SMe 15: R=C(O)NMe ₂

128: R=H 12C: R=C(O)CH ₃

As shown in Scheme 5, compound 1F is reacted with a lithiated protected phenol reagent, e.g., 3-(methoxymethoxy)phenyllithium, to give compound 12A. The protecting group is cleaved in acidic media, e.g., methanolic or aqueous HCl, to give diol 12B, which is converted to phenylacetate 12C with reagents, e.g., acetyl chloride and a base, e.g., pyridine, triethylamine, or diisopropylethylamine. The tertiary alcohol is then reduced as described in Scheme 1 and the acetate group of Example 12 is removed to give Example 13. Example 13 is alkylated or acylated as described in Scheme 4 to give Examples 14 and 15.

·· • · · $ · · ·· ·· • · · * • · · • BBB • · ··»· Β· r ·» • · · • Β · • ··· • · » Β·

»· • B »·

As shown in Scheme 6, the functional group at the meta position of the phenyl ring at the C5 position is introduced using metahalophenyl analogues, e.g. Example 11, prepared as described in Scheme 2. Coupling reactions or aminations according to Stille or Suzuki with catalysts (palladium) e.g. [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex or tetrakis(triphenylphosphine)palladium in the presence of ligands e.g. tributylstannylfuran or morpholine provide carbon or nitrogen bonded groups at the meta position of the aromatic ring at the C5 position, as shown in Examples 16 and 17.

• · • ·

73 • ··· · · · · · · · · · · · • · · · · ··· ···· ·· · · · · · · · Scheme 7 R QXú — (X yJ-H OMe OMe *1 H ^x fP 1F 18 As shown in Scheme 7, compound 1F is allowed to react with magnesium

halides, preferably bromides, to obtain the hemiketal (intermediate), which is then reacted with acid catalysts e.g. para-toluenesulfonic acid, methanesulfonic acid or aqueous hydrochloric acid to obtain optionally substituted analogues e.g. E and Z isomers of compound 18.

The chemical process shown in Scheme 1 was found to be general. This means that various tetracyclic cores could be prepared from a stock of anisoles via their corresponding boronic acids in the manner shown in Scheme 8.

Scheme 8

Scheme 8 illustrates the applicability of the chemical procedures described in Scheme 1 and Examples 1-131 to the synthesis of novel cores with substituents other than alkoxy at the C10 position. Metalation of the ortho-substituted anisoles with a strong base, e.g., n-butyllithium or sec-butyllithium, followed by sequential reaction with a trialkoxyborate, e.g., trimethyl- or triisopropylborate, and acid hydrolysis, as outlined in Scheme 1, provides the appropriately substituted boronic acids, which are then processed to compounds of Formula I using the chemical procedures described above. Further ring processing to obtain cores 1-17 is described below.

...........

Examples of novel tetracyclic cores prepared using the chemical procedure described in Scheme 8 are given below.

Scheme 9

Further derivatization of core 1 using methods well known in the art will provide another tetracyclic coumarin for subsequent processing at the C5 position, as shown in Scheme 9. For example, selective alkylation at the C10 hydroxyl of core 1 with alkylating agents (e.g., methyl iodide) and a base, e.g., potassium carbonate, will provide core 7. Selective derivatization of core 1 at the C7 position with halogenating agents, e.g., bromine or N-bromosuccinimide will provide core 8 - a precursor to the compound of formula I.

• · • · • · • ·

Example 1F

Scheme 10

Scheme 10 shows another chemical procedure for selective chromification. The regioselective chromification of Example 1F, directed by the methoxy group on C10 and the choice of brominating agent, affords cores 9, 10 and 11. These chromified rings were further derivatized at the chromified position(s) by transition metal catalyzed introduction of various functional groups.

R = lower acyl R = lower alkyl

As shown in Scheme 11, the cores having a phenolic hydroxyl functional group were either dehydroxylated (as shown for core 2), acetylated, or alkylated by methods known in the art. See Larock, Comprehensive Organic Transformation. AGuide to Functional Group Preparations VCH Publishers, New York (1989), incorporated herein by reference.

·· ·· ··

Scheme 12 shows the introduction of a substituted cyclohexenyl group by Lewis acid-catalyzed addition of a tert-butyldimethylsilyl-protected enol ether to the C5 position of the compound of Example 2B. After introduction, the diastereoisomers and rearrangement products are separated and the alkoxycarbonyl group is optionally reduced to a hydroxyalkyl group.

As shown in Scheme 13, the vinyl bromide group of compound e.g. Example 147 is further derivatized at the chromium position(s) to provide a variety of R19 substituents by transition metal catalyzed introduction of various functional groups e.g. as described in Scheme 10.

• · • ·

Example 69 nh ₂

Scheme 14

H

Example 177 » ··«·· 0 00000 00 1 0 00 · 0 0 0 1 »000 00 00 ·0 0*

"AC"

OCH ₃ «

H

Example 176

As shown in Scheme 14, introduction of phthalimide to compound Example 69 according to Mitsunobu and removal of the imide group with hydrazine provides the alkylamino group of Example 177, which is further derivatized to compound Example 178 by reaction with di(tert-butyl)dicarbonate.

Example 44

Xi=CON(CH ₃ )2 (Example 182) Xi=CH ₂ OCH ₃ (Example 183)

As shown in Scheme 15, processing of the C5 nitrile of Example 44 to the α,β-unsaturated ester of Example 179 followed by selective reduction of the alkoxycarbonyl group to an alkenyl alcohol (Xi is H) provides precursors for the carbamates and methoxymethyl ethers of Examples 182 and 183.

Example 46

• · · · · · «· * · · ·

H

Example 200

As shown in Scheme 16, conversion of the ester of Example 46 to its Weinreb amide derivative of Example 185 and further reduction to the aldehyde of Example 186 provides precursors for the alkenes of Examples 187, 194, 195 and 200 by reaction of the aldehydes with a quantity of commercially available Wittig Homer-Wadsworth-Emmons reagents.

• 4

9 44 4 9

Example 215: Z=N;X,Y=C

As shown in Scheme 17, the compound of Example 1F is converted to a ring-opened aldehyde using a two-step procedure involving reaction with a reducing agent, e.g., diisobutylaluminum hydride, in an aprotic solvent, e.g., dichloromethane, followed by reaction with a silylating agent, e.g., tert-butyldimethylsilyl chloride, in the presence of a base, e.g., potassium tert-butoxide. Addition of organometallic agents, e.g., lithiopyridines, to the aldehyde produces benzylic alcohols (R = pyridyl), which could then be converted to an analog, e.g., compounds of Examples 213-215 using a two-step procedure involving removal of the silicon group with agents, e.g., tetrabutylammonium fluoride, and further cyclization using combinations of agents, e.g., triethylphosphine and 1,1'-(azodicarbonyl)dipiperidine.

• · · · » · · 1 » · · 4 ♦ · ··

Example 333: X|=-C^CH

Example 335: Xj=-OCH ₃ Example 337: X _t =H

Example X,: R=H Example Xf R=Me

As shown in Scheme 18, the compound of Example 7 is converted to a triflate derivative with reagents such as trifluoromethanesulfonic acid anhydride, then derivatized at the C10 position using the methods described in Scheme 3. Reduction of the compound of Example 335 with reagents such as diisobutylaluminum hydride provides the compound of Example 336. Reaction of the compound of Example 336 with an oxidizing agent such as tetrapropylammoniumruthenate provides the compound of Example 337. Alkylation of the compound of Example 336 could be achieved with reagents such as iodomethane in the presence of a base such as potassium bis(trimethylsilyl)amide to provide an analog such as the compound of Example 338.

Example 340: R=H Example 341: R=Me

As shown in Scheme 19, triflate 3C can also be converted to the vinyl derivative C10 of Example 339 and further to its methyl acetal using the methods described in Schemes 3 and 2. The acetal is reacted with nucleophiles such as 3-(trimethylsilyl)cyclohexene or 3-(dimethylphenylsilyl)-3-methylcyclohexene in the presence of a Lewis acid such as boron trifluoride etherate to provide analogs such as Examples 340 and 341.

• · · • · · • 9 99

Scheme 20 ,0^0

CL^O (CHsh

(CH ₃ ) ₂ N«yS

O

H

Example 343 • 9 9

9 9

9 9

9

99 99

The introduction of sulfur at the C10 position of the compound of Example 3B is shown in Scheme 20. The compound of Example 3B is then reacted with reagents such as dimethylcarbamoyl chloride to give the thionocarbamate, which undergoes thermal rearrangement to form an S-C bond at the C10 position. According to Scheme 2, an allyl group is introduced at the C5 position. Hydrolysis with a strong base such as potassium hydroxide and alkylation of the sulfur with an electrophile such as iodomethane in the presence of a base such as cesium carbonate provides an analog having a thioalkoxy functionality at the C10 position, e.g., compound of Example 343.

4 • 4 4 · • 4 ·

4 4 4

4

4 4 4 44

44 ·4 44

44 4 4 44 4

44 4 4 4·· « 4 44444 44 4

4 4 4 4 4 4

44 44 44

Scheme 21

The method for preparing the compounds of Examples 320-323 is shown in Scheme 21. The compound of Example 2B is reacted with a nucleophile, e.g., tributylvinyltin, in the presence of Lewis acids, e.g., boron trifluoride diethyl etherate, to give the compound of Example 320, which is then coupled with an aryl halide, e.g., iodobenzene, in the presence of a catalyst, e.g., palladium acetate, to give the trans isomers of the compound of Example 321. The Lewis acid/methyl acetal complex is also condensed with tributylphenylacetylenyltin to give the compound of Example 322, which is then partially hydrogenated in the presence of a catalyst, e.g., palladium on BaSO ₄ , to give the cis isomers of the compound of Example 323.

It is apparent from the foregoing schemes and the following examples that the substituents Ri, R2, R3, R4, _R5 , Rg, Rig, Rig-, Rn, Riš, Riš, Y, R2 and _L2 can be determined by selection from appropriate commercially available or known starting materials (e.g. substituted methoxybenzenes) or introduced synthetically using known chemical methods, e.g. according to the methods set forth in Larock Comprehensive Organic Transformations. A Guide to Functional Group Preparations VCH Publishers, New York (1989), incorporated herein by reference.

It will be apparent to those skilled in the art that the selective introduction and removal of protecting groups depending on the nature of the substituents R1, _R2 , R3, R4, R5, R<>, R16, R17, R18, R19, Y, R2 and _L2 can be accomplished in various ways or in a number of steps. Commonly used protecting groups are published in Greene Protective Groups In Organic Synthesis John Wiley & Sons, New York (1981), incorporated herein by reference.

>4 ♦ ·· ·· ·» ·* • · · · » · · « • · » · «·· « • · ···«· 9 9 9

9 · 9 9 9 9

99 99 99

Design examples

Example 1

2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano[3,4-f]quinoline-1H[1]benzopyrano[3,4-f]quinoline

A solution of 1,3-dimethoxybenzene (33.2 g, 240 mmol) in hexanes (20 mL) at 20°C was sequentially treated with n-butyllithium (100 mL of a 2.4 M solution in hexanes, 240 mmol) and N,N,N',N'-tetramethylethylenediamine (1.81 mL, 12 mmol), stirred at 23°C for 1.5 h, cooled to -78°C, treated with triisopropylborate (60.9 mL, 264 mmol) in diethyl ether (60 mL) for 1.5 h, additional diethyl ether (150 mL) was added to maintain stirring, which was carried out at 23°C for 2 h, then the mixture was poured into ice (150 mL) and 3M HCl (150 mL) and extracted with ethyl acetate. The extract was dried (Na ₂ SO ₄ ), filtered, and concentrated to precipitate a white solid from solution. The solid was collected by filtration and washed with hexanes to afford the desired compound.

MS (DCI/NH 3 ) m/z 200 (M+NH ₄ ) ⁺ .

Example 1B

A mixture of Example IA, methyl (5-nitro-2-bromobenzoate) (25.8 g, 99.2 mmol), (21.7 g, 119 mmol), cesium carbonate (97.1 g, 298 mmol) and dichlorobis-(triphenylphosphine)palladium (II) (3.5 g, 5.0 mmol) in DMF (300 mL) was stirred for 24 h at 80°C, cooled to 23°C, treated with water (600 mL) and extracted with ethyl acetate (800 mL). The extract was dried (Na ₂ SO ₄ ) and concentrated to precipitate a pale yellow solid from solution. The mixture was placed in a freezer (-20°C) for 2 h, then filtered to give the title compound. MS (DCI/NH 3 ) m/z 318 (M+H) ⁺ and 335 (M+NKLt/.

Example of IC

A solution of Example 1B (11.1 g, 35.1 mmol) in dichloromethane (60 mL) at -78°C was treated with boron tribromide (25.0 g, 99.8 mmol), heated at 23°C for 1 hour, recooled to 78°C, and treated with methanol (100 mL). The mixture was warmed to 0°C, and the precipitate was collected by filtration and recrystallized from methanol to give the title compound.

MS (DCI/NH 3 ) m/z 275 (M+NH ₄ ) ⁺ .

• 0 ·« 99 99 99

9 9 9 9 9 9 9 9 9 9 9

9 9 9 9 9 9 9 9 9 9

999 99 9 999 9 9 99 9

9 9 9 9 9 9 9 9

9999 99 99 99 99 99

Example ID

A mixture of Example 1C (10.7 g, 41.6 mmol) and CS2CO3 (20.0 g, 61.4 mmol) in DMF (130 mL) at 23°C was treated dropwise with methyl iodide (22.8 g, 161 mmol), stirred for 4 h, treated with water, and extracted with 1:1 ethyl acetate/hexane. The extract was concentrated and the resulting solid was filtered, washed with water (100 mL), and dried in vacuo to give the title compound.

MS (DCI/NH 3 ) m/z 289 (M+NH ₄ ) ⁺ .

Example IE

A suspension of Example ID (11.2 g, 41.3 mmol) in dioxane (400 mL) at 23°C was treated with 10% palladium on carbon (580 mg), heated to 65°C, treated with hydrogen, stirred at atmospheric pressure for 60 hours, filtered hot through seashell powder (Celite®) and concentrated to form a precipitate. The product was filtered and dried in vacuo to give the desired compound. Concentration of the mother liquor to half its original volume gave a second crop of the desired compound. MS (DCI/NH3) m/z 242 (M+H) ⁺ and 259 (M+NR,)*.

Example 1F

A solution of Example IE (4.0 g, 16.6 mmol) and iodine (1.7 g, 6.64 mmol) in acetone (380 mL) in a 1 L sealed ACE glass high pressure vessel at 105°C was stirred for 48 hours, cooled to room temperature, and concentrated. The residue was purified by flash column chromatography on silica gel eluting with a 0 to 12% ethyl acetate/hexanes gradient to provide the title compound.

MS (DCI/NH 3 ) m/z 322 (M+H) ⁺ .

Example 1G

A solution of Example 1F (1.02 g, 3.18 mmol) in THF (20 mL) at -78°C was treated with a solution of phenyllithium (10.9 mL, 19.6 mmol) in cyclohexane/diethyl ether, warmed to -50°C, stirred for 2 h, treated with saturated _NH4Cl , warmed to 25°C, and extracted with ethyl acetate. The extract was dried ( _Na2SO4 ), filtered, and concentrated. The residue was purified by flash chromatography on silica gel _with 20% ethyl acetate/hexanes to give the title compound.

MS (DCI/NH 3 ) m/z 400 (M+H) ⁺ .

«φ ·» φ ♦ ΦΦ φ* ΦΦ • φ φ · · · φ φ φ ΦΦ · φφφ φφφφ φ φ φ φ φφφ φ φ · φφφ φ φ · φ φ φ φφφ φφφφφ φφφφ φφφφ

Example 1

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano[3,4-f]quinoline-1H[1]benzopyrano[3,4-f]quinoline

A solution of Example 1G (0.67 g, 1.67 mmol) in dichloromethane (30 mL) at -78°C was treated with triethylsilane (2.91 g, 25.05 mmol) and _BF3OEt2 (0.95 g, 6.68 mmol), warmed to room temperature, stirred for 16 hours, and treated with saturated NaHCO3. The organic layer was dried ( _Na2SO4 ), filtered, and concentrated. The residue was purified by flash chromatography on silica gel with 5% ethyl acetate/hexanes to provide the title compound.

MS (DCI/NH 3 ) m/z 384 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-de) δ 8.00 (d, 1H), 7.19 (m, 5H), 6.9 (dd, 1H), 6.76 (s, 1H), 6.69 (dd, 1H), 6.55 (d, 1H), 6.43 (d, 1H), 6.2 (s, 1H), 5.38 (s, 1H), 3.8 (s, 3H), 1.83 (s, 3H), 1.22 (s, 3H), 1.14 (s, 3H);

Analytical _calcd for _C2gH25NO2 : C, _81.42 ; H, 6.58; N, 3.65. Found: C, 81.28; H, 6.30; N, 3.47.

Example 2

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(2-propenyl)-1H-[1]benzopyrano[3,4-fJquinoline

Example 2A

A solution of Example IF (6.65 g, 20.69 mmol) in dichloromethane (500 mL) at -78°C was treated dropwise with 1M diisobutylaluminum hydride in hexanes (47.6 mL, 47.6 mmol), stirred for 2 hours, treated successively with saturated aqueous Rochelle salt (300 mL) and ethyl acetate (600 mL) and stirred vigorously for 4 hours. The extract was washed with brine, dried (Na ₂ SO 4 ), filtered and concentrated to give the title compound.

MS (DCI/NH ₃ ) m/z 306 (M-OH) ⁺ .

Example 2B

A solution of Example 2A (4.20 g, 12.99 mmol) in methanol (150 mL) at 0°C was treated with p-toluenesulfonic acid in _H2O (1.2 g, 20% wt.) stirred for 30 min, stirred at room temperature for 1 h, cooled at 0°C for 30 min, and filtered. The solid was washed with hexanes and dried in vacuo to give the title compound. The filtrate was poured into saturated _NaHCO3 and extracted with ethyl acetate.

The extract was washed with brine, dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography on silica gel with 10-20% ethyl acetate/hexanes to provide the additional desired compound.

MS (DCI/NH ₃ ) m/z 306 (M-OHCH ₃ ) ⁺ .

φφ φφ ·· φφ ♦ ΦΦΦ φ φφφφ φφφ φ φ φ φφφ φφφ φ φφ φφ φφ φφ

Example 2

2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-(2-propenyl)-1H-[1]benzopyrano[3,4-fJquinoline

A solution of Example 2B (2.50 g, 7.41 mmol) in dichloromethane (225 mL) was treated with allyltrimethylsilane (4.0 mL, 25.2 mmol), cooled to -78°C, treated dropwise with _BF3- OEt2 (3.1 mL, 25.2 mmol), stirred for 15 min at -78°C, warmed to 0°C for 30 min, treated with saturated _NaHCO3 , and extracted with ethyl acetate. The extract was washed with brine, dried (MgSO4), filtered, and concentrated. The residue was purified by flash chromatography on silica gel with 5-20% ethyl acetate/hexanes to give the title compound.

MS (DCI/NH 3 ) m/z 348 (M+H) ⁺ ;

*H NMR (300 MHz, DMSO-de) δ 7.96 (d, 1H), 7.07 (t, 1H), 6.71 (d, 1H), 6.60 (d, 1H), 6.52 (d, 1H), 6.12 (br s, 1H), 5.82 (m, 1H), 5.76 (dd, 1H), 5.44 (br s, 1H), 5.01, (m, 2H), 3.86 (s, 3H), 2.44 (m, 1H), 2.20 (m, 1H), 2.16 (s, 3H), 1.17 (s, 3H), 1.16 (s, 3H);

Analytical calcd for _C23H25NO2 : C, 79.51; H, 7.25; N, 4.03. Found: C, 79.35; H, 7.30; N, 3.89.

Example 3

2,5-dihydro-2,2,4,N-tetramethyl-5-(2-propenyl)-1H-[1]benzopyrano[3,4-fJquinolin-10-amine

The solution from Example 1C is processed according to the method of Example 1 to give the desired compound.

MS (DCI/NH 3 ) m/z 227 (M+H) ⁺ .

Example 3A

The solution from Example 3A is processed according to the procedure of Example 1F to give the desired compound.

MS (DCI/NH ₃ ) m/z 308 (M+H) ⁺ .

Example 3C

0 ·

0« *0 0» · • 0 0 0 0 0 0 0 0 0 0 ·0

00000 0 ·

0 0 0

0000 00 00 00

0 0 0

0 0 0

A solution of Example 3B (1.38 g, 4.49 mmol), triethylamine (1.92 mL, 13.77 mmol), and 4-dimethylaminopyridine (100 mg) in dichloromethane (50 mL) at -78°C was treated dropwise with trifluoromethanesulfonic anhydride (1.39 g, 4.94 mmol), stirred at -78°C for 30 min, cautiously warmed to room temperature over 1.5 h, poured into saturated NH4Cl, and extracted with ethyl acetate. The extract was washed with water, dried ( _MgSO4 ), filtered, and concentrated. The residue was purified by flash chromatography on silica gel with 10% ethyl acetate/hexanes to give the title compound.

MS (DCI/NH ₃ ) m/z 440 (M+H)'.

3D example

Example 3C is worked up according to the procedure of Examples 2A, 2B and 2 to give the desired compound.

MS (DCI/NH ₃ ) m/z 466 (M+H) ⁺ .

Example 3

2,5-dihydro-2,2,4,N-tetramethyl-5-(2-propenyl)-1H-[1]benzopyrano[3,4-f]quinolin-10-amine A solution of Example 3D (0.165 g, 0.36 mmol), palladium acetate (0.0016 g, 0.007 mmol), (S)-(-)-2,2'-bis(phenylphosphino)-1,T-binaphthyl (0.0055, 0.008 mmol), sodium tert-butoxide (0.051 g, 0.53 mmol), methylamine (0.44 mL of a 2.0 M solution in THF, 0.88 mmol) in toluene (0.5 mL) was heated at 90°C for 4 h in a sealed high-pressure glass ACE vessel, cooled to 0°C, diluted with ethyl acetate (5 mL), and washed with 0.5 M HCl. The organic extract was dried (Na 2 SO 4 ), filtered and concentrated. The residue was purified by flash chromatography on a silica gel column eluting with a gradient of 5-12% ethyl acetate/hexanes to afford the desired compound.

MS (DCI/NH ₃ ) m/z 347 (M+H) ⁺ ;

Η NMR (300 MHz, DMSO-dé) δ 7.83 (d, 1H), 6.94 (dd, 1H), 6.62 (d, 1H), 6.28 (dd, 1H), 6.25 (dd, 1H), 6.05 (d, 1H), 5.86-5.74 (m, 2H), 5.67 (dd, 1H), 5.45 (s, 1H), 5.40 (q, 1H), 5.03 (dd, 1H), 4.98 (dd, 1H), 2.72 (d, 3H), 2.16 (s, 3H), 1.17, (s, 3H), 1.15 (s, 3H);

HRMS m/z calcd for C23H26N2O. 346.2045 (M+H) ⁺ . Found: 346.2049.

Example 4

Methyl 2,5-dihydro-2,2,4-trimethyl-5-(2-propenyl)-1H-[1]benzopyrano[3,4-f]quinoline-10carboxylate • · »« 44 • · · ·

4 ·

444 ·

4444 M

4 4 4 • 4 4 * » · ·

4 4 4 • 4 44

A solution of Example 3D (263 mg, 0.565 mmol), triethylamine (0.10 mL, 0.717 mmol), 1,3bis(diphenylphosphino)propane (26 mg, 0.063 mmol), and DMSO (1.5 mL) in methanol (8 mL) was treated with palladium(II) acetate (12.7 mg, 0.056 mmol) saturated with carbon monoxide (1 atm) for 20 min, heated at 65°C for 3 h, cooled, diluted with ethyl acetate (100 mL), and filtered. The filtrate was washed with brine, dried (MgSO ₄ ), filtered, and concentrated. The residue was purified by flash chromatography on silica gel with 5-10% ethyl acetate/hexanes to give the title compound.

MS (DCI/NH 3 ) m/z 376 (M+H) ⁺ ;

*H NMR δ 7.19 (m, 2H), 7.03 (dd, 1H), 6.78 (d, 1H), 6.60 (d, 1H), 6.30 (m, 1H), 5.85 (m, 2H), 5.46 (m, 1H), 5.05 (dm, 1H), 4.98 (dm, 1H), 3.77 (s, 3H), 2.30 (m, 2H), 2.19 (d, 3H), 1.21 (s, 3H), 1.15 (s, 3H);

HRMS m/z calcd for C24H25NO3: 375.1834 (M+H) ⁺ . Found: 375.1841.

Example 5

10-ethenyl-2,5-dihydro-2,2,4-trimethyl-5-(2-propenyl)-1H-[1jbenzopyrano[3,4-f]quinoline

A solution of Example 3D (103 mg, 0.221 mmol) and (1,3bis(diphenylphosphino)ferrocene)palladium(II) chloride (22 mg, 0.027 mmol) in 1-methyl-2-pyrrolidinone (2 mL) was treated with vinyltributylstannane (0.110 mL, 119 mg, 0.376 mmol), heated at 65°C for 24 h, cooled to room temperature, treated with saturated KF solution, and extracted with ethyl acetate. The extract was washed with brine, dried (MgSO ₄ ), filtered, and concentrated. The residue was purified by flash chromatography on silica gel with 5% ethyl acetate/hexanes to give the title compound.

MS (DCI/NH 3 ) m/z 344 (M+H) ⁺ ;

*H NMR δ 7.22 (d, 1H), 7.15 (m, 2H), 6.99 (dd, 1H), 6.83 (dd, 1H), 6.63 (d, 1H), 6.23 (m, 1H), 5.87 (ddm, 1H), 5.73 (dd, 1H), 5.76 (dd, 1H), 5.47 (m, 1H), 5.33 (dd, 1H), 5.03 (dd, 1H), 4.98 (dm, 1H), 3.77 (s, 3H), 2.44 (m, 1H), 2.28 (m, 1H), 2.18 (d, 3H), 1.21 (s, 3H), 1.15 (s, 3H);

HRMS m/z calcd for _C24H26NO : 344.2014 (M+H) ⁺ . Found: 344.2011.

Example 6

10-ethynyl-2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-(2-propenyl)-1Η-[1]benzopyrano[3,4f]quinoline

Example 6A • Φ ·♦

Φ Φ « ·

Φ · Φ ·

Φ · · · » · Φ Φ φφ ΦΦ

99 • » « * • · ·

Φ »»· • · ΦΦΦΦ ΦΦ

ΦΦ • · · · • · · · • * »ΦΦ * · · *Φ Φ·

A solution of Example 3D (25 mg, 0.054 mmol), tetra-n-butylammonium iodide (40 mg, 0.108 mmol), bis(triphenylphosphine)palladium chloride (7.0 mg, 0.010 mmol), copper (I) iodide (3.8 mg, 0.020 mmol), and triethylamine (0.15 mL, 0.717 mmol) in DMF (0.75 mL) was treated with trimethylsilylacetylene (174 mg, 1.76 mmol), heated at 55°C for 3 h, diluted with ethyl acetate (20 mL), and filtered. The filtrate was washed with saturated NH4Cl, and the aqueous layer was extracted with ethyl acetate. The combined extracts were dried ( _MgSO4 ), filtered, and concentrated. The residue was applied to a 10 x 20 cm TLC plate with 0.25 mm silica gel and eluted with 10% ethyl acetate/hexanes. Extraction of the silica gel with ethyl acetate gave the desired compound.

MS (DCI/NH 3 ) m/z 414 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-d _ó ) δ 8.36 (d, 1H), 7.07 (m, 2H), 6.90 (dd, 1H), 6.60 (d, 1H), 6.34 (m, 1H), 5.80 (m, 2H), 5.46 (m, 1H), 5.04 (dm, 1H), 4.97 (dm, 1H), 2.35 (m, 1H), 2.26 (m, 1H), 2.17 (d, 3H), 1.18 (s, 3H), 1.17 (s, 3H), 0.26 (s, 9H).

Example 6

10-ethynyl-2,5-dihydro-2,2,4-trimethyl-5-(2-propenyl)-1H-[1]benzopyrano[3,4-quinoline

A solution of Example 6A in THF (2.5 mL) was sequentially treated with glacial acetic acid (0.005 mL) and 1M tetra-n-butylammonium fluoride in THF (0.050 mL, 0.050 mmol), stirred at room temperature for 18 hours, and purified according to the procedure of Example 6A to give the desired compound.

MS (DCI/NH 3 ) m/z 342 (M+H) ⁺ ;

*H NMR (300 MHz, DMSO-d ₆ ) δ 8.27 (dd, 1H), 7.15 (t, 1H), 7.07 (d, 1H), 6.91 (dm, 1H), 6.62 (d, 1H), 6.34 (m, 1H), 5.80 (m, 1H), 5.4b (m, 1H), 5.03 (dm, 1H), 4.98 (dm, 1H), 4.41 (s, 1H), 2.44 (m, 2H), 2.17 (s, 3H), 1.18 (s, 6H);

HRMS calculated m/z for C24H23NO: 341.1780 (M+H) ⁺ . Found: 341.1788.

Example 7

2,5-dihydro-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano[3,4-f]quinolin-10-ol

Example 7A

A solution of Example 3B (569 mg, 1.85 mmol) in DMF (8 mL) at 23°C was sequentially treated with imidazole (379 mg, 5.55 mmol) and t-butyldimethylsilyl chloride (418 mg, 2.78 mmol), stirred for 3 hours, poured into water, and extracted with 2:1 hexane/ethyl acetate (22 mL). The extract was washed with water and brine, dried (Na ₂ SO ₄ ), filtered, and concentrated. The residue was purified by flash chromatography on silica gel with 25% ethyl acetate/hexanes to give the title compound.

·· • · « B * ··· • · ··*» *·

Bfc B· • · · · • · · · • Φ·· « · • ft ♦· • ♦ , · · • · · • · · ♦ B *·

MS (DCI/NH3) m/z 422 (M+H) ⁺ . Example 7B

Example 7A was processed according to the method of Examples 1G and 1 to give the desired compound.

Example 7

2,5-Dihydro-2,2,4-trimethyl-5-phenyl-1Η-[1]benzopyrano[3,4-ť]quinolin-10-ol

A solution of Example 7B (0.90 g, 1.87 mmol) in THF (12 mL) at 0°C was treated with 1M tetra-n-butylammonium fluoride in THF (3.37 mL, 3.37 mmol), heated at 23°C for 1 hour, treated with water, and extracted with ethyl acetate. The extract was washed with brine, dried (Na ₂ SO 4 ), filtered, and concentrated. The residue was purified by flash chromatography on a silica gel column, eluting with a gradient of 10-30% ethyl acetate/hexanes, to provide the title compound.

MS (DCI/NH 3 ) m/z 370 (M+H) ⁺ ;

'H NMR (300 MHz, DMSO-d ₆ ) δ 9.63 (s, 1H), 9.16 (d, 1H), 7.13-7.24 (m, 5H), 6.74 (s, 1H), 6.70 (d,lH), 6.8 (d,lH), 6.39 (dd, 1H), 6.26 (dd, 1H), 6.11 (d, 1H), 5.37 (s, 1H), 1.85 (d, 3H), 1.22 (s, 3H), 1.11 (s, 3H);

HRMS _{calculated m/z for C25H23NO2 : 369.1729} (M+H) ⁺ . Found: 369.1736.

Example 8

10-(difluoromethoxy)-2,5-dihydro-2,2,4-trimethyl-5-(2-propenyl)-1H-[1]benzopyrano[3,4fquinoline

Example 8A

A solution of Example 3B (1.11 g, 3.6 mmol) in DMF (10 mL) at 0°C was sequentially treated with sodium t-butoxide (0.38 g, 3.6 mmol) and bromodifluoromethane (10 mL), stirred at 0°C for 6 h, warmed to room temperature for 1 h, treated with saturated NaHCO ₃ solution, and extracted with ethyl acetate. The extract was dried (Na ₂ SO 4 ), filtered, and concentrated. The residue was purified by flash chromatography on silica gel with 59% ethyl acetate/hexanes to give the title compound.

MS (DCI/NH 3 ) m/z 436 (M+H) ⁺ .

Example 8

10-(difluoromethoxy)-2,5 -dihydro-2,2,4-trimethyl-5-(2-propenyl)-1 H-[ 1 ]benzopyrano[3,4·· · · φ · · · · * · · φφφφ · · · · φφφφ • φ · · · · · φφφφ • ··· · · φφφφ φφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφ··· ·· ·· ·· fquinoline

Example 8A is processed according to the method of Examples 2B and 2 to give the desired compound.

MS (DCI/NH 3 ) m/z 384 (M+H) ⁺ ;

'li NMR (300 MHz, DMSO-dg) δ 7.75 (d, 1H), 7.20 (t, 1H), 7.15 (t, 1H), 6.83 (dd,lH), 6.81 (dd, 1H), 6.63 (d, 1H), 6.28 (s, 1H), 5.89-5.75 (m, 2H), 5.46 (s, 1H), 5.04 (dd, 1H), 4.96 (dd,

1H), 2.48-2.40 (m, 1H), 2.29-2.20 (m, 1H), 2.18 (s, 3H), 1.17 (s, 6H);

HRMS calcd for C23H23F2NO2: 383.1697 (M+H) ⁺ . Found: 383.1693,

Example 9

10-ethoxy-2,5-dihydro-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano[3,4-f]quinoline

Example 9A

A solution of Example 3B (28 mg, 0.09 mmol) in DMF (1.0 mL) at 0°C was treated with sodium hydride (2.4 mg of a 60% dispersion in mineral oil, 0.01 mmol), stirred for 1 hour, treated with ethyl bromide (20 mg, .182 mmol), stirred for 30 minutes at room temperature, treated with saturated NaHCO ₃ solution, and extracted with ethyl acetate. The extract was dried (Na ₂ SO ₄ ), filtered, and concentrated. The residue was purified by flash chromatography on silica gel with 5% ethyl acetate/hexanes to give the title compound.

Example 9

10-ethoxy-2,5-dihydro-2,2,4-trimethyl-5-phenyl-1H-[1jbenzopyrano[3,4-fJquinoline

Example 9A is processed according to the method of Examples 1G and 1 to give the desired compound.

MS (DCI/NH ₃ ) m/z 398 (M+H) ⁺ ;

’H NMR (300 MHz, DMSO-dg) δ 8.09 (d, 1H), 7.20-7.15 (m, 5H), 6.78 (dd, 2H), 6.77 (s,

1H), 6.69 (d, 1H), 6.53 (dd, 1H), 6.43 (dd, 1H), 6.18 (d, 1H), 5.39 (d, 1H), 3.99-4.06 (m, 1H),

1.85 (d, 3H), 1.38 (t, 3H), 1.22 (s, 3H), 1.16 (s, 3H);

HRMS calculated m/z for _C27H27NO2 : _397.2042 (M+H) ⁺ . Found: _397.2034 .

Example 10

2,5-dihydro-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano[3,4-f]quinolin-10-ol acetate (ester) • · • ·

A solution of Example 7 (20 mg, 0.05 mmol) in pyridine (1 mL) at 0°C was treated with acetic anhydride (0.1 mL, 1.05 mmol), stirred at room temperature for 14 hours, and concentrated. The residue was purified by flash chromatography on silica gel with 20% ethyl acetate/hexanes to give the title compound.

MS (DCI/NH 3 ) m/z 412 (M+H) ⁺ ;

*H NMR (300 MHz, DMSO-d ₆ ) δ 7.62 (d, 1H), 7.21-7.16 (m, 5H), 6.93 (t, 1H), 6.77 (s, 1H), 6.73 (d, 1H), 6.65 (dd, 1H), 6.62 (dd, 1H), 6.32 (s, 1H), 5.37 (s, 1H), 2.30 (s, 3H), 1.79 (s, 3H), 1.22 (s, 3H), 1.14 (s, 3H);

HRMS calculated m/z for C27H25NO3: 411.1834 (M+H) ⁺ . Found: 411.1842.

Example 11

5-(3-bromo-5-methylphenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1 Η- [ 1 jbenzopyrano [3,4fjquinoline

A solution of Example 2B a (0.520 g, 1.54 mmol) in dichloromethane (50 mL) was cooled to -10°C, treated dropwise with BF3- _OEt2 (0.57 mL, 4.62 mmol), stirred for 30 min at -10°C, treated dropwise with a 0.49 M solution of 3-bromo-5-methylphenylmagnesium bromide in diethyl ether (12.6 mL), stirred for 15 min, treated with saturated _NaHCO3 , and extracted with ethyl acetate. The extract was washed with brine, dried ( _Na2SO4 ), filtered, and concentrated. The residue was purified by flash chromatography on silica gel with 5% ethyl acetate/hexanes to give the title compound.

1H NMR (300 MHz, DMSO-d ₆ ) δ 8.02 (d, 1H), 7.22 (s, 1H), 7.03 (br d, 1H), 6.95 (t, 1H), 6.74 (s, 1H), 6.71 (d, 1H), 6.59 (d, 1H), 6.50 (d, 1H), 6.26 (d, 1H), 5.42 (s, 1H), 4.04 (s, 1H), 3.80 (s, 3H), 2.18 (s, 3H), 1.85 (s, 3H), 1.23 (s, 3H), 1.16 (s, 3H);

_HRMS calculated m/z for _C27H26NO2Br : _475.1147 (M+H) ⁺ . Found: 475.1143.

Example 12

3-(2,5-Dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolin-5yl)phenol acetate (ester)

Example 12A

A solution of 3-methoxymethoxyphenyl bromide (10.85 g, 50.00 mmol) in THF (300 mL) at -78°C was treated with n-butyllithium (2.5 M in hexane, 20 mL), warmed to -30°C, recooled to -78°C, treated with the compound from Example 1F, heated to -50°C, quenched with saturated NH4Cl, warmed to room temperature, decanted _{·· ·· ·· ·· • · · · » · · and concentrated. The residue was treated with water and extracted with ethyl acetate. The extract was washed with water and brine, dried (Na2SO4 )} , filtered and concentrated. The residue was purified by flash chromatography on silica gel 20-25% ethyl acetate/hexanes to give the desired compound.

MS (DCI/NH 3 ) m/z 460 (M+H) ⁺ .

Example 12B

A solution of Example 12A (2.30 g, 5.00 mmol) in methanol (10 mL) was treated with methanol saturated with HCl (50 mL), stirred for 18 h, poured into 1:1 ethyl acetate/sat. NH4Cl and extracted with ethyl acetate. The extract was washed with water and brine, dried ( _Na2SO4 ), _filtered and concentrated to give the title compound.

MS (DCI/NH ₃ ) m/z 416 (M+H) ⁺ .

Example 12C

A solution of Example 12B (2.45 g, 5.89 mmol) and pyridine (2.33 g, 29.4 mmol) in THF (100 mL) was treated with acetyl chloride (0.51 g, 6.48 mmol), stirred for 4 h, allowed to settle, decanted, and concentrated. The residue was treated with saturated NaHCO ₃ and extracted with ethyl acetate. The extract was washed with water and brine, dried (Na ₂ SO ₄ ), filtered, and concentrated. The residue was purified by flash chromatography on silica gel 25-33% ethyl acetate/hexanes to provide the title compound.

MS (DCI/NH ₃ ) m/z 458 (M+H) ⁺ .

Example 12

3-(2,5-Dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolin~5yl)phenol acetate (ester)

Example 12C was processed according to the method of Example 1 to give the desired compound.

MS (DCI/NH ₃ ) m/z 442 (M+H) ⁺ ;

*Η NMR (300 MHz, DMSO-dg) δ 8.01 (d, 1H), 7.26 (t, 1H), 7.07 (d, 1H), 6.98-6.90 (m, 2H),

6.85 (s, 1H), 6.77 (s, 1H), 6.71 (d, 1H), 6.58 (d, 1H), 6.46 (dd, 1H), 6.23 (s, 1H), 5.40 (s, 1H), 3.79 (s, 3H), 2.19 (s, 3H), 1.85 (s, 3H), 1.23 (s, 3H), 1.14 (s, 3H);

Analytical _calcd for _{C25H27NO4-0.25H2O} : C, _75.40 ; H, 6.21; _N , 3.14. Found: C, 75.76; H, 6.21; N, 2.84.

0« • 0 • 0 *

Example 13

3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolin-5-yl)phenol

A solution of Example 12 (0.81 g, 1.84 mmol) in THF (20 mL) and methanol (20 mL) was treated with K2CO3 (2.00 g, 14.5 mmol) in water (6 mL), stirred for 12 h, quenched with saturated NH4Cl, decanted, concentrated, treated with saturated _NaHCO3 , and extracted with ethyl acetate. The extract was washed with water and brine, dried ( _Na2SO4 ), filtered, and concentrated to give the title compound.

MS (DCI/NH 3 ) m/z 400 (M+H) ⁺ ;

^r H NMR (300 MHz, DMSO-de) δ 9.26 (s, 1H), 8.00 (d, 1H), 7.00 (t, 1H), 6.92 (t, 1H), 6.716.66 (m, 2H), 6.63 (d, 1H), 6.58-6.51 (m, 3H), 6.44 (dd, 1H), 6.15 (s, 1H), 5.38 (s, 1H), 3.80 (s, 3H), 1.88 (s, 3H), 1.24 (s, 3H), 1.15 (s, 3H);

Analytical Calcd. for C12H13NCh: C, 78.17; H, 6.30; N, 3.50. Found; C, 77.82; H, 6.42; N, 3.26.

Example 14

2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-[[3-(methylthio)methoxy]phenyl]-1H[1]benzopyrano[3,4-f]quinoline

A solution of Example 13 (420 mg, 1.05 mmol) in DMF (40 mL) at 0°C was treated portionwise with NaH (50 mg, 2.10 mmol) over 5 min, stirred for 10 min, treated with chloromethylmethylsulfide (152 mg, 1.58 mmol), warmed to room temperature, treated with saturated NH4Cl, and extracted with ethyl acetate. The extract was washed sequentially with 1M NaOH and brine, dried ( _Na2SO4 ), filtered, and concentrated. The residue was purified by flash chromatography on silica gel with 5-17% ethyl acetate/hexanes to give the title compound.

MS (DCI/NH 3 ) m/z 460 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-dé) δ 8.01 (d, 1H), 7.14 (t, 1H), 6.92 (t, 1H), 6.83-6.68 (m, 5H), 6.56 (d, 1H), 6.47 (d, 1H), 6.21 (s, 1H), 5.40 (s, 1H), 5.13 (s, 2H), 3.80 (s, 3H), 2.09 (s, 3H), 1.97 (s, 3H), 1.24 (s, 3H), 1.16 (s, 3H);

Analytical calcd for _{C28H29NO3S0.5H2O} : C, _71.76 ; H, 6.45; _N , 2.98. Found: C, 71.93; H, 6.61; N, 2.68.

Example 15 [3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1 H-[1]benzopyrano[3,4-f]quinolin-5yl)phenyl]dimethylcarbamate

Example 13 and N,N-dimethylcarbamoyl chloride are processed according to the method of Example 14 to give the desired compound.

MS (DCI/NH 3 ) m/z 471 (M+H) ⁺ ;

’H NMR (300 MHz, DMSO-cL) δ 8.01 (d, 1H), 7.22 (t, 1H), 7.05 (d, 1H), 6.93 (t, 2H), 6.83 (s, 1H), 6.77 (s, 1H), 6.71 (d, 1H), 6.57 (d, 1H), 6.48 (d, 1H), 6.23 (d, 1H), 5.40 (s, ,1H), 3.80 (s, 3H), 2.97 (s, 3H), 2.85 (s, 3H), 1.86 (s, 3H), 1.24 (s, 3H), 1.14 (s, 3H);

Analytical calcd for C29H30N2O4: C, 74.02; H, 6.42; N, 5.95. Found: C, 74.05; H, 6.36; N, 5.86.

Example 16 [3-(2-Furanyl)-5-methylphenyl]-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline A solution of Example 11 (0.253 g, 0.531 mmol) in 1-methyl-2-pyrrolidinone (25 mL) was deoxygenated with nitrogen, treated with 2-(tributylstannyl)furan (0.33 mL, 1.06 mmol), [1,1'bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane complex (0.045 g, 0.005 mmol), heated at 85°C for 13 hours, cooled to room temperature, diluted with ethyl acetate and saturated KF solution, stirred for 3 hours and extracted with ethyl acetate. The extract was washed with brine, dried (MgSO ₄ ), filtered, and concentrated. The residue was purified by flash chromatography on silica gel with 5-10% ethyl acetate/hexanes to afford the title compound.

MS (DCI/NH 3 ) m/z 464 (M+H) ⁺ ;

'H NMR (300 MHz, DMSO-ds) δ 8.02 (d, 1H), 7.67 (m, 1H), 7.31 (d, 2H), 6.92 (t, 1H), 6.92 (s, 1H), 6.75 (m, 2H), 6.72 (d, 1H), 6.57-6.50 (m, 3H), 5.23 (m, 1H), 5.41 (s, 1H), 3.78 (s, 3H), 2.20 (s, 3H), 1.89 (s, 3H), 1.24 (s, 3H), 1.17 (s, 3H);

Analytical calcd for C31H29NO3: C, 80.32; H, 6.31; N, 3.02. Found: C, 80.08; H, 6.25; N, 2.83.

Example 17

2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-[3-methyl-5-(1-morpholinyl)phenyl]-1H[1]benzopyrano[3,4-f]quinoline

A solution of Example 11 (0.055 g, 0.115 mmol) in toluene (5 mL) was reacted sequentially with bis(dibenzylideneacetone)palladium (0.007 g, 0.012 mmol), (S)-(-)« · ··

0» ·

··· • 0 bis(diphenylphosphino)-1,1'-binaphthyl (0.022 g, 0.035 mmol), morpholine (15 μΐ, 0.173 mmol), and sodium tert-butoxide (0.028 g, 0.289 mmol), stirred at 85°C for 4 h, cooled to room temperature, diluted with ethyl acetate and water, and filtered through seashell powder (Celite®). The extract was washed with brine, dried (Na ₂ SO ₄ ), filtered, and concentrated. The residue was purified by flash chromatography on silica gel 10-33% ethyl acetate/hexanes to give the title compound.

MS (DCI/NH ₃ ) m/z 483 (M+H) ⁺ ;

’H NMR (300 MHz, DMSO-dg) δ 7.97 (d, 1H), 6.93 (t, 1H), 6.68 (m, 2H), 6.54-6.60 (m, 3H), 6.49 (d, 1H), 6.40 (s, 1H), 6.18 (br s, 1H), 5.40 (s, 1H), 3.78 (s, 3H), 3.65 (m, 4H), 2.91 (m, 4H), 2.09 (s, 3H), 1.89 (s, 3H), 1.21 (s, 3H), 1.16 (s, 3H);

_Analytical calcd for _{C31H34N2O3O.25H2O} : C, _76.44 ; H, 7.14; N, 5.75. Found: C, 76.61; H, 7.35; N, 5.47.

Example 18

2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-(phenylmethylene)-1H-[1]benzopyrano[3,4fquinoline

A solution of Example 1F (0.100 g, 0.31 mmol) in THF (5 mL) at -78°C was treated dropwise with a solution of benzylmagnesium bromide (10 mL of a 0.44 M solution in ether, 4.4 mmol) over 10 min, warmed to room temperature for 14 h, treated with saturated _NH4Cl and extracted with ethyl acetate. The extract was dried ( _Na2SO4 ) and concentrated. The residue was dissolved in dichloromethane (10 mL), treated with p-toluenesulfonic acid in _H2O (0.059 g, 0.31 mmol), stirred for 14 h at room temperature, treated with 2% NaOH (10 mL) and extracted with ethyl acetate. The residue was purified by flash chromatography on a silica gel column with 10% ethyl acetate/hexanes to give the desired compound as a mixture of regioisomers which were separated by HPLC (Microsorb, 5% acetone/hexanes) but rapidly interconverted to a 1:1 regioisomeric mixture at room temperature.

MS (DCI/NH 3 ) m/z 396 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-dg) isomer 1: δ 8.12 (d, 1H), 7.16-7.03 (m, 5H), 6.80-6.66 (m, 4H), 6.45 (s, 1H), 6.34 (s, 1H), 5.0 (s, 1H), 3.90 (s, 3H), 1.84 (s, 3H), 1.20 (s, 3H), 0.91 (s, 3H); isomer 2: δ 8.23 (d, 1H), 7.70 (d, 2H), 7.37 (t, 2H), 7.22 (m, 1H), 7.03-7.16 (m, 3H),

6.86 (d, 1H), 6.55 (s, 1H), 5.53 (s, 1H), 5.45 (s, 1H), 3.90 (s, 3H), 1.97 (s, 3H), 1.25 (s, _{6H); HRMS calculated m/z for C27H25NO2 : 395.1885} (M+H) ⁺ . Found: 395.1884.

Example 19

5-(3,5-dichlorophenyl)-2,5-dihydro-10-methoxy~2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline

Example 1F and 3,5-dichlorophenylmagnesium bromide are processed according to the method of Examples 1G and 1 to give the desired compound.

MS (DCI/NH ₃ ) m/z 452 (M+H) ⁺ ;

^f H NMR (300 MHz, DMSO)tr 8.10 (d, 1H), 7.51 (t, Hz, 1H), 7.19 (d, 2H), 7.03 (dd, 1H), 6.87 (s, 1H), 6.80 (d, 1H), 6.b7 (d, 1H), 6.59 (d, 1H), 6.36 (s, 1H), 5.50 (s, 1H), 3.87 (s, 3H), 1.93 (s, 3H), 1.29 (s, 3H), 1.22 (s, 3H);

¹³ C NMR (75 MHz, DMSO) 156.1, 151.1, 145.6, 143.8, 133.8, 133.8, 133.5, 128.1, 127.6, 127.3, 127.2, 127.1, 126.7, 126.7, 117.8, 116.9, 114.1, 113.4, 110.2, 105.9, 73.3, 55.6, 49.7,

29.2, 28.5, 23.2;

HRMS calcd for _{C26H23NO2Cl2 : 451.1106 (} M+H) ⁺ . Found: 451.1113.

Example 20

5-Butyl-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline

Example 1F and n-butyllithium are processed according to the method of Examples 1G and 1 to give the desired compound.

MS (DCI/NH ₃ ) m/z 364 (M+H) ⁺ ;

\Η NMR (300 MHz, DMSO-dg) δ 7.94 (d, 1H), 7.06 (dd, 1H), 6.68 (dd, 1H), 6.58 (d, 1H), 6.54 (dd, 1H), 6.08 (s, 1H), 5.67 (m, 1H), 5.44 (s, 1H), 3.85 (s, 3H), 2.15 (s, 3H), 1.68 (m, 1H), 1.41-1.22 (m, 5H), 1.17 (s, 3H), 1.14 (s, 3H), 0.78 (t, 3H);

Analytical calcd for _C24H29NO2 : C, _79.30 ; H, 8.04; N, 3.85. Found: C, 79.10; H, 8.14; _N , 3.72.

Example 21

2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-[3-(trifluoromethyl)phenyl]-1H-[1]benzopyrano[3,4fquinoline

Example 1F and 3-trifluoromethylphenyl magnesium bromide are processed according to the method of Examples 1G and 1 to give the desired compound.

MS (DCI/NH ₃ ) m/z 452 (M+H) ⁺ ;

^! fl NMR (300 MHz, DMSO-de) δ 8.03 (d, 1H), 7.55 (m, 1H), 7.47 (m, 3H), 6.93 (dd, 1H), 6.88 (s, 1H), 6.73 (d, 1H), 6.58 (d, 1H), 6.48 (d, 1H), 6.29 (s, 1H), 5.43 (s, 1H), 3.79 (s, 3H), 1.85 (s, 3H), 1.23 (s, 3H), 1.17 (s, 3H);

Analytical calcd for C27H24F3NO2: C, 71.82; H, 5.35; N, 3.10. Found: C, 71.73; H, 5.44; N, 3.05.

Example 22

2,5-dihydro-10-methoxy-5-(4-methoxyphenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline

The compound of Example 2B and anisole are treated according to the method of Example 2C to give the desired compound.

MS (DCI/NH ₃ ) m/z 414 (M+H) ⁺ ;

'H NMR (300 MHz, DMSO-de) δ 8.00 (d, 1H), 7.04 (d, 2H), 6.90 (dd, 1H), 6.78 (dd, 2H), 6.70 (dd, 2H), 6.60 (dd, 1H), 6.41 (dd, 1H), 6.18 (s, 1H), 5.37 (s, 1H), 3.79 (s, 3H), 3.65 (s, 3H), 1.83 (s, 3H), 1.22 (s, 3H), 1.13 (s, 3H);

HRMS calculated m/z for C27H27NO3: 413.1991 (M+H) ⁺ . Found: 413.1987.

Example 23

5-(3-Chlorophenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[i]benzopyrano[3,4-quinoline

The compound of Example 1F and 3-chlorophenylmagnesium bromide are treated according to the method of Examples 1G and 1 to give the desired compound.

MS (DCI/NH 3 ) m/z 418 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-de) δ 8.01 (d, 1H), 7.23-7.12 (m, 4H), 6.90 (dd, 1H), 6.77 (s, 1H), 6.70 (d, 1H), 6.55 (dd, 1H), 6.44 (dd, 1H), 6.18 (d, 1H), 5.38 (s, 1H), 3.79 (s, 3H), 1.84 (s, 3H), 1.22 (s, 3H), 1.15 (s, 3H);

HRMS calculated m/z for C26H24NO2Cl: 417.1496 (M+H) ⁺ . Found: 417.1490.

Example 24

2,5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(3-methylphenyl)-1H-[1]benzopyrano[3,4-f]quinoline The compound of Example 1F and 3-methylphenylmagnesium bromide are treated according to the method of Examples 1G and 1 to give the desired compound.

MS (DCI/NH 3 ) m/z 398 (M+H) ⁺ ;

• · • ·

100'Η NMR (300 MHz, DMSO-d ₆ ) δ 7.94 (d, 1H), 7.01-6.91 (m, 4H), 6.84 (dd, 1H), 6.66 (s, 1H), 6.62 (d, 1H), 6.48 (dd, 1H), 6.38 (dd, 1H), 6.11 (d, H), 5.31 (d, 1H), 3.72 (s, 3H), 2.10 (s, 3H), 1.78 (d, 3H), 1.15 (s, 3H), 1.09 (s, 3H);

Analytical calcd for C28H27NO2: C, 81.58; H, 6.85; N, 3.52. Found: C, 81.23; H, 7.18; N, 3.36.

Example 25 (±)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano[3,4-f]quinoline Spectral data are identical to Example 1.

[cc]d ⁼ + 85.1;

Retention time - 11.68 minutes on a Chiralcel OJ 4.6 x 250 mm HPLC column;

Solvent: 95:5 hexane:ethanol;

Flow rate: 1 ml/minute

Example 26 (±)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano[3,4-f]quinoline Enantiomer of Example 1.

The spectral data are identical to example 1.

[α]o = - 84.9;

Retention time = 15.27 minutes on a Chiralcel OJ 4.6 x 250 mm HPLC column;

Solvent: 95:5 hexane:ethanol;

Flow rate: 1 ml/minute.

Example 27

5-(3,5-dimethylphenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano-[3,4fquinoline

Example 1F (0.052 g, 0.162 mmol) in THF (5 mL) was cooled to 0°C, treated dropwise with 0.38 M 3,5-dimethylphenylmagnesium bromide in dimethyl ether (4.4 mL, 1.68 mmol), warmed to room temperature, stirred for 14 h, partitioned between saturated NH4Cl and ethyl acetate, and extracted with ethyl acetate. The extract was washed with brine, dried ( _MgSO4 ), filtered, and concentrated. The residue was purified by flash chromatography on silica gel, eluting with a gradient of 10-25% ethyl acetate/hexanes, to afford the desired lactol.

• · · · · ·

101 • · · · · ·

Lactol (0.043 g, 0.101 mmol) was dissolved in dichloromethane (7 mL), treated with triethylsilane (0.16 mL, 1.01 mmol), cooled to 0°C, treated with _{BF3OEt2 (} 0.12 mL, 1.01 mmol), warmed to room temperature, stirred for 19 h, treated with NaHCO3 and extracted with ethyl acetate. The extract was washed with brine, dried ( _MgSO4 ), and concentrated. The residue was purified by flash chromatography on silica gel with 5-10% ethyl acetate/hexanes to give the title compound.

MS (DCI/NH 3 ) m/z 412 (M+H) ⁺ ;

’H NMR (300 MHz, DMSO-dó) δ 8.00 (d, 1H), 6.92 (t, 1H), 6.78 (m, 3H), 6.70 (d, 1H), 6.69 (s, 1H), 6.56 (dd, 1H), 6.47 (dd, 1H), 6.19 (d, 1H), 5.39 (s, 1H), 3.79 (s, 3H), 2.11 (s, 6H), 1.85 (s, 3H), 1.22 (s, 3H), 1.15 (s, 3H);

Analytical calcd for C28H29NO2: C, 81.72; H, 7.10; N, 3.40. Found: C, 81.59; H, 7.54; N, 3.16.

Example 28

5-(4-Chlorophenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano-[3,4-f]quinoline

The compound of Example 1F and 4-chlorophenylmagnesium bromide are treated according to the method of Examples 1G and 1 to give the desired compound.

MS (DCI/NH 3 ) m/z 418 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-dé) δ 8.01 (d, 1H), 7.24 (q, 4H), 6.92 (t, 1H), 6.76 (s, 1H), 6.70 (d, 1H), 6.57 (d, 1H), 6.43 (d, 1H), 6.24 (br s, 1H), 5.20 (br s, 1H), 3.79 (s, 3H), 1.83 (s, 3H), 1.24 (s, 3H), 1.14 (s, 3H);

Analytical calcd for C20H24NO2Cl: C, 74.72; H, 5.79; N, 3.35. Found: C, 74.73; H, 5.68; N, 3.29.

Example 29

-(3,4-dimethylphenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1Η-[1]benzopyrano-[3,4fquinoline

The compound of Example 1F and 3,4-dimethylphenylmagnesium bromide are treated according to the method of Examples 1G and 1 to give the desired compound.

MS (DCI/NH 3 ) m/z 412 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-cE) δ 7.98 (d, 1H), 6.94 (s, 1H), 6.82 (q, 2H), 6.78 (d, 1H), 6.67 (d, 1H), 6.53 (d, 1H), 6.42 (d, 1H), 6.17 (s, 1H), 5.37 (s, 1H), 3.78 (s, 3H), 2.08 (s, 6H), 1.84 (s, 3H), 1.22 (s, 3H), 1.14 (s, 3H);

102 φ φφφ φ φ φφφφ ··

Analytical Calcd for C12H18C2NO3ITO: C, 79.97; H, 7.19; N, 3.33. Found: C, 79.94; H, 7.25; N, 2.98.

Example 30

5-(4-Fluorophenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline The compound of Example 2B and 4-fluorophenylmagnesium bromide are treated according to the method of Example 11 to give the desired compound.

MS (DCI/NH ₃ ) m/z 402 (M+H) ⁺ ;

’H NMR (300 MHz, DMSO-de) δ 8.03 (d, 1H), 7.16 (m, 2H), 7.03 (t, 2H), 6.88 (t, 1H), 6.7 (s, 1H), 6.68 (d, 1H), 6.55 (d, 1H), 6.41 (d, 1H), 6.22 (s, 1H), 5.38 (s, 1H), 3.79 (s, 3H), 1.82 (s, 3H), 1.23 (s, 3H), 1.14 (s, 3H).

Example 31

5-[3,5-bis(trifluoromethyl)phenyl]-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline

The compound of Example 2B and 4-fluorophenylmagnesium bromide are treated according to the method of Example 11 to give the desired compound.

^! H NMR (300 MHz, DMSO-cU) δ 8.02 (d, 1H), 7.98 (s, 1H), 7.00 (s, 1H), 6.93 (d, 1H), 6.75 (d, 1H), 6.59 (d, 1H), 6.49 (d, 1H), 6.38 (s, 1H), 5.46 (s, 1H), 3.79 (s, 3H), 1.87 (s, 3H), 1.21 (s, 3H), 1.19 (s, 3H);

HRMS calculated m/z for C28H23O2F6N: 519.1633 (M+H) ⁺ . Found: 519.1646;

Analytical calcd for C28H23NO2F6 _1.25H2O : C, 62.05; H, 4.74; N, 2.58. Found: C, 61.96; H, 4.70; N, 2.35.

Example 32 (-)-5-(3,5-Dichlorophenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4]quinoline

Enantiomer of Example 19.

The spectral data are identical to example 19.

[a]n = -208.0;

Retention time = 6.89 minutes on Regis (R,R)-WhelkOl Kromasil 4.6 x 250mm HPLC column; Solvent: 86:10:3 hexane:dichloromethane:ethanol;

Flow rate: 1 ml/minute.

·

103 • ··· · · · · · · · · · · · · • · 9 · · · · · · · · · · 9 9 · · · · · ·

Example 33 (+)-5-(3,5-dichlorophenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4f]quinoline

Enantiomer of Example 19.

The spectral data are identical to example 19.

[a] _D = +210.7;

Retention time = 8.63 min on Regis (R,R)-WhelkOl Kromasil 4.6 x 250mm HPLC column; Solvent: 86:10:3 hexane:dichloromethane:ethanol;

Flow rate: 1 ml/minute

Example 34

5-(3,5-difluorophenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano-[3,4fquinoline

The compound of Example 2B and 3,5-difluorophenylmagnesium bromide are treated according to the method of Example 11 to give the desired compound.

^] H NMR (300 MHz, DMSO-dg) δ 8.01 (d, 1H), 7.05 (m, 1H), 6.93 (t, 1H), 6.79 (s, 3H), 6.71 (d, 1H), 6.59 (9, 1H), 6.50 (d, 1H), 6.30 (s, 1H), 5.43 (s, 1H), 3.81 (s, 3H), 1.87 (s, 3H), 1.23 (s, 3H), 1.16 (s, 3H);

HRMS calculated m/z for C26H23O2F2N: 419.1697 (M+H) ⁺ . Found: 419.1702;

Analytical calcd for C26H23O2F2N0.5H2O: C, _72.88 ; H, 5.65; N, 3.27. Found: C, 72.62; H, 5.58; N, 3.06.

Example 35

2,5-dihydro-10-methoxy-2,2,4,N-tetramethyl-N-phenyl-1Η-[1]benzopyrano-[3,4-f]quinoline-5amine

The compound of Example 1F and N-methylaniline are treated according to the method of Example 2 to give the desired compound.

MS (DCI/NH3) m/z 306 (M-NMePh) ⁺ ;

1H NMR (300 MHz, DMSO-d _ó ) δ 8.03 (d, 1H), 7.25 (t, 2H), 7.08 (m, 2H), 6.99 (t, 1H), 6.86 (s, 1H), 6.80 (t, 1H), 6.70-6.65 (m, 2H), 6.41 (d, 1H), 6.26 (br s, 1H), 5.39 (br s, 1H), 3.87 (s, 3H), 2.47 (s, 3H), 1.74 (s, 3H), 1.24 (s, 3H), 1.11 (s, 3H).

• φ φ ·

104 φ φφφφ • · · · · Φ

Example 36 (-)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-(2-propenyl)-1H-[1]benzopyrano[3,4]quinoline

The compound from Example 2 was purified by flash chromatography on a Chiralcel OJ column with 10% ethanol/hexanes to afford the desired compound.

[a] _D = -1.8 (Cl.2, CHCl ₃ );

MS (DCI/NH ₃ ) m/z 348 (M+H) ⁺ ;

^! H NMR (300 MHz, DMSO-dé) δ 7.96 (d, 1H), 7.07 (t, 1H), 6.71 (d, 1H), 6.60 (d, 1H), 6.52 (d, 1H), 6.12 (br s, 1H), 5.82 (m, 1H), 5.76 (dd, 1H), 5.44 (br s, 1H), 5.01 (m, 2H), 3.86 (s, 3H), 2.44 (m, 1H), 2.20 (m, 1H), 2.16 (s, 3H), 1.17 (s, 3H), 1.16 (s, 3H);

Analytical calcd for C23H25NO2: C, 79.51; H, 7.25; N, 4.03. Found: C, 9.34; H, 7.00; N, 4.07.

Example 37 (+)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-(2-propenyl)-1H-[1]benzopyrano[3,4]quinoline

The compound from Example 2 was purified by flash chromatography on a Chiralcel OJ column with 10% ethanol/hexanes to afford the desired compound.

[a] _D = +2.1(c 1.1,CHC1 ₃ );

MS (DCI/NH 3 ) m/z 348 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-de) δ 7.96 (d, 1H), 7.07 (t, 1H), 6.71 (d, 1H), 6.60 (d, 1H), 6.52 (d, 1H), 6.12 (br s, 1H), 5.82 (m, 1H), 5.76 (dd, 1H), 5.44 (br s, 1H), 5.01 (m, 2H), 3.86 (s, 3H), 2.44 (m, 1H), 2.20 (m, 1H), 2.16 (s, 3H), 1.17 (s, 3H), 1.16 (s, 3H);

Analytical calcd for C23H25NO2: C, 79.51; H, 7.25; N, 4.03. Found: C, 79.29; H, 7.01; N, 3.92.

Example 38

2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano-[3,4-f|quinoline

The compound of Example 2B and triethylsilane are treated according to the method of Example 2 to give the desired compound.

MS (DCI/NH 3 ) m/z 308 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-de) δ 7.82 (d, 1H), 7.05 (t, 1H), 6.72 (dd, 1H), 6.58 (d, 1H), 6.57 (dd, 1H), 6.13 (d, 1H), 5.39 (t, 1H), 5.10 (s, 2H), 3.84 (s, 3H), 2.02 (d, 3H), 1.18 (s, 6H);

• ♦ · · » ♦ * 4 • · ·« ·· » · · · • · · • · ·· • · I · · · · · • · • · • ·

105

Analytical Calcd for C20H21NO2·0.1H20: C, 77.69; H, 6.91; N, 4.53. Found: C, 77.60; H, 7.15; N, 4.33.

Example 39

4-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano-[3,4-f]quinolin-5-yl)-N,Ndimethylbenzenamine

The compound of Example 2B and N,N-dimethylaniline are treated according to the method of Example 2 to give the desired compound.

MS (DCI/NH 2 ) m/z 427 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-dó) δ 7.98 (d, 1H), 6.95 (d, 2H), 6.88 (t, 1H), 6.57 (d, 1H), 6.64 (s, 1H), 6.53 (m, 3H), 6.39 (d, 1H), 6.14 (d, 1H), 5.35 (s, 1H), 3.79 (s, 3H), 2.80 (s, 6H), 1.84 (s, 3H), 1.21 (s, 3H), 1.13 (s, 3H);

Analytical calcd for _{C28H30N2O2-0.25H2O} : C, 78.02; H, 7.13; N, 650. Found: C, 78.29; H, 7.38; N, 6.01.

Example 40

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(5-methoxy-2-thienyl)-1H-[1]benzopyrano-[3,4fquinoline

The compound of Example 2B and 2-methoxythiophene are treated according to the method of Example 2 to give the desired compound.

MS (DCI/NH 3 ) m/z 420 (M+H) ⁺ ;

Ή NMR (500 MHz, DMSO-dó) δ 7.98 (d, 1H), 6.97 (d, 1H), 6.73 (s, 1H), 6.67 (d, 1H), 6.63 (d, 1H), 6.46 (d, 1H), 6.20 (d, 1H), 6.18 (s, 1H), 5.96 (d, 4H), 5.39 (s, 1H), 3.82 (s, 3H), 3.72 (s, 3H), 1.98 (s, 3H), 1.21 (s, 3H), 1.13 (s, 3H);

Analytical calcd for C25H25NO3S: C, 71.57; H, 6.01; N, 3.34. Found: C, 71.54; H, 5.99; N, 3.17.

Example 41

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(5-propyl-2-thienyl)-1H-[1]benzopyrano-[3,4fquinoline

The compound of Example 2B and 2-propylthiophene are treated according to the method of Example 2 to give the desired compound.

· • · 9 9 9 ‘Η NMR (300 MHz, DMSO-dg) δ 8.01 (d, 1H), 6.95 (t, 1H), 6.84 (s, 1H), 6.67 (d, 1H), 6.61 (d, 1H), 6.51 (d, 1H), 6.46 (d, 1H), 6.41 (d, 1H), 6.18 (m, 1H), 5.39 (s, 1H), 3.82 (s, 3H), 2.59 (t, 2H), 1.96 (s, 3H), 1.50 (h, 2H), 1.20 (s, 3H), 1.14 (s, 3H), 0.83 (t, 3H);

HRMS calculated m/z for C27H29NO2S: 431.1919 (M+H) ⁺ . Found: 431.1911.

Example 42

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[4-(1-morpholinyl)phenyl]-1H-[1]benzopyrano-[3,4fquinoline

The compound of Example 2B and 4-phenylmorpholine are treated according to the method of Example 2 to give the desired compound.

MS (DCI/NH 3 ) m/z 469 (M+H) ⁺ ;

¹ H NMR (300 MHz, DMSO-dg) δ 8.00 (d, 1H), 7.00 (d, 2H), 6.92 (t, 1H), 6.76 (d, 2H), 6.68 (d, 2H), 6.55 (d, 1H), 6.44 (d, 1H), 6.16 (m, 1H), 5.36 (s, 1H), 3.79 (s, 3H), 3.62 (m, 4H), 3.05 (m, 4H), 1.81 (s, 3H), 1.22 (s, 3H), 1.13 (s, 3H);

Analytical _calcd. for C30H32N2O20.5H2O: C, 75.45, H, 6.96; N, 5.87. Found. C, 75.46; H, 6.69; N, 5.31.

Example 43

-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano-[3,4-f]quinolin-5-yl)3,3-dimethyl-2-butanone

The compound of Example 2B and (2,2-dimethyl-1-methylenepropoxy)trimethylsilane are treated according to the method of Example 2 to give the desired compound.

MS (DCl/NH 3 ) m/z 406 (M+H)';

Ή NMR (300 MHz, DMSO-dg) δ 7.95 (d, 1H), 7.04 (t, 1H), 6.71 (d, 1H), 6.60 (d, 1H), 6.41 (d, 1H), 6.33 (d, 1H), 6.15 (br s, 1H), 5.43 (s, 1H), 3.87 (s, 3H), 3.26 (m, 1H), 2.36 (m, 1H), 2.13 (s, 3H), 1.16 (s, 3H), 1.15 (s, 3H), 0.89 (s, 9H);

Analytical calcd for _{C26H31NO30.33H2O} : C, _75.90 ; H, 7.76; N, 3.40. Found: C, 75.91; H, 8.17; N, 3.62.

Example 44

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano-[3,4-f]quinoline-5-carbonitrile

The compound of Example 2B and cyanotrimethylsilane are treated according to the method of Example 2 to give the desired compound.

• 000 0 0 0 0 0 0 0 0

0 0 0 00 0 · 0 0 *

000 0 0 0 000 0 0 ♦ 0 0

000 00000

107 ...........* ·’

MS (DCI/NH 3 ) m/z 333 (M+H) ⁺ ;

*H NMR (300 MHz, DMSO-de) δ 7.96 (d, 1H), 7.20 (t, 1H), 6.89 (d, 1H), 6.84 (s, 1H), 6.74 (d, 8H), 6.73 (d, 1H), 6.46 (s, 1H), 5.51 (s, 1H), 3.90 (s, 3H), 2.22 (s, 3H), 1.29 , (s, 3H), 1.09 (s, 3H);

Analytical Calcd for C 12 R 2 O 2 SH 2 O: C, 74.87; H, 6.13; N, 8.31. Found: C, 75.00; H, 6.23; N, 8.34.

Example 45

-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano-[3,4-f]quinolin-5-yl)-2-propanone

The compound of Example 2B and 2-(trimethylsiloxy)propene are treated according to the method of Example 2 to give the desired compound.

’H NMR (300 MHz, DMSO-dg) δ 7.96 (t, 1H), 7.04 (t, 1H,), 6.71 (d, 1H), 6.58 (d, 1H), 6.48 (d, 1H), 6.20 (dd, 1H), 6.16 (s, 1H), 5.4 (s, 1H), 3.87 (s, 3H), 2.91 (q, 1H), 2.16 (s, 3H), 2.04 (s, 3H), 1.15 (d, 6H);

HRMS calculated m/z for C23H25O3N: 363.1834 (M+H) ⁺ . Found: 363.1843;

Analytical calcd for _{C23H25NO3 0.33H2O} : C, 74.79; H, 7.00; N, 3.79. Found: C, 74.77; H, 7.14; N, 3.67.

Example 46

Methyl 2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline-5-acetate The compound of Example 2B and 1-methoxy-1-(tert-butyldimethylsiloxy)ethylene are treated according to the method of Example 2 to give the desired compound.

MS (DCI/NH 3 ) m/z 380 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-dg) δ 8.01 (d, 1H), 7.11 (t, 1H), 6.78 (d, 1H), 6.66 (d, 1H), 6.53 (d, 1H), 6.27 (d, 1H), 6.22 (s, 2H), 5.52 (s, 1H), 3.93 (s, 3H), 3.67 (s, 3H), 2.70 (dd, 1H), 2.64 (d, 1H), 2.27 (s, 3H), 1.22 (d, 6H);

Analytical calcd for € ₂ 3Η ₂ 5θ4ΝΌ _? 5Η ₂ Ο: C, 71.12; H, 6.75; N, 3.61. Found: C, 71.46; H, 6.81; N, 3.45.

Example 47

2-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1 H-[ 1 ]benzopyrano-[3,4-f]quinolin-5-yl)-1 phenylethanone •« ·· ·Β Β· Β Β

BB BB BB BB BB «

Β Β Β ΒΒ Β Β « Β «

Β Β Β Β Β Β Β Β Β Β Β Β · · , _ο Β ββββββββ

The compound of Example 2B and 1-phenyl-1-(trimethylsiloxy)ethylene are treated according to the method of Example 2 to give the desired compound.

1H NMR (300 MHz, DMSO-d ₆ ) δ 8.01 (d, 1H), 7.72 (d, 2H), 7.59 (t, 1H), 7.40 (t, 2H), 6.93 (t, 1H), 6.70 (d, 1H), 6.61 (d, 1H), 6.43 (d, 1H), 6.25 (d, 1H), 6.18 (s, 1H), 5.44 , (s, 1H), 3.90 (s, 3H), 3.66 (q, 1H), 2.95 (d, 1H), 2.16 (s, 3H), 1.16 (s, 6H);

HRMS calculated m/z for C28H27O3N: 425.1991 (M+H) ⁺ . Found: 425.2005.

Example 48

5-[2-(chloromethyl)-2-propenyl]-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1jbenzopyrano[3,4-f]quinoline

The compound of Example 2B and 2-chloromethyl-3-trimethylsilyl-1-propene are treated according to the method of Example 2 to give the desired compound.

Ή NMR (300 MHz, DMSO-ck) δ 7.96 (d, 1H), 7.03 (t, 1H), 6.69 (d, 1H), 6.59 (d, 1H), 6.44 (d, 1H), 6.15 (s, 1H), 5.96 (dd, 1H), 5.45 (s, 1H), 5.27 (s, 1H), 4.95 (s, 1H), 4.17 (q, 2H), 3.87 (s, 3H), 2.55 (d, 1H), 2.26 (dd, 1H), 2.20 (s, 3H), 1.15 (d, 6H);

HRMS m/z calculated for C24H26O2CIN: 395.1652 (M+H) ⁺ . Found: 395.1645;

Analytical calcd for C24H26O2ClNO.333H2O: C, 71.73; H, 6.69; N, 3.49. Found: C, 71.71; H, 6.32; N, 3.35.

Example 49

2,5-Dihydro-10-methoxy-2,2,4-trimethyl-(-methylene)-1H-[1]benzopyrano-[3,4f]quinoline-5-propanol acetate (ester)

The compound of Example 2B and 2-[(trimethylsilyl)methyl]-2-propen-1-yl acetate are treated according to the method of Example 2 to give the desired compound.

^] H NMR (300 MHz, DMSO-d ₆ ) δ 8.02 (d, 1H), 7.10 (t, 1H), 6.75 (dd, 1H), 6.65 (d, 1H), 6.50 (d, 1H), 6.18 (s, 1H), 5.98 (dd, 1H), 5.51 (s, 1H), 5.16 (s, 1H), 4.98 (s, 1H), 4.48 (q, 2H), 3.93 (s, 3H), 2.25 (s, 3H), 1.22 (s, 6H);

HRMS calculated m/z for C26H29O4N: 419.2097 (M+H) ⁺ . Found: 419.2095;

Analytical calcd for _{C26H29O4N0.25H2O} : C, 73.65; H, 7.01; N, 3.30. Found: C, 73.83; H, 6.91; N, 3.20.

Example 50 ·· »9

9 9

9 9

9 9 9

9 9 9

9 99

109

2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-(4-methylphenyl)-1Η-[1]benzopyrano-[3,4f]quinoline

The compound of Example IF and 4-methylphenylmagnesium bromide are treated according to the method of Examples 1G and 1 to give the desired compound.

MS (DCI/NH 3 ) m/z 398 (M+H) ⁺ ;

’H NMR (300 MHz, DMSO-dg) δ 8.00 (d, 1H), 7.02 (q, 4H), 6.89 (t, 1H), 6.72 (s, 1H), 6.69 (d, 1H), 6.55 (d, 1H), 6.41 (d, 1H), 6.18 (br s, 1H), 5.37 (br s, 1H), 3.79 (s, 3H), 2.18 (s, 3H), 1.83 (s, 3H), 1.23 (s, 3H), 1.14 (s, 3H);

Analytical calcd for C27H27NO2: C, 8158; H, 6.85; N, 3.52. Found: C, 8156; H, 7.25; N, 3.29.

Example 51

5-(3-Fluoro-4-methylphenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano-[3,4fquinoline

The compound of Example 2B and 3-fluoro-4-methylphenylmagnesium bromide are treated according to the method of Example 11 to give the desired compound.

MS (DCI/NH 3 ) m/z 416 (M+H) ⁺ ;

11 NMR (300 MHz, DMSO-dg) δ 8.01 (d, 1H), 7.11 (t, 1H), 6.95-6.84 (m, 3H), 6.74 (s, 1H), 6.71 (d, 1H), 6.57 (d, 1H), 6.46 (d, 1H), 6.23 (s, 1H), 5.39 (s, 1H), 3.79 (s, 3H), 2.11 (s, 3H), 1.85 (s, 3H), 1.22 (s, 3H), 1.14 (s, 3H);

Analytical calcd for C27H26NO2F: C, 78.05; H, 6.31; N, 3.37. Found: C, 77.80; H, 6.51; N, 3.06.

Example 52

5-(3-Bromophenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano-[3,4-fJquinoline

The compound of Example IF and 3-bromophenylmagnesium bromide are treated according to the method of Examples 1G and 1 to give the desired compound.

MS (DCI/NH ₃ ) m/z 462 (M+H) ⁺ ;

'H NMR (300 MHz, DMSO-dg) δ 8.02 (d, 1H), 7.36 (m, 1H), 7.30 (m, 1H), 7.17 (m, 2H), 6.93 (t, 1H), 6.79 (s, 1H), 6.72 (d, 1H), 6.58 (d, 1H), 6.48 (d, 1H), 6.24 (br s, 1H), 5.41 (br s, 1H), 3.80 (s, 1H), 1.85 (s, 3H), 1.23 (s, 1H), 1.16 (s, 1H).

Example 53

110

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(phenylmethyl)-1H-[1]benzopyrano-[3,4-f]quinoline

The compound of Example 2B and benzylmagnesium bromide were treated according to the method of Example 11 to give the desired compound MS (DCI/NH3) m/z 398 (M+H) ⁺ ;

*Η NMR (300 MHz, DMSO-dg) δ 8.02 (d, 1H), 7.31 - 7.18 (m, 3H), 7.12 (m, 3H), 6.75 (d, 1H), 6.63 (d, 1H), 6.46 (d, 1H), 6.15 (d, 1H), 5.93 (dd, 1H), 5.43 (s, 1H), 3.89 (s, 3H), 2.98 (dd, 1H), 2.74 (dd, 1H), 2.23 (s, 3H), 1.16 (s, 3H), 1.15 (s, 3H);

Analytical calcd for C27H27NO2 _0.25H2O : C, 80.67, H, 6.89; N, 3.48. Found: C, 80.78; H, 7.08; N, 3.26.

Example 54

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-propyl-1H-[1]benzopyrano-[3,4-f]quinoline

The compound of Example 2B and propylmagnesium bromide are treated according to the method of Example 11 to give the desired compound.

MS (DCI/NH 3 ) m/z 350 (M+H) ⁺ ;

*H NMR (300 MHz, DMSO-dg) δ 7.94 (d, 1H), 7.05 (t, 1H), 6.69 (d, 1H), 6.58 (d, 1H), 6.54 (d, 1H), 6.10 (d, 1H), 5.70 (m, 1H), 5.44 (s, 1H), 3.85 (s, 3H), 2.16 (s, 3H), 1.70 (m, 1H), 1.43 - 1.31 (m, 3H), 1.16 (s, 3H), 1.14 (s, 3H), 0.83 (t, 3H);

Analytical calcd for C23H27NO2: C, 79.05; H, 7.79; N, 4.01. Found: C, 78.76; H, 7.86; N, 3.84.

Example 55

5-(4-Fluorophenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano-[3,4-f]quinoline

The compound of Example 2B and 4-fluorophenylmagnesium bromide are treated according to the method of Example 11 to give the desired compound.

Ή NMR (300 MHz, DMSO-dg) δ 7.99 (d, 1H), 7.11 (d, 1H), 6.92 (m, 2H), 6.71 (s, 1H), 6.68 (s, 1H), 6.55 (d, 1H), 6.43 (d, 1H), 6.21 (s, 1H), 5.39 (s, 1H) 1H), 3.99 (s, 3H), 2.11 (s, 3H), 1.84 (s, 3H), 1.22 (s, 3H), 1.14 (s, 3H);

HRMS m/z calcd for C27H26O2NF: 415.1948 (M+H) ⁺ . Found: 415.1947.

Example 56

5-(3-fluorophenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano-[3,4-f]quinoline

0 >

• · 0

0 ·

0 0

Μ ·· • * · · ♦ 9 9 · » 99 9 9

9 9 ·* 00

0· «

111

00 0

The compound of Example 2B and 3-fluorophenylmagnesium bromide are processed according to the method of Example 11 to obtain the desired compound.

¹ II NMR (300 MHz, DMSO-de) δ 8.03 (d, 1H), 7.22 (q, 1H), 6.90 (m, 4H), 6.78 (s, 1H), 6.73 (d, 1H), 6.56 (d, 1H), 6.46 (d, 1H), 6.24 (s, 1H), 5.40 (s, 1H), 3.79 (s, 3H), 1.85 (s, 3H), 1.20 (s, 3H), 1.15 (s, 3H);

HRMS calculated m/z for C26H24O2NF: 402.1869 (M+H) ⁺ . Found: 402.1865;

Analytical calcd for C26H24O2FN12.25H2O: C, 70.65; H, 6.50; N, 3.17. Found: C, 70.56; H, 6.18; N, 2.83.

Example 57

2.5-Dihydro-10-methoxy-2,2,4,5-tetramethyl-1H-[1]benzopyrano-[3,4-f]quinoline

The compound of Example 2B and methylmagnesium iodide are treated according to the method of Example 11 to give the desired compound.

’H NMR (300 MHz, DMSO-tE) δ 7.91 (d, 1H), 7.02 (8, 1H), 6.67 (d, 1H), 6.54 (s, 1H), 6.52 (d, 1H), 6.08 (s, 1H), 5.87 (q, 1H), 5.43 (s, 1H), 3.85 (s, 3H), 2.16 (s, 3H), 1.25 (d, 3H), 1.18 (s, 3H), 1.13 (s, 3H);

HRMS calculated m/z for C21H23O2N: 321.1729 (M+H) ⁺ . Found: 321.1728.

Example 58

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(1-methyl ethyl)-1H-[1jbenzopyrano-[3,4fjquinoline

The compound of Example 2B and 2-propylmagnesium chloride are treated according to the method of Example 11 to give the desired compound.

1H NMR (300 MHz, DMSO-d ₆ ) δ 7.99 (d, 1H), 7.03 (t, 1H), 6.57 (d, 2H), 6.45 (d, 1H), 6.53 (d, 1H), 6.18 (s, 1H), 5.45 (s, 1H), 5.31 (d, 1H), 3.85 (s, 1H), 2.16 (s, 3H), 1.79 (m, 1H), 1.30 (s, 3H), 1.01 (s, 3H), 0.93 (d, 3H), 0.62 (d, 3H);

HRMS calculated m/z for C23H27O2N: 349.2042 (M+H) ⁺ . Found: 349.2041.

Example 59

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(2-methylpropyl)-1Η-[1]benzopyrano-[3,4fquinoline

The compound of Example 2B and sec-butyl magnesium chloride are treated according to the method of Example 11 to give the desired compound.

·» ·· 99 99 • · · · · * · · * • · · · · · · · · · · • · · 9 99 9 · · * · · • 9 9 9 9 9 9 9 9

112 ..............

^! H NMR (300 MHz, DMSO-cf,) δ 7.93 (d, 1H), 7.03 (t, 1H), 6.67 (d, 1H), 6.51 (q, 2H), 6.08 (s, 1H), 5.77 (dd, 1H), 5.43 (s, 1H), 3.85 (s, 3H), 2.18 (s, 3H), 1.72 (m, 2H), 1.76 (d, 6H), 0.86 (d, 3H), 0.74 (d, 3H);

HRMS calculated m/z for C24H29O2N: 363.2198 (M+H) ⁺ . Found: 363.2208;

Analytical calcd for C24H29NO2: C, 79.30; H, 8.04; N, 3.85. Found: C, 79.63; H, 7.83; N, 3.89.

Example 60

-ethyl-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1Η-[1]benzopyrano-[3,4-f]quinoline

The compound of Example 2B and ethylmagnesium bromide are treated according to the method of Example 11 to give the desired compound.

MS (DCI/NH ₃ ) m/z 336 (M+H) ⁺ ;

’H NMR (300 MHz, DMSO-de) δ 7.92 (d, 1H), 7.03 (t, 1H), 6.67 (d, 1H), 6.54 (t, 2H), 6.10 (s, 1H), 5.55 (dd, 1H), 5.44 (s, 1H), 3.84 (s, 3H), 2.16 (s, 3H), 1.63 (m, 1H), 1.44 (m, 1H), 1.15 (s, 6H), 0.84 (t, 3H);

Analytical calcd for C22H25O2N2.25H2O: C, 77.73; H, 7.56; N, 4.12. Found: C, 77.95; H, 7.60; N, 4.07.

Example 61

2,5-Dihydro-10-methoxy-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano-[3,4fJquinoline-5-carboximidic acid ethyl ester

A solution of Example 44 (0.040 g, 0.120 mmol) in ethanol (5 mL) was cooled to -5°C, saturated with hydrogen chloride gas, stirred for 10 min at -5°C, stirred for 14 h at room temperature, neutralized with NaHCO3, and extracted with diethyl ether. The extract was dried ( _Na2SO4 ), filtered, and concentrated to give the title compound.

MS (DCI/NH 2 O) m/z 379 (M+H) ⁺ ;

^T H NMR (300 MHz, DMSO-cU) δ 7.95 (d, 1H), 7.32 (s, 1H), 7.05 (t, 1H), 6.69 (t, 2H), 6.61 (d, 1H), 6.22 (s, 1H), 6.14 (s, 1H), 5.44 (s, 1H), 3.92 (m, 2H), 3.82 (s, 3H), 2.06 (s, 3H), 1.20 (s, 3H), 1.12 (s, 3H), 1.02 (t, 3H).

Example 62

2,5-dihydro-10-methoxy-2,2,4-trimethyl-methylene-1Η-[1]benzopyrano-[3,4-f]quinoline-5propanol » · * 4

A solution of Example 49 (0.060 g, 0.143 mmol) in 1:1 methanol/water (10 mL) was treated with _K2CO3 (0.080 g, 1.0 mmol), stirred for 24 h at room temperature, neutralized _with 10% HCl, and extracted with ethyl acetate. The extract was washed with brine, dried (MgSO4), filtered, and concentrated. The residue was purified by flash chromatography on silica gel with 25% dichloromethane/ethyl acetate to give the title compound.

1H NMR (300 MHz, DMSO-dg) δ 8.01 (d, 1H), 7.72 (d, 2H), 7.59 (t, 1H), 7.40 (t, 2H), 6.93 (t, 1H), 6.70 (d, 1H), 6.61 (d, 1H), 6.43 (d, 1H), 6.25 (d, 1H), 6.18 (s, 1H), 5.44 (s, 1H), 3.90 (s, 3H), 3.66 (q, 1H), 2.95 (d, 1H), 2.16 (s, 3H), 1.16 (s, 6H),

HRMS calculated m/z for _C28H27O - _N : 425.1991 (M+H) ⁺ . Found: 425.2005.

Example 63

2.5-Dihydro-10-methoxy-2,2,4,N,N-pentamethyl-1H-[1]benzopyrano-[3,4-f]quinoline-5-acetamide

The compound from Example 46 was hydrolyzed with lithium hydroxide in THF to give the corresponding acid, which was then coupled to N,N-dimethylamine using 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide to give the desired compound.

*H NMR (300 MHz, DMSO-dg) δ 7.94 (d, 1H), 7.04 (t, 1H), 6.70 (d, 1H), 6.59 (d, 1H), 6.46 (d, 1H), 6.26 (d, 1H), 6.15 (s, 1H), 5.44 (s, 1H), 3.86 (s, 3H), 2.88 (q, 1H), 2.81 (s, 3H), 2.55 (s, 3H), 2.25 (s, 1H), 2.19 (s, 3H), 1.15 (s, 6H);

HRMS calculated m/z for _C24H28O3N2 : _392.2100 (M+H ₎ ⁺ . Found: _392.2104 ;

Analytical _calcd for _C24H28N2O3 : C, _73.44 ; H, 7.19, 7.35; N, 7.14. Found: C, 73.17; H, 7.19; _N , 6.85.

Example 64

2.5-Dihydro-10-methoxy-2,2,4,N,N-pentamethyl-1H-[1]benzopyrano-[3,4-f)quinoline-5ethanamine

A solution of Example 63 in diethyl ether was reduced at room temperature with lithium aluminum hydride to give the desired compound.

Ή NMR (300 MHz, DMSO-dg) δ 7.93 (d, 1H), 7.03 (t, 1H), 6.68 (8, 1H), 6.54 (t, 1H), 6.12 (s, 1H), 5.76 (dd, 1H), 5.44 (s, 1H), 3.85 (s, 3H), 2.18 (s, 3H), 2.05 (s, 6H), 1.18 (s, 3H), 1.14 (s, 3H);

HRMS m/z calcd for _C24H30O2N2 : _378.2307 (M+H ₎ ⁺ . Found: _378.2307 .

114

Example 65

N-cyclopropyl-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano-[3,4-f]quinoline-5-acetamide

The compound of Example 46 and cyclopropylmethylamine are treated according to the method of Example 63 to give the desired compound.

’H NMR (300 MHz, DMSO-cU) δ 7.94 (d, 1H), 7.70 (d, 1H), 7.03 (t, 1H), 6.68 (d, 1H), 6.58 (d, 1H), 6.43 (d,), 6.23 (dd, 1H), 6.13 (s, 1H), 5.43 (s, 1H), 3.85 (s, 3H), 2.51 (m, 2H), 2.07 (d, 1H), 2.03 (s, 3H), 1.17 (s, 3H), 1.13 (s, 3H), 0.60 (m, 2H), 0.31 (s, ZH);

HRMS m/z calcd for C25H28O3N2: 40.2100 (M+H) ⁺ . Found: 404.2092.

Example 66

2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-(2-propynyl)-1H-[1]benzopyrano-[3,4-f]quinoline

The compound of Example 2B and 2-propynylmagnesium bromide are treated according to the method of Example 11 to give the desired compound.

*H NMR (300 MHz, DMSO-ck,) δ 7.97 (d, 1H), 7.06 (t, 1H), 6.71 (d, 1H), 6.56 (q, 2H), 6.16 (s, 1H), 5.88 (q, 1H), 5.44 (s, 1H), 3.86 (s, 3H), 2.82 (q, 1H), 2.41 (q, 1H), 2.19 (s, 3H), 1.16 (s, 3H);

HRMS m/z calcd for C23H23O2N: 345.1729 (M+H) ⁺ . Found: 345.1738.

Example 67

5-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano-[3,4-f]quinolin-5-yl)-2(5H)furanone

The compound of Example 2B and 2-trimethylsiloxyfuran are treated according to the method of Example 2C to give the desired compound.

MS (DCI/NH 3 ) m/z 390 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-d ₆ ) δ 8.11 (d, 1H), 7.13 (dd, 1H), 6.75 (d, 1H), 6.72 (d, 1H), 6.64 (d, 1H), 6.37 (d, 1H), 6.25 (dd, 1H), 6.23 (d, 1H), 5.83 (d, 1H), 5.47 (s, 1H), 5.12 (dd, 1H), 3.87 (s, 3H), 2.03 (s, 3H), 1.30 (s, 3H), 1.09 (s, 3H);

Analytical calcd for C24H23NO4: C, 74.02; H, 5.95; N, 3.60. Found: C, 73.89; H, 5.94; N, 3.51.

Example 68 «4

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5-(3-Butenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano-[3,4-f]quinoline

The compound of Example 2B and 3-butenylmagnesium bromide are treated according to the method of Example 11 to give the desired compound.

MS (DCI/NH ₃ ) m/z 362 (M+H) ⁺ ;

’H NMR (300 MHz, DMSO-de) δ 7.94 (d, 1H), 7.05 (t, 1H), 6.68 (d, 1H), 6.58 (d, 1H), 6.57 (d, 1H), 6.10 (s, 1H), (5.78 (dddd, 1H), 5.65 (dd, 1H), 5.44 (s, 1H), 5.00 (dd, 1H), 4.93 (dd, 1H), 3.85 (s, 3H), 2.16 (s, 3H), 2.10 (m, 2H), 1.78 (m, 1H), 1.45 (bm, 1H), 1.16 (s, 3H), 1.14 (s, 3H);

HRMS m/z calcd for C24H27NO2: 361.2042 (M+H) ⁺ . Found: 361.2039.

Example 69

2,5-dihydro-10-methoxy-2,2,4-trimethyl-1Η-[1]benzopyrano-[3,4-f]quinoline-5-propanol

The compound from Example 2 (52.0 mg, 0.15 mmol) in THF (4 mL) at 0°C was treated dropwise with 0.5 M 9-BBN (600 µL, 0.30 mmol), stirred overnight at room temperature, cooled to 0°C, sequentially treated with 2.5 M NaOH (400 µL, 1.0 mmol), and 30% H2O2 (250 µL), stirred for 2 hours at room temperature, partitioned between ethyl acetate and water (1:1), and extracted with ethyl acetate. The extract was washed with brine, dried ( _Na2SO4 ), filtered, and concentrated. The residue was purified by flash chromatography on silica gel with 30% ethyl acetate/hexanes to give the title compound.

MS (DCI/NH 3 ) m/z 366 (M+H) ⁺ ;

’H NMR (300 MHz, DMSO-de) δ 7.94 (d, 1H), 7.05 (t, 1H), 6.68 (d, 1H), 6.58 (d, 1H), 6.53 (d, 1H), 6.10 (s, 1H), 5.70 (dd, 1H), 5.44 (s, 1H), 4.36 (t, 1H), 3.85 (s, 3H), 3.33 (m, 2H), 2.16 (s, 3H), 1.40-1.75 (bm, 4H), 1.17 (s, 3H), 1.14 (s, 3H);

HRMS calculated m/z for C23H27NO3: 365.1991 (M+H) ⁺ . Found: 365.1991.

Example 70

10-ethyl-2,5-dihydro-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano-[3,4-f]quinoline

Example 70A

The compound from Example 3C (0.208 g, 0.493 mmol) and tetraethyltin (0.444 g, 1.89 mmol) were combined with (1,3-bis(diphenylphosphino)ferrocene)palladium(II) chloride dichloromethane (0.039 g, 0.047 mmol) in 1-methyl-2-pyrrolidinone (3 mL) at 80°C for 16 hours and concentrated to give the title compound.

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Example 70

10-ethyl-2,5-dihydro-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano-[3,4-f]quinoline

The compound of Example 70A is processed according to the method of Examples 1F, 1G, and 1 to provide the desired compound.

MS (DCI/NH 3 ) m/z 382 (M+H) ⁺ ;

’H NMR (300 MHz, DMSO) δ 7.37 (d, 1H), 7.21-7.16 (m, 5H), 6.85, (dd, 1H), 6.75 (s, 1H), 6.73, (dd, 1H), 6.68 d, 1H), 6.58 (dd, 1H), 6.21 (s, 1H), 5.39 (s, 1H), 3.02-2.75 (tn, 2H), 1.79 (s, 3H), 1.24 (s, 3H), 1.15 (s, 3H), 1.15 (m, 3H);

HRMS calcd for C27H27NO: 381.2093 (M+H) ⁺ . Found: 381.2096.

Example 71

2,5-dihydro-2,2,4,10-tetramethyl-5-phenyl-1H-[ljbenzopyrano-[3,4-f]quinoline

The compound from Example 3C and tetramethyltin are processed according to the method of Example

70, thereby obtaining the desired compound.

MS (DCI/NH 3 ) m/z 368 (M+H) ⁺ ;

Η NMR (300 MHz, DMSO-dé) δ 7.44 (d, 1H), 7.21-7.12 (m, 5H), 6.82 (dd, 1H), 6.74 (d, 1H), 6.71 (s, 1H), 6.69 (dd, 1H), 6.59 (dd, 1H), 6.21 (s, 1H), 5.39 (s, 1H), 2.51 (s, 3H), 1.80 (s, 3H), 1.25 (s, 3H), 1.16 (s, 3H);

HRMS calculated m/z for C26H25NO. 367.1936 (M+H) ⁺ . Found: 367.1931.

Example 72

5-(3,5-Dichlorophenyl)-10-ethyl-2,5-dihydro-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline The compound of Example 70A and 3,5-dichlorophenylmagnesium bromide are processed according to the method of Examples 1G and 1 to provide the desired compound.

MS (DCI/NH 3 ) m/z 450 (M+H) ⁺ ;

^J H NMR (300 MHz, DMSO-dé) δ 7.43 (d, 1H), 7.43 (t, 1H), 7.18 (d, 2H), 6.91 (dd, 1H), 6.80 (dd, 1H), 6.78 (d, 1H), 6.72 (s, 1H), 6.62 (dd, 1H), 6.35 (s, 1H), 5.42 (s, 1H), 3.15-2.75 (m, 2H), 1.79 (s, 3H), 1.27 (s, 3H), 1.14 (s, 3H), 1.13 (t, 3H);

HRMS calculated m/z for C27H25NOCl2: 449.1313 (M+H) ⁺ . Found: 449.1330.

Example 73

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5-(3,5-Dichlorophenyl)-2,5-dihydro-2,2,4,N-tetramethyl-1H-[1]benzopyrano-[3,4-f]quinoline-10amine

The compound of Example 3C and 3,5-dichlorophenylmagnesium bromide are treated according to the method of Example 72 to give the desired compound.

MS (DCI/NH 3 ) m/z 539 (M+H) ⁺ .

Example 73

5-(3,5-dichlorophenyl)-2,5-dihydro-10-methoxy-2,2,4,N-tetramethyl-1H-[1]benzopyrano-[3,4fquinolin-10-amine

The compound of Example 73A is processed according to the method of Example 3 to give the desired compound.

MS (DCI/NH 3 ) m/z 451 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-dó) δ 7.91 (d, 1H), 7.45 (dd, 1H), 7.20 (m, 2H), 6.83 (dd, 1H), 6.75 (d, 1H), 6.71 (s, 1H), 6.22 (dd, 1H), 6.18 (s, 1H), 6.17 (dd, 1H), 5.57 (d, 1H), 5.44 (s, 1H), 2.65 (d, 3H), 1.85 (s, 3H), 1.24 (s, 3H), 1.15 (s, 3H);

HRMS calculated m/z for C26H24N2OCI2: 450.1266 (M+H) ⁺ . Found: 450.1267.

Example 74

5-(3,5-Dichlorophenyl)-2,5-dihydro-2,2,4-trimethyl-N-(2-propenyl)-1H-[1]benzopyrano-[3,4f|quinolin-10-amine

The compound of Example 73A and allylamine are treated according to the method of Example 3 to give the desired compound.

MS (DCI/NH 3 ) m/z 477 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-de) δ 7.99 (d, 1H), 7.49 (dd, 1H), 7.27 (d, 2H), 6.82 (dd, 1H), 6.77 ( d, 1H), 6.75 (s, 1H), ), 6.25 (dd, 1H), 6.21 (s, 1H), 6.20 (dd, 1H), 5.95-5.86 (m, 1H), 5.69-5.65 (m, 1H), 5.48 (s, 1H), 5.18-5.12 (m, 1H), 5.11-5.06 (m, 1H), 3.78-3.70 (m, 2H), 1.88 (s, 3H), 1.30 (s, 3H), 1.20 (s, 3H);

HRMS calculated m/z for C28H26N2OCI2: 476.1422 (M+H) ⁺ . Found: 476.1428.

• ·

118

Example 75

2.5-Dihydro-2,2,4-trimethyl-5-phenyl-10-(2-propynyloxy)-1H-[1]benzopyrano-[3,4-f]quinoline

The compound of Example 7 and propargyl bromide are treated according to the method of Example 9A to give the desired compound.

MS (DCI/NH ₃ ) m/z 408 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-dó) δ 1.12 (s, 3H), 1.23 (s, 3H), 1.83 (s, 3H), 3.59 (t, IH,), 4.81 (d, 2H), 5.39 (br s, IH), 6.19 (br s, IH), 6.47 (d, IH), 6.61 (d, IH), 6.71 (d, 1H), 6.78 (s, 1H), 6.90 (t, 1H), 7.14-7.22 (m, 5H), 8.02 (d, 1H);

Analytical calcd for C28H25NO2: C, 82.53; H, 6.18; N, 3.44. Found: C, 82.64; H, 6.31; N, 3.38.

Example 76

2.5-Dihydro-2,2,4-trimethyl-5-phenyl-10-(2-propenyloxy)-1H-[1]benzopyrano-[3,4-f]quinoline

The compound of Example 7 and allyl bromide are treated according to the method of Example 9A to give the desired compound.

MS (DCI) m/z 410 (M+H) ⁺ ;

¹ H NMR (300 MHz, DMSO-ds) δ 1.15 (s, 3H), 1.23 (s, 3H), 1.84 (s, 3H), 4.51-4.64 (m, 2H), 5.26 (dq, IH), 5.39 (br s, IH), 5.40 (dq, IH), 6.12 (ddt, IH), 6.21 (br s, IH), 6.44 (dd, IH),

6.55 (dd, 1H), 6.69 (d, 1H), 6.77 (s, 1H), 6.88 (t, 1H), 7.15-7.24 (m, 5H), 8.06 (d, 1H);

HRMS m/z calcd for C28H27NO2: 409.2042 (M+H) ⁺ . Found: 409.2039.

Example 77

2.5-Dihydro-2,2,4-trimethyl-5-(2-propenyl)-1H-[1]benzopyrano-[3,4-f]quinoline-10-methanol

A solution of Example 4 (32 mg, 0.085 mmol) in dichloromethane (3 mL) under argon at -78° C. was treated dropwise with diisobutylaluminum hydride (1.0 M) in ^cyclohexane (0.400 mL, 0.40 mmol), heated at 0° C. for 3.5 h, treated with Rochelle salt, separated, and extracted with ethyl acetate. The extract was dried (MgSO ₄ ), filtered, and concentrated. The residue was applied to two 10 x 20 cm thick silica gel plates with 0.25 mm silica gel, eluted with hexanes (3x), then ethyl acetate/hexanes (10:90). The product band was scraped and extracted with ethyl acetate to give the title compound.

MS (DCI/NH 3 ) m/z 348 (M+H) ⁺ ;

Η NMR δ 7.47 (d, 1Η), 7.14 (m, 2H), 6.80 (dd, 1H), 6.64 (d, 1H), 6.17 (m, 1H), 5.81 (ddm, 1H), 5.73 (dd, 1H), 5.46 (m, 1H), 5.32 (dd, 1H), 5.02 (dm, 1H), 4.94 (dm, 1H), 4.62 (m, 2H), 2.30 (m, 2H), 2.17 (s, 3H), 1.19 (s, 3H), 1.16 (s, 3H);

HRMS M/z calcd for C23H25NO2: 347.1885 (M+H) ⁺ . Found: 347.1897.

Example 78

2,5-dihydro-2,2,4-trimethyl-5-(2-propenyl)-1H-[1]benzopyrano-[3,4-f]quinoline-10carboxylic acid

The compound of Example 74 and chlorotris(triphenylphosphate)rhodium chloride are treated according to the method of Example 3 to give the desired compound.

MS (DCI/NH 3 ) m/z 437 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-d ₆ ) δ 7.91 (d, 1H), 7.44 (dd, 1H), 7.19 (d, 2H), 6.74 (d, 1H), 6.70 (s, 1H), 6.69 (dd, 1H), 6.26 (dd, 1H), 6.22 (s, 1H), 6.11 (dd, 1.0 Hz, 1H), 5.43 (s, 1H), 5.15 (s, 2H), 1.84 (s, 3H), 1.23 (s, 3H), 1.15 (s, 3H).

Example 79

5-(3,5-dichlorophenyl)-10-ethoxy-2,5-dihydro-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano-[3,4fjquinoline

The compound of Example 9A and 3,5-dichlorophenylmagnesium bromide are treated according to the method of Examples 1G and 1 to give the desired compound.

MS (DCI) m/z 466 (M+H) ⁺ ;

'HNMR (300 MHz, DMSO-dó) δ 8.10 (d, 1H), 7.46 (t, 1H), 7.13 (d, 2H), 6.95 (dd, 1H), 6.81 (s, 1H), 6.72 (d, 1H), 6.60 (d, 1H), 6.51 (d, 1H), 6.32 (d, 1H), 5.44 (s, 1H), 3.99-4.12 (m, 1H), 1.87 (s, 3H), 1.37 (t, 3H), 1.23 (s, 3H), 1.20 (s, 3H);

HRMS calculated m/z for C27H25NO2Cl2: 465.1262 (M+H) ⁺ . Found: 465.1277.

Example 80

5-(3,5-Dichlorophenyl)-2,5-dihydro-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano-[3,4-f]quinolinol-ol

The compound of Example 7A and 3,5-dichlorobenzylmagnesium bromide are treated according to the method of Examples 7B and 7 to give the desired compound.

MS (DCI) m/z 438, 440 (M+H) ⁺ ;

• ·

120 'H NMR (300 MHz, DMSO-dg) δ 9.79 (s, 1H), 8.18 (d, 1H), 7.44 (t, 1H), 7.12 (dd, 2H), 6.79 (d, 1H), 6.77 (s, 1H), 6.73 (d, 1H), 6.45 (d, 1H), 6.28 (dd, 1H), 6.23 (d, 1H), 5.43 (s, 1H), 1.87 (d, 3H), 1.22 (s, 3H), 1.16 (s, 3H);

HRMS calculated m/z for C25H21Cl2NO2: 437.0949 (M+H) ⁺ . Found: 437.0955.

Example 81

5-(3,5-Dichlorophenyl)-2,5-dihydro-2,2,4-trimethyl-1H-[1]benzopyrano-[3,4-f]quinolin-10ylmethylcarbonate

The compound of Example 80 and methyl chloroformate are treated according to the method of Examples 7B and 7 to give the desired compound.

MS (DCI/NH ₃ ) m/z 496 (M+H) ⁺ ;

^X H NMR (300 MHz, DMSO-cL) δ 7.58 (d, 1H), 7.45 (t, 1H), 7.24 (m, 2H), 7.02 (t, 1H), 6.82 (s, 1H), 6.80 (dd, 1H), 6.75 (dd, 1H), 6.74 (d, 1H), 6.48 (s, 1H), 5.43 (s, 1H), 3.79 (s, 3H), 1.79 (s, 3H), 1.25 (s, 3H), 1.13 (s, 3H);

Analytical calcd for C27H23NO4Cl2: C, 65.33; H, 4.67; N, 2.82. Found: C, 65.12; H, 4.55, N, 2.79.

Example 82

2,5-dihydro-2,2,4-trimethyl-5-(2-propenyl)-1H-[1]benzopyrano[3,4-f]quinolin-10-ol

The compound of Example 7A and allylmagnesium bromide are treated according to the method of Examples 7B and 7 to give the desired compound.

MS (DCI/NH 3 ) m/z 334 (M+H) ⁺ ;

Η NMR (300 MHz, DMSO-dg) δ 9.77 (s, 1H), 8.10 (d, 1H), 6.88 (t, 1H), 6.58 (d, 1H), 6.53 (d, 1H), 6.35 (d, 1H), 6.05 (s, 1H), 5.89-5.72 (m, 2H), 5.44 (s, 1H), 5.03 (d, 1H), 4.99 (d, 1H), 2.50-2.40 (m, 1H), 2.25-2.18 (m, 1H), 2.16 (s, 3H), 1.16, (s, 3H), 1.15 (s, 3H);

HRMS calculated m/z for C22H23NO2: 333.1729 (M+H) ⁺ . Found: 333.1734.

Example 83

10-(Bromodifluoromethoxy)-2,5-dihydro-2,2,4-trimethyl-5-(2-propenyl)-1H-[1]benzopyrano[3,4-fJquinoline

The compound of Example 82 and dibromodifluoromethane are treated according to the method of Examples 7B and 7 to give the desired compound.

MS (DCI/NH 3 ) m/z 462 (M+H) ⁺ ;

• · * • 0 · »000 0 0 0 · ‘h NMR (300 MHz, DMSO-de) δ 7.60 (d, 1H), 7.21 (t, 1H), 7.0 (m, 1H), 6.95 (dd, 1H), 6.64 (d, 1H), 6.35 (s, 1H), 5.89-5.76 (m, 2H), 5.46 (s, 1H), 5.04 (dd, 1H), 4.96 (dd, 1H), 2.55-2.44 (m, 1H), 2.33-2.25 (m, 1H), 2.18 (s, 3H), 1.19, (s, 3H), 1.17 (s, 3H);

HRMS calculated m/z for C15H16F16N16Br: 461.0802 (M+H) ⁺ . Found: 461.0815.

Example 84 [3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1-benzopyrano[3,4-f]quinolin-5-yl)phenyl]methylcarbonate

The compound of Example 13 and methyl chloroformate are treated according to the method of Example 10 to give the desired compound.

MS (DCI/NH 3 ) m/z 458 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-ds) δ 8.01 (d, 1H), 7.25 (t, 1H), 7.12 (d, 1H), 7.01 (q, 1H), 6.90 (q, 2H), 6.78 (s, 1H), 6.72 (d, 1H), 6.57 (q, 1H), 6.44 (q, 1H), 6.20 (d, 1H), 5.39 (s, 1H), 3.80 (s, 3H), 3.63 (s, 3H), 1.83 (s, 3H), 1.22 (s, 3H), 1.16 (s, 3H);

Analytical Calcd for C28H27NO5: C, 73.50; H, 5.94; N, 3.06. Found: C, 73.63; H, 6.20;

N, 2.86.

Example 85

2.5-Dihydro-10-methoxy-5-(3-methoxyphenyl)-2,2,4-trimethyl-1H-[1]benzopyrano-[3,4fquinoline

The compound of Example 13 and methyl iodide are treated according to the method of Example 14 to give the desired compound.

MS (DCI/NH3) m/z 414 (M+H);

Ή NMR (300 MHz, DMSO-dé) δ 8.01 (d, 1H), 7.13 (t, 1H), 6.92 (t, 1H), 6.75-6.67 (m, 5H), 6.57 (dd, 1H), 6.46 (dd, 1H), 6.20 (d, 1H), 5.39 (s, 1H), 3.80 (s, 3H), 3.63 (s, 3H), 1.88 (s, 3H), 1.22 (s, 3H), 1.16 (s, 3H);

Analytical calcd for C27H27NO3: C, 78.42; H, 6.58; N, 3.38. Found: C, 78.58; H, 6.55;

N, 3.23.

Example 86

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[3-(2-propenyloxy)phenyl]-1H-[1jbenzopyrano[3,4-fquinoline

The compound of Example 13 and allyl bromide are treated according to the method of Example 14 to give the desired compound.

MS (DCI/NH 3 ) m/z 440 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-dg) δ 8.02 (d, 1H), 7.13 (t, 1H), 6.92 (t, 1H), 6.78-6.67 (m, 5H),

6.56 (d, 1H), 6.46 (d, 1H), 6.20 (d, 1H), 5.95 (m, 1H), 5.40 (s, 1H), 5.31 (dd, 1H), 5.21 (dd, 1H), 4.42 (d, 2H), 3.80 (s, 3H), 1.86 (s, 3H), 1.23 (s, 3H), 1.16 (s, 3H);

Analytical calcd for C29H29NO3: C, 79.24; H, 6.64; N, 3.18. Found: C, 78.87; H, 6.46; N, 3.07.

Example 87

2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-[3-(phenylmethoxy)phenyl]-1H-[1]benzopyrano-[3,4fquinoline

The compound of Example 13 and benzyl bromide are treated according to the method of Example 14 to give the desired compound.

MS (DCI/NH 3 ) m/z 490 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-dg) δ 8.06 (d, 1H), 7.40 (m, 5H), 7.18 (t, 1H), 6.97 (t, 1H), 6.906.85 (m, 2H), 6.80-6.74 (m, 3H), 6.62 (d, 1H), 6.48 (d, 1H), 6.24 (d, 1H), 5.45 (s, 1H), 5.03 (d, 2H), 3.85 (s, 3H), 1.92 (s, 3H), 1.29 (s, 3H), 1.21 (s, 3H);

Analytical calcd for C33H31NO3: C, 80.95; H, 6.38; N, 2.86. Found: C, 80.81; H, 6.24; N, 2.96.

Example 88

5-[3-(cyclopropylmethoxy)phenyl]-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H[1]benzopyrano-[3,4-fJquinoline

The compound of Example 13 and cyclopropylmethyl bromide are treated according to the method of Example 14 to give the desired compound.

MS (DCI/NH 3 ) m/z 454 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-dg) δ 8.01 (d, 1H), 7.12 (t, 1H), 6.92 (t, 1H), 6.74-6.68, (m, 5H), 6.55 (d, 1H), 6.46 (d, 1H), 6.20 (s, 1H), 5.39 (s, 3H), 3.79 (s, 3H), 3.66 (d, 2H), 1.86 (s, 3H), 1.23 (s, 3H), 1.16 (s, 3H), 1.12 (m, 1H), 0.50 (q, 2H), 0.24 (q, 2H);

Analytical calcd for C30H31NO3: C, 79.44; H, 6.88; N, 3.08. Found: C, 79.12; H, 6.72; N, 2.99.

• ·

Example 89

2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-[3-[2-(1-piperidinylethoxyjphenylj-1H[1]benzopyrano-[3,4-quinoline)

The compound of Example 13 and 1-(2-chloroethyl)piperidine are treated according to the method of Example 14 to give the desired compound.

MS (DCI/NH ₃ ) m/z 511 (M+H) ⁺ ;

'li NMR (300 MHz, DMSO-cU) δ 8.01 (d, 1H), 7.12 (t, 1H), 6.92 (t, 1H), 6.77-6.68 (m, 5H), 6S7 (d, 1H), 6.46 (d, 1H), 6.20 (d, 1H), 5.39 (s, 1H), 3.91 (t, 2H), 3.80 (s, 3H), 2.55 (t, 2H), 2.35 (b, 4H), 1.92 (s, 3H), 1.46 (b, 4H), 1.36 (b, 2H), 1.22 (s, 3H), 1.16 (s, 3H);

Analytical calcd for C33H38N2O3 _0.5H2O : C, 76.27; H, 7.56; N, 5.39. Found: C, 76.26; H, 7.38; N, 5.28.

Example 90

5-(3-hexyloxyphenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano-[3,4fquinoline

The compound of Example 13 and hexyl iodide are treated according to the method of Example 14 to give the desired compound.

MS (DCI/NH 3 ) m/z 484 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-d ₆ ) δ 8.01 (d, 1H), 7.09 (t, 1H), 6.92 (t, 1H), 6.75-6.67 (m, 5H),

6.56 (dd, 1H), 6.46 (dd, 1H), 6.18 (d, 1H), 5.40 (s, 1H), 3.81 (t, 2H), 3.79 (s, 3H), 1.87 (s, 3H), 1.60 (m, 2H), 1.36-1.23 (b, 6H), 1.22 (s, 3H), 1.16 (s, 3H), 0.86 (t, 3H);

HRMS m/z calcd for C32H37NO3: 483.2773 (M+H) ⁺ . Found: 483.2776.

Example 91

5-[3-(2,4-dinitrophenoxy)phenyl]-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-fquinoline

The compound of Example 13 and 1-fluoro-2,4-dinitrobenzene are treated according to the method of Example 14 to give the desired compound.

MS (DCI/NH ₃ ) m/z 566 (M+H) ⁺ ;

’H NMR (300 MHz, DMSO-ck) δ 8.87 (d, 1H), 8.38 (dd, 1H), 7.88 (d, 1H), 7.40 (t, 1H), 7.207.08 (m, 2H), 7.20-7.08 (m, 2H), 6.81 (s, 1H), 6.72 (d, 1H), 6.68 (d, 1H), 6.62 (d, 1H), 6.46 (dd, 1H), 6.24 (d, 1H), 5.40 (s, 1H), 3.78 (s, 3H), 1.90 (s, 3H), 1.19 (s, 3H), 1.13 (s, 3H);

• 0 • · • · · 0

124

0000 ·· » 0 0 0 00 00

Analytical calcd for C32H27N3O7: C, 67.95; H, 4.81; N, 7.42. Found: C, 68.20; H, 5.05; N, 7.20.

Example 92

2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-[3-(2-propynyloxy)phenyl]-1H-[1]benzopyrano[3,4-f]quinoline

The compound of Example 13 and propargyl bromide are treated according to the method of Example 14 to give the desired compound.

MS (DCI/NH 3 ) m/z 566 (M+H) ⁺ ;

1 H NMR (300 MHz, DMSO-cU) δ 8.00 (d, 1H), 7.13 (t, 1H), 6.92 (t, 1H), 6.80-6.68 (m, 5H),

6.56 (d, 1H), 6.48 (d, 1H), 6.18 (d, 1H), 5.39 (s, 1H), 4.67 (d, 2H), 3.80 (s, 3H), 3.50 (t, 1H), 1.87 (s, 3H), 1.23 (s, 3H), 1.16 (s, 3H);

Example 93

3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano-[3,4f]quinolin-5-yl)phenol 4-methylbenzenesulfonate (ester)

The compound of Example 13 and p-toluenesulfonyl chloride are treated according to the method of Example 15 to give the desired compound.

MS (DCI/NH 3 ) m/z 554 (M+H) ⁺ ;

^! H NMR (300 MHz, DMSO-dé) δ 7.99 (d, IH), 7.47 (d, 2H), 7.36 (d, 4H), 7.22 (t, IH), 7.13 (d, IH), 6.97 (t, IH), 6.85-6.78 (m, 2H), 6.70 (d, IH), 6.68 (s, IH), 6.59 (dd, 1H), 6.37 (dd, 1H), 6.24 (d, 1H), 5.39 (s, 1H), 3.80 (s, 3H), 2.43 (s, 3H), 1.74 (s, 3H), 1.24 (s, 3H), 1.18 (s, 3H);

Analytical calcd for C33H31NO5S: C, 71.58; H, 5.64; N, 2.52. Found: C, 71.49; H, 5.75; N, 2.40.

Example 94

4-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano-[3,4-f]quinolin-5yl)phenol acetate (ester)

The compound of Example IF and 4-methoxymethoxyphenyl bromide are treated according to the method of Examples 12A-C to provide the desired compound.

MS (DCI/NH 3 ) m/z 442 (M+H) ⁺ ;

♦ · ·· ···· 9 9 9 9

9 9 · · · · 9 9 9 9

Φ ··« 9 · · ··* · · · · * φ 9 9 9 9 9 9 9 9

125 ..............

’Η NMR (300 MHz, DMSO-dg) δ 8.02 (d, 1H), 7.19 (d, 2H), 6.99 (d, 2H), 6.91 (t, 1H), 6.79 (s, 1H), 6.71 (d, 1H), 6.58 (d, 1H), 6.46 (dd, 1H), 6.21 (d, 1H), 5.39 (s, 1H), 3.79 (s, 3H), 2.19 (s, 3H), 1.83 (s, 3H), 1.22 (s, 3H), 1.15 (s, 3H);

Analytical calcd for C28H27NO4: C, 76.16; H, 6.16; N, 3.17. Found: C, 75.79; H, 6.24; N, 3.03.

Example 95

4-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano-[3,4-f]quinolin-5yl)phenol

The compound of Example 94 is processed according to the method of Example 13 to give the desired compound.

MS (DCI/NH 3 ) m/z 400 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-dg) δ 9.29 (s, 1H), 8.05 (d, 1H), 7.00 (d, 2H), 6.95 (t, 1H), 6.74 (d, 2H), 6.72 (s, 1H), 6.63-6.58 (m, 3H), 6.44 (dd, 1H), 6.15 (s, 1H), 5.41 (s, 1H), 3.83 (s, 3H), 1.90 (s, 3H), 1.28 (s, 3H), 1.20 (s, 3H);

Analytical calcd for C26H25NO3: C, 78.17; H, 6.30; N, 3.50. Found: C, 78.59; H, 6.20; N, 3.12.

Example 96

2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-[[4-(methylthio)methoxy]phenyl]-1H[ 1 ]benzopyrano-[3,4-f]quinoline

The compound of Example 95 is processed according to the method of Example 14 to give the desired compound.

MS (DCI/NH 3 ) m/z 460 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-dg) δ 8.01 (d, 1H), 7.17 (d, 2H), 6.90 (t, 1H), 6.82 (d, 2H), 6.72 (s, 1H), 6.69 (d, 1H), 6.56 (d, 1H), 6.42 (d, 1H), 6.17 (s, 1H), 5.38 (s, 1H), 5.16 (s, 2H), 3.80 (s, 3H), 2.11 (s, 3H), 1.85 (s, 3H), 1.23 (s, 3H), 1.16 (s, 3H);

Analytical calcd for C28H29NO3S: C, 73.17; H, 6.35; N, 3.04. Found. C, 72.86; H, 6.62; N, 2.69.

Example 97 [4-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-fquinolin-5-yl)phenyl]dimethylcarbamate • ·

126 .......*.....

The compound of Example 95 and dimethylcarbanoyl chloride are treated according to the method of Example 15 to give the desired compound.

MS (DCI/NH 2 ) m/z 471 (M+H) ⁺ ;

*H NMR (300 MHz, DMSO-cU) δ 8.01 (d, 1H), 7.15 (d, 2H), 6.98 (d, 2H), 6.90 (d, 1H), 6.76 (s, 1H), 6.70 (d, 1H), 6.57 (d, 1H), 6.44 (d, 1H), 6.22 (d, 1H), 5.40 (s, 1H), 3.80 (s, 3H), 2.98 (s, 3H), 2.85 (s, 3H), 1.86 (s, 3H), 1.23 (s, 3H), 1.15 (s, 3H).

Example 98

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[4-(phenylmethoxy)phenyl]-1H-[1]benzopyrano-[3,4fquinoline

The compound of Example 95 and benzyl bromide are treated according to the method of Example 14 to give the desired compound.

MS (DCI/NH 2 ) m/z 490 (M+H) ⁺ ;

’H NMR (300 MHz, DMSO-cU) δ 8.02 (d, 1H), 7.40-7.28 (m, 4H), 7.08 (d, 2H), 6.90 (t, 1H), 6.84 (d, 2H), 6.72 (s, 1H), 6.70 (d, 1H), 6.55 (d, 1H), 6.41 (d, 1H), 6.15 (s, 1H), 5.37 (s, 1H), 4.96 (s, 2H), 3.80 (s, 3H), 1.85 (s, 3H), 1.23 (s, 3H), 1.15 (s, 3H);

Analytical calcd for C33H31NO3: C, 80.95; H, 6.38; N, 2.86. Found: C, 81.02; H, 6.25; N, 2.76.

Example 99

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[3-(methoxymethoxy)phenyl]-1H-[ljbenzopyrano[3,4-f]quinoline

The compound of Example 13 and methoxymethyl chloride are treated according to the method of Example 14 to give the desired compound.

MS (DCl/NH 3 ) m/z 444 (M+H) ⁺ ;

’H NMR (300 MHz, DMSO-ds) δ 8.01 (d, 1H), 7.14 (t, 1H), 6.92 (t, 1H), 6.83-6.75 (m, 4H), 6.70 (d, 1H), 6.58 (d, 1H), 6.47 (q, 1H), 6.21 (s, 1H), 5.40 (s, 1H), 5.06 (s, 2H), 3.80 (s, 3H), 3.30 (s, 3H), 1.89 (s, 3H), 1.24 (s, 3H), 1.16 (s, 3H);

HRMS calculated m/z for C28H29NO4: 443.2097 (M+H) ⁺ . Found: 443.2098.

Example 100

1-morpholinecarboxylate [(2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano[3,4-f]quinolin-5-yl)phenyl]

127 • 9 ·' *♦ ·· ** *· ··»· ·«·» · · · · • ··· · · ···· ♦ · * • ··· · · · · · «····· ·* · · · · *·

The compound of Example 13 and morpholine are treated according to the method of Example 15 to give the desired compound.

MS (DCI/NH 3 ) m/z 513 (M+H) ⁺ ;

’H NMR (300 MHz, DMSO-dg) δ 8.01 (d, 1H), 7.22 (t, 1H), 7.05 (d, 1H), 6.93 (t, 2H), 6.83 (s, 1H), 6.77 (s, 1H), 6.71 (d, 1H), 6.57 (d, 1H), 6.48 (q, 1H), 6.23 (d, 1H), 5.40 (s, 1H), 3.80 (s, 3H), 3.60 (t, 4H), 3.50 (b, 4H), 1.86 (s, 3H), 1.24 (s, 3H), 1.14 (s, 3H);

HRMS calculated m/z for C31H32N2O5: 512.2311 (M+H) ⁺ . Found: 512.2328.

Example 101

2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-[3-((methylsulfinyl)methoxy]phenyl]- 1H[ 1 ]benzopyrano-[3,4-f]quinoline

A solution of Example 14 (12 mg, 0.005 mmol) in methanol (1 mL) at 0°C was treated sequentially with _TeO2 (1.6 mg, 0.01 mmol) and acetic acid (50 mg, 0.83 mmol), stirred at room temperature, treated with saturated _NaHCO3 solution, and extracted with dichloromethane. The extract was washed with water and brine, dried ( _MgSO4 ), filtered, and concentrated to give

MS (DCI/NH 3 ) m/z 476 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-dg) δ 8.01 (dd, 1H), 7.15 (dt, 1H), 6.92 (m, 3H), 6.78 (t, 1H), 6.74 (s, 1H), 6.70 (d, 1H), 6.58 (d, 1H), 6.47 (d, 1H), 6.19 (d, 1H), 5.40 (d, 1H), 5.12 (dd, 1H), 4.93 (q, 1H), 3.79 (d, 3H), 2.57 (d, 3H), 1.87 (d 3H), 1.24 (d, 3H), 1.16 (d, 3H);

HRMS calculated m/z for C28H29NO4S: 475.1817 (M+H) ⁺ . Found: 475.1819.

Example 102

O-(3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano-[3,4f]quinolin-5-yl)phenyl] ester

The compound of Example 13 and thiocarbanoyl chloride are treated according to the method of Example 16 to give the desired compound.

MS (DCI/NH ₃ ) m/z 487 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-dg) δ 8.01 (d, 1H), 7.22 (t, 1H), 7.13 (d, 1H), 6.92 (t, 1H), 6.85 (d, 1H), 6.78 (s, 1H), 6.72 (s, 1H), 6.59 (d, 1H), 6.57 (d, 1H), 6.45 (d, 1H), 6.21 (s, 1H), 5.39 (s, 1H), 3.80 (s, 3H), 3.29 (s, 3H), 3.22 (s, 3H), 1.86 (s, 3H), 1.24 (s, 3H), 1.14 (s, 3H).

128

Φ V »Φ • φ · φ • # · φ ··· * * ♦ ·>·Φ ·· φφ • · · » · » · • Φ • Φ ·· «

Φ 1 ř

> « ·* *· • · « ·

Φ · · · • · · ·

Φ · · ·

Example 103

2.5- dihydro-10-methoxy-2,2,4-trimethyl-5 -[3 -(methylthio)phenyl] -1 Η- [ 1 ] benzopyrano- [3,4fjquinoline

Example 103A

A solution of 3-bromophenylmethoxymethyl ether (3.50 g, 15.0 mmol) in THF (150 mL) at -78°C was treated with n-butyllithium (2.5 M in hexanes, 6.00 mL) over 5 min, heated at -30°C, cooled to -78°C, treated with the compound from Example 1F at once, heated at -40°C, quenched with saturated NH4Cl, warmed to room temperature, and allowed to settle. The supernatant was decanted and concentrated. The residue was partitioned between water and ethyl acetate. The organic layer was washed sequentially with water and brine, dried ( _Na2SO4 ), and concentrated. The residue was flash chromatographed on a silica gel column with 20-25% ethyl acetate/hexanes to provide the title compound.

MS (DCI/NH 3 ) m/z 476 (M+H) ⁺ .

Example 103

2.5- dihydro-10-methoxy-2,2,4-trimethyl-5-[3 -(methylthio)phenyl]-1 Η- [ 1 jbenzopyrano- [3,4fjquinoline

A solution of Example 103A (20 mg, 0.042 mmol) and triethylsilane (49 mg, 0.42 mmol) in dichloromethane (1 mL) at room temperature was treated with BF3- _OEt2 (60 mg, 0.42 mmol), stirred for 24 h, and treated with saturated NaHCO3. The aqueous layer was extracted with dichloromethane, and the combined extracts were washed sequentially with 1M NaOH and brine, dried ( _Na2SO4 ), filtered, and concentrated. The residue was flash chromatographed on a silica gel column with 10-25% ethyl acetate/hexane to give the title compound.

MS (DCI/NH 3 ) m/z 430 (M+H) ⁺ ;

*H NMR (300 MHz, DMSO-d ₆ ) δ 8.01 (d, 1H), 7.15 (t, 1H), 7.05 (s, 1H), 7.03 (d, 1H), 6.93 (t, 1H), 6.89 (s, 1H), 6.74 (s, 1H), 6.70 (d, 1H), 6.57 (d, 1H), 6.46 (d, 1H), 6.19 (d, 1H), 5.40 (s, 1H), 3.78 (s, 3H), 3.33 (s, 3H), 1.88 (s, 3H), 1.22 (s, 3H), 1.16 (s, 3H);

HRMS calculated m/z for _C27H27NO2S : _429.1763 (M+H) ⁺ . Found: _429.1764 .

Example 104

O-[3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano-[3,4-f]quinolin-5yl)phenyl]methylcarbonothioate

129 • · · · · • ·

The compound of Example 95 and methylthiochloroformate are treated according to the method of Example 15 to give the desired compound.

MS (DCI/NH ₃ ) m/z 474 (M+H) ⁺ ;

¹ H NMR (300 MHz, DMSO-dg) δ 8.00 (d, 1H), 7.26 (t, 1H), 7.12 (d, 1H), 7.01 (q, 1H), 6.89 (t, 1H), 6.87 (s, 1H), 6.78 (s, 1H), 6.72 (d, 1H), 6.57 (q, 1H), 6.44 (q, 1H), 6.20 (d, 1H), 5.39 (s, 1H), 3.78 (s, 3H), 2.35 (s, 3H), 1.83 (s, 3H), 1.22 (s, 3H), 1.16 (s, 3H);

Analytical calcd for C28H27NO4S: C, 71.01; H, 5.74; N, 2.95. Found: C, 70.77; H, 5.74; N, 2.79.

Example 105 [3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl]-5-phenyl-1H-[1]benzopyrano[3,4-f]quinolin-5-yl)phenyl]trifluoromethanesulfonate

Solution from Example 13 (100 mg, 0.25 mmol), triethylamine (70 μΐ, 0.5 mmol) and

4-Dimethylaminopyridine (catalytic amount) in dichloromethane (10 mL) at -78°C was treated dropwise with trifluoromethanesulfonic anhydride (50 μΐ, 0.30 mmol), stirred for 30 min at -78°C, poured into saturated NaHCO ₃ solution, and extracted with ethyl acetate. The extract was washed successively with water and brine, dried (bRSCL), filtered, and concentrated. The residue was purified by flash chromatography on a silica gel column with 1585% ethyl acetate/hexanes to give the desired compound.

MS (DCI/NH 3 ) m/z 532 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-dg) δ 8.02 (d, 1H), 7.44 (t, 1H), 7.30 (m, 2H), 7.17 (s, 1H), 6.93 (t, 1H), 6.83 (s, 1H), 6.71 (d, 1H), 6.57 (d, 1H), 6.43 (d, 1H), 6.28 (d, 1H), 5.40 (s, 1H), 3.78 (s, 3H), 1.83 (s, 3H), 1.22 (s, 3H), 1.15 (s, 3H);

Analytical calcd for C27H24NO5SF3: C, 61.01; H, 4.55; N, 2.64. Found: C, 61.17; H, 4.60; N, 2.51.

Example 106

5-(3-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)phenyl]-2,5-dihydro-10-methoxy-2,2,4-trimethyl-5phenyl-1Η-[1jbenzopyrano-[3,4-f]quinoline

The compound from Example 52 (92.9 mg, 0.20 mmol), 2-trimethylstannyl-4,4-dimethyloxazoline (210 mg, 0.80 mmol) and [l,r-is(diphenylphosphino)ferrocene]dichloropalladium complex (16 mg, 0.02 mmol) in l-methyl-2-pyrrolidinone (2 ml) were purged with N ₂ , heated at 85°C for 3 h, partitioned between ethyl acetate (50 ml) and saturated KF • · · · · · · · · · · · · · 0 • 0

130 (30 mL), stirred for 1 hour and filtered through seashell powder (Celite®). The filtrate was washed with water, brine, dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography on silica gel with 0-30% ethyl acetate/hexanes to give the desired compound.

MS (DCI/NH 3 ) m/z 481 (M+H) ⁺ ;

^! H NMR (300 MHz, DMSO-d ₆ ) δ 8.02 (d, 1H), 7.64 (d, 1H), 7.62 (s, 1H), 7.41 (d, 1H), 7.32 (t, 1H), 6.92 (t, 1H), 6.82 (s, 1H), 6.71 (d, 1H), 6.56 (dd, 1H), 6.47 (dd, 1H), 6.25 (d, 1H), 5.40 (s, 1H), 4.02 (s, 2H), 3.78 (s, 3H), 1.84 (s, 3H), 1.25 (s, 3H), 1.22 (s, 6H), 1.16 (s, 3H); Analytical calcd for C31H32N2O3 0.7H2O: C, 75.49; H, 6.85; N, 5.68. Found: C, 75.83; H, 6.88; N, 5.29.

Example 107

Ethyl 3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano-[3,4-f]quinolin-5yl)benzoate

Example 106 (48 mg, 0.1 mmol) in 1.5 M sulfuric acid in ethanol (5 mL) was refluxed for 16 h, cooled, poured into saturated NaHCO ₃ solution, and extracted with ethyl acetate. The extract was washed with brine, dried (Na 2 SO ₄ ), filtered, and concentrated. The residue was purified by flash chromatography on silica gel with 30% ethyl acetate/hexanes to give the title compound.

MS (DCI/NH 3 ) m/z 456 (M+H) ⁺ ;

’H NMR (300 MHz, DMSO-do) δ 8.02 (d, 1H), 7.76 (m, 2H), 7.48 (d, 1H), 7.38 (t, 1H), 6.91 (t, 1H), 6.85 (s, 1H), 6.72 (d, 1H), 6.56 (dd, 1H), 6.46 (dd, 1H), 6.26 (d, 1H), 5.40 (s, 1H), 4.23 (q, 2H), 3.78 (s, 3H), 1.84 (s, 3H), 1.25 (t, 3H), 1.24 (s, 3H), 1.16 (s, 3H);

HRMS m/z calcd for C29H30NO4: 456.2175 (M+H) ⁺ . Found: 456.2175.

Example 108

-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1Η-[1]benzopyrano-[3,4-f]quinolin-5yl)benzoic acid

Example 107 (20 mg, 0.04 mmol) and LiOHH ₂ O (16.8 mg, 0.4 mmol) in 1:1:1 THF/methanol/water (3 mL) were stirred for 48 h and concentrated. The residue was dissolved in 1M NaOH (2 mL), washed with diethyl ether, treated with 1M HCl to adjust the pH to 3, and extracted with ethyl acetate. The extract was dried (Na ₂ SO ₄ ), filtered, and concentrated to give the title compound.

• · • ·

131

MS (DCI/NH 3 ) m/z 428 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-d ₆ ) δ 8.02 (d, 1H), 7.73 (m, 2H), 7.46 (d, 1H), 7.35 (t, 1H), 6.91 (t, 1H), 6.83 (s, 1H), 6.71 (d, 1H), 6.55 (dd, 1H), 6.46 (dd, 1H), 6.22 (d; 1H), 5.40 (s, 1H), 3.78 (s, 3H), 1.83 (s, 3H), 1.24 (s, 3H), 1.16 (s, 3H);

Analytical calcd for C27H25NO4: C, 72.86; H, 5.89; N, 3.28. Found: C, 72.89; H, 6.00; N, 2.94.

Example 109

2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-[3-methyl-5-(2-propenyl)phenyl]-1H[ 1 ]benzopyrano-[3,4-f]quinoline

The compound of Example 52 and allyltributyltin are treated according to the method of Example 16 to give the desired compound.

MS (DCI/NH 3 ) m/z 438 (M+H) ⁺ ;

*H NMR (300 MHz, DMSO-d ₆ ) δ 7.99 (d, 1H), 6.91 (t, 1H), 6.80 (m, 3H), 6.70 (s, 1H), 6.68 (d, 1H), 6.56 (dd, 1H), 6.44 (dd, 1H), 6.16 (d, 1H), 5.78 (ddt, 1H), 5.39 (s, 1H), 4.94 (dq, 1H), 4.88 (dq, 1H), 3.78 (s, 3H), 3.17 (d, 2H), 2.13 (s, 3H), 1.86 (s, 3H), 1.22 (s, 3H), 1.16 (s, 3H);

Analytical calcd for C30H31NO2: C, 82.35; H, 7.14; N, 3.20. Found: C, 81.99; H, 7.14; N, 2.98.

Example 110

-[3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano-[3,4-f]quinolin-5-yl)-5methylphenyl]ethanone

The compound of Example 52 and tributyl(1-ethoxyvinyl)tin in dichloroethane (20 mL) were treated with silica gel (1.0 g) and formic acid (10 drops), heated at 40°C for 6 hours, treated with water and extracted with ethyl acetate. The extract was washed with brine, dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography on silica gel with 5-10% ethyl acetate/hexanes to give the title compound.

MS (DCI/NH 3 ) m/z 440 (M+H) ⁺ ;

^! H NMR (300 MHz, DMSO-d ₆ ) δ 8.01 (d, 1H), 7.61 (s, 1H), 7.51 (s, 1H), 7.28 (s, 1H), 6.92 (t, 1H), 6.80 (s, 1H), 6.72 (d, 1H), 6.56 (dd, 1H), 6.49 (dd, 1H), 6.24 (m, 1H), 5.40 (s, 1H), 3.78 (s, 3H), 2.44 (s, 3H), 2.26 (s, 3H), 1.84 (s, 3H), 1.23 (s, 3H), 1.16 (s, 3H).

• · • · • · · ·

132

Example 111

3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano-[3,4-f]quinolin-5-yl)5-trimethylbenzenemethanol

A solution of Example 110 (0.022 g, 0.050 mmol) in THF (5 mL) at 0°C was treated with methylmagnesium chloride (3M in THF, 0.83 μΐ), warmed to room temperature, stirred for 1 h, treated with saturated NH ₄ Cl solution, separated and extracted with ethyl acetate. The extract was washed with brine and dried (MgSO ₄ ), filtered and concentrated to give the title compound.

MS (DCI/NH 3 ) m/z 456 (M+H) ⁺ ;

Η NMR (300 MHz, DMSO-dg) δ 7.98 (d, 1H), 7.11 (s, 1H), 7.08 (s, 1H), 6.91 (t, 8H), 6.786.63 (m, 3H), 6.55 (d, 1H), 6.46 (d, 1H), 6.18 (m, 1H), 5.39 (s, 1H), 4.84 (s, 1H), 3.73 (s, 3H), 2.(14 (s, 3H), 1.88 (s, 3H), 1.24 (s, 3H), 1.23 (s, 3H), 1.22 (s, 3H), 1.16 (s, 3H).

Example 112

5-[3-(2-furanyl)phenyl]-2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano[3,4-quinoline

The compound of Example 52 and 2-(tributylstannyl)furan are treated according to the method of Example 16 to give the desired compound.

MS (DCI/NH 3 ) m/z 456, 450 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-dg) δ 8.0 (d, 1H), 7.69 (s, 1H), 7.48 (d, 1H), 7.23 (t, 1H), 7.05 (d, 1H), 6.88 (t, 1H), 6.81 (s, 2H), 6.70 (d, 1H), 6.54 (m, 2H), 6.47 (d, 1H), 6.23 (s, 1H), 5.41 (s, 1H), 3.78 (s, 3H), 1.88 (s, 3H), 1.24 (s, 3H), 1.16 (s, 3H);

Analytical calcd for C30H27NO3H2O: C, 77.07; H, 6.25; N, 3.00. Found: C, 77.27; H, 5.97; N, 3.23.

Example 113

2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-[3-methyl-5-(ΙΗ-pyrrolidin-1 yl)phenyl]-1H[1jbenzopyrano-[3,4-f| quinoline

The compound of Example 11 and pyrrolidine are treated according to the method of Example 17 to give the desired compound.

MS (DCI/NH 3 ) m/z 467 (M+H) ⁺ ;

• · · · ·

133 η NMR (300 MHz, DMSO-de) δ 7.97 (d, 1H), 6.93 (t, 1H), 6.67 (s, 1H), 6.67 (d, 1H), 6.56 (d, 1H), 6.49 (d, 1H), 6.22 (s, 1H), 6.14 (m, 3H), 5.39 (s, 1H), 3.79 (s, 3H), 3.04 (m, 4H), 2.07 (s, 3H), 1.92 (s, 3H), 1.87 (m, 4H), 1.21 (s, 3H), 1.17 (s, 3H).

Example 114

3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano-[3,4-f]quinoline-5-methyl)5,N-dimethylbenzenamine

The compound of Example 11 and methylamine are treated according to the method of Example 17 to give the desired compound.

MS (DCl/NHs) m/z 427 (M+H) ⁺ ;

Η NMR (300 MHz, DMSO-de) δ 7.98 (d, 1H), 6.92 (t, 1H), 6.67 (d, 1H), 6.61 (s, 1H), 6.56 (d, 1H), 6.46 (d, 1H), 6.18 (br s, 2H), 6.14 (br s, 1H), 6.10 (s, 1H), 5.58 (q, 1H), 5.38 (br s, 1H), 3.79 (s, 3H), 2.50 (d, 3H), 2.04 (s, 3H), 1.90 (s, 3H), 1.22 (s, 3H), 1.15 (s, 3H); Analytical calcd for _{C28H30N2O2O.5H2O} : C, _77.21 ; H, 7.17; N, 6.43. Found: C, 77.65; H, 7.13; N, 5.97.

Example 115

3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1Η-[1]benzopyrano-[3,4-ylquinolin-5-yl)-5methyl-N-(2-propenyl)benzamide

The compound of Example 11 and allylamine are treated according to the method of Example 17 to give the desired compound.

MS (DCI/NH 3 ) m/z 453 (M+H) ⁺ ;

*H NMR (300 MHz, DMSO-dé) δ 7.98 (d, 1H), 6.92 (t, 1H), 6.67 (d, 1H), 6.56 (d, H), 6.45 (d, 1H), 6.24 (br s, 1H), 6.14 (m, 3H), 5.76 (m, 1H), 5.63 (t, 1H), 5.37 (br s, 1H), 5.10 (qd, 1H), 5.02 (qd, 1H), 3.79 (s, 3H), 3.50 (m, 2H), 2.02 (s, 3H), 1.89 (s, 3H), 1.22 (s, 3H), 1.15 (s, 3H);

Analytical calcd for C23H25NO2: C, 79.51; H, 7.25; N, 4.03. Found: C, 79.35; H, 7.30; N, 3.89.

Example 116

3-(2,5-Dihydro-10-methoxy-2,2,4-trimethyl-1Η-[1]benzopyrano-[3,4-f]quinolin-5-yl)-N-(2methoxyethyl)-5-methylbenzenamine

134 • · · ·

The compound of Example 11 and 2-methoxyethylamine are treated according to the method of Example 17 to give the desired compound.

Ή NMR (300 MHz, DMSO-dg) δ 7.98 (d, 1H), 6.95 (t, 1H), 6.65 (d, 1H), 6.60 (s, 1H), 6.54 (d, 1H), 6.44 (d, 1H), 6.22 (s, 1H), 6.17 (s, 2H), 6.13 (s, 1H), 5.41 (t, 10H), 5.38 (s, 1H), 3.79 (s, 3H), 3.26 (q, 2H), 3.20 (s, 3H,), 2.98 (q, 2H), 2.03 (s, 3H), 1.90 (s, 3H), 1.22 (s, 3H), 1.15 (s, 3H).

Example 117

3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1Η-[1]benzopyrano-[3,4-f]quinolin-5-yl)-N-(2-propenyl)benzenamine

The compound of Example 52 and allylamine are treated according to the method of Example 17 to give the desired compound.

MS (DCl/NH 3 ) m/z 439 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-dg) δ 7.99 (d, 1H), 6.91 (t, 1H), 6.86 (t, 1H), 6.67 (d, 1H), 6.63 (s, 1H), 6.55 (d, 1H), 6.44 (m, 2H), 6.33 (m, 2H), 6.14 (d, 1H), 5.78 (m, 2H), 5.37 (s, 1H), 5.12 (qd, 1H), 5.03 (qd, 1H), 3.79 (s, 3H), 3.51 (m, 2H), 1.88 (s, 3H), 1.22 (s, 3H), 1.14 (s, 3H);

Analytical calcd for C29H30N2O2: C, 79.42; H, 6.89; N, 6.39. Found: C, 79.03; H, 7.05; N, 6.17.

Example 118

N'-[3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano-[3,4-f]quinolin-5-yl)-5methylphenyl]-N,N-dimethylurea

A solution of Example 115 (0.112 g, 0.247 mmol) in 10% ethanol/water (10 mL) was treated with 1,4-diazabicyclo[2.2.2]octane (0.056 g, 0.495 mmol) and chlorotris(triphenylphosphine)-rich complex (0.115 g, 0.124 mmol), refluxed for 15 h, poured into 5% HCl, stirred for 20 min, neutralized with NaHCO ₃ , and extracted with ethyl acetate. The extract was washed with brine, dried (Na 2 SO ₄ ), filtered, and concentrated. The residue was purified by flash chromatography on a silica gel column with 20-33% ethyl acetate/hexanes to give the title compound.

Aniline (0.030 g, 0.073 mmol) was dissolved in 2:1/toluene:THF (7 mL), reacted sequentially with diisopropylethylamine (38 μΐ, 0.218 mmol) and N,N-dimethylcarbamoyl chloride (20 μΐ, 0.218 mmol), refluxed for 18 hours, cooled, reacted with water and extracted • 4 • 4

135 with ethyl acetate. The extract was washed with brine, dried (MgSO ₄ ), filtered and concentrated. The residue was purified by flash chromatography on a silica gel column with 25-50% ethyl acetate/hexanes to give the title compound.

1H NMR (300 MHz, DMSO-dg) δ 8.15 (s, 1H), 7.98 (d, 1H), 7.10 (br s, 2H), 6.91 (t, 1H), 6.69 (d, 1H), 6.63 (s, 1H), 6.56 (d, 1H), 6.54 (s, 1H), 6.46 (d, 1H), 6.16 (br s, 1H), 538 (s, 1H), 2.85 (s, 6H), 2.09 (s, 3H), 1.86 (s, 3H), 1.24 (s, 3H), 1.14 (s, 3H); HRMS m/z calcd for C30H39N3O3: 484.2600 (M+H) ⁺ . Found: 484.2601.

Example 119

N-[3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano-[3,4-f]quinolin-5yl)phenyl]benzenemethanamine

The compound of Example 11 and benzylamine are treated according to the method of Example 17 to give the desired compound.

’H NMR (300 MHz, DMSO-cU) δ 7.97 (d, 1H), 7.23 (m, 5H), 6.80 (m, 2H), 6.65 (d, 1H), 6.59 (s, 1H), 6.53 (d, 2H), 6.49 (s, 1H), 6.16 (m, 3H), 6.16 (t, 1H), 6.12 (s, 1H), 5.35 (s, 1H), 4.10 (b, 2H), 3.78 (s, 3H), 1.83 (s, 3H), 1.22 (s, 3H), 1.14 (s, 3H);

HRMS m/z calcd for C33H32O2N2: 488.2464 (M+H) ⁺ . Found: 488.2468.

Example 120

5-((3,5-dichlorophenyl)methylene]-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1jbenzopyrano[3,4-f]quinoline

The compound of Example 1F and 3,5-dichlorobenzylmagnesium bromide are treated according to the method of Example IB to give the desired compound.

MS (DCI/NH 3 ) m/z 464 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-dg) isomer 1: δ 8.17 (d, 1H), 7.32 (s, 1H), 6.96 (s, 2H), 6.816.74 (m, 4H), 6.45 (s, 2H), 5.11 (s, 1H), 3.93 (s, 3H), 1.88 (s, 3H), 1.22 (s, 3H), 0.89 (s, 3H); isomer 2: δ 8.29 (d, 1H), 7.78 (s, 2H), 7.45 (s, 1H), 7.23 (t, 1H), 7.18 (d, 1H), 7.16 (d, 1H), 6.84 (d, 1H), 6.66 (s, 1H), 5.59 (s, 1H), 5.47 (s, 1H), 3.93 (s, 3H), 1.96 (s, 3H), 1.27 (s, 6H); HRMS calculated m/z for C27H23Cl2NO2: 463.1106 (M+H) ⁺ . Found: 463.1112.

Example 121

5-[(4-chlorophenyl)methylene]-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline • · · · • · · · ♦ · · • · · · • · •··9 99

136

9 9 9 ·· « ·

9 9 9 * » * *

9 9 9 9 9 9 9 • 9 99999 99 9 ·· 9 9 9 9 9

The compound of Example IF and 4-chlorobenzylmagnesium bromide are treated according to the method of Example IB to give the desired compound.

MS (DCI/NH ₃ ) m/z 430 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-de) isomer 1: δ 8.26 (d, IH), 7.75 (d, Hz, 2H), 7.42 (d, 2H), 7.18 (t, 2H), 6.89 (d, IH), 6.74 (d, IH), 6.61 (s, IH), 5.54 (s, IH), 5.46 (s, IH). 3.91 (s, 3H), 1.97 (s, 3H), 1.26 (s, 6H); isomer 2: δ 8.13 (s, 1H), 7.18 (t, 1H), 7.04 (d, 2H), 6.82-6.71 (m, 5H), 6.46 (s, 1H), 6.41 (s, 1H), 5.04 (s, 1H), 3.91 (s, 3H), 1.84 (s, 3H), 1.22 (s, 3H), 0.90 (s, 3H); HRMS calculated m/z for C27H24CINO2: 429.1496 (M+H) ⁺ . Found: 429.1500.

Example 122

2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-[[3-(trifluoromethyl)phenylmethylene]-1H[ 1 ]benzopyrano-[3,4-f|quinoline

The compound of Example 1F and 3-trifluoromethylmagnesium bromide are treated according to the method of Example IB to give the desired compound.

MS (DCI/NH 3 ) m/z 464 (M+H) ⁺ ;

1 H NMR (300 MHz, DMSO-cL) isomer 1: δ 8.28 (d, IH), 8.13 (s, IH), 7.98 (d, IH), 7.657.56 (m, IH), 7.33-7.39 (m, IH), 7.21 (t, IH), 6.83-6.78 (m, 2H), 6.75 (t, IH), 6.64 (s, 1H), 5.68 (s, 1H), 5.48 (s, 1H), 3.92 (s, 3H), 1.99 (s, 3H), 1.27 (s, 6H); isomer 2: δ 8.17 (d, IH), 7.65-7.56 (m, IH), 7.45 (d, IH), 7.39-7.33 (m, IH), 7.27 (d, IH), 7.17 (t, IH), 6.83-6.78 (m, 2H), 6.75 (t, IH), 6.56 (s, IH), 6.40 (s, 1H), 5.01 (s, 1H), 3.92 (s, 3H), 1.88 (s, 3H), 1.19 (s, 3H), 0.78 (s, 3H);

HRMS calculated m/z for C28H24F3NO2: 463.1759 (M+H) ⁺ . Found: 463.1762.

Example 123

5-[(2,6-difluorophenyl)methylene]-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1jbenzopyrano[3,4-quinoline

The compound of Example 1F and 2,6-difluorobenzylmagnesium bromide are treated according to the method of Example IB to give the desired compound.

MS (DCI/NH 3 ) m/z 432 (M+H) ⁺ ;

¹ H NMR (300 MHz, DMSO-d ₆ ) isomer 1: δ 8.32 (d, IH), 7.19 -7.08 (m, 3H), 6.92 (t, IH),

6.81 - 6.76 (m, 2H), 6.64 (s, 1H), 6.54 (d, 1H), 5.49 (s, 1H), 5.46 (s, 1H), 3.92 (s, 3H), 2.11 (s, 3H), 1.25 (s, 6H); isomer 2: δ 8.18 (d, IH), 7.38 (t, IH), 7.19-7.08 (m, 3H), 6.81-6.76 (m, • ·

2H), 6.67 (d, 1H), 6.21 (s, 1H), 6.19 (s, 1H), 4.96 (s, 1H), 3.93 (s, 3H), 1.91 (s, 3H), 1.16 (s, 3H), 0.61 (s, 3H);

_HRMS calculated m/z for _C27H23F2NO2 . _431.1697 (M+H) ⁺ . Found: _431.1704 .

Example 124

5-[(2-chlorophenyl)methylene]-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1Η-[ 1jbenzopyrano[3,4-fJquinoline

The compound of Example 1F and 2-chlorobenzylmagnesium bromide are treated according to the method of Example IB to give the desired compound.

MS (DCI/NH?) m/z 430 (M+H) ⁺ ;

¹ H NMR (300 MHz, DMSO-do) isomer 1: δ 8.11 (d, 1H), 7.47 (d, 1H), 7.40 (d, 1H), 7.237.10 (m, 3H), 6.84-6.74 (m, 2H), 6.71 (s, 1H), 6.66 (s, 1H), 6.01 (s, 1H), 5.47 (s, 1H), 3.93 (s, 3H), 2.02 (s, 3H), 1.25 (s, 6H); isomer 2: δ 8.27 (d, 1H), 8.18 (d, 1H), 7.41 (t, 1H), 7.26 (d, 1H), 7.01 (t, 1H), 6.84-6.74 (m, 4H), 6.47 (s, 1H), 6.37 (s, 1H), 5.00 (s, 1H), 3.93 (s, 3H), 1.88 (s, 3H), 1.18 (s, 3H), 0.73 (s, 3H);

HRMS calculated m/z for _C27H24ClNO2 : _429.1496 (M+H) ⁺ . Found: _429.1497 .

Example 125

5-[(2,6-dichlorophenyl)methylene]-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[ljbenzopyrano[3,4-quinoline

The compound of Example 1F and 2,6-dichlorobenzylmagnesium bromide are treated according to the method of Example IB to give the desired compound.

MS (DCI/NH 2 ) m/z 464 (M+H) ⁺ ;

*H NMR (300 MHz, DMSO-d _ó ) isomer 1: δ 8.27 (d, 1H), 7.16 (m, 2H), 7.07 (t, 1H), 6.816.76 (m, 3H), 6.68 (d, 1H), 6.30 (s, 1H), 5.47 (s, 1H), 4.90 (s, 1H), 3.93 (s, 3H), 1.96 (s, 3H), 1.15 (s, 3H), 0.59 (s, 3H); isomer 2: δ 8.37 (d, 1H), 7.45 (d, 2H), 7.31 (t, 1H), 7.16 (m, 2H),

6.77 (m, 1H), 6.65 (s, 1H), 6.44 (d, 1H), 6.34 (s, 1H), 5.60 (s, 1H), 3.91 (s, 3H), 2.20 (s, 3H), 1.25 (s, 6H);

HRMS calculated m/z for _C27H23Cl2NO2 : _463.1106 ( _M +H) ⁺ . Found: _463.1114 .

Example 126

5-[(2-fluorophenyl)methylene]-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-fJquinoline

138 • 9 99 99 99

9 9 9 9 9 9 9 • · · 9 9 9 9

99999 9 999

9 9 9 9

999 9 99 ·· ·» ♦ · 99

9 · * • · · · • · · · • 9 9 9

99

The compound of Example 1F and 2-fluorobenzylmagnesium bromide are treated according to the method of Example 1B to give the desired compound.

MS (DCI/NHs) m/z 414 (M+H) ⁺ ;

¹ H NMR (300 MHz, DMSO-dg) isomer 1: δ 8.30 (d, 1H), 8.23 (m, 1H), 7.28 (m, 1H), 7.19 (t, 1H), 7.18 (d, 1H), 6.93 -6.75 (m, 3H), 6.76 (d, 1H), 6.65 (s, 1H), 5.77 (s, 1H), 5.49 (s, 1H), 3.93 (s, 3H), 2.01 (s, 3H), 1.25 (s, 6H); isomer 2: δ 8.17 (d, 1H), 7.28 (m, 2H), 7.18 (d, 1H),

7.14-7.06 (m, 2H), 6.79 (m, 2H), 6.72 (d, 1H), 6.41 (s, 1H), 6.38 (s, 1H), 5.00 (s, 1H), 3.93 (s, 3H), 1.87 (s, 3H), 1.18 (s, 3H), 0.76 (s, 3H);

HRMS calculated m/z for C27H24FNO2: 413.1791 (M+H) ⁺ . Found: 413.1788.

Example 127

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[(4,5-dihydro-4,4-dimethyl-2-oxazolyl)methylene]1H-[1]benzopyrano-[3,4-f]quinoline

The compound of Example 1F and 4,4-dimethyl-2-oxazoline-2-methyllithium are treated according to the method of Example 1B to give the desired compound.

MS (DCI/NH 3 ) m/z 417 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-d ₆ ) isomer 1: δ 8.34 (d, 1H), 7.19 (t, 1H), 6.83-6.78 (m, 2H), 6.74-6.70 (m, 2H), 5.48 (s, 1H), 5.08 (s, 1H), 3.98 (s, 2H), 3.92 (s, 3H), 1.99 (s, 3H), 1.22 (s, 3H), 1.20 (s, 9H); isomer 2: δ 8.06 (d, 1H), 7.14 (m, 1H), 6.80 (m, 1H), 6.76 (m, 1H), 6.72 (m, 1H), 6.42 (s, 1H), 5.96 (s, 1H), 5.35 (s, 1H), 3.90 (s, 3H), 3.72 (m, 2H), 1.93 (s, 3H), 1.32 (s, 3H), 1.20 (s, 6H), 1.11 (s, 3H);

HRMS calculated m/z for C26H28N2O3: 417.2178 (M+H) ⁺ . Found: 417.2176.

Example 128

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(2-pyridinylmethylene)-1H-[1]benzopyrano-[3,4fquinoline

The compound of Example 1F and 2-methylpyridyllithium are treated according to the method of Example 1B to give the desired compound.

MS (DCI/NH 3 ) m/z 397 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-d ₆ ) isomer 1: δ 8.50 (m, 1H), 8.31 (d, 1H), 8.25 (d, 1H), 7.83 (t, 1H), 7.20 (d, 1H), 7.19 (m, 1H), 6.95 (d, 1H), 6.83 (d, 1H, ), 6.78 (d, 1H), 6.64 (s, 1H), 5.77 (s, 1H), 5.49 (s, 1H), 3.92 (s, 3H), 2.00 (s, 3H), 1.27 (s, 6H), isomer 2: δ 8.43 (m, 1H), 8.15 (d, 1H), 7.48 (t, 1H), 7.22 (d, 1H), 7.15 (d, 1H), 7.08 (m, 1H), 6.88 (d, 1H), 6.78 (d, 1H), 6.77 ·· • ·

139 ♦ · « 4 • · I ·

4 999 4

4 4

99

44

4 4 4 • * · · • · · · • · · · • 9 4 9 (t, 1H), 6.46 (s, 1H), 6.38 (s, 1H), 4.99 (s, 1H), 3.92 (s, 3H), 1.87 (s, 3H), 1.21 (s, 3H), 0.89 (s, 3H);

HRMS calculated m/z for C26H24N2O2: 397.1916 (M+H) ⁺ . Found: 397.1923.

Example 129

2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(2-thienyl)-1H-[1]benzopyrano-[3,4-f]quinoline

The compound of Example 1F and 2-thienyllithium are treated according to the method of Example IB to give the desired compound.

MS (DCI/NH ₃ ) m/z 391 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-dé) δ 8.01 (d, 1H), 7.38 (d, 1H), 6.95 (dd, 1H), 6.93 (s, 1H), 6.81 (dd, 1H), 6.68 (d, 1H), 6.65 (d, 1H), 6.64 (d, 1H), 6.46 (d, 1H), 6.21 (d, 1H), 5.39 (s, 1H),

3.81 (s, 3H), 1.95 (d, 3H), 1.21 (s, 3H), 1.15 (s, 3H).

Example 130

2.5-Dihydro-9,10-dimethoxy-2,2,4-trimethyl-5-(2-propenyl)-1H-[1]benzopyrano-[3,4fquinoline

1,2,4-Trimethoxybenzene is processed according to Schemes 1 and 2 to give the desired compound.

MS (DCI/NH 3 ) m/e 378 (M+H) ⁺ ;

*H NMR (300 MHz, DMSO-d ₆ ) δ 7.93 (d, 1H), 6.82 (d, 1H), 6.61 (dd, 2H), 6.22 (d, 1H),

5.81 (ddt, 1H), 5.70 (dd, 1H), 5.44 (s, 1H), 5.01 (m, 2H), 3.76 (s, 3H), 3.67 (s, 3H), 2.35 (m, 2H), 2.16 (s, 3H), 1.17 (s, 3H), 1.16 (s, 3H).

Example 131

5-(2-cyclohexen-1-yl)-2,5-dihydro-9,10-dimethoxy-2,2,4-trimethyl-1H-[1]benzopyrano-[3,4fquinoline

1,2,4-Trimethoxybenzene is processed according to the method of Example 130, but replacing 3-trimethylsilylcyclohexene with allyltrimethylsilane, to give the desired compound.

MS (DCI/NH ₃ ) m/e 418 (M+H) ⁺ ;

’H NMR (300 MHz, DMSO d<0 δ 8.03 (d, 1H), 8.01 (d, 1H), 6.83 (d, 1H), 6.82 (d, 1H), 6.60 - 6.69 (m, 4H), 6.31 (d, 1H), 6.27 (d, 1H), 5.6-5.8 (m, 4H), 5.35-5.52 (m, 4H), 5.11 (m, 1H), 5.09 (m, 1H), 3.77 (s, 6H), 3.69 (s, 3H), 3.68 (s, 3H), 2.25 (m, 4H), 2.13 (s, 3H), 2.10 (s, 3H), 1.95 (m, 4H), 1.6 (m, 4H), 1.31 (s, 3H), 1.29 (s, 3H), 1.07 (s, 3H), 1.04 (s, 3H).

• 0 00

0 0 0

140

000 • 0

0000 0· «00 0 0

0 0 » 0 0 0 0 0 00 (249978) Example 132 claim_

2,5-dihydro-10-methoxy-5-(3-methyl-3-butenyl)-2,2,4-trimethyl-1H-[ljbenzopyrano-[3,4fjquinoline

The compound of Example 2B and 3-methyl-1-trimethylsilyl-2-butene (prepared according to Fleming et al. Synthesis 1979, 446) are treated according to the method of Example 2 to give the desired compound.

MS (DCI/NH3) m/e (M+H) ⁺ 376;

^! H NMR (300 MHz, DMSO-de) δ 8.10 (d, J=8 Hz, 1H), 7.01 (t, J=8 Hz, 1H), 6.65 (d, >8 Hz,

1H), 6.62 (d, J=8 Hz, 1H), 6.49 (d, J =8 Hz, 1H), 6.25 (br s, 1H), 5.57 (s, 1H), 5.55 (dd,J =17, 11Hz, 1H), 5.41 (s, 1H), 4.64-4.56 (m, 2H), 3.83 (s, 3H), 2.14 (s, 3H), 1.31 (s, 3H), 1.01 (s, 3H), 0.86 (s, 3H), 0.83 (s, 3H);

¹³ C NMR (100 MHz, DMSO-cU) δ 156.31, 153.48, 145.02, 143.74, 133.05, 128.73, 127.10, 126.82, 126.27, 119.20, 118.15, 114.05, 113.11, 110.85, 109.36, 105.24, 78.33, 55.69, 49.12, 44.84, 29.53, 26.14, 23.53, 23.43, 23.35;

Analytical calcd for C25H29NO2 1/4H2O: C, 79.02; H, 7.82; N, 3.69. Found: C, 79.09;

H, 7.94; N, 3.59.

Example 133

2.5-Dihydro-10-methoxy-5-(5,5-dimethyl-3-cyclohexenyl)-2,2,4-trimethyl-1H[1]benzopyrano-[3,4-f]quinoline

The compound of Example 2B and 5,5-dimethyl-1-trimethylsilyl-2-cyclohexene (prepared from

5,5-dimethyl-2-cyclohexen-1-ol according to Tsuji, et al, Org. Chem. 1996, 61, 5779) are processed according to the method of Example 2 to give the desired compound as an inseparable 1.8:1 mixture of diastereoisomers.

Major isomer:

MS (DCI/NH3) m/e (M+H) ⁺ 416;

*H NMR (300 MHz, DMSO-de) δ 8.08 (d, J=8 Hz, 1H), 7.07 (t, J=8 Hz, 1H), 6.69 (d, J=8 Hz, 1H), 6.64 (d, J=8 Hz, 1H), 6.25 (br s, 1H), 5.85 (m, 1H), 5.62-5.71 (m, 1H), 5.46 (s, 1H), 5.45 (d, J=10 Hz, 1H), 3.86 (s, 3H), 2.41-2.33 (m, 1H), 2.11 (s, 3H), 1.84-1.72 (m, 1H), 1.681.48 (m, 2H), 1.30 (s, 3H), 1.35-1.21 (m, 1H), 1.01 (s, 3H), 0.76 (s, 3H), 0.53 (s, 3H); Analytical calcd for C28H33NO2 I/2H2O: C, 79.21; H, 8.07; N, 3.30. Found: C, 79.31; H, 7.75; N, 3.11.

• *

141 • · 0 · 0 0 · ♦ · · 0 0 0 0 • ··· 0 0 · 000 • ♦ 0 t ·· ·· 00 00

0 0 • · 0

0 0

0 0

Minor isomer:

'H NMR (300 MHz, DMSO-cL) δ 8.02 (d, J=8 Hz, 1H), 7.09 (t, J =8 Hz, 1H), 6.70 (d, J=8 Hz, 1H), 6.64 (d, J=8 Hz, 1H), 6.57 (d, J-8 Hz, 1H), 6.20 (br s, 1H), 5.60-5.52 (m, 1H), 5.50 (d, J=10 Hz, 1H), 5.14 (m, 1H), 5.41 (m, 1H), 3.86 (s, 3H), 2.41-2.33 (m, 1H), 2.09 (s, 3H), 1.91-1.78 (m, IH), 1.68-1.48 (m, 2H), 1.35-1.21 (m, 1H), 1.28 (s, 3H), 1.07 (s, 3H), 0.92 (s, 3H), 0.51 (s, 3H).

Example 134 rel (5R,2'R) 2,5-dihydro-10-methoxy-5-(2-oxo-3-tetrahydropyranyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline

The compound of Example 2B and 3,4-dihydro-6-(trimethylsiloxy)-2H-pyran were treated according to the method of Example 2 to give 41% of the compound of Example 134 and 48% of the compound of Example 135.

MS (DCI/NH3) m/ml 406 (M+H) ⁺ ;

Η NMR (300 MHz, DMSO-cL) δ 8.12 (d, J=8 Hz, 1H), 7.05 (t, J=8 Hz, 1H), 6.67 (d, J=8 Hz, 1H), 6.63 (d, J=9 Hz, 1H), 6.49 (d, J =8 Hz, 1H), 6.42 (d, J=5 Hz, 1H), 6.21 (d, J=2 Hz, 1H), 5.44 (br s, 1H), 4.35-4.00 (m, 2H), 3.86 (s, 3H), 2.77-2.67 (m, 1H), 2.17 (s, 3H), 2.01-1.50 (m, 4H), 1.27 (s, 3H), 1.01 (s, 3H);

¹³ C NMR (100 MHz, DMSO-d _ó ) δ 169.93, 156.40, 152.16, 145.53, 133.80, 128.46, 127.75, 127.20, 126.66, 117.38, 116.74, 113.45, 112.07, 109.23, 109.19, 105.44, 98.19, 72.79, 69.09, 55.62, 49.44, 46.37, 29.45, 27.13, 23.20, 21.46, 20.22, 19.61;

Analytical calcd for C25H27NO4 1/ _2H2O : C, 72.44; H, 6.81; N, 3.38. Found: C, 72.66; H, 6.92; N, 2.91.

Example 135 anti (5R,2'S) 2,5-dihydro-10-methoxy-5-(2-oxo-3-tetrahydropyranyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline

The compound of Example 2B and 3,4-dihydro-6-(trimethylsiloxy)-2H-pyran were processed according to the method of Example 2 to give 41% of the compound of Example 135 and 48% of the compound of Example 135A.

MS (DCI/NH 3 ) m/e 406 (M+H) ⁺ ;

’H NMR (300 MHz, DMSO-cL) δ 8.12 (d, J=8 Hz, 1H), 7.05 (t, J=8 Hz, 1H), 6.67 (d, J=8 Hz, 1H), 6.63 (d, J=9 Hz, 1H), 6.49 (d, J=8 Hz, 1H), 6.42 (d, J=5 Hz, 1H), 6.21 (d, J=2 Hz, 1H),

1» *9

142 u ♦* ·♦ *· *· ·· * * · · · ♦ · ··>·· • · · · ♦ ♦ · » · « « * 999 9 9 9 999 99 99 9

9999 99

9

99

5.44 (br s, 1H), 4.35-4.00 (m, 2H), 3.86 (s, 3H), 2.77-2.67 (m, 1H), 2.17 (s, 3H), 2.01-1.50 (m, 4H), 1.27 (s, 3H), 1.01 (s, 3H);

13CNMR000 MHz, DMSO-d ₆ ) δ 169.93, 156.40, 152.16, 145.53, 133.80, 128.46, 127.75, 127.20, 126.66, 117.38, 116.74, 113.45, 112.07, 109.23, i09.19, 105.44, 98.19, 72.79, 69.09, 55.62, 49.44, 46.37, 29.45, 27.13, 23.20, 21.46, 20.22, 19.61;

Analytical calcd for C25H27NO4 1/2H2O: C, 72.44; H, 6.81; N, 3.38. Found: C, 72.66; H, 6.92; N, 2.91.

Example 135A

Anti (5R,2'S)2,5-dihydro-10-methoxy-5-(2-oxo-3-tetrahydropyranyl)-2,2,4-trimethyl-1H[l]benzopyrano-[3,4-f]quinoline

MS (DCI/NH ₃ ) ml 406 (M+H) ⁺ ;

1lf NMR (300 MHz, DMSO-de) δ 8.06 (d, J=9 Hz, 1H), 7.06 (t, J=8 Hz, 1H), 6.70 (d, J=8 Hz, 1H), 6.65 (d, J=9 Hz, 1H), 6.50 (d, J=8 Hz, 1H), 6.27 (d, J=8 Hz, 1H), 6.21 (d, J=2 Hz, 1H), 5.46 (s, 1H), 4.01-4.10 (m, 2H), 3.87 (s, 3H), 2.81 (m, 1H), 2.14 (m, 3H), 1.68 -1.61 (m, 2H), 1.27 (s, 3H), 1.16-1.36 (m, 2H), 1.03 (s, 3H);

¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 172.14, 156.33, 150.95, 145.21, 134.18, 127.71, 127.38, 127.20, 126.73, 118.09, 116.66, 113.53, 112.78, 110.56, 105.45, 71.40, 66.76, 55.52, 49.49, 29.46, 27.38, 23.69, 21.05, 20.79;

Analytical calcd for C25H27NO4 1/4H2O: C, 73.24; H, 6.76; N, 3.42. Found: C, 72.89; H, 7.07; N, 3.05.

Example 136

2,5-dihydro-10-methoxy-5-(3-cyclopentenyl)-2,2,4-trimethyl-1H~[1]benzopyrano-[3,4fquinoline

The compound of Example 2B and cyclopenten-2-yltrimethylsilane are treated according to the method of Example 2 to give the desired compound as an inseparable mixture of two diastereoisomers (1.5:1).

MS (DCl/NH,) m/z 374 (M+H) ⁺ ; NMR (300 MHz, DMSO-d ₆ )

Major diastereoisomer: δ 8.05 (d, 1H), 7.09 (t, 1H), 6.72 (d, 1H), 6.66 (d, 1H), 6.58 (d, 1H), 6.19 (s, 1H), 5.77 (ddd, 1H), 5.50 (d, 1H), 5.43 (s, 1H), 5.19 (ddd, 1H), 3.87 (s, 3H), 2.90 (m, 1H), 2.43-2.15 (m, 2H), 2.09 (s, 3H), 1.97-1.70 (m, 2H), 1.31 (s, 3H), 1.09 (s, 3H);

• φ φ • 4 · • ··♦

143

Φ φφφφ ·· ΦΦ ΦΦ

Minor diastereoisomer: δ 8.07 (d, ΙΗ), 7.08 (t, 1Η), 6.70 (d, 1H), 6.66 (d, 1H), 6.61 (d,

1H), 6.22 (s, 1H), 5.82-5.70 (m, 2H), 5.48 (d, 1H), 5.41 (d, 1H), 3.88 (s, 3H), 2.92 (m, 1H),

2.30 (m, 1H), 2.20 (m, 1H), 2.15 (s, 3H), 1.50 (m, 2H), 1.33 (s, 3H), 1.05 (s, 3H);

HRMS calculated m/z for C25H27NO2: 373.2042. Found: 373.2049.

Example 137

2.5-Dihydro-10-methoxy-5-(3-cyclohexenyl)-2,2,4-trimethyl-1H-[1]benzopyrano-[3,4fquinoline

The compound of Example 2B and cyclohexen-2-yltrimethylsilane are treated according to the method of Example 2 to give the desired compound as an inseparable mixture of two diastereoisomers (1.1:1).

MS (DCI/NH ₃ ) m/z 388 (M+H) ⁺ ;

^] H NMR (300 MHz, DMSO-d ₆ )

Major diastereomer: δ 8.05 (d, 1H), 7.06 (t, 1H), 6.67 (d, 1H), 6.64 (d, 1H), 6.59 (d,

1H), 6.19 (s, 1H), 5.82 (m, 1H), 5.72 (m, 1H), 5.41 (s, 1H), 5.40 (d, 1H), 3.87 (s, 3H), 2.29, (m, 1H), 2.13 (s, 3H), 1.95-1.80 (m, 2H), 1.72-1.50 (m, 2H), 1.38-1.10 (m, 2H), 1.30 (s, 3H),

1.02 (s, 3H);

Minor diastereoisomer: δ 8.03 (d, 1H), 7.07 (t, 1H), 6.68 (d, 1H), 6.63 (d, 1H), 6.57 (d,

1H), 6.15 (s, 1H), 5.62 (m, 1H), 5.54 (m, 1H), 5.46 (s, 1H), 5.09 (m, 1H), 3.85 (s, 3H), 2.29 (m, 1H), 2.10 (s, 3H), 1.95-1.80 (m, 2H), 1.72-1.50 (m, 2H), 1.38-1.10 (m, 2H), 1.28 (s, 3H),

1.05 (s, 3H);

HRMS calculated m/z for C26H29NO2: 387.2198. Found: 387.2206.

Example 138

2.5-Dihydro-10-methoxy-5-(3-butenyl)-2,2,4-trimethyl-1H-[1]benzopyrano-[3,4-f]quinoline

The compound of Example 2B and 2-butenyltrimethylsilane are treated according to the method of Example 2 to give the desired compound as an inseparable mixture of two diastereoisomers (1.3:1).

MS (DCI/NH ₃ ) m/z 362 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-d6)

Major diastereomer: δ 8.04 (d, 1H), 7.05 (t, 1H), 6.69 (d, 1H), 6.64 (d, 1H), 6.47 (d,

1H), 6.16 (s, 1H), 5.88 (ddd, 1H), 5.54 (d, 1H), 5.46 (s, 1H), 4.93 (ddd, 1H), 4.74 (ddd, 1H),

3.86 (s, 3H), 2.37 (bm, 1H), 2.17 (s, 3H), 1.30 (s, 3H), 1.02 (s, 3H), 0.71 (d, 3H);

144 »» ·* 99 99 99

9 9 9 9 9 9 9 9 9 9 9 • · · 9 9 9 9 9 9 9 9 9

999 9 9 · ··«·· « · >

• · · · · · · 9 9

9 9 99 99 99 99 99

Minor diastereoisomer: δ 8.03 (d, ΙΗ), 7.08 (t, 1H), 6.67 (d, 1H), 6.64 (d, 1H), 6.58 (d, 1H), 6.10 (s, 1H), 5.51 (ddd, 1H), 5.47 (d, 1H), 5.40 (s, 1H), 4.78 (ddd, 1H), 4.74 (ddd, 1H), 3.86 (s, 3H), 2.38 (bm, 1H), 2.11 (s, 3H), 1.28 (s, 3H), 1.05 (s, 3H), 1.01(d, 3H);

Analytical calcd for C24H27NO2: C, 79.74; H, 7.53; N, 3.87. Found: C, 79.41; H, 7.63; N, 3.43.

Example 139

2,5-dihydro-10-methoxy-5-(1-ethenyl-1-cyclohexyl)-2,2,4-trimethyl-1Η-[1jbenzopyrano[3,4-quinoline

Compound 2B and 2-cyclohexylideneethyltrimethylsilane are treated according to the method of Example 2 to give the desired compound.

MS (DCI/NH 3 ) m/z 416 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-d ₆ ) δ 8.10 (d, 1H), 7.00 (t, 1H), 6.63 (d, 1H), 6.60 (dd, 1H), 6.47(dd, 1H), 6.20 (dd, 1H), 5.45 (s, 1H), 5.40 (s, 1H), 5.14 (dd, 1H), 4.81 (dd, 1H), 4.53 (dd, 1H), 3.85 (s, 3H), 2.15 (s, 3H), 1.78 (m, 1H), 1.45-0.80 (m, 9H), 1.32 (s, 3H), 1.03 (s, 3H); Analytical calcd for C28H33NO2: C, 80.93; H, 8.00; N, 3.37. Found: C, 80.57; H, 8.02; N, 3.22.

Example 140

2,5-dihydro-10-methoxy-5-(4,4-dimethyl-3-cyclohexenyl)-2,2,4-trimethyl-1H[1]benzopyrano-[3,4-quinoline

The compound of Example 2B and (4,4-dimethylcyclohexen-2-yl)trimethylsilane are treated according to the method of Example 2 to give the desired compound as an inseparable mixture of two diastereoisomers (2:1).

MS (DCI/NH 3 ) m/z 416 (M+H) ⁺ ;

’H NMR (300 MHz, DMSO-d6)

Major diastereoisomer: δ 8.07 (d, 1H), 6.99 (t, 1H), 6.63 (d, 1H), 6.62 (d, 1H), 6.48 (d, 1H), 6.23 (s, 1H), 5.72 (d, 1H), 5.48 (m, 1H), 5.40 (m, 2H), 3.84 (s, 3H), 2.16 (s, 3H), 2.05 (m, 1H), 1.75 (wm, 2H), 1.30 (s, 3H), 1.12 (m, 2H), 1.02 (s, 6H), 0.51 (s, 3H);

Minor diastereoisomer: δ 8.04 (d, 1H), 7.06 (t, 1H), 6.68 (d, 1H), 6.62 (d, 1H), 6.57 (d, 1H), 6.19 (s, 1H), 5.68 (dd, 1H), 5.50-5.38 (m, 3H), 3.86 (s, 3H), 2.14 (s, 3H), 2.08 (m, 1H), 1.71 (m, 1H), 1.42 (m, 1H), 1.30 (s, 3H), 1.07 (m, 2H), 1.02 (s, 3H), 0.91 (s, 3H), 0.84 (s, 3H);

145 ·· ♦» tt φφ «« «· • · » · a · · · · « · t ··« a a φ · ···· • · ·» · · 9 «···· ·« t • ·Φ« ···«« ·♦·· ί· 99 99 99

HRMS calculated m/z for C28H33NO2: 415.2511. Found: 415.2527.

Example 141

2.5-Dihydro-10-methoxy-5-(1-methylene-2-cyclohexyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-quinoline

The compound of Example 2B and 1-(trimethylsilylmethyl)cyclohexene are treated according to the method of Example 2 to give the desired compound as an inseparable mixture of two diastereoisomers (4:1).

MS (DCI/NH 3 ) m/z 402 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-d6)

Major diastereoisomer: δ 8.07 (d, 1H), 7.03 (t, 1H), 6.65 (d, 1H), 6.63 (d, 1H), 6.40 (d, 1H), 6.22 (s, 1H), 5.89 (d, 1H), 4.75 (d, 1H), 4.56 (d, 1H), 3.87 (s, 3H), 2.38 (m, 1H), 2.23 (m, 1H), 2.21 (s, 3H), 1.97 (bm, 2H), 1.55-1.05 (m, 6H), 1.34 (s, 3H), 1.01 (s, 3H);

Minor diastereoisomer: δ 8.09 (d, 1H), 7.05 (t, 1H), 6.68 (d, 1H), 6.57 (d, 1H), 6.56 (d, 1H), 6.11 (s, 1H), 5.86 (d, 1H), 5.40 (s, 1H), 4.33 (d, 1H), 3.91 (d, 1H), 3.87 (s, 3H), 2.48 (m, 1H), 2.22 (m, 1H), 2.20 (s, 3H), 1.94 (bm, 1H), 1.75-1.05 (m, 6H), 1.29 (s, 3H), 0.97 (s, 3H); HRMS calculated m/z for C27H31NO2: 401.2355. Found: 401.2351.

Example 142

2.5-Dihydro-10-methoxy-5-(1-oxo-2-cyclohexyl)-2,2,4-trimethyl-1Η-[1jbenzopyrano-[3,4fjquinoline

The compound of Example 2B and 1-(trimethylsilyloxy)cyclohexene are treated according to the method of Example 2 to give the desired compound as a single diastereoisomer.

MS (DCI/NH 3 ) m/z 404 (M+H) ⁺ ;

*H NMR (300 MHz, DMSO-dg) δ 8.04 (d, 1H), 7.02 (t, 1H), 6.67 (d, 1H), 6.63 (d, 1H), 6.39 (d, 1H), 6.37 (d, 1H), 6.17 (s, 1H), 5.44 (s, 1H), 3.80 (s, 3H), 2.70 (ddd, 1H), 2.25 (m, 2H), 2.15 (s, 3H), 1.84 (bm, 1H), 1.62-1.25 (m, 4H), 1.28 (s, 3H), 1.09 (m, 1H), 1.00 (s, 3H). HRMS m/z calcd for C26H29NO3: 403.2147. Found: 403.2142.

Example 143

2.5-Dihydro-10-methoxy-5-(3-cyclooctenyl)-2,2,4-trimethyl-1H-[ljbenzopyrano-[3,4fjquinoline ··

9 9 • · • 000

146 •

• ·· « • · 0 ·

0 · 0

0 000 0

0 0 «0 00 «0

0 0

0 0 0 0 0

0 0

00

The compound of Example 2B and cycloocten-2-yltrimethylsilane were treated according to the method of Example 2 to give the title compound as an inseparable mixture of two diastereoisomers (7:5). MS (DCI/NH3) m/z 416 (M+H) ⁺ ;

’H NMR (300 MHz, DMSO-cL)

Major diastereoisomer: δ 8.03 (dd, IH), 7.07 (t, IH), 6.62 (d, IH), 6.57 (d, IH), 6.39 (d, IH), 6.17 (s, IH), 5.59 (m, 2H), 5.44 (s, IH), 5.14 (dd, IH), 3.88 (s, 3H), 2.18 (s, 3H), 2.040.84 (m, 17H);

Minor diastereoisomer: δ 8.00 (d, IH), 7.00 (t, IH), 6.70 (d, IH), 6.66 (d, IH), 6.58 (d, IH), 6.12 (s, IH), 5.59 (m, 2H), 5.48 (s, IH), 5.38 (dd, IH), 3.88 (s, 3H), 2.18 (s, 3H), 2.040.84 (m, 17H);

HRMS calculated m/z for C28H33NO2: 415.2511. Found: 415.2498.

Example 144

2.5-Dihydro-10-methoxy-5-(3-cycloheptenyl)-2,2,4-trimethyl-1H-[1]benzopyrano-[3,4fquinoline

The compound of Example 2B and cyclohepten-2-yltrimethylsilane are treated according to the method of Example 2 to give the desired compound as an inseparable mixture of two diastereoisomers (1:1).

MS (DCI/NH 3 ) m/z 402 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-dé) diastereoisomer A: δ 8.04 (d, 1H0, 7.04 (t, IH), 6.68 (d, IH), 6.63 (d, IH), 6.51 (d, IH), 6.22 (s, IH), 5.97 (m, IH), 5.73 (m, IH), 5.58 (m, IH), 5.47 (s, 1H), 3.87 (s, 3H), 2.42-0.98 (m, 18H);

diastereoisomer B: δ 8.01 (d, IH), 7.08 (t, IH), 6.70 (d, IH), 6.62 (d, 1H), 6.56 (d, IH), 6.21 (s, IH), 5.58 (m, 2H), 5.49 (s, IH), 5.32 (m, IH), 3.87 (s, 3H), 2.42-0.98 (m, 18H);

HRMS calculated m/z for C27H31NO2: 401.2355. Found: 401.2351.

Example 145

2.5-Dihydro-10-methoxy-5-(1-cyclohexenylmethyl)-2,2,4-trimethyl-1H-[1]benzopyrano-[3,4fquinoline

The compound of Example 2B and 2-methylenecyclohexyldimethylphenylsilane are treated according to the method of Example 2 to give the desired compound.

MS (DCI/NH 3 ) m/z 402 (M+H) ⁺ ;

• ·

147 . ··: · : : ·· ···· ·· ·· ·· ’Η NMR (300 MHz, DMSO-dg) δ 7.96 (d, 1H), 7.05 (t, 1H), 6.68 (d, 1H), 6.58 (d, 1H), 6.45 (d, 1H), 6.10 (s, 1H), 5.85 (dd, 1H), 5.43 (s, 1H), 5.18 (bs, 1H), 3.85 (s, 3H), 2.45-1.12 (m, 19H);

HRMS calculated m/z for C27H31NO2: 401.2355. Found: 401.2342;

Analytical calcd for C27H31NO2: C, 80.76; H, 7.78; N, 3.49. Found: C, 80.76; H, 8.00; N, 3.25.

Example 146

2.5-Dihydro-10-methoxy-5-(3,3-dimethyl-6-cyclohexenyl)-2,2,4-trimethyl-1H[1]benzopyrano-[3,4-f]quinoline

The compound of Example 2B and (6,6-dimethylcyclohexen-2-yl)methylphenylsilane are treated according to the method of Example 2 to give the desired compound as an inseparable mixture of two diastereoisomers (5:1).

MS (DCI/NH 3 ) m/z 416 (M+H) ⁺ ;

'H NMR (300 MHz, DMSO-d)

Major diastereoisomer: δ 8.04 (d, 1H), 7.06 (t, 1H), 6.68 (d, 1H), 6.63 (d, 1H), 6.58 (d, 1H), 6.21 (s, 1H), 5.67 (dd, 1H), 5.49-5.38 (m, 3H), 3.86 (s, 3H), 2.29-0.82 (m, 20H); Minor diastereoisomer: δ 8.01 (d, 1H), 7.07 (t, 1H), 6.68 (d, 1H), 6.63 (d, 1H), 6.57 (d, 1H), 6.16 (s, 1H), 5.56-5.33 (m, 3H), 4.97 (dd, 1H), 3.86 (s, 3H), 2.29-0.82 (m, 20H);

HRMS calculated m/z for C28H33NO2. 415.2511. Found: 415.2527.

Analytical calcd for C28H33NO2: C, 80.93; H, 8.00; N, 3.37. Found: C, 80.92; H, 7.98; N, 3.25.

Example 147

2.5-Dihydro-10-methoxy-5-(2-bromo-3-propenyl)-2,2,4-trimethyl-1Η-[1]benzopyrano-[3,4fquinoline

The compound of Example 2B and (2-bromoallyl)trimethylsilane are treated according to the method of Example 2 to give the desired compound.

MS (DCI/NH 3 ) m/z 426 (M+H) ⁺ ;

*H NMR (300 MHz, DMSO-dg) δ 8.00 (d, 1H), 7.08 (t, 1H), 6.72 (d, 1H), 6.62 (d, 1H), 6.47 (d, 1H), 6.17 (s, 1H), 6.02 (dd, 1H), 5.51 (d, 1H), 5.47 (s, 1H), 5.42 (s, 1H), 3.87 (s, 3H), 2.89 (dd, 1H), 2.44 (dd, 1H), 2.26 (s, 3H), 1.17 (s, 3H), 1.15 (s, 3H), • · • ·

148

Analytical calcd for C111NCEBr: C, 64.79; H, 5.67; N, 3.29. Found: C, 64.70; H, 5.65; N, 3.09.

Examples 148 - 150

The compound from Example 2B (1.25 g, 3.70 mmol) and 1-[r-t-butyldimethylsiloxy-1 methoxyalkylidene]-2-cyclohexene were treated according to the method of Example 2 to give a mixture of diastereoisomers of unsaturated ester adducts (1.21 g, 73%), which were processed in the next step.

The above mixture (120 g, 2.69 mmol) was dissolved in THF (100 mL), cooled to 0°C, treated slowly with Dibal-H (13.5 mL of ΙΜ/hex solution, 13.5 mmol) via syringe, stirred for 30 min, diluted with 250 mL of saturated aqueous Rochelle salt and 300 mL of ethyl acetate, and stirred overnight. The layers were separated, the aqueous phase was extracted with ethyl acetate (2x), the combined organic layers were washed with brine, and dried (MgSO ₄ ). The resulting residue was purified by column chromatography on silica gel, eluting with a gradient of 20% to 30% methyl t-butyl ether in hexanes, to give Examples 148-150.

Example 148 rel (5R,3'R) 2,5-dihydro-10-methoxy-5-(1-hydroxymethyl-3-cyclohexenyl)-2,2,4-trimethyl-1H-[1]benzopyrano-[3,4-f]quinoline MS ( _DCI7NH3 ) m/e 418 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-dg) δ 8.01 (d, J=8 Hz, 1H), 7.07 (t, J=8 Hz, 1H), 6.69 (d, J=8 Hz, 1H), 6.63 (d, >9 Hz, 1H), 6.57 (d, J=8 Hz, 1H), 6.17 (d, J=2 Hz, 1H). 5.50 (d, J=10 Hz, 1H), 5.39 (br s, 1H), 5.05 (br s, 1H), 4.42 (t, 1H), 3.85 (s, 3H), 3.64 (d, >6 Hz, 2H), 2.27 (η, 1H), 2.05 (s, 3H), 1.95-1.86 (m, 2H), 1.78-1.21 (m, 4H), 1.28 (s, 3H), 1.09 (s, 3H);

Analytical calcd for _C27H31NO31 / _2H2O : C, 76.03; H, 7.56; N, 3.28. Found: C, 76.34; H, 7.71; N, 3.20.

Example 149 rel (5R,3'S) 2,5-dihydro-10-methoxy-5-(1-hydroxymethyl-3-cyclohexenyl)-2,2,4-trimethyl1H-[1]benzopyrano[3,4-f]quinoline MS (DCI/ _NH3 ) m/e 418 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-dg) δ 8.40 (d, J=9 Hz, 1H), 7.07 (t, J=8 Hz, 1H), 6.67 (d, J=8 Hz, 1H), 6.63 (d, J=8 Hz, 1H), 6.59 (d, J=8 Hz, 1H), 6.20 (d, >8 Hz, 1H), 6.20 (s, 1H), 5 (78, J=s

149 • · • ·

Hz, 1H), 5.45 (s, 1H), 5.37 (d, J=10 Hz, 1H), 4.60 (dd, J=5Hz, 1H), 3.85 (s, 3H), 3.75 (s, 2H), 2.37 (m, 1H), 2.12 (s, 3H), 1.70 (m, 2H), 1.60 (m, 1H), 1.30 (s, 3H), 1.15 (m, 2H), 1.02 (s, 3H);

¹³ C NMR (75 MHz, DMSO-d _ó ) δ 156.3, 151.5, 145.0, 139.6, 133.7, 130.2, 128.0, 127.1, 126.9, 120.8, 120.3, 118.5, 116.5, 113.0, 110.2, 105.2, 105.2, 76.2, 65.1, 55.6, 49.4, 36.9, 29.6, 26.8, 23.7, 21.3.

Example 150

2,5-dihydro-10-methoxy-5-(3-hydroxymethyl-3-cyclohexenyl)-2,2,4-trimethyl-1H[1]benzopyrano-[3,4-f]quinoline MS (DCI/NH3) m/e 418 (M+H) ⁺ ;

'H NMR (300 MHz, DMSO-d ₆ ) δ 8.06 (d, J=8 Hz, 1H), 7.01 (t, J=8 Hz, 1H), 6.59 (d, J=8 Hz, 1H), 6.52 (d, J=8 Hz, 1H), 6.27 (s, 1H), 6.03 (s, 1H), 5.38 (s, 1H), 5.23 (m, 1H), 4.75 (m, 2H), 3.51 (s, 3H), 3.47 (m, 1H), 2.95 (m, 1H), 2.19 (s, 3H), 1.70-1.35 (m, 6H), 1.31 (s, 3H), 1.03 (s, 3H);

¹³ C NMR (75 MHz, DMSO-dé) δ 156.4, 154.4 (145.1), 132.9, 129.2, 128.0, 127.6, 126.9, 126.1, 119.3, 118.6, 114.3, 113.1, 109.0, 105.5, 73.5, 64.4, 55.9, 49.2, 48.6, 29.7, 26.5, 25.6, 24.3, 23.5, 18.3;

Analytical calcd for C27H31NO31/ _4H2O : C, 76.84; H, 7.52; N, 3.32. Found: C, 76.93; H, 7.73; N, 3.18.

Example 151

2,5-dihydro-10-methoxy-5-(3-indolyl)-2,2,4-trimethyl-1H-[1]benzopyrano-[3,4-quinoline

The compound of Example 2B and indole are treated according to the method of Example 2 to give the desired compound.

MS (DCI/NH 3 ) m/e 423 (M+H) ⁺ ;

^] H NMR (300 MHz, DMSO-de) δ 10.89 (d, 1H), 8.01 (d, 1H), 7.83 (dd, 1H), 7.27 (dd, 1H), 7.04 (m, 3H), 6.80 (t, 1H), 6.68 (d, 1H), 6.54 (s, 1H), 6.53 (d, 1H), 6.28 (d, 1H), 6.12 (s, 1H), 5.35 (s, 1H), 3.83 (s, 3H), 1.89 (s, 3H), 1.22 (s, 3H), 1.14 (s, 3H)

Analytical calcd for C28H26N2O2: C, 79.59; H, 6.20; N, 6.62. Found: C, 79.58; H, 6.28; N, 6.36.

Example 152

150 • · φφφφ • · φφφφ φφφφφ φφ · • ·φφ· ·· φφ φφ rel (5S,3 'S) 2,5-dihydro-10-methoxy-5-(l-methyl-3-cyclohexenyl)-2,2,4-trimethyl-lH[ 1 ]benzopyrano-[3,4-f]quinoline

The compound from Example 148 (0.512 g, 1.23 mmol) was dissolved in CH2Cl2 (5 mL), cooled to 0°C, treated with (i-Pr) _2NEt (0.32 mL, 1.84 mmol), methanesulfonyl chloride (0.11 mL, 1.47 mmol) and stirred for 1 h. The reaction mixture was treated dropwise with lithium triethylborohydride (4.70 mL of 1M/THF solution, 4.70 mmol), stirred for 60 min, treated with 10 mL of 1M NaOH, 0.6 mL of 30% H2O2, stirred for 2 h and extracted with ethyl acetate. The organic layer was washed with H2O, saturated aqueous NaHCO3, brine, dried ( _MgSO4 ) and concentrated. The residue was purified by silica gel column chromatography with 5 and then 7% ethyl acetate in hexanes to give 0.362 g (74%) of the desired product as a colorless foam.

MS (DCI/NH 3 ) m/e 402 (M+H) ⁺ ;

'H NMR (300 MHz, DMSO-d ₆ ) δ 8.02 (d, J=8 Hz, 1H), 7.06 (t, J=8 Hz, 1H), 6.68 (d, >8 Hz, 1H), 6.64 (d, J=8 Hz, 1H), 6.56 (d, J =8 Hz, 1H), 6.16 (s, 1H), 5.49 (d, >10 Hz, 1H), 5.41 (br s, 1H), 4.83 (br s, 1H), 3.85 (s, 3H), 2.31-2.17 (m, 1H), 2.06 (s, 3H), 1.99-1.21 (m, 6H), 1.49 (s, 3H), 1.29 (s, 3H), 1.08 (s, 3H).

Example 153 rel (5R,3'S) 2,5-dihydro-10-methoxy-5-(1-methyl-3-cyclohexenyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline

The compound of Example 149 is processed according to the method of Example 152 to give the desired compound.

MS (DCI/NH 3 ) m/e 402 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-dg) δ 8.04 (d, >9 Hz, 1H), 7.07 (t, J=8 Hz, 1H), 6.68 (d, J=8 Hz, 1H), 6.63 (d, J=9 Hz, 1H), 6.61 (d, J =8 Hz, 1H), 6.22 (d, J =2 Hz, 1H). 5.55 (br s, 1H), 5.45 (br s, 1H), 5.35 (d, >10 Hz, 1H), 3.86 (s, 3H), 2.34-2.18 (m, 1H), 2.12 (s, 3H), 1.97-0.88 (m, 6H), 1.61 (s, 3H), 1.30 (s, 3H), 1.02 (s, 3H);

Analytical calcd for C27H31NO2 IMH2O: C, 79.87; H, 7.82; N, 3.45. Found: C, 79.81; H, 8.28; N, 3.39.

Example 154 (-) (5S,3'S) 2,5-dihydro-10-methoxy-5-(1-methyl-3-cyclohexenyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline • · • 9

151 • · · ·

The compound from Example 152 was subjected to HPLC on a WHELK-0 1 (RR) column with 2% EtOH in hexanes as the mobile phase to afford the desired compound.

[α] _D ²⁰ - 155.9° (c 0.85, CHCl ₃ );

MS (DCI/NH?) m/e 402 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-d ₆ ) δ 8.02 (d, J=9 Hz, 1H), 7.06 (t, J=8 Hz, 1H), 6.68 (d, >8 Hz, 1H), 6.64 (d, J=9 Hz, 1H), 6.57 (d, J=8 Hz, 1H), 6.20 (d, J=2 Hz, 1H), 5.49 (d, J=10 Hz, 1H), 5.42 (br s, 1H), 4.83 (br s, 1H), 3.85 (s, 3H), 2.30-2.18 (m, 1H), 2.06 (s, 3H), 1.97-1.20 (m, 6H), 1.49 (s, 3H), 1.29 (s, 3H), 1.08 (s, 3H);

Analytical Calcd for _C27H31NO21 / _4H2O : C, _79.87 ; _H , 7.82; N, 3.45. Found: C, 79.80;

H, 8.15; N, 3.41.

Example 155 (-) (5S,3'R) 2,5-dihydro-10-methoxy-5-(1-hydroxymethyl-3-cyclohexenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline

The compound from Example 149 was subjected to HPLC on a (R,R) WHELK-0 1 column with EtOH in hexanes as the mobile phase to give the desired product.

[α] _D ²⁰ - 233.9° (c 1.27, CHCl ₃ );

MS (DCl/NH,) m/e 418 (M+H) ⁺ ;

’H NMR (300 MHz, DMSO-dó) δ 8.05 (d, J=9 Hz, 1H), 7.08 (d, J=8 Hz, 1H), 6.68 (d, J=8 Hz, 1H), 6.63 (d, >9 Hz, 1H), 6.61 (d, J=8 Hz, 1H), 6.23 (br s, 1H), 5.78 (br s, 1H), 5.46 (br s, 1H), 5.37 (d, J=10 Hz, 1H), 4.65 (t, J=6 Hz, 1H), 3.86 (s, 3H), 3.76 (m, 2H), 2.36-2.22 (m, 2H), 2.12 (s, 3H), 1.87-1.77 (m, 2H), 1.65-1.53 (m, 1H), 1.30 (s, 3H), 1.27-0.92 (m, 2H),

I, O2 (s, 3H).

Example 156 (+) (5R,3'S) 2,5-dihydro-10-methoxy-5-(1-hydroxymethyl-3-cyclohexenyl)-2,2,4-trimethyl1H-[1]benzopyrano[3,4-f]quinoline

The compound from Example 149 was subjected to HPLC on a (R,R) WHELK-O 1 column with a mobile phase of 6% EtOH in hexanes to afford the desired product.

[α] _D ²⁰ + 234.6° (c 0.85, CHCl ₃ );

MS (DCI/NH 3 ) m/e 418 (M+H) ⁺ ;

^! H NMR (300 MHz, DMSO-dó) δ 8.05 (d, >9 Hz, 1H), 7.07 (t, 3=8 Hz, 1H), 6.68 (d, J=8 Hz, 1H), 6.63 (d, J=9 Hz, 1H), 6.61 (d, J=8 Hz, 1H), 6.22 (br s, 1H), 5.78 (br s, 1H), 5.45 (br • Φ

152

0 · ·· a· ·· * ·0 0 0 · · · ···· 0 00 0 0 0 00··· «· _e

0··· 00 «· s, 1Η), 5.37 (d, J=10 Hz, 1H), 4.63 (t, J=6 Hz, 1H), 3.86 (s, 3H), 3.78-3.73 (m, 2H), 2.36-2.22 (m, 2H), 2.12 (s, 3H), 1.87-1.77 (m, 2H), 1.65-1.52 (m, 1H), 1.34-0.93 (m, 2H), 1.30 (s, 3H), 1.02 (s, 3H).

Example 157 (-)-(5S,3'R) 2,5-dihydro-10-methoxy-5-(1-methyl-3-cyclohexenyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline

The compound of Example 155 is processed according to the method of Example 152 to give the desired compound.

MS (DCI/NH3) m/e (M+H) ⁺ 402;

’ll NMR (300 MHz, DMSO-de) δ 8.04 (d,J =8 Hz, 1H), 7.07 (t,J =8 Hz, 1H), 6.68 (d, J=8 Hz, 1H), 6.63 (d, J=8 Hz, 1H), 6.62 (d, J=8 Hz, 1H), 6.23 (br s, 1H), 5.55 (br s, 1H), 5.45 (br s, 1H), 5.35 (d,J =10 Hz, 1H), 3.86 (s, 3H), 2.33-2.18 (m, 1H), 2.12 (s, 3H), 1.95-1.45 (m, 4H), 1.61 (s, 3H), 1.34-0.88 (m, 2H), 1.30 (s, 3H), 1.02 (s, 3H).

[α]η ^2θ - 224.1° (c 0.73, CHCl 3 );

Analytical calcd for C27H31NO2 1/2H2O: C, 78.99; H, 7.86; N, 3.41. Found: C, 79.14; H, 8.07; N, 3.03.

Example 158 (+)-(5R,3'S) 2,5-dihydro-10-methoxy-5-(1-methyl-3-cyclohexenyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline

The compound of Example 156 is processed according to the method of Example 152 to give the desired compound.

MS (DCI/NH 3 ) m/e 402 (M+H) ⁺ ;

'H NMR (300 MHz, DMSO-d _ó ) δ 8.04 (d, J=9 Hz, 1H), 7.07 (d, J=8 Hz, 1H), 6.67 (d, J=8 Hz, 1H), 6.63 (d, J=9 Hz, 1H), 6.59 (d, J=8 Hz, 1H), 6.22 (br s, 1H), 5.55 (m, 1H), 5.45 (br s, 1H), 5.35 (d, J=10 Hz, 1H), 3.86 (s, 3H), 2.27 (m, 1H), 2.12 (s, 3H), 1.94, 1.05 (m, 6H), 1.61 (s, 3H), 1.30 (s, 3H), 1.02 (s, 3H).

Example 159

2,5-dihydro-10-methoxy-5-(1-chloromethyl-3-cyclohexenyl)-2,2,4-trimethyl-1H[ 1 ]benzopyrano[3,4-f]quinoline • · · #

153

·· ·0 00 00 • · · 0 0 00 0

0 0 0 0 00 0 < 00000· 0 0 · • · 0 0 0 0 0 ·· ·0 00 00

The compound from Example 148 (0.110 g, 0.264 mmol) was combined with methanesulfonyl chloride (49 μΐ, 0.632 mmol), (i-Pr) ₂ NEt (53 μΐ, 0.695 mmol), lithium chloride (11 mg, 0.264 mmol) in 2 mL THF containing 2 drops DMF and the reaction mixture was stirred at room temperature for several hours. The reaction mixture was diluted with ethyl acetate and washed with saturated aqueous bicarbonate, brine, dried over MgSO 4 and purified by column chromatography on silica gel with 20% ethyl acetate in hexanes to give 106 mg (92%) of the title compound as a foam.

MS (DCI/NH ₃ ) m/e 436 (M+H) ⁺ ;

¹ H NMR (300 MHz, DMSO-d ₆ ) δ 8.03 (d, J-8 Hz, 1H), 7.08 (t, J-8 Hz, 1H), 6.66 (dd, J-8 Hz, 2H), 6.55 (d, J-8 Hz, 1H), 6.25 (br s, 1H), 5.53 (d, J-10 Hz, 1H), 5.39 (s, 1H), 5.25 (s, 1H), 3.91 (s, 2H), 3.84 (s, 3H), 2.30 (m, 1H), 2.05 (s, 3H), 1.35-2.00 (m, 6H), 1.30 (s, 3H), 1.10 (s, 3H).

Example 160 rel (5R,3'R) 2,5-dihydro-10-methoxy-5-(1-methoxymethyl-3-cyclohexenyl)-2,2,4-trimethyl1H-[1]benzopyrano[3,4-f]quinoline

The compound of Example 148 is processed according to the method of Example 152 using sodium methoxide instead of lithium triethylborohydride to give the desired compound.

MS (DCI/NH ₃ ) m/e 432 (M+H) ⁺ ;

1H NMR (400 MHz, DMSO-cL) δ 8.02 (d, J-9 Hz, 1H), 7.07 (t, J-8 Hz, 1H), 6.69 (d, J-9 Hz, 1H), 6.64 (d, J-9 Hz, 1H), 6.57 (d, J-9 Hz, 1H), 5.53 (d, J-10 Hz, 1H). 1H), 5.11 (s, 1H), 3.85 (s, 3H), 3.58 (dd,J -12+32 Hz, 1H), 3.06 (s, 3H), 2.30 (br m, 1H), 2.07 (s, 3H), 1.50-2.00 (br m, 4H), 1.35 (m, 1H), 1.30 (s, 3H), 1.10 (s, 3H);

¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 156.2, 150.9, 145.0, 137.0, 133.7, 133.6, 130.4, 128.1,

127.1, 127.1, 123.5, 117.9, 116.4, 113.5, 113.1, 110.1, 105.4, 105.3, 105.0, 76.2, 75.4, 56.4, 55.6,49.5, 36.9, 29.7, 23.4, 25.5, 25.3, 25.2, 24.2, 20.2.

Example 161 rel (5R,3R) 2,5-dihydro-10-methoxy-5-(1-methylthiomethyl-3-cyclohexenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline •« ·* • 9 9 9

9 9 • 999 9 • · ··<· 99 ·· 99

9 9 9 • · · · • · ··· ♦ · 9

154 ·· 99

9 9 9 • 9 9 9

9 9 9 • · · · ·* »·

The compound of Example 148 was processed according to the method of Example 152 using lithium thiomethoxide instead of lithium triethylborohydride to give the title compound as a white foam.

MS (DCI/NH ₃ ) m/e 448 (M+H) ⁺ ;

’H NMR (300 MHz, DMSO-d^) δ 8.02 (d, J=8 Hz, 1H), 7.08 ( t, >8 Hz, 1H), 6.69 (d, J=8 Hz, 1H), 6.65 (d, J=9 Hz, 1H), 6.57 (d, J=9 Hz, 1H), 6.23 (s, 1H), 5.49 (d, J=10 Hz, 1H), 5.40 (s, 1H), 5.00 (s, 1H), 3.86 (s, 2H), 2.30 (br m, 2H), 2.07 (s, 3H), 1.81 (s, 3H), 1.40-1.78 (br m, 6H), 1.30 (s, 3H), 1.09 (s, 3H);

¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 156.2, 151.0, 145.0, 135.7, 133.8, 130.3, 128.2, 127.1, 127.1, 123.5, 118.1, 116.5, 113.4, 113.1, 110.1, 105.3, 75.7, 55.5, 49.5, 40.8, 37.5, 29.7, 27.3,

26.2, 25.7 (24.2), 20.6, 13.7.

Example 162 rel (5R,3'S) 2,5-dihydro-10-methoxy-5-(1-acetoxymethyl-3-cyclohexenyl)-2,2,4-trimethyl1H-[1]benzopyrano[3,4-f]quinoline

The compound from Example 149 (0.100 g, 0.239 mmol) was combined with acetic anhydride (27 μΐ, 0.288 mmol), DMAP (2 mg, catalytic amount), (i-Pr) ₂ NEt (50 μΐ, 0.288 mmol) in dichloromethane (6 mL). The reaction mixture was stirred for 1 h at room temperature, diluted with ethyl acetate and washed with saturated aqueous bicarbonate, brine, dried (MgSO ₄ ) and purified by silica gel column chromatography with 20% ethyl acetate in hexanes to give 89 mg (81%) of the title compound as a white solid.

MS (DCI/NH 2 ) m/e 460 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-de) δ 8.05 (d, 3=8 Hz, 1H), 7.08 (t, J=8 Hz, 1H), 6.68 (d, J=8 Hz, 1H), 6.64 (d, J=8 Hz, 1H), 6.62 (d, J=8 Hz, 1H), 6.23 (s, 1H), 5.82 (s, 1H), 5.46 (s, 1H), 5.40 (d, J=10 Hz, 1H), 4.38 (s, 2H), 3.86 (s, 3H), 2.33 (br m, 1H), 2.12 (s; 3H), 2.03 (s, 3H), 1.85 (br m, 2H), 1.60 (br m, 1H), 1.30 (s, 3H), 1.02-1.28 (br m, 3H), 1.02 (s, 3H);

Analytical calcd for C29H33NO4: C, 75.79; H, 7.24; N, 3.05. Found: C, 76.14; H, 7.47; N, 3.02.

Example 163 rel (5R,3R) 2,5-dihydro-10-methoxy-5-(1-acetoxymethyl-3-cyclohexenyl)-2,2,4-trimethyl1H-[1]benzopyrano[3,4-f]quinoline * »

155 ··· · · • é · ·» ♦· • · · • ·«· • « · 9 • · · · « • · · ·

9 ··

The compound of Example 148 was processed according to the method of Example 162 to give the title compound as a white solid.

MS (DCI/NH 2 ) m/e 460 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-dg) δ 8.02 (d, J =8 Hz, 1H), 7.08 (t, J=8 Hz, 1H), 6.70 (d, J=8 Hz, 1H), 6.65 (d, J=8 Hz, 1H), 6.58 (d, >8 Hz, 1H), 6.18 (s, 1H), 5.55 (d, J=10 Hz, 1H), 5.39 (s, 1H), 5.16 (s, 1H), 4.22 (s, 2H), 3.85 (s, 3H), 2.40 (br, J-8 Hz, 1H), 2.06 (s, 3H), 1.96 (s, 3H), 1.32-1.95 (br m, 3H), 1.28 (s, 3H), 1.06 (s, 3H);

Analytical calcd for C29H33NO4: C, 75.79; H, 7.24; N, 3.05. Found: C, 75.53; H, 7.32; N, 2.84.

Example 164 rel (5R,3'R) 2,5-dihydro-10-methoxy-5-(1-methoxymethyl-3-cyclohexenyl)-2,2,4-trimethyl-1 H-[1 jbenzopyrano[3,4-f]quino-1 in

The compound of Example 149 was processed according to the method of Example 152 using sodium methoxide instead of lithium triethylborohydride to give the title compound as a white foam.

MS (DCI/NH3) m/e432 (M+H) ⁺ ;

’H NMR (300 MHz, DMSO-dg) δ 8.05 (d, J=9 Hz, 1H), 7.07 (t, J=8 Hz, 1H), 6.67 (d, J=8 Hz, 1H), 6.64 (d, J=8 Hz, 1H), 6.60 (d, J=8 Hz, 1H), 6.59 (d, J=8 Hz, 1H), 6.20 (s, 1H), 5.78 (s, 1H), 5.45 (s, 1H), 5.39 (d, J=10 Hz, 1H), 3.70 (s, 2H), 3.14 (s, 3H), 2.30 (br m, 1H), 2.12 (s, 3H), 1.81 (br m, 2H), 1.60 (br m, 1H), 1.30 (s, 3H), 1.15 (br m, 2H), 1.02 (s, 3H);

Analytical calcd for C28H33NO3 1/4H2O: C, 77.12; H, 7.74; N, 3.21. Found: C, 77.17; H, 7.55; N, 3.15.

Example 165 rel (5R,3R) 2,5-dihydro-10-methoxy-5-(1-(N,N-dimethylamino)methyl-3-cyclohexenyl)2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline

The compound of Example 148 was processed according to the method of Example 152 using dimethylamine instead of lithium triethylborohydride to give the title compound as a white foam.

MS (DCI/NH 3 ) m/e 445 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-de) δ 8.01 (d, >8 Hz, 1H), 7.07 (t, J=8 Hz, 1H), 6.69 (d, J=8 Hz, 1H), 6.64 (d, J=8 Hz, 1H), 6.57 (d, J=8 Hz, 1H), 6.22 (s, 1H), 5.50 (d, J=10 Hz, 1H), 5.39 (s,

156

ΙΗ), 5.03 (s, 1H), 3.85 (s, 3H), 2.62 (d, J=11Hz, 1H), 2.50 (d, J=11Hz, 1H), 2.25 (br s, 1H), 2.06 (s, 6H), 1.98 (s, 3H), 1.40-1.95 (br m, 6H), 1.30 (s, 3H), 1.25 (br m, 1H), 1.11 (s, 3H); Analytical calcd. for C29H36N2O23/4H2O: C, 76.03; H, 8.25; N, 6.11. Found: C, 75.90; H, 7.81; N, 5.90.

Example 166 rel (5R,3'S) 2,5-dihydro-10-methoxy-5-(1-methylthiomethyl-3-cyclohexenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline

The compound of Example 149 was processed according to the method of Example 152 using sodium thiomethoxide instead of lithium triethylborohydride to give the title compound as a white foam.

MS (DCI/NH 3 ) m/e 448 (M+H) ⁺ ;

^! H NMR (300 MHz, DMSO-d ₆ ) δ 8.05 (d, J=9 Hz, 1H), 7.07 (t, J=8 Hz, 1H), 6.68 (d, J=8 Hz, 1H), 6.63 (d, J =8 Hz, 1H), 6.61 (d, J-8 Hz, 1H), 6.24 (s, 1H), 5.71 (s, 1H), 5.46 (s, 1H), 5.39 (d, J=10 Hz, 1H), 3.86 (s, 3H), 3.02 (s, 2H), 2.17-2.41 (br m, 2H), 2.11 (s, 3H), 1.912.10 (br m, 2H), 1.88 (s, 3H), 1.30 (s, 3H), 1.25 (s, 3H), 1.05-1.25 (br m, 3H), 1.02 (s, 3H); Analytical calcd for C28H33NO2S 1/2H2O: C, 73.65; H, 7.50; N, 3.07. Found: C, 73.37; H, 7.46; N, 2.97.

Example 167 rel (5R,3R) 2,5-dihydro-10-methoxy-5-(1-(N-morpholino)methyl-3-cyclohexenyl)-2,2,4-trimethyl-1H-[1-benzopyrano[3,4-f]quinoline

The compound of Example 148 is processed according to the method of Example 152 using morpholine instead of lithium triethylborohydride to give the title compound as a white foam.

MS (DCI/NH 3 ) m/e 487 (M+H) ⁺ ;

’H NMR (300 MHz, DMSO-dg) δ 8.01 (d, J=9 Hz, 1H), 7.07 (t, J=8 Hz, 1H), 6.68 (d, J=8 Hz, 1H), 6.65 (d, J=8 Hz, 1H), 6.56 (d, J=8 Hz, 1H), 6.22 (s, 1H), 5.49 (d, J=llHz, 1H), 5.41 (s, 1H), 5.04 (s, 1H), 3.85 (s, 3H), 3.52 (br s, 3H), 2.68 (d, J=12 Hz, 1H), 2.56 (d, J=12 Hz, 1H), 2.25 (br s, 1H), 2.15 (br s, 2H), 2.05 (s, 3H), 1.40-2.00 (br m, 6H), 1.32 (s, 3H), 1.20-1.28 (br m, 6H), 1.17 (s, 3H);

Analytical calcd for C31H38N2O3: C, 76.51; H, 7.87; N, 5.76. Found: C, 76.24; H, 8.05; N, 5.52.

157

Example 168 rel (5R,3'R) 2,5-dihydro-10-methoxy-5-(1-(N-methyl-N-methylsulfonylamino)methyl-3-cyclohexenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline

The compound from Example 170 (0.80 g, 0.186 mmol) was combined with methanesulfonyl chloride (15 μΐ, 0.195 mmol), (i-Pr^NEt (48 μΐ, 0.279 mmol) and THF at °0 C for 1.5 h. The product was applied directly to a silica gel column and eluted with hexanes, then 40% ethyl acetate in hexanes to give 88 mg (93%) of the title compound as a white solid.

MS (DCI/NH ₃ ) m/e 509 (M+H) ⁺ ;

^[ H NMR (300 MHz, DMSO-cL) δ 8.02 (d, J=9 Hz, 1H), 7.08 (t, J=8 Hz, 1H), 6.69 (d, J=8 Hz, 1H), 6.65 (d, J=9 Hz, 1H), 6.58 (d, J=9 Hz, 1H), 6.20 (s, 1H), 5.53 (d, 3=5 Hz, 1H), 5.41 (s, 1H), 5.11 (s, 1H), 3.85 (s, 3H), 3.46 (d, J =13 Hz, 1H), 3.24 (d, J=13 Hz, 1H), 2.82 (s, 3H), 2.53 (s, 3H), 2.30 (br, 1H), 2.08 (s, 2H), 1.5-2.0 (br m, 6H), 1.35 (br m, 1H), 1.30 (s, 3H), 1.25 (m, 1H), 1.11 (s, 3H);

Analytical calcd for _C29H36N2O4S : C, _68.47 ; H, 7.13; N, 5.51. Found: C, 68.20; H, 7.09; N, 5.36.

Example 169 rel (5R,3'S) 2,5-dihydro-10-methoxy-5-(1-(N,N-dimethylamino)methyl-3-cyclohexenyl)2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline

The compound of Example 149 was processed according to the method of Example 152 using dimethylamine instead of lithium triethylborohydride to give the title compound as a white foam.

MS (DCI/NH ₃ ) m/e 445 (M+H) ⁺ ;

^X H NMR (300 MHz, DMSO-d<0 δ 8.05 (d, J=9 Hz, 1H), 7.05 (t, J=8 Hz, 1H), 6.67 (d, J=8 Hz, 1H), 6.63 (d, J=8 Hz, 1H), 6.60 (d, J=8 Hz, 1H), 6.213 (s, 1H), 5.69 (s, 1H), , 5.46 (s, 1H), 5.42 (d, J=10 Hz, 1H), 3.86 (s, 3H), 2.70 (br, 1H), 2.30 (br m, 1H), 2.11 (s, 3H), 2.05 (br, 4H), 1.85 (br, 2H), 1.56 (m, 1H), 1.30 (s, 3H), 1.10-1.25 (m, 3H), 1.02 (s, 3H);

Analytical calcd for _C29H3eN2O21 /2H2O: C, 76.79; H, 8.22; _N , 6.18. Found: C, 76.49; H, 8.23; N, 5.95.

Example 170 rel (5R,3R) 2,5-dihydro-10-methoxy-5-(1-(N-methylamino)methyl-3-cyclohexenyl)-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4-f]quinoline

The compound of Example 148 was processed according to the method of Example 152 using methylamine instead of lithium triethylborohydride to give the title compound as a white foam.

MS (DCI/NH 2 ) m/e 431 (M+H) ⁺ ;

^J H NMR (300 MHz, DMSO-ck) δ 8.00 (d, J=8 Hz, IH), 7.05 (t, J=8 Hz, IH), 6.68 (d, 3-7 Hz, IH), 6.63 (d, J=7 Hz, IH), 6.57 (d, J=7 Hz, IH), 6.22 (s, IH), 5.76 (s, IH), 5.53 (d J=10 Hz, IH), 5.41 (s, IH), 5.14 (br s, IH), 3.85 (s, 3H), 3.02 (s, 2H), 2.30 (br m, IH), 2.22 (s, 3H), 2.07 (s, 3H), 1.74 (br m, 2H), 1.80-1.4 (br m, 4H), 1.30 (s, 3H), 1.25 (s, 1H), 1.10 (s, 3H);

Analytical calcd for C28H33N2O2 1.25H2O: C, 74.22; H, 8.12; N, 6.18. Found: C, 74.05; H, 7.81; N, 6.00.

Example 171

2,5-dihydro-10-methoxy-5-(2-methyl-3-propenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline

A solution of Example 147 (51 mg, 0.12 mmol) and tetramethyltin (66.5 μϊ, 0.048 mmol) in 1 mL of HMPA was degassed with N2 for 20 min, dichlorobis(triphenylphosphine)palladium(II) complex (9.8 mg, 0.012 mmol) was added, and the reaction mixture was heated at 85°C for 60 h, cooled to room temperature, and stirred vigorously with 30 mL of ethyl acetate and 30 mL of saturated aqueous KF for 3 h. The mixture was then filtered through a pad of celite and the layers were separated. The organic layer was washed with water, brine, and dried ( _Na2SO4 ). Concentration followed by silica gel column chromatography (15% ethyl acetate/hexanes) provided the title compound.

MS (DCI/NH 3 ) m/z 362 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-cU) δ 7.94 (d, IH), 7.05 (t, IH), 6.68 (d, IH), 6.58 (d, IH), 6.42 (d, IH), 6.12 (d, IH), 5.91 (dd, IH), 5.44 (s, IH), 4.77 (s, IH), 4.54 (s, IH). 3.87 (s, 3H), 2.43 (m, 1H), 2.20 (s, 3H), 2.09 (m, 1H), 1.74 (s, 3H), 1.16 (s, 3H).

HRMS calculated m/z for C24H27NO2: 361.2042. Found: 361.2047.

Example 172 • · • · i cn ~ · ··· · <

¹⁵⁹ .ί.. ..· ·..· ..· *

2.5-Dihydro-10-methoxy-5-(1,3-butadiene-2-yl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4f]quinoline

The compound of Example 147 and tributyl(vinyl)tin are treated according to the method of the previous example to give the desired compound.

MS (DCI/NH ₃ ) m/z 374 (M+H) ⁺ ;

^j H NMR (300 MHz, DMSO-dg) δ 8.00 (d, 1H), 7.05 (t, 1H), 6.70 (dd, 1H), 6.60 (d, 1H), 6.47 (dd, 1H), 6.36 (dd, 1H), 6.18 (d, 1H), 5.95 (dd, 1H), 5.43 (s, 1H), 5.16 (s, 1H), 5.12 (s, 1H), 5.05 (d, 1H), 5.00 (d, 1H), 3.87 (s, 3H), 2.55 (dd, 1H), 2.22 (dd, 1H), 2.10 (s, 3H), 1.20 (s, 3H), 1.12 (s, 3H).

Example 173

2.5-Dihydro-10-methoxy-5-(2-carbomethoxy-3-propenyl)-2,2,4-trimethyl-1H[l]benzopyrano[3,4-f]quinoline

A mixture of Example 147 (64 mg, 0.15 mmol), bis(triphenylphosphine)dicarbonylnickel (144 mg, 0.225 mmol), and triethylamine (42 µL, 0.30 mmol) in 5 mL of MeOH was refluxed for 16 h, cooled, and partitioned between ethyl acetate and water. The organic layer was washed with brine, dried (Na ₂ SO ₄ ), and concentrated. The residue was purified by flash chromatography on silica gel (15% ethyl acetate/hexanes) to give the title compound.

MS (DCI/NH 3 ) m/z 406 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-de) δ 8.01 (d, 1H), 7.06 (t, 1H), 6.70 (dd, 1H), 6.60 (d, 1H), 6.41 (dd, 1H), 6.12 (dd, 1H), 6.01 (dd, 1H), 5.43 (s, 1H), 5.36 (s, 1H), 3.87 (s, 3H), 3.68 (s, 3H), 2.60 (dd, 1H), 2.43 (dd, 1H), 2.21 (s, 3H), 1.20 (s, 3H), 1.12 (s, 3H);

Analytical Calcd for C25H27NOL C, 74.05; H, 6.71; N, 3.45. Found: C, 73.81; H, 6.61; N, 3.38.

Example 174

2.5-Dihydro-10-methoxy-5-(1,2-dihydroxy-3-propyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f|quinoline

A solution of Example 2 (50 mg, 0.144 mmol) in pyridine (3 mL) at 0°C was treated with OsO ₄ (370 μΐ, 0.144 mmol), stirred at room temperature for 48 h, treated with saturated aqueous sodium bisulfite (3 mL), stirred for 4 h, and filtered through Celite, which was repeatedly washed with EtOAc. The organic filtrate was washed with water, brine, dried (Na ₂ SO ₄ ), and concentrated. The residue was purified by flash column chromatography • · • ·

160 silica gel (95:5 methylene chloride/methanol) to give the desired compound as an inseparable mixture of two diastereoisomers (2:1).

MS (DCI/NH 3 ) m/z 382 (M+H) ⁺ ;

1 H NMR (300 MHz, DMSO-d6);

Major diastereoisomer: δ 7.94 (d, 1H), 7.05 (t, 1H), 6.67 (d, 1H), 6.57 (d, 1H), 6.53 (d, 1H), 6.13-6.05 (m, 2H), 5.42 (s, 1H), 4.80 (d, 1H), 4.38 (t, 1H), 3.85 (s, 3H), 3.65 (bm, 1H), 3.19-3.00 (m, 2H), 2.21 (s, 3H), 1.83 (m, 2H), 1.19 (s, 3H), 1.11 (s, 3H);

Minor diastereoisomer: δ 7.96 (d, 1H), 7.07 (t, 1H), 6.68 (d, 1H), 6.58 (d, 1H), 6.55 (d, 1H), 6.13 (s, 1H), 5.97 (dd, 1H), 5.42 (s, 1H), 4.50 (t, 1H), 4.45 (d, 1H), 3.85 (s, 3H), 3.453.30 (m, 3H), 2.23 (s, 3H), 1.80-1.58 (m, 2H), 1.21 (s, 3H), 1.09 (s, 3H);

Analytical calcd for _{C23H27NO4.0.35H2O} : C, 71.24; H, 7.20; N, 3.61. Found: C, 71.24; H, 7.28; N, 3.49.

Example 175

2,5-dihydro-10-methoxy-5-(1,2-epoxy-3-propenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fjquinoline

A mixture of Example 174 (50 mg, 0.13 mmol), triphenylphosphine (38 mg, 0.14 mmol), diethyl azodicarboxylate (25 mg, 0.14 mmol) and 3 Å molecular sieves (50 mg) in benzene (5 mL) was refluxed for 48 h, cooled and partitioned between EtOAc and water. The organic layer was washed with water, brine, dried (Na ₂ SO ₄ ) and concentrated. The residue was purified by flash chromatography on silica gel (8:2 hexane/EtOAc) to give the title compound as an inseparable mixture of two diastereoisomers (1.3:1).

MS (DCI/NH 3 ) m/z 364 (M+H) ⁺ ;

*H NMR (300 MHz, DMSO-d6);

Major diastereoisomer: δ 7.93 (d, 1H), 7.09 (t, 1H), 6.72 (d, 1H), 6.60 (d, 1H), 6.58 (d, 1H), 6.14 (s 1H), 5.95 (m, 1H), 5.44 (s, 1H), 3.85 (s, 3H), 3.04 (m, 1H), 2.72 (dd, 1H), 2.35 (dd, 1H), 2.17 (s, 3H), 2.05-1.35 (m, 2H), 1.16 (s, 3H), 1.14 (s, 3H);

Minor diastereoisomer: δ 7.95 (d, 1H), 7.08 (t, 1H), 6.71 (d, 1H), 6.59 (d, 1H), 6.57 (d, 1H), 6.15 (s 1H), 5.93 (m, 1H), 5.44 (s, 1H), 3.85 (s, 3H), 2.90 (m, 1H), 2.65 (dd, 1H), 2.28 (m, 1H), 2.17 (s, 3H), 2.05-1.58 (m, 2H), 1.17 (s, 3H), 1.13 (s, 3H);

HRMS calculated m/z for C23H35NO3: 363.1834. Found: 363.1846.

Example 176

161

• · · · · · ·

2,5-dihydro-10-methoxy-5-(1-(N-phthalimido)-3-propyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-quinoline

Example 69 (250 mg, 0.68 mmol), phthalimide (103 mg, 0.7 mmol), triphenylphosphine (184 mg, 0.7 mmol) and diethyl azodicarboxylate (110 μΐ, 0.7 mmol) in THF (15 mL) were stirred for 24 h and partitioned between EtOAc and water. The organic layer was washed with water, brine, dried (Na ₂ SO ₄ ) and concentrated. The residue was purified by flash chromatography on silica gel (3:1 hexane/EtOAc) to give the title compound.

MS (DCI/NH 3 ) m/z 495 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-de) δ 7.88 (d, 1H), 7.81 (s, 4H), 6.82 (t, 1H), 6.58 (d, 1H), 6.42 (d, 1H), 6.40 (d, 1H), 6.10 (s, 1H), 5.61 (dd, 1H), 5.40 (s, 1H), 3.78 (s, 3H), 3.48 (t, 2H), 2.16 (s, 3H), 1.75-1.40 (bm, 4H), 1.22 (s, 3H), 1.16 (s, 3H);

HRMS calculated m/z for C31H30N2O4: 494.2206. Found: 494.2198.

Example 177

2,5-dihydro-10-methoxy-5-(1-amino-3-propyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4]quinoline

The compound from Example 176 (118 mg, 0.24 mmol) was treated with hydrazine (12.8 mg, 0.4 mmol) in refluxing ethanol (8 mL) for 16 h, cooled, and filtered to remove solids. The filtrate was concentrated and purified by flash chromatography on silica gel (9.5:0.5 methylene chloride/methanol) to give the title compound.

MS (DCI/NH 3 ) m/z 365 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-de) δ 7.94 (d, 1H), 7.05 (t, 1H), 6.68 (d, 1H), 6.57 (d, 1H), 6.54(d, 1H), 6.08 (s, 1H), 5.66 (dd, 1H), 5.43 (s, 1H), 3.85 (s, 3H), 2.43 (t, 2H), 2.17 (s, 3H), 1.80-1.22 (m, 4H), 1.16 (s, 3H), 1.15 (s, 3H);

Analytical calcd for C23H28N2O2O.30H2O: C, 74.69; H, 7.79; N, 7.57. Found: C, 74.50; H, 7.78; N, 7.31.

Example 178

2,5-dihydro-10-methoxy-5-(1-(hydrazinocarbonylamino)-3-propyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-quinoline • ·

162

The compound from Example 177 (65 mg, 0.178 mmol) was reacted with triphosgene (19 mg, 0.0646 mmol) and triethylamine (50 μΐ, 0.36 mmol) in refluxing THF (6 mL) for 3 h, cooled and concentrated to give the crude isocyanate.

This crude isocyanate (0.089 mmol) in THF (10 mL) was treated with hydrazine (4.5 mmol), stirred for 2 h under nitrogen, concentrated, and the resulting residue was purified by flash chromatography on a silica gel column (9:1 dichloromethane/methanol) to afford the desired compound.

MS (DCI/NH 3 ) m/z 423 (M+H) 1 H NMR (300 MHz, DMSO-d ₆ ) δ 7.94 (d, 1H), 7.06 (t, 1H), 6.79 (bs, 1H), 6.68 (dd, 1H), 6.57 (d, 1H), 6.54 (dd, 1H), 6.22 (bt, 1H), 6.10 (d, 1H), 5.63 (dd, 1H), 5.44 (s, 1H), 3.96 (bs, 2H), 3.85 (s, 3H), 2.92 (m, 2H), 2.15 (s, 3H), 1.58-1.20 (m, 4H), 1.16 (s, 3H), 1.15 (s, 3H); HRMS (M+H) ⁺ calculated m/z for C24H30N4O3: 423.2396. Found. 423.2413.

Example 179 (E) 2,5-Dihydro-10-methoxy-5-(2-carbomethoxy-1-ethenyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline

The compound from Example 44 (0.087 g, 0.26 mmol) was dissolved in CH2Cl2 (10 mL), cooled to -23°C, treated dropwise with 0.52 mL of 1M Dibal-H/heptane solution (0.52 mmol) and stirred for 1 h. The reaction mixture was poured into 30 mL of 0.5 M HCl, stirred for 30 min, extracted with ethyl acetate, the combined organic layers were washed with brine and dried (Na2SO4) to give the aldehyde (intermediate) as a yellow foam.

The resulting yellow foam was dissolved in THF (8 mL), cooled to 0°C, treated with methyl(triphenylphosphoranylidene)acetate (0.130 g, 0.39 mmol), stirred overnight at room temperature and then at 45°C for 1 h. The reaction mixture was cooled, diluted with saturated aqueous NH4Cl, extracted with ethyl acetate, and the combined organic layers were washed with brine and dried (MgSO4). The resulting residue was purified by column chromatography on silica gel 90:10-hexane:ethyl acetate to afford 0.043 g (42%) of the desired compound.

MS (DCI/NH 2 ) m/e 392 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-dé) δ 7.99 (d, J-9 Hz, 1H), 7.05 (t, J= 8 Hz, 1H), 6.86 (dd, J=4, 16 Hz, 1H), 6.69 (d, J= 7 Hz, 1H), 6.67 (d, J = Hz, 1H), 6.61 (d, >8 Hz, 1H), 6.41 (dd, J=2, 4 Hz, 1H), 6.26 (d, J=2 Hz, 1H), 5.63 (dd, J=2, 16 Hz, 1H), 5.45 (br s, 1H), 3.84 (s, 3H), 3.56 (s, 3H), 2.08 (s, 3H), 1.19 (s, 3H), 1.15 (s, 3H);

• ·

163.3 ^C NMR (100 MHz, DMSO-cL) δ 165.19, 156.18, 151.64, 146.45, 145.59, 133.53, 128.39,

127.17, 123.57, 117.17, 116.54, 113.85, 109.82, 105.78, 71.93, 55.80, 55.59, 51.57, 49.75,

29,56,29,15,28,70,23,45;

Analytical calcd for C24H25NO4 1/ _4H2O : C, 72.80; H, 6.49; N, 3.54. Found: C, 73.00; H, 6.56; N, 3.34.

Example 180 (Z)-2,5-dihydro-10-methoxy-5-(1-propenyl)-2,2,4-trimethyl-1H-[1-benzopyrano[3,4-]quinoline

The aldehyde (intermediate) from Example 179 and ethyltriphenylphosphonium iodide are treated according to the method of Example 187 to give the desired compound.

MS (DCI/NH 3 ) m/e 348 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-d ₆ ) δ 7.90 (d, J-8 Hz, 1H), 6.97 (t, J-6 Hz, 1H), 6.67 (d, J-8,Hz,

1H), 6.52 (d, J-8 Hz, 1H), 6.48 (d,J -12 Hz, 1H), 6.26 (d, J= 7 Hz, 1H), 6.10 (s, 1H), 5.59 (m, 1H), 5.41 (s, 2H), 3.83 (s, 3H), 2.08 (s, 3H), 1.79 (d, J-7 Hz, 3H), 1.23 (s, 3H), 1.11 (s, 3H); ¹³ C NMR (125 MHz, DMSO-d 6 ) δ 156.1, 152.4, 145.4, 132.4, 131.0, 130.2, 127.7, 127.2, 127.0, 126.7, 116.9, 116.4, 113.7, 113.0, 109.9, 105.4, 69.4, 55.6, 49.7, 29.6, 28.3, 23.0, 13.8; Analytical calcd. for C ₂₃ H ₂ 5O ₂ N 1.0H ₂ O: C, 75.59; H, 7.45; N, 3.83. Found: C, 75.53;

H, 7.20; N, 3.62.

Example 181 (E) 2,5-dihydro-10-methoxy-5-(3-hydroxy-1-propenyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline ml ethereal suspension of L1AIH4 (0.200 g, 5.17 mmol) was treated dropwise at room temperature with 15 ml ethereal solution of _A1C13 (0.230 g, 1.72 mmol), stirred for 15 min, then treated dropwise with 20 ml ethereal solution from Example 179. After stirring for 1 h at room temperature, 2 ml _H2O was carefully added followed by the addition (dropwise) of 15% NaOH until a white paste settled at the bottom of the flask. The ether solution was decanted, the paste was washed several times with ether, and the combined organic layers were washed with brine and dried (MgSO ₄ ). The residue was purified by silica gel column chromatography with 25% then 33% ethyl acetate in hexanes to give 0.195 g (78%) of the title compound as a colorless foam.

*H NMR (300 MHz, DMSO-4) δ 7.95 (d, J=8 Hz, 1H), 7.01 (t, J=8 Hz, 1H), 6.64 (d, J=9 Hz, 1H), 6.61 (d, J=9 Hz, 1H), 6.52 (d, J=8 Hz, 1H), 6.18 (br d, J=4 Hz, 1H), 6.08 (s, 1H), 5.735.66 (m, 1H), 5.51 (5.43, J=m Hz, 1H), 5.41 (s, 1H), 4.65 (t, J=5Hz, 1H), 3.83 (s, 3H), 3.77 (t, J=5Hz, 2H), 2.12 (s, 3H), 1.19 (s, 3H), 1.13 (s, 3H);

MS (FAB) m/e calcd for C23H25NO3: 363.183. Found: 363.1839.

Example 182 (E) 2,5-Dihydro-10-methoxy-5-(3-(N,N-dimethylaminocarbonyloxy)-1-propenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline

The compound from Example 181 (0.035 g, 0.096 mmol) was dissolved in DMF (5 mL), treated with NaH (0.012 g of a 60% dispersion in oil, 0.289 mmol) at room temperature, stirred for 10 min, treated dropwise with N,N-dimethylcarbamoyl chloride (44 μΐ, 0.481 mmol) and stirred for 30 min. The reaction mixture was diluted with 10 mL of saturated aqueous NH4Cl, extracted with ethyl acetate. The organic layer was washed with _H2O , brine, dried ( _MgSO4 ), concentrated and purified by silica gel column chromatography with 25% then 33% ethyl acetate in hexanes to give 0.033 g (79%) of the title compound as a colorless foam:

MS (DCI/NH 3 ) m/e 509 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-d ₆ ) δ 7.94 (d, J=9 Hz, 1H), 7.02 (t, J=8 Hz; 1H), 6.66 (d, J=8 Hz, 1H), 6.63 (d, J=9 Hz, 1H), 6.53 (d, J=8 Hz, 1H), 6.17 (m, 2H), 5.82 (dd, J=16, 4 Hz, 1H), 5.49-5.42 (m, 1H), 5.42 (s, 1H), 4.31 (d, J=6 Hz, 2H), 3.82 (s, 3H), 2.71 (m, 6H), 2.09 (s, 3H), 1.20 (s, 3H), 1.12 (s, 3H);

¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 156.1, 155.1, 151.8, 145.4, 133.0, 131.5, 130.0, 129.8,

127.6, 127.0, 126.8, 117.3, 116.9, 113.7, 113.5, 110.0, 105.6, 72.9, 63.8, 55.7, 55.6, 49.7,

29.3, 28.5, 28.4, 23.3;

MS (FAB) m/e calcd for C26H30N2O4: 434.2206. Found: 434.2209.

Example 183 (E) 2,5-dihydro-10-methoxy-5-(3-methoxymethoxy-1-propenyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline

The compound from Example 181 (0.026 g, 0.072 mmol) was dissolved in dichloroethane (5 mL), cooled to 0°C, treated with (i-Pr) ₂ NEt (62 μΐ, 0.358 mmol) followed by chloromethyl methyl ether (16 μΐ, 0.215 mmol), the bath was removed, and the mixture was heated at 55°C for 14 h. The mixture was partitioned between ethyl acetate and saturated aqueous NH4Cl. The organic layer was washed with brine, dried ( _MgSO4 ), and purified by silica gel column chromatography with 10% ethyl acetate in hexanes to give 0.012 g (41%) of the title compound as an amber oil.

'H NMR (300 MHz, DMSO-d ₆ ) δ 7.94 (d, J=8 Hz, 1H), 7.02 (t, J=8 Hz, 1H), 6.66 (d, J=9 Hz, 1H), 6.63 (d, J=9 Hz, 1H), 6.53 (d, J=8 Hz, 1H), 6.19 (br d, J=3 Hz, 1H), 6.14 (d, J=2 Hz, 1H), 5.78 (dd, J=16, 4 Hz, 1H), 5.42 (s, 1H), 4.31 (ABq, J=8, 6 Hz, 2H), 3.84 (m, 2H), 3.82 (s, 3H), 3.09 (s, 3H), 2.11 (s, 3H), 1.20 (s, 3H), 1.13 (s, 3H);

MS (FAB) m/e calcd for C25H29NO4: 407.2097. Found: 407.2090.

Example 184

2,5-dihydro-10-methoxy-5-(3-hydroxy-3-propenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline

The compound from Example 44 (0.58 g, 1.74 mmol) was dissolved in CH2Cl2 (40 mL), cooled to 45°C, treated dropwise with 2.09 mL of 1 M Dibal-H/heptane solution (2.09 mmol) and stirred for 1 h. The reaction mixture was poured into 75 mL of 0.5 M HCl, stirred for 30 min, extracted with ethyl acetate, the combined organic layers were washed with brine, dried ( _Na2SO4 ) and concentrated to give 0.55 g of the crude aldehyde as a yellow foam.

The resulting aldehyde (0.048 g, 0.143 mmol) was dissolved in THF (5 mL), cooled to 0°C, and treated cautiously with vinylmagnesium bromide (0.72 mL 1M/THF, 0.72 mmol). After stirring for 15 min, the mixture was partitioned between ethyl acetate and brine. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were washed with brine, dried (Na ₂ SO 4 ), concentrated, and purified by silica gel column chromatography with 20% ethyl acetate in hexanes to afford the title compound (0.027 g, 53%) as an inseparable 1:1 mixture of diastereoisomers.

Major diastereoisomer: ’H NMR (300 MHz, DMSO-dó) δ 7.97 (d, J=8 Hz, 1H), 7.04 (t, J=8 Hz, 1H), 6.68 (d, J =8 Hz, 1H), 6.59 (d, J=8 Hz, 1H), 6.48 (d, J=8 Hz, 1H), 6.03 (br s, 1H), 5.61 (s, 1H), 5.46 (m, 1H), 5.36 (m, 1H), 4.97-5.10 (m, 1H), 4.87 (m, 1H), 3.94 (m, 1H), 3.85 (s, 3H), 2.19 (s, 3H), 1.23 (s, 3H), 1.10 (s, 3H);

Minor diastereoisomer: MS (DCI/NH3) m/e 364 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-dó) δ 8.02 (d, J=8 Hz, 1H), 7.07 (t, J=8 Hz, 1H), 6.68 (d, J=8 Hz, 1H), 6.62 (d, 3=8 Hz, 1H), 6.61 (d, J=8 Hz, 1H), 6.16 (br s, 1H), 5.95 (m, 1H), 5.58 (s, 1H), 5.41 (s, 1H), 4.97-5.10 (m, 2H), 3.94 (m, 1H), 3.85 (s, 3H), 2.11 (s, 3H), 1.27 (s, 3H), 1.01 (s, 3H);

9

166

999

999

MS (DCI/NH 3 ) m/e (M+H) ⁺ 364;

Analytical calcd for C23H25NO3 3/4H2O: C, 73.29; H, 7.09; N, 3.72. Found: C, 73.67; H, 6.80; N, 3.81.

Example 185

Methyl 2-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolin-5yl)acetylhydroxamate

The compound from Example 46 (0.150 g, 0.395 mmol) was added dropwise to a solution of N,O-dimethylhydroxylamine hydrochloride (0.192 g, 1.98 mmol) and trimethylaluminium (1.0 mL, 2.0 mmol) and the resulting mixture was heated at 40°C for 2 hours, quenched with methanol and partitioned between methylene chloride and saturated aqueous Rochelle salt. The organic layer was washed with saturated aqueous sodium bicarbonate, brine and dried (MgSO4). The crude product was purified by flash chromatography on a silica gel column with 4% then 10% ethyl acetate in methylene chloride to give the title compound (62%) as a white foam.

MS (DCI/NH 2 ) m/e 409 (M+H) ⁺ ;

’Η NMR (300 MHz, DMSO-dg) δ 7.79 (d, J=8 Hz, 1H), 7.05 (dd, J=8 Hz, 1H), 6.73 (d, >8 Hz, 1H), 6.61 (d,J =8 Hz, 1H), 6.48 (d, J=8 Hz, 1H), 6.25 (dd, J=2+10 Hz, 1H), 6.16 (s, 1H), 5.43 (s, 1H), 3.87 (s, 3H), 3.25 (br s, 3H), 3.04 (br s, 3H), 2.34 (m, 1H), 2.18 (s, 3H), 1.17 (s, 6H);

Analytical calcd for C24H28N2O4: C, 70.57; H, 6.91; N, 6.86. Found: C, 70.74; H, 7.11; N, 6.59.

Example 186

2-(2,5-dihydro-10-methoxy-5-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolin-5yl)acetaldehyde

The compound from Example 185 (0.334 g, 0.817 mmol) was dissolved in THF (20 mL), cooled to -78°C, and treated with 1M Dibal-H in toluene (1.71 mL, 1.71 mmol) over 5 min and stirred for 1 h. The reaction mixture was poured into saturated Rochelle salt, the layers were separated, the aqueous phase was extracted with CH2Cl2, the combined organic layers were washed with saturated aqueous sodium bicarbonate, brine, dried ( _MgSO4 ), and purified by column chromatography on silica gel with 30% ethyl acetate in hexanes to afford 0.265 g (93%) of the desired product as a colorless foam.

167

MS (DCI/NH ₃ ) m/e 350 (M+H) ⁺ ;

*H NMR (300 MHz, DMSO-dg) δ 9.65 (s, 1H), 7.95 (d,J =9 Hz, 1H), 7.05 (dd, >8 Hz, 1H), 6.73 (d, >8 Hz, 1H), 6.60 (d, >8 Hz, 1H), 6.45 (d, >8 Hz, 1H), 6.35 (dd, >3+10 Hz, 1H), 6.20 (s, 1H), 5.45 (s, 1H), 3.85 (s, 3H), 2.85 (m, 1H), 2.60 (m, 1H), 2.15 (s, 3H), 1.17 (s, 3H), 1.15 (s, 3H);

Analytical calcd for C22H23NO31/4H2O: C, 74.66; H, b.69; N, 3.96. Found: C, 74.32; H, 6.30; N, 3.86.

Example 187

2,5-dihydro-10-methoxy-5-(2-cyclohexylideneylethyl)-2,2,4-trimethyl-1H[ 1 ]benzopyrano[3,4-f]quinoline

Cyclohexyltriphenylphosphonium bromide (Grim, S. O.; Ambrus, J. H.; J.Org. Chem. 1968, 33, 2993-2994,) (0.234 g, 0.55 mol) was suspended in (5:3) THF:ether (8.0 ml), cooled to -10°C, treated with 220 μΐ 2.5 M n-butyllithium, stirred for 10 min, compound of Example 186 was added as a solution in THF and the reaction was stirred at room temperature for 12 h, refluxed for 15 min and cooled. Diethyl ether was added and the reaction mixture was filtered and concentrated. The resulting residue was purified by silica gel column chromatography with 10:1 to 5:1 hexane:ethyl acetate to give 0.033 g (51%) of the desired compound:

Melting point 130 - 135 C°;

MS (DCI/NH 3 ) m/e 416 (M+H) ⁺ ;

'H NMR (300 MHz, DMSO-dg) δ 7.03 (t, >9 Hz, 1H), 6.67 (d,J =8 Hz, 1H), 6.57 (d, >9 Hz, 1H), 6.50 (d, >8 Hz, 1H), 6.11 (s, 1H), 5.64 (dd, >10, 10 Hz, 1H), 5.43 (s, 1H), 5.04 (t, >7 Hz, 1H), 3.85 (s, 3H), 2.10 (s, 3H), 2.0 (b, 2H), 1.81 (t, >7 Hz, 2H), 1.45 (b, 3H), 1.3 (b,

3H), 1.17 (s, 3H), 1.15 (s, 3H);

¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 165.0, 151.1, 145.4, 140.5, 133.41, 132.2, 127.5, 127.0,

126.8, 116.5, 116.3, 116.0, 113.0, 110.3, 105.3, 73.9, 55.5, 49.6, 36.6, 30.5, 28.9, 28.7, 28.1, 27.9, 27.0, 26.2,23.8.

Example 188

2,5-dihydro-10-methoxy-5-(2-cyclopentylideneylethyl)-2,2,4-trimethyl-1H[ 1 ]benzopyrano[3,4-f] quinoline * · ·· • · « · * · • ·

168 ··· 9

• » « · • · · · • » · · • · · t ·» »·

The compound of Example 186 and cyclopentyltriphenylphosphonium bromide (Ramirez, F.; Levy, S. JACS 1957, 79, 67-69, ) are treated according to the method of Example 187 to give the desired compound.

'H NMR (300 MHz, DMSO-dg) δ 7.94 (d, J = Hz, 1H), 7.02 (t, J =8 Hz, 1H), 6.67 (d, J=8 Hz, 1H), 6.57 (d, J=9 Hz, 1H), 6.48 (d, >7 Hz, 1H), 6.10 (s, 1H), 5.56 (dd, J=10, 8 Hz, 1H), 5.43 (s, 1H), 5.22 (b, 1H), 3.85 (s, 3H), 2.14 (s, 6H), 1.77 (b, 2H), 1.49 (b, 4H), 1.17 (s, 3H), 1.14 (s, 3H);

¹³ C NMR (75 MHz, DMSO-d ₆ ) δ 156.1, 151.2, 145.4, 144.6, 133.4, 132.3, 127.6, 127.0,

126.8, 116.4, 116.1, 115.3, 113.3, 113.1, 110.3, 105.3, 73.6, 55.6, 49.6, 33.1, 29.0, 28.7, 28.0,

25.8, 25.7, 23.8;

HRMS (FAB) m/e calcd for C27H32O2N: 401.2355. Found: 401.2342.

Example 189

2,5-Dihydro-10-methoxy-5-(2-cycloheptylidenylethyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinolin

The compound of Example 186 and cycloheptyltriphenylphosphonium bromide (Albright, T. A.; Freeman, W. J.; Schweizer, E. E. JACS 1974, 97, 2942-2943) are treated according to the method of Example 186 to give the desired compound.

MS (DCI/NH 3 ) m/e 430 (M+H) ⁺ ;

Η NMR (300 MHz, DMSO-d _ó ) δ 7.94 (d, J=9 Hz, 1H), 7.02 (t, J=8 Hz, 1H), 6.67 (d, J-8 Hz, 1H), 6.57 (d, J=9 Hz, 1H), 6.49 (d, J=8 Hz, 1H), 6.12 (s, 1H), 5.69 (dd, J=10, 9 Hz, 1H), 5.43 (s, 1H), 5.12 (t, J=7 Hz, 1H), 3.85 (s, 3H), 2.13 (s, 6H), 1.90 (b, 2H), 1.38 (b, 3H), 1.27 (m, 4H), 1.17 (s, 3H), 1.14 (s, 3H), 0.82 (m, 3H);

¹³ C NMR (75 MHz, DMSO-d ₆ ) δ 156.1, 151.1, 145.4, 142.2, 133.4, 132.2, 128.6, 127.6, 127.0, 126.8, 120.0, 116.3, 116.0, 113.0, 110.3, 105.3, 73.6, 65.7, 55.6, 49.6, 37.3, 33.2, 31.1,

29.8, 29.3, 29.2, 29.0, 28.6, 28.5, 26.2, 23.8, 23.2;

Analytical calcd for C29H35O2N2 3/ _4H2O : C, 72.70; H, 8.52; N, 2.92. Found: C, 72.50; H, 8.11; N, 2.47.

Example 190

2,5-dihydro-10-methoxy-5-(3-methyl-2-butenyl)-2,2,4-trimethyl-1 H-[ 1 ]benzopyrano[3,4fjquinoline ·* ·« • · · · • · · * • · · t · • · * ·· ·· • ·

169

The compound of Example 186 and isopropyltriphenylphosphonium iodide are treated according to the method of Example 187 to give the desired compound.

Η NMR (300 MHz, DMSO-dg) Ó 7.94 (d, J=8 Hz, 1H), 7.37 (s, 1H), 7.03 (t,J =8 Hz, 1H),

6.67 (d,J =7 Hz, 1H), 6.57 (d, J=8 Hz, 1H), 6.49 (d,J =8 Hz, 1H), 6.11 (s, 1H), 5.65 (dd, J=10, 9 Hz, 1H), 5.43 (s, 1H), 5.12 (t, J=7 Hz, 1H), 3.85 (s, 3H), 2.14 (s, 3H), 1.63 (s, 3H), 1.31 (s, 3H), 1.17 (s, 3H), 1.15 (s, 3H);

¹³ C NMR (100 MHz, DMSO-dg) δ 156.1, 151.1, 145.4, 133.4, 132.8, 132.2, 127.6, 127.0, 126.9, 119.8, 116.4, 116.1, 113.3, 113.1, 110.3, 105.3, 73.7, 55.6, 49.6, 31.5, 29.0, 28.7, 25.6,

23.8, 17.5;

HRMS (FAB) calcd for C25H29O2N: 375.2198. Found: 375.2189.

Example 191 trans 2,5-dihydro-10-methoxy-5-(2-butenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4]quinoline

The compound of Example 186 and ethyltriphenylphosphonium bromide are treated according to the method of Example 186 to give the desired compound.

MS (DCI/NH 3 ) m/e 362 (M+H) ⁺ ;

³ H NMR (300 MHz, DMSO-dg) δ 7.96 (d,J =8 Hz, 1H), 7.05 (dd, J=8 Hz, 1H), 6.70 (d, J=8 Hz, 1H), 6.60 (d, J=8 Hz, 1H), 6.51 (d, J=8 Hz, 1H), 6.10 (s, 1H), 5.72 (dd, J=4+]0 Hz, 1H), 5.45 (m, 3H), 3.86 (s, 3H), 2.43 (m, 1H), 2.20 (m, 1H), 2.15 (s, 3H), 1.30 (d, J=5Hz, 3H), 1.17 (s, 3H), 1.15 (s, 3H).

Example 192 trans 2,5-dihydro-10-methoxy-5-(2-penten-1-yl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4]quinoline

The compound of Example 186 (0.050 g, 0.143 mmol) and propyltriphenylphosphonium bromide (165.6 mg, 0.429 mmol) were treated according to the method of Example 187 to give the desired compound.

MS (DCI/NH 3 ) m/e 376 (M+H) ⁺ ;

^! H NMR (300 MHz, DMSO-dé) δ 7.95 (d, J=9 Hz, 1H), 7.05 (dd, J=8 Hz, 1H), 6.70 (d, J=8 Hz, 1H), 6.60 (d, J=8 Hz, 1H), 6.50 (d, J=8 Hz, 1H), 6.09 (s, 1H), 5.70 (dd, J=3, 10 Hz, 1H), 5.44 (s, 1H), 5.38 (ss, >5 Hz, 2H), 3.86 (s, 3H), 2.41 (m, 1H), 2.19 (m, 1H), 2.15 (s, 3H),

1.70 (m, 2H), 1.15 (s, 6H), 0.75 (t, 3=7 Hz, 3H).

φ · • · φφ ·«

170

Example 193

2,5-dihydro-10-methoxy-5-(1,1-difluoro-1-propen-3-yl)-2,2,4-trimethyl-1H[l]benzopyrano[3,4-f]quinoline

The compound of Example 186 (0.050 g, 0.143 mmol) and diphenylphosphoranyldifluoromethane (Edwards, M. L., et. al. Tet. Let. 1990,31, 5571-74) were treated according to the method of Example 187 to give the desired compound.

Ή NMR (300 MHz, DMSO-dó) δ 7.98 (d, J=8 Hz, 1H), 7.08 (t, J=8 Hz, 1H), 6.71 (d, J=9 Hz, 1H), 6.62 (d, J=9 Hz, 1H), 6.57 (d, J=9 Hz, 1H), 6.17 (s, 1H), 5.73 (dd, J =4.10 Hz, 1H), 5.46 (s, 1H), 4.53 (m, 1H), 3.86 (s, 3H), 2.32 (m, 1H), 2.16 (s, 3H), 2.11 (m, 1H), 1.17 (s, 3H), 1.15 (s, 3H);

HRMS (FAB) m/e calcd for 383.1697. Found: 383.1689.

Example 194 (E) Methyl 2-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolin-5-yl)-2-butanoate

The compound of Example 186 (0.040 g, 0.115 mmol) and methyl(triphenylphosphoranylidene)acetate (115 mg, 0.344 mmol, Aldrich) were treated according to the method of Example 179 to give 0.037 g (80%) of the title compound as a white foam.

MS (DCI/NH 2 ) m/e 406 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-dó) δ 7.95 (d, J=9 Hz, 1H), 7.07 (dd, J=8 Hz, 1H), 6.85 (m, 1H), 6.72 (d, J=8 Hz, 1H), 6.60 (d, J=8 Hz, 1H), 6.50 (d, J=8 Hz, 1H), 6.15 (s, 1H), 5.87 (dd, J=3+l0 Hz, 1H), 5.80 (d, J=14 Hz, 1H), 5.45 (s, 1H), 3.88 (s, 3H), 3.65 (s, 3H), 2.60 (m, 1H), 2.45 (m, 1H), 2.15 (s, 3H), 1.15 (br s, 6H), ¹³ C NMR (75 MHz, DMSO-d ₆ ) δ 165.8, 156.2, 150.5, 145.6, 144.8, 133.6, 131.3, 127.4,

Analytical calcd for C25H27NO4 1/2H2O: C, 72.44; H, 6.81; N, 3.38. Found: C, 72.55;

H, 6.71; N, 3.22.

Example 195 (E)

2,5-dihydro-10-methoxy-5-(4-hydroxy-2-buten-1-yl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline ·· ·· • · * » • · · • ··· · • · ···· ··

171 « · · · • · · o • · ··· * φ · · *♦ «· ·* ♦ · « • · · • · · • · 9 ·· »· 99

Example 194 (0.063 g, 0.155 mmol) in Et2O was treated dropwise with a slurry containing _LiAlH4 (0.044 g, 1.16 mmol) and AlCl3 (0.041 g, 0.308 mmol) over 1 hour. The reaction mixture was diluted with Et2O and treated with 2 drops of H2O followed by 15% NaOH until a white paste formed. The Et2O was decanted and the paste was washed with Et2O (2x). The combined organic layers were washed with saturated aqueous sodium bicarbonate, brine, dried ( _MgSO4 ), and purified by column chromatography on silica gel with 6% then 10% ethyl acetate in methylene chloride to give 0.031 g (5% %) of the desired compound.

MS (DCI/NH 3 ) m/e 378 (M+H) ⁺ ;

*H NMR (300 MHz, DMSO-dg) δ 7.94 (d, J-9 Hz, 1H), 7.07 (dd, J=8 Hz, 1H), 6.70 (d, E8 Hz, 1H), 6.60 (d, >8 Hz, 1H), 6.54 (d, J=8 Hz, 1H), 6.12 (s, 1H), 5.70 (dd, J -3+10 Hz, 1H),

5.4-5.69 (m, 3H), 4.63 (dd, J-1 Hz, 1H), 3.87 (m, 5H), 3.31 (s, 3H), 2.40 (m, 1H), 2.15 (s, 3H), 1.15 (s, 6H);

Analytical calcd for _{C24H27NO3IMH2O} : C, 75.47; H, 7.26; N, 3.67. Found: C, 75.62; H, 7.40; N, 3.59.

Example 196 (E) 2,5-Dihydro-10-methoxy-5-(4-(N,N-dimethylaminocarbonyloxy)-2-buten-1-yl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline

The compound of Example 195 and disuccinimidyl carbonate are treated according to the method of Example 200 to give the succinate ester (intermediate).

The succinate ester (intermediate) and N,N-dimethylamine are treated according to the method of Example 200 to give the desired compound.

MS (DCI/NH 3 ) m/e 449 (M+H) ⁺ ;

^J H NMR (400 MHz, DMSO-dg) δ 7.95 (d, J=9 Hz, 1H), 7.07 (t,J -8 Hz, 1H), 6.70 (d, J=8 Hz, 1H), 6.59 (d, J=8 Hz, 1H), 6.52 (d, J-8 Hz, 1H), 6.09 (s, 1H), 5.74 (dd, J=3.10 Hz, 1H), 5.65 (m, 1H), 5.48 (m, 1H), 5.43 (s, 1H), 3.85 (s, 3H), 3.79 (d, >5 Hz, 2H), 2.45 (m, 1H), 2.20 (m, 1H), 2.15 (s, 3H), 1.17 (s, 3H), 1.16 (s, 3H);

¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 156.1, 150.9, 145.5, 133.6, 132.0, 129.0, 128.6, 127.4,

127.1, 127.0, 116.2, 115.9, 113 (3), 113.2, 110.3, 105.4, 73.5, 72.0, 56.9, 55.6, 49.7, 35.0, 28.9,23.3;

Analytical calcd for C27H32N2Cl: C, 72.30; H, 7.19; N, 6.25. Found: C, 72.10; H, 7.11; N, 5.98.

172

Example 197 (E) 2,5-dihydro-10-methoxy-5-(4-(N-methylaminocarbonyloxy)-2-buten-1-yl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline

The succinate ester (intermediate) from Example 196 and methylamine are treated according to the method of Example 200 to give the desired compound.

MS (DCI/NH ₃ ) m/e 435 (M+H) ⁺ ;

’H NMR (300 MHz, DMSO-de) δ 7.95 (d, J=8 Hz, IH), 7.05 (t, J=8 Hz, IH), 6.95 (m, IH),

6.70 (d, 3=8 Hz, IH), 6.57 (d, J=8 Hz, IH), 6.52 (d, J=8 Hz, IH), 6.08 (s, IH), 5.70 (m, 2H), 5.50 (m, IH), 5.43 (s, IH), 4.35 (d, J=5 Hz, 2H), 3.85 (s, 3H), 2.56 (d, J=5 Hz, 3H), 2.42 (m, 1H), 2.20 (m, 1H), 2.15 (s, 3H), 1.15 (s, 6H);

Analytical calcd for C26H30N2O4: C, 71.87; H, 6.96; N, 6.45. Found: C, 71.66; H, 7.25; N, 6.07.

Example 198 (E) 2,5-dihydro-10-methoxy-5-(2-butenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline The compound from Example 195 (0.080 g, 0.212 mmol) was dissolved in CH2Cl2 (10 mL), cooled to -10°C, treated with (i-Pr) _2NEt (55 μΐ, 0.318 mmol), followed by methanesulfonyl chloride (20 μΐ, 0.255 mmol), stirred for 1 h and warmed to room temperature. The mixture was cooled again to -10°C and treated dropwise with lithium triethylborohydride (635 μΐ, 0.635 mmol), stirred for 1 hour, warmed to room temperature, treated with 5.0 mL IN NaOH followed by 0.11 mL 30% H2O2 and stirred for 30 minutes. The mixture was partitioned between aqueous and ethyl acetate layers. The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with water, brine and dried ( _Na2SO4 ). Purification by column chromatography on silica gel with a mobile phase of 15:1 then 7:1 hexanes:ethyl acetate gave 0.029 g (3% yield) of the desired compound.

Ή NMR (360 MHz, DMSO-de) δ 7.93 (d, J=9 Hz, IH), 7.04 (t, J=8 Hz, IH), 6.68 (d, J=8 Hz,

IH), 6.57 (d, J=8 Hz, IH), 6.51 (d, J=7 Hz, IH), 6.11 (s, IH), 5.67 (dd, J=10 Hz, IH), 5.41 (t, J=9 Hz, IH), 5.34 (t, J=llHz, IH), 3.85 (s, 3H), 2.34 (m, IH), 2.15 (s, 3H), 1.59 (dd, J=5 Hz, 3H), 1.17 (s, 3H), 1.15 (s, 3H);

¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 156.2, 151.0, 145.4, 133.4, 132.1, 127.1, 127.0, 126.9,

126.6, 125.5, 115.9, 113.2, 110.0, 105.3, 73.7, 55.5, 49.6, 35.4, 28.9, 28.8, 23.9, 17.8;

HRMS (FAB) calcd for C24H28O2N: m/e 362.2120. Found: 362.2119.

173

Example 199

2.5-Dihydro-10-methoxy-5-(2-hydroxyethyl)-2,2,4-trimethyl-1H-[ljbenzopyrano[3,4fjquinoline

The compound from Example 46 (0.100 g, 0.264 mmol) was treated with 1M Dibal-H in toluene (0.544 mL, 0.544 mmol) at -78°C, warmed to room temperature, diluted with methanol and partitioned between methylene chloride and saturated aqueous Rochelle salt. The organic layer was washed with 1N HCl, saturated aqueous sodium bicarbonate, brine and dried (MgSO4). The resulting crude product was purified by flash chromatography on silica gel with 10% ethyl acetate in methylene chloride to give (8%) of the title compound as a white solid.

MS (DCI/NH 2 ) m/e 352 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-d^) δ 7.95 (d, .1=8 Hz, 1H), 7.05 (dd, J=8 Hz, 1H), 6.69 (d, J=8 Hz, 1H), 6.59 (d, J=8 Hz, 1H), 6.55 (d, J=8 Hz, 1H), 6.10 (s, 1H), 5.95 (dd, J=2.10 Hz, 1H), 5.43 (s, 1H), 4.61 (t, J=6 Hz, 1H), 3.84 (s, 3H), 3.52 (m, 1H), 2.20 (s, 3H), 1.80 (m, 1H), 1.50 (m, 1H), 1.19 (s, 3H), 1.16 (s, 3H).

Example 200

2.5-Dihydro-10-methoxy-5-(2-(N-benzylcarbonyloxy)ethyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-quinoline

The compound from Example 199 (0.200 g, 0.57 mmol) was combined with N,N'-disuccinimidyl carbonate (0.217 g, 0.85 mmol), (i-Pr) ₂ NEt (0.30 mL, 1.71 mmol) and acetonitrile (2 mL), stirred at room temperature for 2 h and partitioned between CH ₂ Cl ₂ and saturated aqueous bicarbonate. The organic layer was washed with brine, dried (MgSO 4 ) and purified by column chromatography on silica gel with 6% ethyl acetate in dichloromethane to give 0.252 g (9(^/o) of the succinate ester as a white foam.

The succinate ester (0.020 g, 0.041 mmol), benzylamine (6.6 μΐ, 0.061 mmol) and CH ₂ Cl ₂ (3 mL) were combined and stirred for 20 min at room temperature. The reaction mixture was diluted with CH ₂ Cl ₂ and the organic layer was washed with H ₂ O, saturated aqueous sodium bicarbonate, brine, dried (MgSO ₄ ) and purified by silica gel column chromatography with 20% ethyl acetate in hexanes to give 19 mg (97% yield) of the title compound as a white solid.

MS (DCI/NH ₃ ) m/e 485 (M+H) ⁺ ;

• · · ·

174 • · · · · · · „ - φ · · · · · φφφ · φ · φφφ · · · · ♦ * · φ φ ·ΦΦΦ ’Η NMR (400 MHz, DMSO-ck) δ 7.95 (d, J=9 Hz, ΙΗ), 7.68 (t, J=6 Hz, 1H), 7.25 (m, 3H), 7.07 (t, J=8 Hz, 1H). 6.71 (d, J=8 Hz, 1H), 6.59 (dd, J=8 Hz, 1H), 6.11 (s, 1H), 5.86:(d, J=8 Hz, 1H), 5.40 (s, 1H), 4.18 (m, 2H), 4.00 (m, 2H), 3.85 (s, 3H), 2.12 (s, 3H), 1.90 (m, 1H),

1.71 (m, 1H), 1.17 (s, 3H), 1.15 (s, 3H);

¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 156.3, 156.1, 150.7, 145.6, 139.7, 133.5, 131.9, 128.2, 127.5, 127.2, 127.1, 127.0, 126.7, 116.3, 115.9, 113.2, 113.2, 110.2, 110.1, 105.6, 70.3, 60.2, 55.6, 49.6, 43.7, 31.5, 28.8, 28.7, 23.8;

Analytical calcd for C30H32N2O5 _H2O : C, 71.69; H, 6.82; N, 5.57. Found: C, 71.45; H, 6.83; N, 5.56.

Example 201

2,5-dihydro-10-methoxy-5-(2-(N-morphoblinocarbonyloxy)ethyl))-2,2,4-trimethyl 1-1H[ 1 ]benzopyrano[3,4-f]quinoline

The succinate ester (intermediate) from Example 200 and morpholine are treated according to the method of Example 200 to give the desired compound.

MS (DCI/NH 3 ) m/e 465 (M+H) ⁺ ;

^X H NMR (400 MHz, DMSO-ck) δ 7.95 (d, J=9 Hz, 1H), 7.07 (t, J=8 Hz, 1H), 6.71 (d, J=8 Hz, 1H), 6.60 (d, J =8 Hz, 1H), 6.57 (d, >8 Hz, 1H), 6.10 (s, 1H), 5.88 (dd, J=3+10 Hz, 1H), 5.44 (s, 1H), 4.05 (m, 2H), 3.85 (s, 3H), 3.75 (m, 4H), 2.16 (s, 3H), 1.85 (m, 1H), 1.78 (m, 1H), 1.16 (s, 3H), 1.15 (s, 3H);

¹³ C NMR (100 MHz, DMSO-d _ó ) δ 156.2, 154.4, 150.6, 145.6, 133.5, 131.8, 127.3, 127.2,

127.1, 116 (1), 115.9, 113.2, 113.2, 110.1, 105.6, 70.3, 65.8, 61 (2), 55.6, 49.7, 43.7, 43.6, 31.3, 29.0,28.9, 23.8;

Analytical calcd for C27H32N2O51/4H2O: C, 69.14; H, 6.98; N, 5.97. Found: C, 68.96; H, 7.05; N, 5.94.

Example 202

2,5-dihydro-10-methoxy-5-(2-(N-(2-methoxyethyl)aminocarbonyloxy)ethyl)-2,2,4-trimethyl1 Η- [ 1 jbenzopyrano [3,4-f] quinoline

The succinate ester (intermediate) from Example 200 and 2-methoxyethylamine are treated according to the method of Example 200 to give the desired compound.

MS (DCI/NH 3 ) m/e 453 (M+H) ⁺ ;

• · • ·

175 • · · · • · · • · · · · • · • · · · · · ³ H NMR (500 MHz, DMSO-40 δ 7.95 (d, J=8 Hz, IH), 7.13 (m, IH), 7.04 (t, J=8 Hz, IH), 6.70 (d, J=8 Hz, IH), 6.56 (d, J-8 Hz, IH), 6.08 (s, IH), 5.85d (10, IH), 5.45 (s, IH), 3.95 (m, 2H), 3.85 (s, 3H), 3.25 (s, 3H), 3.12 (m, 2H), 2.15 (s, 3H), 1.92 (m, IH), 1.72 (m, IH), 1.15 (d, 6H);

¹³ C NMR (125 MHz, DMSO-d ₆ ) δ 156.1, 156.1, 150.7, 145.6, 133.5, 131.9, 127.6, , 127.1,

127.1, 116.3, 116.0, 113.2, 113.2, 110.2, 105.6, 70.7, 70.3, 60.0, 57.8, 55.6, 49.6, 31.5, 28.8, 28.8, 23.8.

Example 203

2,5-dihydro-10-methoxy-5-(2-(N-methylaminocarbonyloxy)ethyl-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline

The succinate ester (intermediate) from Example 200 and methylamine are treated according to the method of Example 200 to give the desired compound.

MS (DCI/NH 3 ) m/e 409 (M+H) ⁺ ;

’H NMR (500 MHz, DMSO-dg) δ 7.95 (d, J=8 Hz, IH), 7.04 (t, J=8 Hz, IH), 6.93 (m, IH),

6.70 (d, J=8 Hz, IH), 6.60 (d, J=8 Hz, IH), 6.56 (d, >8 Hz, IH), 6.08 (s, IH), 5.85d (10, IH), 5.45 (s, IH), 3.95 (m, 2H), 3.85 (s, 3H), 2.59 (d, 3H), 2.15 (s, 3H), 1.92 (m, 1H), 1.72 (m, 1H), 1.15 (d, 6H);

¹³ C NMR (125 MHz, DMSO-ds) δ 156.6, 156.1, 150.7, 145.6, 133.5, 131.9, 127.5, 127.2,

127.1, 116.3 (116.0), 113.2, 113.2, 113.2, 105.6, 70.3, 60.0, 55.6, 49.6, 31.5, 28.8, 28.8, 26.9,

23.7;

Analytical calcd for C24H28N2O4: C, 70.57; H, 6.91; N, 6.86. Found: C, 70.30; H, 6.91; N, 6.58.

Example 204

2,5-dihydro-10-methoxy-5-(2-(N,N-dimethylaminocarbonyloxy)ethyl)-2,2,4-trimethyl-1H[ 1 jbenzopyrano [3,4-fquinoline

The succinate ester (intermediate) from Example 200 and N,N-dimethylamine were treated according to the method of Example 200 to give the title compound as a white solid. MS (DCI/NH3) m/e 423 (M+H) ⁺ ;

’H NMR (300 MHz, DMSO-dé) δ 7.95 (d, J-8 Hz, IH), 7.05 (t, J=8 Hz, IH), 6.69 (d, J=8 Hz, IH), 6.56 (dd, J=8 Hz, 2H), 6.12 (s, IH), 5.86 (dd, J-3+10 Hz, IH), 5.44 (s, IH), 3.96 (m, » · · · · • · · · <

• · »· · · ·

176

2H), 3.85 (s, 3H), 2.86 (s, 3H), 2.83 (s, 3H), 2.18 (s, 3H), 1.95 (m, 1H), 1.76 (m, 1H), 1.15 (s, 6H).

Example 205

2,5-dihydro-10-methoxy-5-(2-methoxymethoxyethyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline

The compound from Example 199 (0.040 g, 0.114 mmol) was combined with chloromethylmethyl ether (13 μΐ, 0.171 mmol), (i-Pr) ₂ NEt (40 μΐ, 0.228 mmol) and methylene chloride (5 mL) and heated at reflux for 3 h. The reaction mixture was partitioned between H ₂ O and ethyl acetate layers, the aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with saturated aqueous sodium bicarbonate solution, brine, dried over MgSO 4 and purified by column chromatography on silica gel with 2% then 5% ethyl acetate in methylene chloride to give 45 mg (4(j%) of the desired product.

MS (DCI/NH 2 ) m/e 396 (M+H) ⁺ ;

’H NMR (300 MHz, DMSO-dg) δ 7.95 (d, J-9 Hz, 1H), 7.05 (t, J-8 Hz, 1H), 6.70 (d, J-8 Hz, 1H), 6.60 (d, J-8 Hz, 1H), 6.55 (d, J-8 Hz, 1H), 6.14 (s, 1H), 5.89 (dd, J-3+10 Hz, 1H), 5.45 (s, 1H), 4.55 (s, 2H), 3.85 (s, 3H), 3.58 (m, 1H), 3.25 (s, 3H), 2.18 (s, 3H), 1.85 (m, 1H), 1.65 (m, 1H), 1.19 (s, 3H), 1.13 (s, 3H);

Analytical calcd for C24H29NO41/ _4H2O : C, 72.07; H, 7.43; N, 3.50. Found: C, 71.90; H, 7.33; N, 3.24.

Example 206

2.5-Dihydro-10-methoxy-5-(2,2-dimethylethoxycarbonylamino)methyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-quinoline

Example 206A

2,5-dihydro-10-methoxy-5-(aminomethyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline ml ethereal suspension of LIAHIH4 (0.050 g, 1.31 mmol) was treated dropwise at room temperature with 5.0 ml ethereal solution of AlCl3 (0.59 g, 4.4 mmol), stirred for 30 min and treated dropwise with 4.0 ml ethereal solution from Example 44. After stirring for 1 h at room temperature, 2.0 ml _H2O was carefully added dropwise, followed by 15% NaOH until a white paste was formed. The ethereal solution was decanted, the paste was washed several times with ether, and the combined organic layers were washed with brine and dried _{( Na2SO4} ). The residue \ΊΊ > ·· ·· ·· • · · · · · * • · · · · · · · · · · · · · · · · · · · · · > ·· ·· ·· ·· was purified by column chromatography on silica gel with a mobile phase of CH ₂ Cl ₂ :CH 3 OH (8:1) to give 0.031 g (69%) of the amino methyl analogue, which was used in the next step.

Example 206

2,5-dihydro-10-methoxy-5-(2,2-dimethylethoxycarbonylamino)methyl)-2,2,4-trimethyl-1H[ 1 ]benzopyrano[3,4-f]quinoline

The above aminomethyl analogue (0.065 g, 0.19 mmol) was dissolved in dichloromethane (6.0 mL), cooled to 0°C, and treated with BoC ₂ O (0.93 g, 0.42 mmol). Allow to stand at room temperature overnight due to warming. 10 mL of H ₂ O was added and the phases were separated. The organic layer was washed with brine and dried (Na ₂ SO 4 ). The residue was purified by column chromatography on silica gel CH ₂ Cl ₂ :CH 3 OH (8:1) to give 0.080 g (95%) of the desired compound.

Melting point 130-135°C;

Η NMR (400 MHz, DMSO-dé) δ 7.98 (d, J=9 Hz, 1H), 7.70 (t, J=9 Hz; 1H), 6.79 (t, >5 Hz, 1H), 6.67 (d, J=9 Hz, 1H), 6.60 (d, J=9 Hz, 1H), 6.53 (d, J=8 Hz, 1H) 6.12 (s, 1H), 5.80 (dd, J=10, 10 Hz, 1H), 5.42 (s, 1H), 3.85 (s, 3H), 3.14 (m, 1H), 2.86 (m, 1H), 2.19 (s, 3H), 1.47 (s, 3H), 1.21 (s, 3H), 1.12 (s, 3H), .84 (m, 1H);

¹³ C NMR (100 MHz, DMSO,4) δ 156.1, 155.5, 150.9, 145.4, 133.4, 131.5, 129.5, 128.6, 127.8, 126.9, 117.1, 116.4, 113.4, 112.7, 110.5, 105.3, 77.7, 72.3, 67.4, 55.6, 49.5, 41.5, 29.8, 29.2, 28.3, 28.2, 23.4, 23.2, 22.3;

HRMS (FAB) m/e calcd for Ο ₂ 6Η ₃₂ Ν ₂ Ο ₄ : 436.2362. Found: 436.2360.

Example 207

2,5-dihydro-10-methoxy-5-(ethoxycarbonylamino)methyl)-2,2,4-trimethyl-1H[ 1 jbenzopyrano [3,4-f] quinoline

Example 206A (0.047 g, 0.14 mmol) in THF (10 mL) was treated with triethylamine (21.0 μΐ, 0.14 mmol). Ethyl chloroformate (14.1 μΐ, 0.14 mmol) was then added dropwise. After 30 min, the reaction mixture was poured into H ₂ O, the aqueous layer was extracted with ethyl acetate, and the combined organic layers were washed 1× with H ₂ O, 1× with brine, and dried (Na ₂ SO ₄ ). The residue was purified on a silica gel column with 3:2 hexanes:ethyl acetate to afford 0.047 g (80%) of the title compound as a solid.

Ή NMR (300 MHz, DMSO-cL) δ 7.98 (d, J=8 Hz, 1H), 7.13 (t, 1H), 7.03 (t, J=8 Hz, 1H), 6.67 (d, J=8 Hz, 1H), 6.57 (d, J=8 Hz, 1H), 6.54 (d, J=8 Hz, 1H), 6.13 (s, 3H), 5.83 (dd, 1H), ·· ··

178 ···· ·· • · · • · · • * · • · ·

5.43 (s, 1H), 3.94 (m, 2H), 3.85 (s, 3H), 3.13 (m, 1H), 2.94 (m, 1H), 2.21 (s, 3H), 1.20 (s, 3H), 1.17 (s, 3H), 1.11 (s, 3H);

¹³ C NMR (75 MHz, DMSO-do) δ 156.1, 150.8, 145.5, 133.4, 129.4, 127.7, 127.0, 117.0, 116.4, 113.5, 112.7, 110.6, 105.4, 72.2, 59.7, 55.6, 49.6, 41.8, 29.2, 28.3, 23.5, 14.6;

HRMS m/e calcd for C24H28N2O4: 408.2049. Found: 408.2044.

Example 208

2,5-dihydro-10-methoxy-5-(carboethoxy)-2,2,4-trimethyl-1 H-[ 1 ]benzopyrano[3,4-f] quinoline To the compound of Example 61 was added 2.0 mL of 5% aqueous HCl, 5.0 mL of H2O, and enough ethanol to make the solution homogeneous, then heated at 35°C for 1 hour, saturated aqueous sodium bicarbonate to pH 7. The reaction mixture was extracted with ethyl acetate. The organic layers were washed with _H2O , brine, and dried (Na2SO4). The residue was purified by column chromatography on silica gel with a mobile phase of 7:1-5:1-3:2 hexanes:ethyl acetate to give 0.041 g (48%) of the title compound as a solid. MS (DCI/NH ₃ ) m/e 380 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-dó) δ 7.90 (d, J=9 Hz, 1H), 7.04 (t, J=8 Hz, 1H), 6.64 (d, J=8 Hz, 1H), 6.61 (m, 2H), 6.32 (s, 1H), 6.21 (s, 1H), 5.45 (s, 1H), 3.90 (m, 2H), 3.84 (s, 3H), 1.17 (s, 3H), 1.15 (s, 3H), .93 (t, J=7 Hz, 3H);

¹³ C NMR (100 MHz, DMSO-do) δ 169.4, 156.2, 152.5, 145.4, 133.1, 127.6, 126.9, 126.0,

118.2, 117.7, 114.7, 109.8, 105.7, 73.0, 60.7, 55.6, 49.9, 28.9, 28.7, 22.8, 13.7;

Analytical calcd for C23H25NO4 1/ _4H2O : C, 71.95; H, 6.68; N, 3.65. Found: C, 72.21; H, 6.41; N, 3.85.

Example 209

2,5-Dihydro-10-methoxy-5-(cyclopentyl)-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4-f]quinoline The compound of Example 2B and cyclopentylmagnesium bromide are treated according to the method of Example 11 to give the desired compound.

MS (DCI/NH 3 ) m/e 376 (M+H) ⁺ ;

¹ ϊ I NMR (300 MHz, DMSO-dó) δ 8.01 (d, J=8 Hz, 1H), 7.03 (t, J=8 Hz, 1H), 6.65 (d, J=8 Hz,

1H), 6.59 (d, J = 9 Hz, 1H), 6.52 (d, J=8 Hz, 1H), 6.20 (s, 1H), 5.46 (s, 3H), 3.85 (s, 3H), 2.16 (s, 3H), 1.50 (m, 5H), 1.30 (s, 3H), 1.16 (m, 3H), 1.01 (s, 3H);

¹³ C NMR (100 MHz, DMSO-do) δ 156.2, 151.7, 145.0, 133.7, 131.6, 128.1, 126.7, 117.7,

116.4, 113.3, 112.6, 109.9, 105.0, 76.5, 49.2, 42.5, 29.8, 29.5, 27.5, 26.6, 24.8, 24.6, 23.6;

179 »· ·« • · · · • · ·

B ··· B

B ·

BBBBB ··

BB

B · · • · ·

B ··· • ·

BB

B B B • · · • · ·

B B B • B

Analytical calcd for C25H29O2NI/2H2O. C, 78.09; H, 7.86; N, 3.64. Found: C, 78.09; H, 7.52; N, 3.42.

Example 210

2,5-dihydro-10-methoxy-5-(1-methylpropa-1,2-dienyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline

The compound of Example 2B and propargylmagnesium bromide (Gaoni, Y.; Leznoff, C. C.; Sondheimer, F. J. Am. Chem. Soc. 1968, 90, 4940-4945, ) are treated according to the method of Example 11 to give the desired compound.

Melting point 59-63°;

*H NMR (300 MHz, DMSO-dó) δ 7.84 (d, J=8 Hz, 1H), 7.03 (t, J =6 Hz, 1H), 6.68 (d, J=6 Hz, 1H), 6.55 (d, J=8 Hz, 2H), 6.04 (s, 1H), 5.97 (s, 1H), 5.40 (s, 1H), 4.94 (m, 1H), 4.23 (m, 1H), 3.82 (s, 3H), 2.11 (s, 3H), 1.70 (s, 3H), 1.21 (s, 3H), 1.10 (s, 3H);

¹³ C NMR (100 MHz, DMSO-de) δ 156.1, 151.2, 150.5, 145.1, 132.6, 130.5, 127.9, 127.1,

127.0, 126.7, 126.5, 117 (5), 117.1, 114.7, 113.3, 112.9, 110.1, 106.3, 98.6, 76.2, 75.6, 55.9,

49.6, 29.4, 28.4, 22.5, 16.0;

MS m/e calcd for C24H25O2N: 359.1885. Found: 359.1893.

Example 211

2,5-dihydro-10-methoxy-5-(3,4,5-trifluorophen1)-2,2,4-trimethyl-1H-[1jbenzopyrano[3,4f]quinoline

The compound of Example 2B and 3,4,5-trifluorophenylmagnesium bromide are treated according to the method of Example 11 to give the desired compound.

MS (DCI/NH 3 ) m/e 438 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-cU) δ 8.04 (d, J=8 Hz, 1H), 6.94 -7.02 (m, 3H), 6.77 (s, 1H), 6.74 (d, J=9 Hz, 1H), 6.62 (d, J=8 Hz, 1H), 6.51 (d, J=8 Hz, 1H), 6.31 (br s, 1H), 5.43 (s, 1H), 3.81 (s, 3H), 1.85 (s, 3H), 1.23 (s, 3H), 1.15 (s, 3H);

Analytical calcd for C26H22NO2F31/4H2O: C, 70.66; H, 5.13; N, 3.17. Found: C, 70.89; H, 5.19; N, 2.93.

Example 212

2,5-dihydro-10-methoxy-5-(cyclohexyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f|quinoline

180

The compound of Example 2B and cyclohexylmagnesium bromide are treated according to the method of Example 11 to give the desired compound.

MS (DCI/NH ₃ ) m/e 308 (M+H) ⁺ ;

Major fraction: li NMR (300 MHz, DMSO-d _ó ) δ 8.03 (d, J=9 Hz, 1H), 7.05 (t, J=8 Hz, 1H), 6.72 (d, J=8 Hz, 1H), 6.61 (d, J=9 Hz, 1H), 6.59 (s, 1H), 6.15 (d, J=8 Hz, 1H), 5.40 (m, 2H), 3.86 (s, 3H), 2.01 (s, 3H), 1.61 (m, 1H), 1.56-1.41 (m, 2H), 1.35-0.96 (m, 6H), 1.29 (s, 3H), 1.18 (s, 3H), 0.95-0.77 (m, 2H);

Analytical calcd for C26H31NO2 1/2H2O: C, 78.6; H, 8.09; N, 3.51. Found: C, 78.24; H, 7.72; N, 3.70.

Example 213

2.5-Dihydro-10-methoxy-5-(2-pyridyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline

Example 213A

2.5-Dihydro-10-methoxy-5-(2-pyridyl)-2,2,4-trimethyl-1H-[1jbenzopyrano[3,4-quinoline

To a solution of Example 2A (1.42 g, 4.39 mmol) in THF (40 mL) at 0°C was added a solution of potassium tert-butoxide (1.48 g, 13.2 mmol) in THF (13 mL). The mixture was stirred for 45 min at 0°C, then a solution of TBSC1 (1.46 g, 9.66 mmol) in THF (9 _; 5 mL) was added dropwise. The solution was stirred at 0°C for 30 min, then saturated aqueous NH4Cl (10 mL) was added and extracted with EtOAc (2 x 30 mL). The combined organics were washed with brine (8 mL) and dried (Na2SO4). Filtration and concentration gave a brown residue which was purified by flash chromatography with 2% EtOAc/CFECE to give the desired product as a yellow solid (994 mg, 2.28 mmol, 52%).

MS (DCI/NH 3 ) m/z 438 (M+H) ⁺ .

Example 213

2.5-Dihydro-10-methoxy-5-(2-pyridyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-quinoline

A solution of 2-lithiopyridine (normally 1 M in THF) was prepared by adding n-BuLi (680 μΐ of a 2.5 M solution in hexanes, 1.70 mmol) to a solution of 2-bromopyridine (285 mg, 1.80 mmol) in THF (17 mL) at -78°C. This solution was stirred for 20 min, then the above-prepared solution of the aldehyde (211 mg, 0.480 mmol) in THF (2.0 mL) was added dropwise at -78°C. The solution was stirred at -78°C for 30 min, then saturated aqueous NH4Cl (7 mL) was added and extracted with EtOAc (2 x 30 mL). The combined organics were washed with brine

181 • Φ φφ ·· ·· ·· ·· φ φ · · φ *· · · ·· ί φ φ φ · φ · φ φ φφ * • ··· φ · · φφφ · φ ·· · • 9 Φ · · · · · ·

999 9 9 9 99 99 Φ® 99 (10 ml) and dried (Na ₂ SO ₄ ). Filtration and concentration gave a brown residue which was used without further purification.

The crude material prepared above was dissolved in THF (10 mL) at 23°C and treated with tetrabutylammonium fluoride (500 μΐ of a 1 M solution in THF, 0.500 mmol). After 1 h, the reaction mixture was concentrated in vacuo, resuspended in EtOAc (20 mL), and then washed with water (5 mL), brine (5 mL), and dried (Na ₂ SO ₄ ). Filtration and concentration afforded a brown residue, which was used without further purification.

This crude residue was dissolved in THF (10 mL) and the solution was cooled to 0°C. To this solution was added triethylphosphine (48 mg, 0.410 mmol), followed by a solution of 1,1'(azodicarbonyl)dipiperidine (103 mg, 0.410 mmol) in THF (1.5 mL). The solution was stirred for 30 min at 0°C, then at 23°C for 7 h. The reaction mixture was concentrated and purified by flash chromatography (mobile phase 25% EtOAc/hexane) to give the desired product (13 mg, 0.034 mmol, 8%) as a colorless solid.

MS (DCI/NH ₃ ) m/z 385 (M+H) ⁴ ;

Ή NMR (300 MHz, DMSO) δ 8.45 (br d, >6.6 Hz, 1H), 7.98 (d, >8.0 Hz, 1H), 7.61 (td, >6.5, 1.8 Hz, 1H), 7.19-7.13 (m, 2 H), 6.91 (t, >6.6 Hz, 1H), 6.72 (s, 1H), 6.68 (d, J = 7.9 Hz, 1H), 6.57 (br d, 1=6.7 Hz, ,1 H), 6.44 (dd, >6.5, 1.0 Hz, 1H), 6.17 (br s, 1H), 5.37 (br s,

1H), 3.80 (s, 3H), 1.80 (s, 3H), 1.23 (s, 3H), 1.13 (s, 3H);

HRMS (FAB) calcd for (M+H) ⁺ for C ₂ 5 H 2 5 N ₂ O ₂ .· 385.1916 . Found: 385.1910.

Example 214

2,5-Dihydro-10-methoxy-5-(3-pyridyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline The desired compound was prepared according to the method of Example 213 in 49% yield.

MS (DCI/NH ₃ ) m/z 385 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO) δ 8.38 (d, >2.4 Hz, 1H), 8.35 (dd, >5.6, 2.0 Hz, 1H), 8.02 (d, >8.0 Hz, 1H), 7.49 (br d, >6.9 Hz, 1H), 7.25 (dd, >6.9, 5.5 Hz, 1H), 6.92 (t, >9 Hz, 1H), 6.86 (s, 1H), 6.72 (d, >8.1Ηζ, 1H), 6.58 (d, >6.7 Hz, 1H), 6.45 (d, >6.4 Hz, 1H), 6.38 (br s, 1H), 5.41 (br s, 1H), 3.80 (s, 3H), 1.83 (s, 3 H), 1.23 (s, 3H), 1.15 (s, 3H);

¹³ C NMR (125 MHz, DMSO) δ 156.0, 151.2, 149.4, 148.8, 145.6, 135.7, 134.7, 133.2, 128.5,

127.3, 127.2, 127.0, 123.2, 117.7, 117.2, 113.9, 113.7, 110.2, 105.7, 73.0, 55.5, 49.8, 29.5, 28.5,23.4;

HRMS (FAB) calculated m/z for _C25H25N2O2 : _385.1916 (M+H ₎ +. Found: _385.1915 .

182 ·« *· • · · * • · · • ··· · • · ···· 99 « 4 4 · · * · • · 4 · · · · · • 4 4 · · 4 4 · *

9 9 9 9 9

99 99

Analytical calcd for C25H24N2O2. C, 78.09; H, 6.29; N, 7.28. Found: C, 76.98; H, 6.60; N, 6.93.

Example 215

2,5-Dihydro-10-methoxy-5-(4-pyridyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline The desired compound was prepared according to the method of Example 213 in 20% yield.

MS (DCI/NH 3 ) m/z 385 (M+H) ⁺ ;

*Η NMR (300 MHz, DMSO) δ 8.43 (br d, J=4.3 Hz, 2 H), 8.04 (d, >8.0 Hz, 1H), 7.15 (d, >4.2 Hz, 2 H), 6.96 (t, >6.7 Hz, 1H), 6.81 (s, 1H), 6.75 (d, >7.9 Hz, 1H), 6.59 (d, >6.8 Hz, 1H), 6.53 (d, >6.8 Hz, 1H), 6.37 (br s, 1H), 5.43 (br s, 1H), 3.79 (s, 3H), 1.88 (s, 3H),

1.26 (s, 3H), 1.18 (s, 3H);

¹³ C NMR (125 MHz, DMSO) δ 156.1, 151.4, 149.4 (2), 148.2, 145.6, 133.4, 133.3, 128.3, 127.3 (2), 127.0, 122.9, 117.9, 117.0, 113.9, 110.2, 105.6, 105.0, 103.0, 73.4, 49.8, 29.4,

28.6, 23.2;

HRMS (FAB) m/z calcd for C25H25N2O2: 385.1916 (M+H) ⁺ . Found: 385.1906.

The chemical procedure with core 2 described in Schemes 1-21 and Examples 1-215 was used to prepare the compounds of Examples 216-226.

Example 216

10-chloro-9-hydroxy-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4fquinoline

MS (DCI/NH 3 ) m/z 368 (M+H) ⁺ ;

*H NMR (300 MHz, DMSO) δ 9.34 (s, 1H), 7.87 (d, >8 Hz, 1H), 6.72 (d, >8 Hz, 1 H), 6.66 (d, >8 Hz, 1H), 6.58 (d, >8 Hz, 1H), 6.21 (br s, 1H), 5.81-5.71 (m, 1H), 5.62 (dd >10, 3 Hz, 1H), 5.41 (br s, 1H), 4.98 (dd, >10, 2 Hz, 1H), 4.93 (dd, >17, 2 Hz, 1H), 2.42-2.34 (m, 1H), 2.26-2.20 (m, 1H), 2.11 (s, 3 H), 1.16 (s, 3H), 1.11 (s, 3H);

HRMS (FAB) calculated m/z for C22H22CINO2: 367.1339. Found: 367.1336.

Example 217

10-chloro-9-hydroxy-5-phenyl-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4-f]quinoline MS (DCI/NH ₃ ) m/z 404 (M+H) ⁺ ;

183 ’Η NMR (300 MHz, DMSO) δ 9.46 (s, 1H), 7.96 (d, >8 Hz, 1H), 7.26-7.12 (m, 3 H), 7.147.07 (m, 1H), 6.87 (dd, >8, 2 Hz, 1H), 6.72 (d, J=8 Hz, 1H). 6.68 (s, 1H), 6.58 (app s, 2H), 6.37 (br s, 1H), 5.40 (br s, 1H), 1.80 (s, 3H), 1.26 (s, 3H), 1.17 (s, 3H);

HRMS (FAB) calculated m/z for C25H22CINO2: 403.1339. Found: 403.134 4.

Example 218

10-chloro-9-hydroxy-5-(3-trifluoromethylphenyl)-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-f]quinoline

MS (DCI/NH 3 ) m/z 472 (M+H) ⁺ ;

Η NMR δ 9.45 (s, 1H), 7.98 (d, 1H, >8.5Hz), 7.54 (m, 4H), 6.85 (d, 1H, >8.5Hz), 6.75 (m, 2H), 6.57 (d, 1H, >8.5Hz), 6.42 (m, 1H), 5.39 (m, 1H), 1.91 (s, 3H), 1.24 (s, 3H), 1.11 (s, 3H);

Analytical calcd for C26H21CIF3NO2: 471.1213. Found: 471.1216.

Example 219

10-chloro-9-hydroxy-5-(3,5-dimethylphenyl)-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-f]quinoline

MS (DCI/NH 3 ) m/z 432 (M+H) ⁺ ;

’H NMR δ 9.52 (s, 1H), 7.95 (d, 1H, J=8.5Hz), 6.82 (m, 2H), 6.71 (m, 2H), 6.61 (s, 2H), 6.36 (m, 1H), 6.42 (m, 1H), 5.40 (m, 1H), 2.31 (s, 6H), 1.92 (d, 3H, >1.4Hz), 1.24 (s, 2H), 1.14 (s, 2H);

HRMS (FAB) m/z calcd for C27H26CINO2: 421.1652. Found: 431.1650.

Example 220 rel-{5 S,3' R)-9-hydroxy-10-methoxy-5-[1-hydroxymethyl-3-cyclohexenyl]-2,2,4-trimethyl-2,5-dihydro-1 H-[1]benzopyrano[3,4- f ]quinoline MS (DCI/NH3) m/z 438 (M+H) ⁺ ;

*H NMR (300 MHz, DMSO) δ 9.56 (s, 1H), 8.01 (d, >8 Hz, 1H), 6.77 (app s, 2H), 6.67 (d, >8 Hz, 1H), 6.39 (br s, 1H), 5.48 (d, >10 Hz, 1H), 5.42 (br s, 1H), 5.10 (br s, 1H), 4.42 (t, J =6 Hz, 1H), 3.65 (br d, >6 Hz, 2 H), 2.28-2.18 (m, 2 H), 2.05 (hr s, 3 H), 1.94-1.87 (m, 2 H), 1.75-1.64 (m, 1H), 1.52-1.42 (m, 1H), 1.36-1.27 (m, 1H), 1.29 (s, 3H), 1.10 (s, 3H);

HRMS (FAB) m/z calcd for C26H28CINO3: 437.1758. Found: 437.1756.

• · ·

184

Lactol-9-tert-butyldimethylsilyl ether at the C5 position of the 2-nucleus and 3-cyclopentenyltrimethylsilane are treated according to the above method to give a (2:1) mixture of diastereoisomers, which is subjected to HPLC on a (R,R) WHELK-0 1 column with a mobile phase of 2% EtOH in hexanes to give the individual enantiomers.

Example 221 (-) 2,5(S)-Dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(3S-cyclopentenyl)-1H[1]benzopyrano[3,4-f]quinoline [a] _D ²³ = -220° (c 0.012, CHCl ₃ );

MS (DCI/NH 3 ) m/z 394 (M+H) ⁺ ;

*H NMR (300 MHz, DMSO-dg) δ 9.55 (s, 1H), 8.00 (d, 1H), 6.75 (d, 1H), 6.72 (d, 1H), 6.63 (d, 1H), 6.36 (s, 1H), 5.73 (ddd, 1H), 5.44 (d, 1H), 5.40 (s, 1H), 5.17 (ddd, 1H), 2.78 (m, 1H), 2.35 (m, 1H), 2.15 (m, 1H), 2.05 (s, 3H), 1.80 (m, 1H), 1.72 (m, 1H), 1.27 (s, 3H), 1.05 (s, 3H);

¹³ C NMR (400 MHz, DMSO-d ₆ ) δ 148.7, 146.0, 144.0, 134.0, 133.6, 132.7, 129.9, 127.9,

127.0, 123.7, 116.6, 115.8, 115.4, 114.2, 112.4, 76.1, 49.6, 48.2, 31.7, 29.8, 27.8, 27.3, 24.4.

Example 222 (-) 2,5(S)-Dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(3R-cyclopentenyl)-1H[1]benzopyrano[3,4-f]quinoline [a] _D ²³ = -232° (c 0.010, CHCl ₃ );

MS (DCI/NH 3 ) m/z 394 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-dg) δ 9.50 (bs, 1H), 8.02 (d, 1H), 6.75 (d, 1H), 6.72 (d, 1H), 6.63 (d, 1H), 6.39 (s, 1H), 5.74 (ddd, 1H), 5.60 (ddd, 1H), 5.46 (s, 1H), 5.39 (d, 1H), 2.83 (m, 1H),

2.26 (m, 1H), 2.14 (m, 1H), 2.09 (s, 3H), 1.55-1.40 (m, 2H), 1.27 (s, 3H), 1.01 (s, 3H);

¹³ C NMR (400 MHz, DMSO-d ₆ ) δ 148.7, 146.0, 144.6, 134.1, 132.8, 132.0, 131.7, 127.8,

126.8, 123.6, 117.4, 115.9, 115.8, 115.5, 114.2, 112.3, 76.4, 49.4, 48.0, 31.7, 29.5, 27.2, 24.5,

23.8.

Example 223

10-Chloro-9-hydroxy-5-(3,5-dichlorophenyl)-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-quinoline

185

MS (DCI/NH ₃ ) m/z 472 (M+H) ⁺ ;

*H NMR δ 9.40 (s, 1H), 8.01 (d, 1H, J=8.5Hz), 7.43 (m, 4H), 6.85 (d, 1H, J=8.5Hz), 6.71 (m, 1H), 6.57 (d, 1H, >8.5Hz), 6.42 (m, 1H), 5.47 (m, 1H), 1.81 (s, 3H), 1.29 (s, 3H), 1.09 (s, 3H);

HRMS (FAB) _{calculated m/z for C25H20Cl3NO2 :} 471.0559. Found: _471.0556 .

Example 224 (+)-(5R,3'S) 2,5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(3-cyclopentenyl)-1H[1]benzopyrano[3,4-f]quinoline [a] _D ²³ = + 256° (c 0.046, CHCl ₃ ),

MS (DCI/NH 3 ) m/z 394 (M+H) ⁺ ;

^] H NMR (300 MHz, DMSO-de) δ 9.50 (bs, 1H), 8.02 (d, 1H), 6.75 (d, 1H), 6.72 (d, 1H), 6.63 (d, 1H), 6.39 (s, 1H), 5.74 (ddd, 1H), 5.60 (ddd, 1H), 5.46 (s, 1H), 5.39 (d, 1H), 2.83 (m, 1H),

2.26 (m, 1H), 2.14 (m, 1H), 2.09 (s, 3H), 1.55-1.40 (m, 2H), 1.27 (s, 3H), 1.10 (s, 3H);

¹³ C NMR (400 MHz, DMSO-d ₆ ) δ 148.7, 146.0, 144.6, 134.1, 132.8, 132.0, 131.7, 127.8,

126.8, 123.6, 117.4, 115.9, 115.8, 115.5, 114.2, 112.3, 76.4,49.4, 48.0, 31.7, 29.5, 27.2, 24.5,

23.8.

Example 225 (+)-(5R,3'R) 2,5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(3-cyclopentenyl)-1H[1]benzopyrano[3,4-f]quinoline [α]d ²³ =+244° (c 0.165, CHCl3);

MS (DCI/NH 3 ) m/z 394 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-d _ó ) δ 9.55 (s, 1H), 8.00 (d, 1H), 6.75 (d, 1H), 6.72 (d, 1H), 6.63 (d, 1H), 6.36 (s, 1H), 5.73 (ddd, 1H), 5.44 (d, 1H), 5.40 (s, 1H), 5.17 (ddd, 1H), 2.78 (m, 1H), 2.35 (m, 1H), 2.15 (m, 1H), 2.05 (s, 3H), 1.80 (m, 1H), 1.72 (m, 1H), 1.27 (s, 3H), 1.05 (s, 3H);

¹³ C NMR (400 MHz, DMSO-d ₆ ) δ 148.7, 146.0, 144.0, 134.0, 133.6, 132.7, 129.9, 127.9,

127.0, 123.7, 116.6, 115.8, 115.4, 114.2, 112.4, 76.1, 49.6, 48.2, 31.7, 29.8, 27.8, 27.3, 24.4.

Example 226

10-chloro-9-hydroxy-5-(3,4-difluorophenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4fquinoline • · • · · · ·

186

MS (DCI/NH 3 ) m/z 440 (M+H) ⁺ ;

'H NMR δ 9.41 (s, 1H), 7.94 (d, 1H, J=8.5Hz), 6.96 (m, 3H), 6.75 (m, 3H), 6.57 (d, 1H, 3=8.5Hz), 6.45 (m, 1H), 5.47 (m, 1H), 1.81 (s, 3H), 1.29 (s, 3H), 1.09 (s, 3H);

HRMS (FAB) calculated m/z for C25H20ClF2NO2: 429.1150. Found: 429.1152.

The chemical procedure with core 3 described in Schemes 1-21 and Examples 1-215 was used to prepare the compound of Example 227.

Example 227

9- 10-methylenedioxy-5-phenyl-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4-f]quinoline MS (DCI/NH3) m/z 298 (M+H) ⁺ ;

’H NMR (200 MHz, DMSO-dg) 7.72 (d, J=8.1Hz, 1H), 7.20 (m, 5H), 6.82 (s, 1H), 6.75 (d, J=8.8 Hz, 1H), 6.50 (d, J=8.1Hz, 1H), 6.26 (s, 1H), 6.27 (d, J=8.8 Hz, 1H), 6.05 (s, 1H), 5.98 (s, 1H), 5.4 (s, 1H), 1.87 (s, 2H), 1.20 (s, 2H), 1.17 (s, 2H).

The chemical procedure with core 4 described in Schemes 1-21 and Examples 1-215 was used to prepare the compounds of Examples 228-231.

Example 228

5-(3-Propenyl)-9-chloro-10-ethenyl-2,2,4-trimethyl-1H-2,5-dihydro-[ljbenzopyrano[3,4fjquinoline ’H NMR δ 7.93 (d, 1H, J=8.5Hz), 7.20 (d, 1H, J=8.5Hz), 6.70 (d, 1H, J=8.5Hz), 6.64 (d, 1H, J=8.5Hz), 6.34 (m, 1H), 5.81 (m, 2H), 5.46 (m, 1H), 5.03 (dm, 1H, J=10.5Hz), 4.98 (dm, 1H, J=17.1 Hz), 3.65 (s, 3H), 2.44 (m, 1H), 2.28 (m, 1H), 2.18 (s, 3H), 1.19 (s, 3H), 1.17 (s, 3H); HRMS (ESI) m/z calcd for C23H25CINO2: 381.1495. Found: 381.1490.

Example 229

9-chloro-10-methoxy-5-phenyl-2,2,4-trimethyl-2,5-dihydro-1H-[ljbenzopyrano[3,4-fquinoline ’H NMR δ 7.98 (d, 1H, J=8.5Hz), 7.42 (m, 1H), 7.21 (m, 5H), 7.00 (d, 1H, J=8.5Hz), 6.75 (m, 1H), 6.57 (d, 1H, J=8.5Hz), 6.42 (m, 1H), 5.47 (m, 1H), 3.65 (s, 3H), 1.81 (s, 3H), 1.29 (s, 3H), 1.09 (s, 3H);

HRMS (ESI) m/z calcd for C26H24CINO2: 417.1495. Found: 417.1497.

Example 230

187

5-(3-Propenyl)-9-chloro-10-difluoromethoxy-2,2,4-trimethyl-2,5-dihydro-1H[ 1 jbenzopyrano [3,4-f] quinoline 'H NMR δ 7.58 (d, 1H, J=8.5Hz), 7.14 (m, 2H), 6.80 (dd, 1H, J=7.3Hz), 6.64 (d, 1H, J=8.5Hz), 6.24 (m, 1H), 5.81 (m, 2H), 5.46 (m, 1H), 5.02 (dm, 1H, J=10.5Hz), 4.94 (dm, 1H, J= 17.1 Hz), 2.30 (m, 2H), 2.17 (s, 3H), 1.19 (s, 3H), 1.16 (s, 3H);

MS (ESI) m/z: 418 (M+H);

Calcd for C23H22CIF2NO2: 417.1307. Found: 417.1304.

Example 231

9-chloro-10-difluoromethoxy-5-phenyl-2,2,4-trimethyl-2,5-dihydro-1H-[l]benzopyrano[3,4f]quinoline ^! H NMR δ 7.77 (d, 1H, J=8.5Hz), 7.44 (m, 1H), 7.22 (m, 5H), 7.12 (d, 1H, J=8.5Hz), 6.84 (s, 1H), 6.76 (t, 1H, J=75Hz), 6.74 (d, 1H, J=8.5Hz), 6.51 (m, 1H), 5.39 (m, 1H), 1.78 (s, 3H), 1.26 (s, 3H), 1.14 (s, 3H);

MS (ESI) m/z: 454 (M+1);

Calcd for C26H22CIF2NO2: 453.1307. Found: 453.1304.

The chemical procedure with core 5 described in Schemes 1-21 and Examples 1-215 was used to prepare the compounds of Examples 232-233.

Example 232

8-fluoro-10-methoxy-5-phenyl-2,2,4-trimethyl-2,5-dihydro-1H-[l]benzopyrano[3,4-f]quinoline *H NMR δ 7.95 (d, 1H, J=8.5Hz), 7.30 (m, 2H), 7.20 (m, 5H), 7.00 (d, 1H, J=8.5Hz), 6.82 (s, 1H), 6.43 (m, 1H), 5.38 (m, 1H), 3.56 (s, 3H), 2.17 (s, 3H), 1.25 (s, 3H), 1.13 (s, 3H);

MS (ESI) m/z: 402 (M+H); Calcd for C26H24FNO2: 401.1791. Found: 401.1795. Analytical calcd for C26H24FNO2: C, 77.78; H, 6.02; N, 2.49. Found: C, 77.66; H, 5.90; N, 2.28.

Example 233

5-(3-Propenyl)-8-fluoro-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H-[l]benzopyrano[3,4f] quinoline *H NMR δ 7.95 (d, 1H,J =8.5Hz), 7.30 (m, 2H), 7.20 (m, 5H), 7.00 (d, 1H,J =8.5Hz), 6.82 (s, 1H), 6.43 (m, 1H), 5.38 (m, 1H), 3.56 (s, 3H), 2.17 (s, 3H), 1.25 (s, 3H), 1.13 (s, 3H);

MS (ESI) m/z: 402 (M+1);

188 ...... ·· ··'

Calcd for C26H24FNO2: 401.1791. Found: 401.1795.

The 6-core chemistry described in Schemes 1-21 and Examples 1-215 was used to prepare the compounds of Example 234.

Example 234

10-Methoxy-9-fluoro-5-(3-propenyl)-2,2,4-trimethyl-2,5-dihydro-1H-[1]benzopyrano[3,4fquinoline

MS (DCI/NH 3 ) m/z 366 (M+H) ⁺ ;

¹ H NMR (300 MHz, DMSO) δ 7.87 (d, J=8.5 Hz, 1H), 7.00 (dd, J=8.8, 2.2 Hz, 1H), 6.64 (d, J=8.1 Hz, 1H), 6.63 (d, J=8.8 Hz, 1H), 6.31 (d, J=1.1 Hz, 1H), 5.90-5.80 (m, 1 H), 5.79-5.75 (m, 1H), 5.46 (s, 1H), 5.05-4.95 (m, 2 H), 3.79 (s, 3 H), 2.17 (d, J=1.1 Hz, 1H), 1.17 (s, 6 H); HRMS calculated for C23H24FNO2 is 366.1869. Found: 366.1869.

The chemical procedure with core 7 described in Schemes 1-21 and Examples 1-215 was used to prepare the compounds of Examples 235-296.

Example 235

10-Methoxy-9-hydroxy-5-(3-propenyl)-2,2,4-trimethyl-2,5-dihydro-1H-[ljbenzopyrano[3,4fj quinoline 'H NMR (300 MHz, DMSO) δ 8.69 (s, 1H), 7.92 (d, J=8.5,1H), 6.62 (d, J=8.5 Hz, 1H) = 8.5 Hz, 1H), 6.48 (d, J=8.5, 1H), 6.16 (d, J=1.7 Hz, 1H), 5.81 (ddt, J=17.3, 10.3, 6.6 Hz, 1H), 5.67 (dd, J=9.8, 3.3 Hz), 5.44 (s, 1H), 5.02 (dd, J=10.3, 1.8 Hz, 1H), 4.98 (dd, J=17.3, 1.8 Hz, 1H), 2.47-2.41 (m, 1H), 2.34-2.27 (m, 1H), 2.16 (s, 3H), 1.18 (s, 3H), 1.16 (s, 3H);

¹³ C NMR (75 MHz, DMSO) δ 145.8, 145.1, 143.9, 142.9, 134.4, 133.4, 132.7, 127.5, 126.5,

117.8, 117.0, 116.3, 116.1, 114.3, 113.6, 112.4, 73.3, 59.3,49.7, 36.4, 29.2, 28.9, 23.9.

MS (DCI/NH 3 ) m/z 364 (M+H) ⁺ ;

Analytical calcd for C23H24N2O2: C, 76.01; H, 6.93; N, 3.85. Found: C, 75.85; H, 7.18; N, 3.66.

Example 236 (+/-) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline

MS (DCI/NH 3 ) m/z 404 (M+H) ⁺ ;

_. 1H), 5.33 (d, 1H), 3.65 (s, 3H), 2.28 (m, 1H), 2.12 (s, 3H), 1.86 (m, 2H), 1.55 (m, 1H), 1.31 (s, 3H), 1.26-1.14 (m, 3H), 1.03 (s, 3H); ¹³ C NMR (400 MHz, DMSO-d ₆ ) δ 145.4, 145.0, 144.1, 143.5, 133.6, 130.7, 128.1, 127.9, 127.7, 126.1, 118.4, 117.8, 116.5, 114.4, 113.4, 112.1,75.9, 59.3,49,4,37.2, 29.6, 27.1,24.7, 24.6, 23.7,21.2.

Example 237 (+/-) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(1-methylcyclohexen-3-yl)-1H[1]benzopyrano[3,4-f]quinoline MS (DCI/NH3) m/z 718 (M+H) ⁺ ;

*H NMR (300 MHz, DMSO-d _ó ) δ 8.66 (s, 1H), 8.00 (d, J = 8.5 Hz, 1H), 6.65 (d, J = 8.5 Hz, 1H), 6.62 (d, J = 8.5 Hz, 1H), 6.55 (d, J = 8.5 Hz, 1H), 6.24 (d, J = 1 5Hz, 1H), 5.51 (br s, 1H), 5.44 (br s, 1H), 5.30 (d, J = 9.5 Hz, 1H), 3.65 (s, 3H), 2.30 - 2.20 (m, 1H), 2.11 (s, 3H), 1.80 -1.54 (m, 3H), 1.60, (s, 3 H), 1.30 (s, 3H), 1.28-1.08 (m, 3H), 1.03 (s, 3H);

¹³ C NMR (75 MHz, DMSO-d _ó ) δ 145.3, 144.9, 144.0, 143.6, 134.7, 133.5, 130.9, 128.0,

126.1, 121.8, 118.3, 117.9, 116.5, 114.3, 113.3, 112.1, 76.2, 59.3, 49.4, 37.5, 29.6, 29.5, 27.1,

24.5,23.8, 23.7,21.6.

Example 238 (-) (5S,3'S)-9-hydroxy-5-[1-methyl-3-cyclohexenyl]-10-methoxy-2,2,4-trimethyl-2,5dihydro-1H-[1]benzopyrano[3,4-f]quinoline [α] _D =-158.8°;

MS (DCI/NH 3 ) m/z 718 (M+H) ⁺ ;

¹ H NMR (300 MHz, DMSO-dó) δ 8.66 (s, 1H), 8.00 (d, J=8.5 Hz, 1H), 6.65 (d, J=8.5Hz, 1H), 6.62 (d, J=8.5Hz, 1H), 6.55 (d, J=8.5Hz, 1H), 6.24 (d, J=1.5Hz, 1H), 5.51 (br s, 1H), 5.44 (br s, 1H), 5.30 (d, J = 5Hz, 1H), 3.65 (s, 3H), 2.30-2.20 (m, 1H), 2.11 (s, 3H), 1.80 1.54 (m, 3H), 1.60 (s, 3 H), 1.30 (s, 3H), 1.28-1.08 (m, 3H), 1.03 (s, 3H);

¹³ C NMR (75 MHz, DMSO-d ₆ ) δ 145.3, 144.9, 144.0, 143.6, 134.7, 133.5, 130.9, 128.0,

126.1, 121.8, 118.3, 117.9, 116.5, 114.3, 113.3, 112.1,76.2, 59.3, 49.4, 37.5, 29.6,29.5,27.1,

24.5,23.8, 23.7,21.6.

Analytical calcd for C27H31NO3: C, 77.67; H, 7.48; N, 3.35. Found: C, 77.65; H, 7.67; N, 3.36.

• · • · ·♦ ··

190 • · · · • · · · · • · · · · · · · · · ·

Example 239 (+) (5R,3'R)-9-hydroxy-5-[1-methyl-3-cyclohexenyl]-10-methoxy-2,2,4-trimethyl-2,5dihydro-1H-[1Jbenzopyrano[3,4-f]quinoline [α] _D = +157.9°

MS (DCI/NH 3 ) m/z 718 (M+H) ⁺ ;

H NMR (300 MHz, DMSO-d ₆ ) δ 8.66 (s, 1H), 8.00 (d, J=8.5Hz, 1H), 6.65 (d, J=8.5Hz, 1H),

6.62 (d, J=8.5 Hz, 1H), 6.55 (d, J=8.5 Hz, 1H), 6.24 (d, J=1.5 Hz, 1H), 5.51 (br s, 1H), 5.44 (br s, 1H), 530 (d, J=9.5 Hz, 1H), 3.65 (s, 3H), 2.30-2.20 (m, 1H), 2.11 (s, 3H), 1.80-1.54 (m, 3H), 1.60, (s, 3H), 1.30 (s, 3H), 1.28-1.08 (m, 3H), 1.03 (s, 3H);

¹³ C NMR (75 MHz, DMSO-d ₆ ) δ 145.3, 144.9, 144.0, 143.6, 134.7, 133.5, 130.9, 128.0,

126.1, 121.8, 118.3, 117.9, 116.5, 114.3, 113.3, 112.1, 76.2, 59.3, 49.4, 37.5, 29.6, 29.5, 27.1,

24.5, 23.8,23.7,21.6.

Analytical calcd for C27H31NO3: C, 77.67; H, 7.48; N, 3.35. Found: C, 77.65; H, 7.67; N, 3.36.

Example 240 (+) (5R,3'S)-9-hydroxy-5-[1-methyl-3-cyclohexenyl]-10-methoxy-2,2,4-trimethyl-2,5dihydro-1H-[1]benzopyrano[3,4-f]quinoline [a] _D -+78.0°

MS (DCI/NH 3 ) m/z 718 (M+H) ⁺ ;

*H NMR (300 MHz, DMSO-d ₆ ) δ 8.74 (s, 1H), 7.99 (d, J=8.8 Hz, 1H), 6.66 (d, J=8.8 Hz, 1H), 6.62 (d, J=8.5 Hz, 1H), 6.52 (d, J=8.5 Hz, 1H), 6.24 (d, J=1.5 Hz, 1H), 5.41 (br s, 1H), 5.41 (d, J=10.3 Hz, 1H), 4.84 (br s, 1H), 3.63 (s, 3H), 2.34-1.35 (m, 7H), 2.06 (s, 3H), 1.49, (s, 3H), 1.30 (s, 3H), 1.09 (s, 3H);

¹³ C NMR (75 MHz, DMSO-d ₆ ) δ 145.3, 145.0, 144.0, 143.2, 135.5, 133.3, 131.3, 128.4,

126.2, 120.5, 118.1, 117.9, 116.5, 114.4, 113.5, 112.0, 75.3, 59.3, 49.5, 36.8, 29.4, 27.5, 25.0, 24.1,23.7, 20.2.

HRMS calcd for C27H31NO3: 417.2304. Found: 417.2305.

Example 241 (-) (5S,3'R)-9-hydroxy-5-[1-methyl-3-cyclohexenyl]-10-methoxy-2,2,4-trimethyl-2,5dihydro-1 H- [1 Jbenzopyrano [3,4-f] quinoline [a] _D = -79.4° ··· · ·

191 ► ··· ·· ·· ·· ·· ·· ♦ * · · · · · · • ♦ · · · · · · • · · · · · · · · · · · · · · · · · · « ·· ·· ··

MS (DCI/NH 3 ) m/z 718 (M+H) ⁺ ;

'H NMR (300 MHz, DMSO-d ₆ ) δ 8.74 (s, 1H), 7.99 (d, J=8.8 Hz, 1H), 6.66 (d, J=8.8 Hz, 1H), 6.62 (d, J=8.5 Hz, 1H), 6.52 (d, J=8.5 Hz, 1H), 6.24 (d, J=1.8 Hz, 1H), 5.41 (br s, 1H), 5.41 (d, J=10.3 Hz, 1H), 4.84 (br s, 1H), 3.63 (s, 3H), 2.34-1.35 (m, 7H), 2.06 (s, 3H), 1.49, (s, 3H), 1.30 (s, 3H), 1.09 (s, 3H);

¹³ C NMR (75 MHz, DMSO-d ₆ ) δ 145.3, 145.0, 144.0, 143.2, 135.5, 133.3, 131.3, 128.4,

126.2, 120.5, 118.1, 117.9, 116.5, 114.4, 113.5, 112.0, 75.3,59.3,49.5,36.8,29.4, 27.5,25.0,

24.1.23.7.20.2.

Analytical calcd for C27H31NO3: C, 77.67; H, 7.48; N, 3.35. Found: C, 77.55; H, 7.56; N, 3.34.

Example 242 rel-(5S,3'R)-9-hydroxy-5-[1-hydroxymethyl-3-cyclohexenyl]-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H-[1]benzopyrano[3,4-f]quinoline MS (DCI/NH3) m/z 434 (M+H) ⁺ ;

'H NMR (300 MHz, DMSO-d ₆ ) δ 8.72 (s, 1H), 7.98 (d, J =8.8 Hz, 1H), 6.65 (d, J=8.8 Hz, 1H), 6.62 (d, J=8.8 Hz, 1H), 6.52 (d, J=8.8 Hz, 1H), 6.23 (br s, 1H), 5.43-5.39 (m, 2H), 5.06 (br s, 1H), ), 4.44 (t, J=5.1Hz, 1H), 3.69-3.67 (m, 1H), 3.67 (s, 3H), 232-2.22 (m, 1H), 2.05 (s, 3H), 1.94 -1.88 (m, 2H), 1.74-1.61 (m, 2H), 1.55-1.45 (m, 2H), 1.29 (s, 3H), 1.10 (s, 3H);

¹³ C NMR (75 MHz, DMSO-d ₆ ) δ 145.4, 145.0, 144.0, 143.1, 140.4, 133.5, 131.2, 128.2,

126.2, 120.5, 118.0, 118.0, 116.5, 114.4, 113.5, 112.1, 75.4, 65.6, 59.4, 49.5, 37.0, 29.8, 27.8,

25.8, 25.1,24.3,20.3.

Analytical calcd for C27H31NO4: C, 74.80; H, 7.21; N, 3.23. Found: C, 74.59; H, 7.21; N, 3.22.

Example 243 (+/-) (5S,3'R) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(1-methylcyclohexen-3yl)-1H-[1]benzopyrano[3,4-f]quinoline MS (DCI/NH3) m/z 718 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-d ₆ ) δ 8.66 (s, 1H), 8.00 (d, J = 8.5 Hz, 1H), 6.65 (d, J = 8.5 Hz, 1H), 6.62 (d, J = 8.5 Hz, 1H), 6.55 (d, 1 = 8.5 Hz, 1H), 6.24 (d, J = 1.5 Hz, 1H), 5.51 (br s, •φφφ φφφφ • · · · φ φ · • φφφ φ φ φ φφφ • φ φ · ·

ΦΦΦΦ ΦΦΦ _Μ ··

192 ·· φφ φ φ φ φ φ φ φ φ φ φ φ φ • φ φ φ φφ φφ

1Η), 5.44 (br s, IH), 5.30 (d, J = 9.5 Hz, IH), 3.65 (s, 3 H), 2.30 - 2.20 (m, IH), 2.11 (s, 3 H), 1.80 -1.54 (m, 3 H), 1.60 (s, 3 H), 1.30 (s, 3 H), 1.28 - 1.08 (m, 3H), 1.03 (s, 3H);

¹³ C NMR (75 MHz, DMSO-d ₆ ) δ 145.3, 144.9, 144.0, 143.6, 134.7, 133.5, 130.9, 128.0,

126.1, 121.8, 118.3, 117.9, 116.5, 114.3, 113.3, 112.1,76.2, 59.3,49.4,37.5,29.6, 29.5,27.1,

24.5,23.8, 23.7,21.6.

Example 244 rel (5S, 3'R)-9-hydroxy-5-[1-methoxymethyl-3-cyclohexenyl]-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H-[1]benzopyrano[3,4-f]quinoline MS (DCI/NH3) m/z 448 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-d ₆ ) δ 8.75 (s, IH), 8.00 (d, J=8.5 Hz, IH), 6.67 (d, J=8.5 Hz, IH), 6.62 (d, J=8.5 Hz, IH), 6.54 (d, J=8.5 Hz, IH), 6.27 (d, J=1.5 Hz, IH), 5.46 (d, J=9.9 Hz, IH), 5.38 (br s, IH), 5.21 (br s, IH), 4.33-4.29 (m, IH), 3.66-3.63 (m, IH), 3.65 (s, 3 H), 3.64 (s, 3 H), 2.32-1.45 (m, 7 H), 2.04 (s, 3 H), 1.29 (s, 3 H), 1.07 (s, 3H);

Analytical calcd for C28H33NO4: C, 75.14; H, 7.43; N, 3.13. Found: C, 74.81; H, 7.35; N, 3.05.

Example 245

2,5-dihydro-9-hydroxy-10-methoxy-5-propyl-2,2,4-trimethyl-1H-[1jbenzopyrano[3,4fjquinoline

Lactol-9-TBS-ether at the C5 position of nucleus 7 and n-propylmagnesium chloride are treated according to the method of Example 251 to give the desired compound:

'H NMR (300 MHz, DMSO-d ₆ ) δ 8.66 (s, IH), 7.90 (d, J-9 Hz, IH), 6.60 (d, J=8 Hz, IH), 6.59 (s, IH), 6.49 (d, J=9 Hz, IH), 6.14 (br s, IH), 5.57 (m, IH), 5.44 (br s, IH). 3.63 (s, 3H), 2.15 (s, 3H), 1.79-1.61 (m, 1H), 1.48-1.08 (m, 5H), 1.16 (s, 6H), 0.78 (t, J=7 Hz, 3H);

¹³ C NMR (75 MHz, DMSO-d ₆ ) δ 145.7, 144.9, 143.9, 143.1, 133.5, 127.5, 126.4, 117.9,

116.3, 116.2, 114.2, 113.4, 112.1, 73.6, 59.3, 49.7; 31.9, 29.1, 28.8, 27.7, 23.8, 21.7, 13.9; MS (DCl/NH 3 ) m/e (M+H) ⁺ 380;

Analytical calcd for C24H29NO31/ _4H2O : C, 75.07; H, 7.74; N, 3.65. Found: C, 74.78; H, 7.86; N, 3.29.

Lactol-9-TBS-ether at the _C5 position of nucleus 7 and 3-cycloheptenyltrimethylsilane are treated as above to give a mixture (5:1) of diastereoisomers, which is φ φ • ♦ • •Φ

193 φ φφ φ φφ φφ φ « φ • · φ φ φ φ φ φ φ φφ subjected to HPLC on a (R,R) WHELK-0 1 column with a mobile phase of 2% EtOH in hexanes, yielding two levorotatory enantiomers.

Example 246 (-) (5S,3'S)2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cycloheptenyl)-1H[ 1 jbenzopyrano [3,4-f]quinoline 'H NMR (300 MHz, DMSO-d ₆ ) δ 8.70 (s, 1H), 7.96 (d, 1H), 6.65 (d, 1H), 6.64 (d, 1H), 6.21 (s, 1H), 5.55 (ddd, 1H), 5.53 (d, 1H), 5.46 (s, 1H), 5.31 (ddd, 1H), 3.65 (s, 3H), 2.45 (m, 1H), 2.14 (m, 3H), 2.05-1.84 (m, 4H), 1.46 (m, 1H), 1.29 (s, 3H), 1.27-1.15 (m, 4H), 1.04 (s, 3H); ¹³ C NMR (400 MHz, DMSO-d ₆ ) δ 145.3, 144.9, 144.0, 143.1, 133.7, 132.1, 131.6, 131.2,

128.1, 126.1, 118.3, 117.9, 116.5, 114.4, 113.3, 112.1, 74.5, 59.3, 49.5, 38.9, 29.5, 29.0, 28.7, 27.8, 27.2, 26.3, 23.8;

HRMS calcd m/z for C27H31NO3: 417.2304 (M)+. Found: 417.2319. [α] _D = -134° (c 1.15, _CHCl3 ).

Example 247 (-) (5S,3'R) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cycloheptenyl)-1H[1]benzopyrano[3,4-f]quinoline MS (DCI/NH3) m/z 418 (M+H) ⁺ ;

*H NMR (300 MHz, DMSO-d ₆ ) δ 8.66 (s, 1H), 7.97 (d, 1H), 6.65 (d, 1H), 6.59 (d, 1H), 6.45 (d, 1H), 6.22 (s, 1H), 5.93 (ddd, 1H), 5.72 (ddd, 1H), 5.50 (d, 1H), 5.45 (s, 1H), 3.65 (s, 3H), 2.38 (m, 1H), 2.13 (s, 3H), 2.04 (m, 1H), 1.82-1.70 (m, 2H), 1.50-1.05 (m, 5H), 1.30 (s, 3H), 1.02 (s, 3H);

^,3 C NMR (400 MHz, DMSO-d ₆ ) δ 145.2, 144.8, 143.8, 143.2, 133.9, 133.6, 131.1, 130.8,

128.0, 126.1, 118.6, 118.0, 116.5, 114.4, 113.4, 112.2, 75.3, 59.2, 49.4, 41.9, 30.0, 29.6, 28.3, 28.0, 27.3,26.1,23.9;

HRMS calculated m/z for C27H31NO3: 417.2304 (M') ⁺ . Found: 417.2288.

[α] _D = -122° (c 0.74, CHCl3).

Example 248

2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-phenyl-1 H-[ 1 jbenzopyrano [3,4f] quinoline *H NMR (300 MHz, DMSO), δ 8.53 (s, 1H), 7.93 (d, J=8.7 Hz, 1H), 7.20-7.14 (m, 5H), 6.73 (d, >8.7 Hz, 1H), 6.66 (s, 1H), 6.42 (d, >8.9 Hz, 1H), 6.33 (d, J =8.7 Hz, 1H), 6.22 (d, >1.7 Hz, 1H), 5.37 (s, 1H), 3.55 (s, 3H), 1.80 (s, 3H), 1.24 (s, 3 H), 1.14 (s, 3H);

194 »· ·· ·· .« ,. ,, ^ř · * · · ·· · · · « .* *·«ί ί*·· ···» • ··· · · · ·*. « , , , , • * φφ φ φ φ · ►φφφ φφ φφ φφ φφ

C NMR (300 MHz, DMSO), δ 145.7, 144.8, 143.8, 143.6, 139.3, 133.1, 132.7, 130.2,

128.3, 127.8, 127.6, 127.5, 126.4, 126.1, 123.8, 118.4, 117.8, 114.1, 114.0, 112.8, 112.2,

74.9, 59.0, 49.7, 29.7, 28.4, 23.2;

MS ESI m/z 400 (M+H) ⁺ ; HRMS calcd for C26H25NO2 is 399.1834. Found: 399.1839.

Example 249

2.5 -dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl- 5 -(3,5-difluoropheny 1)-1H[ 1 jbenzopyrano[3,4-fquinoline ’H NMR (300 MHz, DMSO), δ 8.68 (s, 1H), 7.95 (d, >8.4 Hz, 1H), 7.06 (tt, >9.2, 22 Hz, 1H), 6.82 (dd, J=8.1, 1.8 Hz, 2H); 6.77 (d, >8.4 Hz, 1H), 6.70 (s, 1H), 6.48 (d, >8.4 Hz, 1H), 6.42 (d, >8.4 Hz, 1H), 6.32 (d, >1.5 Hz), 5.42,(s, 1H), 3.56 (s, 3H), 1.84 (d, >1.1Hz, 3H), 1)25 (s, 3H), 1.15 (s, 3H);

^.3 C NMR (300 MHz, DMSO), δ 163.6 (d, >12.81Hz), 160.4 (d, >12.81Hz), 145.9, 145.2,

144.5, 144.4 (t, >7.93 Hz), 143.6, 143.3, 133.1, 129.0, 127.3, 126.6, 118.2, 117.9, 117.2,

114.5 (d, >6.1Ηζ), 112.4, 111.4, 103.5, 73.8, 64.9, 59.1, 49.9, 29.6, 28.5, 23.2;

MS ESI m/z 436 (M+H) ⁺ ;

HRMS calcd for C26H22F2NO2 is 435.1646. Found: 435.1657.

Example 250

2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3,4,5-trifluorophenyl)-1H[ 1 jbenzopyrano[3,4-fquinoline 'li NMR (300 MHz, DMSO), δ 8.76 (s, 1H), 8.02 (d, J =8.4 Hz, 1H), 7.08 (dd, >6.98, 1.8 Hz, 1H), 6.86 (dd, >7.3, 2.2 Hz, 1H), 6.83 (d, >8.8 Hz, 1H), 6.73 (s, 1H), 6.55 (d, >8.8 Hz, 1H), 6.47 (d, >8.8 Hz, 1H), 6.38 (d, >1.5 Hz, 1H), 5.46 (s, 1H), 3.62 (s, 3H), 1.88 (d, >1.1Hz, 3H), 1.30 (s, 3H), 1.13 (s, 3H);

ⁿ CNMR(300 MHz, DMSO), δ 146.0, 145.3, 143.6, 143.1, 133.1, 128.7, 127.3, 126.7, 118.1 (d, 3=15.87 Hz), 117.1, 116.0, 115.9, 15.8, 114.05 (d, J =9.16 Hz), 113.0, 112.7, 112.4,

73.5, 59.1, 49.8, 29.7, 28.4, 23.3.

MS ESI m/z 454 (M+H) ⁺ ;

HRMS calcd for C26H22F2NO2 is 453.1552. Found: 453.1571.

Example 251 •··» ··

195 • ·· ·· ·· ·· • «··· .·«« « ···· ·«·· ·· . · · ··» « . .. .

• · · · · ♦ .

·· ♦· *» ··

5-butyl-2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4]quinoline

Lactol-9-tert-butyldimethylsilyl ether at the C5 position of nucleus 7 (0.057 g, 0.122 mmol) was dissolved in 1,2-dichloroethane (5 mL), cooled to -10°C and treated dropwise with _BF3 -OEt2 (46 mL, 0.366 mmol). The resulting dark green solution was treated dropwise with ethereal n-butylmagnesium chloride (0.19 mL of a 2M/Et2O solution, 0.380 mmol). The solution turned yellow-brown. The reaction mixture was partitioned between saturated aqueous sodium bicarbonate and ethyl acetate. The aqueous layer was extracted with ethyl acetate, the combined organic layers were washed with brine, dried (MgSO4) and concentrated to a yellow oil.

The resulting yellow oil was dissolved in THF (5 mL), cooled to 0°C, and treated with tetrabutylammonium fluoride solution (0.14 mL of a 1M/THF solution, 0.14 mmol). After 10 min, the mixture was quenched with saturated aqueous ammonium chloride and buffer (pH 7) and the layers were separated. The aqueous layer was extracted with ethyl acetate, the combined organic layers were washed with brine, dried (MgSO 4 ), and concentrated. The residue was purified by silica gel column chromatography eluting with 25% ethyl acetate in hexanes to give 0.032 g (7% yield) of the desired compound.

'H NMR (300 MHz, DMSO-4) δ 8.70 (s, 1H), 7.90 (d, J=8 Hz, 1H), 6.60 (d, J=8 Hz, 1H), 6.59 (s, 1H), 6.49 (d, J=8 Hz, 1H), 6.16 (br s, 1H), 5.61 (m, 1H), 5.44 (br s, 1H), 3.63 (s, 3H), 2.16 (s, 3H), 1.77-1.63 (m, 1H), 1.47-1.26 (m, 3H), 1.17 (s, 3H), 1.16 (s, 3H), 0.83 (m, 3H); ¹³ C NMR (75 MHz, DMSO-d ₆ ) δ 145.7, 144.9, 143.9, 143.1, 133.5, 133.3, 127.5, 126.4,

117.9, 116.3, 114.2, 113.4, 112.1, 73.2, 59.3, 49.7, 34.1, 29.1, 28.9, 23.9, 18.6, 13.4;

MS (DCI/NH3) m/e (M+H) ⁺ 366; Analytical calcd for C23H27NO31.25H2O: C, 71.20; H, 7.66; N, 3.61. Found: C, 71.48; H, 7.32; N, 3.52

Lactol-9-TBS-ether at the C5 position of core 7 and 3-cyclopentenyltrimethylsilane are treated as above to give a 1:1 mixture of diastereoisomers, which is subjected to HPLC on a (R,R) WHELK-0 1 column with a mobile phase of 2% EtOH in hexanes to give the individual enantiomers.

Example 252 (-) (5S,3'S) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cyclopentenyl)-1H[1]benzopyrano[3,4-f]quinoline

000

196 • · · · 0 «

0 0 0 0 0 *00 0 0 • ··· 0 0 · • 0 0 0

0 0 * · 0 · · • * · 0 • · 0 0 • · 0 t

0 0 0 ·· ··

MS (DCI/NH ₃ ) m/z 390 (M+H) ⁺ ;

^X H NMR (300 MHz, DMSO-dé) δ 8.68 (s, 1H), 8.01 (d, 1H), 6.65 (d, 1H), 6.62 (d, 1H), 6.51 (d, 1H), 6.22 (s, 1H), 5.72 (dd, 1H), 5.41 (d, 1H), 5.40 (s, 1H), 5.17 (dd, 1H), 3.63 (s, 3H),

2.90-2.80 (m, 1H), 2.41-2.32 (m, 1H), 2.23-2.10 (m, 1H), 2.06 (s, 3H), 1.89-1.71 (m, 2H), 1.30 (s, 3H), 1.08 (s, 3H);

¹³ C NMR (400 MHz, DMSO-d ₆ ) δ 145.5, 145.0, 143.9, 143.4, 133.5, 132.3, 132.2, 130.2,

128.1, 126.4, 117.8, 116.9, 116.4, 114.4, 113.4, 111.9, 75.7, 59.3, 49.5, 48.7, 31.6, 29.8, 27.6,

27,1,24,2;

HRMS calcd m/z for C25H27NO3: 389.1991 (M') ⁺ . Found: 389.1994.

[a] _D = -120° (c 0.800, CHCl ₃ ).

Example 253 (-) (5S,3'R) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cyclopentenyl)-1H[1]benzopyrano[3,4-f]quinoline MS (DCI/ _NH3 ) m/z 390 (M+H) ⁺ ;

Η NMR (300 MHz, DMSO-dé) δ 8.67 (s, 1H), 8.02 (d, 1H), 6.65 (d, 1H), 6.62 (d, 1H), 6.53 (d, 1H), 6.25 (s, 1H), 5.77 (ddd, 1H), 5.69 (ddd, 1H), 5.47 (s, 1H), 5.37 (s, 1H), 3.66 (s, 3H),

2.90 (m, 1H), 2.34-2.13 (m, 2H), 2.10 (s, 3H), 1.55-1.41 (m, 2H), 1.31 (s, 3H), 1.04 (s, 3H) ¹³ C NMR (400 MHz, DMSO-d ₆ ) δ 145.5, 144.9, 144.0, 143.9, 133.6, 132.0, 131.7, 131.5

127.9, 126.2, 117.7, 117.6, 116.5, 114.4, 113.3, 111.9, 76.1, 59.3, 49.4, 48.6, 31.7, 29.5, 27.1,

24.6, 23.7;

HRMS calcd m/ _{z for C25H27NO3 : 389.1991} . Found: 389.1998. [α] _D = -132° (c 0.76, _CHCl3 ).

Example 254

2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3,4-difluoropheny 1)-1H[ 1 ]benzopyrano[3,4-f]quinoline ^! H NMR (300 MHz, DMSO-dé), δ 8.65 (s, 1H), 7.96 (d, J=8.8 Hz, 1H), 7.31-7.17 (m, 2H), 6.98-6.95 (m, 1H), 6.76 (d, J=8.8 Hz, 1H), 6.67 (s, 1H), 6.48 (d,J =8.4 Hz, 1H), 6.38 (d, J=8.4 Hz, 1H), 6.29 (d, J=1.5 Hz), 5.40 (s, 1H), 3.57 (s, 3 H), 1.82 (d, J=1.5 Hz), 1.25 (s, 3 H), 1.14 (s, 3 H);

197

ΦΦ »· • * * ♦ φ φ # * · · · · • · *··* 99 »· «· • Φ · · • · · · • · ··» ·

Φ · Φ *Φ *· •Φ ΦΦ • · • Φ Φ Φ • Φ ¹² C-NMR (75 MHz, DMSO-dó) δ 145.9, 145.1, 143.6, 143.3, 137.3, 132.9, 129.5, 127.4,

126.6, 125.2, 118.3, 117.8, 117.3, 117.1, 117.0, 116.8, 114.4, 114.3, 112.3, 73.8, 59.1,49.8, 29.7, 28.4, 23.3;

HRMS calcd for C26H22O2F2 is 435.1646. Found: 435.1638.

Example 255

2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(4-fluorophenyl)-1H-[1]benzopyrano[3,4fjquinoline

MS (DCI/NH3) 418 (M+H) ⁺ ;

Η NMR (300 MHz, DMSO-dó), δ 8.58 (s, 1H), 7.95 (d, J =8.8 Hz, 1H), 7.23-7.19 (m, 2 H), 7.03 (dd, J=8.8, 8.8 Hz, 2 H), 6.74 (d, J=8.8 Hz, 1H), 6.66 (s, 1H), 6.44 (d, J=8.8 Hz, 1H), 6.34 (d, J=8.8 Hz, 1H), 6.24 (d, J=1.5 Hz), 5.38 (s, 1H), 3.57 (s, 3 H), 1.80 (d, J=1.5 Hz), 1.24 (s, 3 H), 1.14 (s, 3 H);

HRMS calcd for C26H24NO2F is 417.1740. Found: 417.1745.

Example 256

2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-trifluoromethylphenyl)-1H[ 1 J benzopyrano [3,4-f]quinoline MS APCI m/z 468 (M+H) ⁺ ;

NMR (300 MHz, DMSO), δ 8.62 (s, 1H), 7.97 (d, J=8.8 Hz, 1H), 7.61-7.41 (m, 3H), 7.36 (s, 1H), 6.75 (s, 1H), 6.44 (d, J=8.4 Hz, 1H), 6.35 (d, J=8.4, 1H), 6.30 (d, J=1.5 Hz, 1H), 5.40 (s, 1H), 3.52 (s, 3H), 1.80 (d, J=1.5Hz, 3H), 1.24 (s, 3H), 1.15 (s, 3H);

¹³ C NMR (300 MHz, DMSO), δ 145.9, 145.0, 143.5, 140.9 (d, 3=17.01Hz), 140.9, 133.0,

132.6, 129.3, 129.2, 127.4, 126.6, 124.4, 118.3, 118.0, 117.4, 114.5 (d, J=7.32 Hz), 112.3, 74.2, 58.9, 49.8, 29.5, 29.4, 23.3.

HRMS calcd for C27H24F2NO2 is 467.1708. Found: 467.1708.

Example 257

2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-5-bistrifluoromethylphenyl)-1H[ 1 ]benzopyrano[3,4-f]quinoline MS APCI m/z 536 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO), δ 8.69 (s, 1H), 8.00 (d, J=8.8 Hz, 1H), 7.96 (s, 1H), 7.80 (s, 2H), 6.90 (s, 1H), 6.79 (d, J=8.4 Hz, 1H), 6.46 (d, J=8.8 Hz, 1H). 6.39 (d, J=1.3 Hz, 1H), 6.37 *· ·· • · · · • · » • · * » » • ·

198 ·· · · · • · · · • · ··· * · · * * · 9 *· »· • · · · • · · · • · · · • · · « ·· tt (d, J=8.4 Hz, 1H), 5.43 (s, 1H), 3.51 (s, 3H), 1.80 (d, J=0.73 Hz, 3H), 1.24 (s, 3H), 1.15 (s, 3H);

¹³ C NMR (300 MHz, DMSO), δ 146.1, 145.3, 143.6, 142.9, 133.2, 130.1, 129.7, 129.5,

127.2, 126.7, 124.9, 118.2, 117.2, 114.8, 112.3, 73.5, 58.8, 49.8, 29.4, 28.3, 23.3.

HRMS calcd for C28H22F6NO2 is 535.1582. Found: 535.1573.

Example 258

2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-trifluoromethyl-4-chlorophenyl)-1H[1]benzopyrano[3,4-fquinoline MS (APCI) m/z 502 (M+H) ⁺ ;

^! H NMR (300 MHz, DMSO), δ 8.70 (s, 1H), 7.97 (d, J=8.8 Hz, 1H), 7.70-7.60 (m, 3H), 6.78 (s, 1H), 7.55 (s, 1H), 6.46 (d, >8.8 Hz, 1H), 6.38 (s, 1H), 6.36 (d, J=8.8 Hz, 1H), 5.41 (s, 1H), 3.53 (s, 3H), 1.79 (s, 3H) 1.28 (s, 3H), 1.14 (s, 3H);

¹³ C NMR (300 MHz, DMSO), δ 166.9, 146.0, 145.2, 143.6, 143.1, 139.6, 134.1, 133.0,

131.7, 131.5, 128.6, 127.3, 126.7, 114.6, 112.3, 73.7, 59.0, 49.8, 67.4, 29.6, 29.8, 28.3, 23.3,

23.2, 22.4, 13.8, 10.8.

HRMS calcd for C27H22ClF2NO2 501.1319. Found: 501.1326.

Example 259

2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2-methylpropyl)-1H[ljbenzopyrano[3,4-fquinoline

Lactol-9-tert-butyldimethylsilyl ether at the C5 position of nucleus 7 and iso-butylmagnesium chloride are treated according to the method of Example 251 to give the desired compound.

' II NMR (300 MHz, DMSO-d ₆ ) δ 8.69 (s, 1H), 7.90 (d, J-8 Hz, 1H), 6.61 (d, >8 Hz, 1H), 6S9 (d, J=8 Hz, 1H), 6.48 (d, J=8 Hz, 1H), 6.16 (br s, 1H), 5.71 (m, 1H), 5.44 (br s, 1H), 3.63 (s, 3H), 2.17 (s, 3H), 1.82-1.60 (m, 2H), 1.43-1.18 (m, 1H), 1.17 (s, 3H), 1.16 (s, 3H), 0.97 (d, J=7 Hz, 3H), 0.76 (d, J=7 Hz, 3H);

¹³ C NMR (75 MHz, DMSO-dé) δ 145.8, 144.8, 143.8, 143.0, 133.5, 133.3, 127.5, 126.4,

117.9, 116.3, 116.1, 114.2, 113.4, 112.1, 71.8, 59.3, 49.6, 29.1, 28.9, 24.6, 24.0, 23.3, 21.2;

MS (FAB Hi Res) m/e calcd for C24H29NO3: 379.2147. Found: 379.2159.

Example 260

199

00 00 *• 0 0 0 0 0 0 0 0 0 0 0 0 0

0 000 0 0 0 0 0 » 0 0 0 00 00

3-fluorine-4»0 ·· * · · · • ♦ ·

0

0000 00

2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-fluoro-4-chlorophenyl)-1H[ 1 jbenzopyrano [3,4-fquinoline

Lactol-9-tert-butyldimethylsilyl ether at the C5 position of nucleus 7 and chlorophenylmagnesium bromide are treated according to the method of Example 251 to give the desired compound.

Ή NMR (300 MHz, DMSO-cL) δ 8.72 (s, 1H), 7.91 (d, J=8 Hz, 1H), 6.59 (d, J =8 Hz, 1H), 6.59 - 6.48 (d, J=8 Hz, 1H), 6.16 (br s, 1H), 5.71 (m, 1H), 5.44 (br s, 1H), 3.63 (s, 3H), 2.17 (s, 3H), 1.82-1.60 (m, 2H), 1.43-1.18 (m, 1H), 1.17 (s, 3H), 1.16 (s, 3H), 0.97 (d, J-7 Hz, 3H), 0.76 (d, 3=7 Hz, 3H).

Example 261

2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-butenyl)-1H-[ljbenzopyrano[3,4fjquinoline

Lactol-9-tert-butyldimethylsilyl ether at the C5 position of nucleus 7 and 1-butenyl-4-magnesium bromide are treated according to the method of Example 251 to give the desired compound.

Example 262

2,5-dihydro-9-hydroxy-10-methoxy-5-(phenylmethyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline

Lactol-9-TBS-ether at the C5 position of nucleus 7 and benzylmagnesium bromide are treated according to the method of Example 251 to give the desired compound.

'H NMR (300 MHz, DMSO-cL) δ 8.77 (s, 1H), 7.97 (d, J=9 Hz, 1H), 7.34-7.13 (m, 3H), 7.11 (s, 1H), 7.10 (d, J=7 Hz, 1H), 6.67 (m, J=8 Hz, 1H), 6.65 (m, J=8 Hz, 1H), 6.42 (d, J=9 Hz, 1H), 6.20 (br s, 1H), 5.86 (dd, J=10, 3 Hz, 1H), 5.42 (br s, 1H), 3.69 (s, 3H), 2.99 (dd, J=10, 14 Hz, 1H), 2.77 (dd, J=3, 15 Hz, 1H), 2.23 (s, 3H), 1.16 (s, 3H), 1.15 (s, 3H);

¹³ C NMR (125 MHz, DMSO-d _ó ) δ 145.8, 145.0, 144.0, 142.8, 138.0, 133.3, 132.4, 128.9 (2C), 121.1 (2C), 127.4, 126.4, 126.1, 117.9, 116.3, 116.2, 114.4, 113.7, 112.5, 74.5, 59.4,

49.7, 37.9, 29.2, 29.0, 24.3;

MS (DCI/NH3) m/e (M+H) ⁺ 414; Analytical calcd for _{C27H27NO31 /4H2O : C} , 77.58; H, 6.63; N, 3.35. Found: C, 77.70; H, 7.07; N, 3.19.

Example 263 • B

B B

B B • · · · · · ·

B · · · • B · · <

200 (-) (5S,3R) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-[1-ethyl-3-cyclohexenyl]1H-[1]benzopyrano[3,4-f]quinoline

The mixture of diastereoisomers from Example 277 was resolved into its enantiomers on a Chiracel OJ column by HPLC with a mobile phase of hexane:2-propanol (95:5) to give the desired product.

’H NMR (300 MHz, DMSO-de) δ 8.67 (s, 1H), 7.99 (d, J=9 Hz, 1H), 6.65 (d, J=9 Hz, 1H), 6.62 (d, J=9 Hz, 1H), 6.53 (d, J=8 Hz, 1H), 6.22 (s, 1H), 5.44 (d, J=12 Hz, 2H), 5.30 (d, J=10 Hz, 1H), 3.62 (s, 3H), 3.50-2.26 (m, 1H), 2.11 (s, 3H), 1.89-1.72 (m, 3H), 1.25-1.17 (m, 2H), 1.03 (2, 3H), .088 (t, J=7 Hz, 3H);

¹³ C NMR (75 MHz, DMSO-de) δ 145.4, 144.9, 144.0, 143.7, 140.1, 133.6, 130.9, 127.9, 126.1, 120.0; 118.2, 117.8, 116.6, 114.3, 113.3, 112.0, 76.2, 59.3, 49.4, 37.7, 30.2, 29.6, 27.7,

27.2, 24.9, 23.7, 21.6, 12.3.

Example 264 (-) (S) 5-cyclopentyl-2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline

Lactol-9-TBS-ether at the C5 position of core 7 and cyclopentylmagnesium chloride are worked up according to the method of Example 251. The resulting racemate is resolved into enantiomers by HPLC on a (R,R)-WHELK-O1 column with a mobile phase of 2% EtOH in hexanes to give the desired compound as the first eluent:

Ή NMR (300 MHz, DMSO-cL) δ 8.66 (s, 1H), 8.00 (d8, 1H), 6.63 (d8, 1H), 6.61 (d, J=8 Hz, 1H), 6.48 (d, J=8 Hz, 1H), 6.24 (br s, 1H), 5.45 (br s, 1H), 5.35 (d, J=10 Hz, 1H), 3.65 (s, 3H), 2.15 (s, 3H), 2.12-1.97 (m, 1H), 1.60-1.43 (m, 4H), 1.42-1.22 (m, 2H), 1.19-1.07 (m, 2H), 1.31 (s, 3H), 1.02 (s, 3H);

MS (DCI/NH3) m/e (M+H) ⁺ 392.

Example 265 (+) (R) 5-cyclopentyl-2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline

The racemate of Example 264 was resolved into its enantiomers by HPLC on a (R,R)WHELK-Oi column with 2% EtOH in hexanes as the mobile phase to give the desired compound as the second eluent.

Ή NMR (300 MHz, DMSO-de) δ 8.66 (s, 1H), 8.00 (d8, 1H), 6.63 (d8, 1H), 6.61 (d, J=8 Hz, 1H), 6.48 (d, J=8 Hz, 1H), 6.24 (br s, 1H), 5.45 (br s, 1H), 5.35 (d, J=10 Hz, 1H), 3.65 (s,

201 ··· · · · ··· · · • · · · · <

• · ·· ·· ··

3H), 2.15 (s, 3H), 2.12-1.97 (m, 1H), 1.60-1.43 (m, 4H), 1.42-1.22 (m, 2H), 1.19-1.07 (m, 2H), 1.31 (s, 3H), 1.02 (s, 3H);

MS (DCI/NH ₃ ) m/e (M+H) ⁺ 392.

Example 266

2,5-dihydro-9-hydroxy-10-methoxy-5-(3-propynyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline

Lactol-9-TBS-ether at the C5 position of the 7 nucleus and propargylmagnesium bromide (Gaoni, Y.:, Leznoff, C.C:, Sondheimer, J Am. Chem. Soc., 1968, 90, 4940-4945,) are treated according to the method of Example 251 to give the desired compound.

Ή NMR (300 MHz, DMSO-dg) δ 8.77 (s, 1H), 7.92 (d, J=9 Hz, 1H), 6.63 (dd, >9, 8 Hz, 2H), 6.54 (m, 1H), 6.17 (s, 1H), 5.82 (dd, J =9, 9 Hz, 1H), 5.44 (s, 1H). 3.68 (s, 3H), 2.78 (t, 1H), 2.44-2.36 (m, 2H), 2.18 (s, 3H), 1.17 (d, >5 Hz, 6H);

¹³ C NMR (75 MHz, DMSO-dg) δ 145.9, 145.5, 145.4, 145.2, 143.9, 142.3, 133.5, 132.6,

131.4, 127.4, 126.5, 117.4, 116.5, 115.8, 114.5, 114.0, 112.6, 91.4, 80.7, 72.5, 59.4, 49.8,

29.3, 29.0, 23.9, 23.3, 22.4.

Example 267

2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2-propyl)-1Η-[1]benzopyrano[3,4fjquinoline

Lactol-9-TBS-ether at the _C5 position of nucleus 7 and isopropylmagnesium chloride are treated according to the method of Example 251 to give the desired compound.

'H NMR (300 MHz, DMSO-d _ó ) δ 8.65 (s, 1H), 7.99 (d8, 1H), 6.64 (d, >8 Hz, 1H), 6.61 (d, >8 Hz, 1H), 6.51 (d, >8 Hz, 1H), 6.22 (br s, 1H), 5.44 (br s, 1H), 5.26 (d, >10 Hz, 1H), 3.64 (s, 3H), 2.16 (s, 3H), 1.85-1.67 (m, 1H), 1.30 (s, 3H), 1.02 (s, 3H), 0.93 (d, >6 Hz, 3H), 0.64 (7, 3H);

¹³ C NMR (75 MHz, DMSO-d ₆ ) δ 145.3, 144.8, 144.0, 143.7, 133.5, 131.6, 128.2, 126.1,

118.4, 117.9, 116.5, 114.3, 113.2, 112.0, 77.7, 59.3, 49.4, 30.7, 29.7, 27.2, 23.9, 19.5, 17.9; MS (DCI/NH3) m/e (M+H) ⁺ 366; Analytical calcd for C23H27NO31/4H2O: C, 74.67; H, 7.49; N, 3.79. Found: C, 74.81; H, 7.39; N, 3.67.

Example 268 • « • · • · « «

202

2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(5-methoxy-2-thienyl)-1H[ 1 ]benzopyrano[3,4-f]quinoline

Lactol-9-TBS-ether at the C5 position of nucleus 7 and 2-methoxythiophene are treated according to the method of Example 276 to give the desired compound.

’Η NMR (300 MHz, DMSO-dó) δ 8.63 (s, 1H), 7.93 (d, J=8 Hz, 1H), 6.70 (d, J=8 Hz, 1H),

6.65 (s, 1H), 6.50 (d, J=8 Hz, 1H), 6.39 (d, J=9 Hz, 1H), 6.28 (d, J=3 Hz, 1H), 6.23 (br s, 1H), 5.97 (d, J=3 Hz, 1H), 5.38 (br s, 1H), 3.72 (s3), 3.59 (s, 3H), 1.97 (s, 3H), 1.22 (s, 3H), 1.13 (s, 3H), ¹³ C NMR (75 MHz, DMSO-do) δ 166.2, 145.7, 145.1, 143.6, 143.5, 132.9, 130.2, 128.7,

127.6, 126.4, 126.0, 118.3, 117.2, 117.2, 114.2, 112.4, 102.7, 71.5, 59.7, 59.1, 49.8, 29.8,

28.6, 22.9; MS (DCI/NH3) m/e (M+H) ⁺ 436; Analytical calcd for C25H25NO4S I/4H2O: C, 68.24; H, 5.84; N, 3.18. Found: C, 68.52; H, 6.19; N, 3.00.

Example 269 (±) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2,3,4,5,6-pentafluorophenyl)-1H[1]benzopyrano[3,4-f]quinoline

Lactol-9-TBS-ether at the C5 position of the 7 core and pentafluorophenylmagnesium bromide are treated to give the desired compound, which is purified by flash chromatography with a mobile phase of 4:1 hexane/EtOAc.

MS (DCI/NH 3 ) m/z 490 (M+H) ⁺ ;

*H NMR (300 MHz, DMSO-dó) δ 8.75 (s, 1H), 7.83 (d, 1H), 6.82 (5, 1H), 6.67 (d, 1H), 6.44 (d, 1H), 6.33 (d, 1H), 6.19 (s, 1H), 5.37 (s, 1H), 3.53 (s, 3H), 1.77 (s, 3H), 1.17 (s, 3H), 1.06 (s, 3H);

¹³ C NMR (400 MHz, DMSO-do) δ 146.1, 145.8, 143.8, 142.9, 133.4, 128.4, 127.0, 126.2,

118.6, 118.1, 117.6, 114.5, 114.2, 113.3, 112.2, 105.0, 68.6, 58.9,49.9, 29.8, 28.3,23.1;

Analytical calcd for C26H20NO3F5 0.5H2O: C, 62.65; H, 4.25; N, 2.81. Found: C, 62.4; H, 4.28; N, 2.73.

Example 270 (+/-) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(S)-(3(S)-1hydroxymethylcyclopenten-3-yl)-1H-[1]benzopyrano[3,4-f]quinoline MS (DCI/NH3) m/z 420(M+H) ⁺ ;

« · ^f H NMR (400 MHz, DMSO-dg) 1H NMR (200 MHz, DMSO-dg) δ 8.77 (s, 1H), 8.04 (d, 1H), 6.67 (d, 1H), 6.62 (d, 1H), 6.52 (d, 1H), 6.24 (bs, 1H), 6.12 (dd, 1H), 5.50 (d, 1H), 5.42 (bs, 1H), 2.64 (s, 2H), 2.57 (s, 2H), 2.75-1.09 (m, 14H).

Example 271

Lactol-9-TBS-ether at the C5 position of core 7 and 3-cyclohexenyltrimethylsilane are treated as above to give a 3:2 mixture of diastereoisomers, which is subjected to HPLC on a (R,R) WHELK-0 1 column with a mobile phase of 2% EtOH in hexanes to give the individual enantiomers.

Example 272 (-) (5S,3'S) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cyclohexenyl)-1H[1]benzopyrano[3,4-f]quinoline

MS (DCI/NH 3 ) m/z 404 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-d ₆ ) δ 8.70 (s, 1H), 7.99 (d, 1H), 6.65 (d, 1H), 6.62 (d, 1H), 6.52 (d, 1H), 6.20 (d, 1H), 5.61 (ddd, 1H), 5.46 (d, 1H), 5.41 (s, 1H), 5.10 (dd, 1H), 3.66 (s, 3H), 2.27 (m, 1H), 2.10 (s, 3H), 1.99-1.72 (m, 2H), 1.70-1.55 (m, 3H), 1.35 (m, 1H), 1.29 (s, 3H), 1.06 (s, 3H);

¹³ C NMR (400 MHz, DMSO-dg) δ 145.4, 145.0, 143.4, 143.0, 133.5, 131.0, 128.9, 128.1,

126.4, 126.3, 117.9, 116.5, 114.4, 113.5, 112.1, 75.2, 59.3, 49.5, 36.9, 29.7, 27.6, 25.5, 24.6,

24.3, 20.0;

[α] ²³ D = -162° (c 0.11, CHCl ₃ ).

Example 273 (-) (5S,3R) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cyclohexenyl)-1H[1]benzopyrano[3,4-f]quinoline

MS (DCI/NH 3 ) m/z 404 (M+II) ¹ ;

³ H NMR (300 MHz, DMSO-dg) δ 8.70 (s, 1H), 8.01 (d, 1H), 6.65 (d, 1H), 6.62 (d, 1H), 6.53 (d, 1H), 6.27 (d, 1H), 5.82-5.65 (m, 2H), 5.45 (s, 1H), 5.33 (d, 1H), 3.65 (s, 3H), 2.28 (m, 1H), 2.12 (s, 3H), 1.86 (m, 2H), 1.55 (m, 1H), 1.31 (s, 3H), 1.26-1.14 (m, 3H), 1.03 (s, 3H); ¹³ C NMR (400 MHz, DMSO-dg) δ 145.4, 145.0, 144.1, 143.5, 133.6, 130.7, 128.1, 127.9,

127.7, 126.1, 118.4, 117.8, 116.5, 114.4, 113.4, 112.1, 75.9, 59.3, 49.4, 37.2, 29.6, 27.1, 24.7,

24.6, 23.7, 21.2;

• · ·

204 [α] ²³ ο = -158° (c 0.50, CHC1 ₃ ).

Example 274

2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2-thienyl)-1H-[1]benzopyrano[3,4fquinoline

A 0.24 M solution of 2-thienylzinc chloride was prepared by diluting 2-thienyllithium (1.0 mL of a 1M THF solution, 1.0 mmol) with ethyl ether (2 mL), cooling to 0°C, then reacting the reaction mixture with ZnCl ₂ (1.1 mL of a 1M/Et ₂ O solution, 1.10 mmol) and allowing it to warm to room temperature. The resulting heterogeneous mixture was stirred vigorously.

The lactol-9-TBS-ether at the C5 position of the 7 core and the 2-thienylzinc chloride prepared above are treated according to the method of Example 251 to give the desired compound:

if NMR (300 MHz, DMSO-dg) δ 8.65 (s, 1H), 7.95 (d, J-9 Hz, 1H), 7.39 (dd, J-5, 1Hz, 1H), 6.85-6.82 (m, 2H), 6.74 (m, 1H), 6.72 (d, J=8 Hz, 1H), 6.48 (d, J-8 Hz, 1H), 6.37 (d, J=9 Hz, 1H), 6.28 (br s, 1H), 5.39 (br s, 1H), 3.59 (s, 3H), 1.93 (s, 3H), 1.22 (s, 3H), 1.14 (s, 3H);

¹³ C NMR (75 MHz, DMSO-d ₆ ) δ 145.7, 145.1, 143.7, 143.6, 143.5, 133.0, 130.8, 127.9,

127.5, 127.0, 126.5, 126.4, 118.3, 117.1, 114.4, 114.2, 112.4, 70.9, 59.0, 49.8, 29.7, 28.6, 23.0; MS (DCI/NH3) m/e (M+H) ⁺ 406; Analytical calcd for C24H23NO3S: C, 71.09; H, 5.72; N, 3.45. Found: C, 70.93; H, 6.00; N, 3.27.

Example 275 (±) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2-methylphenyl)-1H[1]benzopyrano[3,4-f]quinoline

Lactol-9-TBS-ether at the C5 position of the 7 core and o-tolylmagnesium bromide are treated to give the desired product, which is purified by flash chromatography with a mobile phase of 4:1 hexane/EtOAc.

MS (DCI/NH ₃ ) m/z 414 (M+H) ⁺ ;

*H NMR (300 MHz, DMSO-dg) δ 8.43 (s, 1H), 7.79 (d, 1H), 7.02 (d, 1H), 6.92 (dt, 1H), 6.72 (t, 1H), 6.59 (d, 1H), 6.55 (s, 1H), 6.54 (d, 1H), 6.24 (d, 1H), 6.12 (d, 1H), 6.07 (s, 1H), 5.20 (s, 1H), 3.48 (s, 3H), 2.44 (s, 3H), 1.54 (s, 3H), 1.09 (s, 3H), 0.98 (s, 3H);

¹³ C NMR (400 MHz, DMSO-d ₆ ) δ 145.9, 145.0, 143.9, 143.6, 137.5, 136.6, 132.6, 130.6,

130.5, 128.8, 128.1, 127.6, 126.4, 124.9, 118.7, 118.2, 117.8, 114.1, 114.0, 111.7, 73.7, 59.2, 49.8, 30.0, 28.3, 22.5, 19.3;

90S · · · · ·

Á<vD · · · · · * · ·

Analytical calcd for C27H27NO3: C, 78.42; H, 6.58; N, 3.39. Found: C, 78.07; H, 6.85; N, 3.09.

Example 276

2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2-acetoxymethyl-3-propenyl)-1H[ 1 jbenzopyrano [3,4-f] quinoline

Lactol-9-TBS-ether at the C5 position of nucleus 7 (0.150 g, 0.321 mmol) was dissolved in dichloromethane (15 mL), treated with 2-[(trimethylsilyl)methyl)-2-propen-1-yl acetate (0.180 g, 0.962 mmol), cooled to -78°C, treated dropwise with BF3-Et2O, and warmed to 0°C. After 10 min, the reaction mixture was partitioned between saturated aqueous bicarbonate and ethyl acetate, the layers were separated, the aqueous layer was extracted with ethyl acetate, the combined organic layers were washed with brine, dried ( _MgSO4 ), and concentrated.

The resulting yellow solution was dissolved in THF (10 mL), cooled to 0°C, and treated with tetrabutylammonium fluoride solution (0.35 mL of a 1M/THF solution, 0.35 mmol). After 10 min, the mixture was quenched by addition of saturated aqueous ammonium chloride and buffer (pH 7) and the layers were separated. The aqueous layer was extracted with ethyl acetate, the combined organic layers were washed with brine, dried (MgSO ₄ ), and concentrated. The residue was purified by silica gel column chromatography with 25% ethyl acetate in hexanes to give 0.125 g (89%) of the desired compound.

Η NMR (300 MHz, DMSO-dó) δ 8.74 (s, 1H), 7.92 (d, J=8 Hz, 1H), 6.63 (d, J=8 Hz, 1H), 6.62 (d, J=8 Hz, 1H), 6.41 (d, J=9 Hz, 1H), 6.21 (br s, 1H), 5.85 (dd,J =2, 10 Hz, 1H), 5.44 (s, 1H), 5.08 (s, 1H), 4.92 (s, 1H), 4.58 (ABq, J=13, 30 Hz, 2H), 3.65 (s, 3H), 2.23 (m, 2H), 2.17 (s, 3H), 1.99 (s, 3H), 1.18 (s, 3H), 1.15 (s, 3H); MS (DCI/NH3) m/e (M+H) ⁺ 436; Analytical calcd for C26H29NO5: C, 71.71; H, 6.71; N, 3.22. Found: C, 71.34; H, 6.98; N, 3.12.

Example 277 (+) (5R,3'S) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-[1-ethyl-3-cyclohexenyl]1H-[1]benzopyrano[3,4-f]quinoline

To a 77 mL solution of 0.36 M THF dimethylphenylsilylmethylcopperate (27.7 mmol) (Fleming, I.; Newton, T. W. J. Chem. Soc. Perkin Trans. / ,1984, 1805.) at -23°C was added 3-ethyl-cyclohex-2-en-1-one (2.73 g, 27.0 mmol). The mixture was stirred for 1 h at -23°C, then for 2 h at 0°C, treated with N-phenyl-bis• · ·

206 (trifluoromethanesulfonimide) (4.43 g, 26.4 mmol), allowed to warm to room temperature and stirred for 18 hours. The reaction mixture was quenched with saturated aqueous sodium bicarbonate, filtered through celite and the layers were separated. The organic layer was washed with saturated aqueous sodium bicarbonate, brine and dried (Na ₂ SO ₄ ). The product was purified by column chromatography on silica gel with hexanes to give the triflate (intermediate) as a pale yellow oil.

The above triflate (0.70 g, 1.28 mmol) was combined with tributyltin hydride (0.92 g, 2.13 mmol) in THF and tetrakistriphenylphosphine palladium in THF (0.44 g, 3.5 mmol) and LiCl (0.45 g, 10.7 mmol) were added dropwise at room temperature. After the addition was complete, the reaction was refluxed for 24 h, cooled, filtered through a pad of celite, and stirred vigorously with saturated potassium fluoride solution for 2 h. The mixture was filtered through celite, diluted with ethyl acetate, and the layers were separated. The organic layer was washed with saturated aqueous sodium bicarbonate, brine, and dried (Na ₂ SO ₄ ). The product was purified by silica gel column chromatography with hexanes to give 3-ethyl-3-dimethylphenylsilylcyclohexene as a colorless oil.

Lactol-9-TBS-ether at the C5 position of nucleus 7 and 3-ethyl-3-dimethylphenylsilyl-cyclohexene are treated according to the method of Example 276 to give the product as a mixture of diastereoisomers which is separated on a (R,R,) Whelk-Ol column by HPLC with hexane:ethanol (98:2) as the mobile phase to give the desired compound:

Ή NMR (500 MHz, DMSO-cf) δ 8.01 (d, >8 Hz, 1H), 6.63 (d, >8 Hz, 1H), 6.61 (d, >9

Hz, 1H), 6.53 (d, J=9 Hz, 1H), 6.20 (s, 1H), 5.48 (s, 1H), 5.44 (s, 1H), 5.32 (d, J=9 Hz, 1H), 3:64 (s, 3H), 2.26 (m, 1H), 1.90-1.73 (m, 3H), 1.60 (m, 1H), 1.26-1.18 (m, 2H), 1.03 (s, 3H), .088 (t, J=7 Hz, 3H);

¹³ C NMR (50 MHz, DMSO-d ₆ ) δ 145.3, 144.8, 144.0, 143.6, 140.3, 133.5, 130.8, 127.8, 12ó.0, 120.0, 118.1, 117.8, 116.5, 114.2, 113.2, 111.9, 76.1, 59.2, 49.4,

37.5, 30.1, 29.5, 27.7, 27.1, 24.8, 23.6, _21.6 , 12.2; MS m/e calcd _{for C28H33O3N} : 431.2460. Found: 431.2467.

Lactol-9-TBS-ether at the C5 position of core 7 and cyclohexylmagnesium chloride are treated to give a mixture of compounds from Examples 278 and 279, which are separated by flash chromatography with a mobile phase of 4:1 hexane/EtOAc.

Example 278

207 « Φ · φ • · · φ φ φ φ φ • · φφφφ φ φ φ φ φ ♦ φ

2,5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-cyclohexyl-1H-[1]benzopyrano[3,4fquinoline

MS (DCI/NH 3 ) m/z 406 (M+H) ⁺ ;

11 NMR (300 MHz, DMSO-dé) δ 8.66 (s, 1H), 7.96 (d, 1H), 6.61 (d, 1H), 6.59 (d, 1H), 6.47 (d, 1H), 6.18 (d, 1H), 5.42 (s, 1H), 5.30 (d, 1H), 3.64 (s, 3H), 2.13 (s, 3H), 1.87 (m, 1H), 1.60-1.48 (m, 3H), 1.28 (s, 3H), 1.20-0.80 (m, 7H), 1.00 (s, 3H);

¹³ C NMR (400 MHz, DMSO-d ₆ ) δ 145.3, 144.8, 144.1, 143.8, 133.5, 131.1, 128.1, 126.1,

118.5, 117.9, 116.6, 114.4, 113.2, 112.0, 76.8, 59.3, 49.4, 29.7, 29.5, 28.0, 27.2, 25.8, 25.6,

25.3, 23.8;

Example 279

2,5,5-trihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-quinoline MS (DCI/NH3) m/z 324 (M+H)';

’H NMR (300 MHz, DMSO-cU) δ 8.78 (s, 1H), 7.81 (d, 1H), 6.62 (d, 1H), 6.57 (d, 1H), 6.53 (d, 1H), 6.22 (s, 1H), 5.40 (s, 1H), 5.05 (s, 2H), 3.62 (s, 3H), 2.01 (s, 3H), 1.19 (s, 6H);

¹³ C NMR (400 MHz, DMSO-d ₆ ) δ 146.6, 145.4, 145.3, 144.0, 131.5, 130.8, 128.1, 126.2, 118.2, 118.0, 117.2, 113.9, 113.2, 111.2, 67.1, 59.4, 49.9, 29.0, 22.9;

Example 280

2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2-hydroxymethyl-3-propenyl)-1H[ 1 ]benzopyrano[3,4-quinoline

The compound from Example 276 (0.032 g, 0.074 mmol) was dissolved in THF/MeOH/H2O (5 mL/1 mL/0.5 mL), cooled to 0°C, treated with _K2CO3 (0.051 g, 0.367 mmol) and allowed to warm to room temperature and stir for 12 hours. The mixture was partitioned between saturated aqueous _ammonium chloride and ethyl acetate, the aqueous layer was extracted with ethyl acetate, the combined organic layers were washed with brine, dried ( _MgSO4 ), and concentrated. The residue was purified by silica gel column chromatography eluting with 25% then 50% ethyl acetate*/^/hexanes to give 0.022 g (7(j%)) of the desired compound.

*H NMR (300 MHz, DMSO-d _ň ) δ 8.71 (s, 1H), 7.92 (s, >9 Hz, 1H), 6.62 (d, >9 Hz, 1H),

6.61 (d, >8 Hz, 1H), 6.41 (d, >8 Hz, 1H), 6.18 (d, >1Ηζ, 1H), 5.86 (dd, >11, 1Hz, 1H), 5.43 (br s, 1H), 5.02 (m, 1H), 4.80 (t, >6 Hz, 1H), 4.74 (br s, 1H), 3.90-3.78 (m, 2H), 3.65 (s, 3H), 2.50-2.36 (m, 1H), 2.23-2.10 (m, 1H), 2.19 (s, 3H), 1.17 (s, 3H), 1.16 (s, 3H);

208 • Φ ·· ► · · ♦ » Φ Φ 9 » Φ ΦΦΦ

ΦΦ 99 • Φ Φ «

Φ Φ 9 9

9 9 9

9 9 9

99 ¹³ C NMR (125 MHz, DMSO-d ₆ ) δ 145.9, 145.8, 144.9, 143.8, 142.8, 133.2, 132.8, 127.6,

126.4, 117.7, 116.2, 116.2, 114.2, 113.6, 112.6, 110.6, 72.1, 63.7, 59.4, 49.7, 35.4, 29.2, 28.9, 23.9; MS (DCI/NH?) m/e (M+H) ⁺ 394.

Example 281

Methyl 2-[2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]5quinoline acetate

The lactol-9-TBS-ether at the C1 position of the 7 nucleus is treated according to the method of Example 46 to give the silylated product (intermediate).

ti NMR (300 MHz, DMSO-dé) δ 7.94 (d, J=9 Hz, IH), 6.64 (dd, J=9, 3 Hz, IH), 6.49 (d, J=9 Hz, IH), 6.27 (s, IH), 6.14 (dd, J=10, 3 Hz, IH), 4.45 (s, IH), 3.63 (s, 3H), 3.61 (s, 3H), 2.76-2.55 (m, 2H), 2.20 (s, 3H), 1.18 (s, 3H), 1.16 (s, 3H), 1.00 (s, 9H), 0.21 (s, 3H), 0.16 (s, 3H); MS (APCI) m/e (M+H) ⁺ 510, (MH)' 508.

The silylated intermediate (0.030 g, 0.058) prepared above was dissolved in THF (1 mL), cooled to 0°C, and treated with tetrabutylammonium fluoride (58 μL of ΙΜ/THF solution, 0.058 mmol). After 5 min, the mixture was poured into saturated aqueous NH4Cl and extracted with ethyl acetate. The combined organic layers were washed with brine and dried ( _MgSO4 ). The product was purified by silica gel column chromatography eluting with 40% methyl t-butyl ether in hexanes to give the title compound (0.019 g, 82% yield) as a white solid.

'ϊΐ NMR (300 MHz, DMSO-d ₆ ) δ 8.80 (s, IH), 7.93 (d, J=9 Hz, IH), 6.64 (d, J=9 Hz, IH),

6.61 (d, J=9 Hz, IH), 6.43 (d, J=9 Hz, IH), 6.25 (s, IH), 6.10 (dd, J-10, 3 Hz, IH), 5.45 (s, IH), 3.66 (s, 3H), 3.60 (s, 3H), 2.77-2.52 (m, 2H), 2.21 (s, 3H), 1.18 (s, 3H), 1.16 (s, 3H); MS (APCI) m/e (M+H) ⁺ 396, (MH)' 394.

Example 282 (Z) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2-butenyl)-1H[1]benzopyrano[3,4-f]quinoline

The silylated product (intermediate) from Example 281 (0.445 g, 0.87 mmol) was dissolved in THF (4 mL), cooled to 0° C., treated dropwise with Dibal-H (2.69 mL of a 1M/THF solution, 2.69 mmol) and stirred for 30 minutes. The reaction mixture was poured into a saturated aqueous solution of Rochelle's salt and 100 mL of ethyl acetate and stirred for 1 hour. The layers were separated, the aqueous layer was extracted with ethyl acetate, the combined organic layers were • ·

209 «· 00 ♦ 0 0 ·

0 0 t • 0 0 0 0 0

9 0

0· ·0

99

0 0 0

0 0 0

9 9 9

9 9 9

99 was washed with saturated aqueous sodium bicarbonate, brine and dried (MgSO ₄ ). The residue was purified by silica gel column chromatography eluting with 20% then 30% methyl-t-butyl ether in hexanes, then 6% ethyl acetate in dichloromethane to give the primary alcohol (0.293 g, 70%) as a white solid.

1H NMR (300 MHz, DMSO-cU) δ 7.92 (d, J =9 Hz, 1H), 6.65 (d, J=9 Hz, 1H), 6.61 (d, J=9 Hz, 1H), 6.57 (d, J=9 Hz, 1H), 6.21 (s, 1H), 5.88 (dd, J=10, 3 Hz, 1H). 5.43 (s, 1H), 4.62 (t, J=5 Hz, 1H), 3.61 (s, 3H), 2.19 (s, 3H), 1.90-1.75 (m, 2H), 1.62-1.47 (m, 2H), 1.17 (s, 3H), 1.15 (s, 3H), 0.99 (s, 9H), 0.20 (s, 3H), 0.15 (s, 3H); MS (APCI) m/e (M+H) ⁺ 482, (MH)' 480.

A stirred solution of oxalyl chloride (22 μΐ, 0.249 mmol) in THF (2 mL) was cooled to -78°C, treated with DMSO (24 μΐ, 0.332 mmol), stirred for 5 min, and treated dropwise with the above-prepared solution of the primary alcohol (0.080 g, 0.166 mmol) in 2 mL of THF. The resulting mixture was stirred for 40 min, treated with triethylamine (92.5 μΐ, 0.664 mmol), stirred for a further 10 min, and allowed to warm to 0°C. After 30 min at 0°C, the reaction mixture was partitioned between aqueous and dichloromethane layers, the aqueous layer was extracted with dichloromethane, and the combined organic layers were dried (MgSO ₄ ). The product was purified by silica gel column chromatography eluting with 20% then 30% ethyl acetate in hexanes to give the aldehyde (0.059 g, 73%) as a white solid.

Ή NMR (300 MHz, DMSO-dé) δ 9.65 (s, 1H), 7.93 (d, >9 Hz, 1H), 6.67 (d, J=9 Hz, 1H), 6.65 (d, J=9 Hz, 1H), 6.48 (d, J =9 Hz, 1H), 6.33 (m, 2H), 5.46 (s, 1H), 3.63 (s, 3H), 2.87 (m, 1H), 2.65 (m, 1H), 2.18 (s, 3H), 1.19 (s, 3H), 1.14 (s, 3H), 1.00 (s, 9H), 0.21 (s, 3H), 0.15 (s, 3H); MS (APCI) m/e (M+H) ⁺ 480, (MH)' 478.

A solution of ethyltriphenylphosphonium bromide (0.130 g, 0.351 mmol) in THF:Et2O (3 mL, 3:2) was cooled to 0°C and treated dropwise with n-BuLi (140 μΐ of 2.5 M/hexanes, 0.351 mmol). The resulting dark red solution was stirred for 30 min at 0°C, cooled to -78°C, and treated with the aldehyde prepared above (0.056 g, 0.117 mmol) in THF (2 mL). The reaction mixture was stirred for 5 min at -78°C, warmed to 0°C for 40 min, and quenched by the addition of water. The layers were separated, the aqueous layer was extracted with dichloromethane, and the combined organic layers were washed with brine and dried ( _MgSO4 ). The product was purified by silica gel column chromatography using a gradient of 5% to 20% ethyl acetate in hexanes to afford the silyl ether (intermediate) (0.050 g, 87%) as a white solid.

• · · * ·

210 • 9 4

9

9

4949 44 • · · • 4 ♦ • ··· ·

94

44' Η NMR (300 MHz, DMSO-cU) δ 7.92 (d, J=9 Hz, 1H), 6.65 (d, J=9 Hz, 1H,), 6.63 (d, J=9 Hz, TH), 6.20 (s, 1H,), 5.68 (dd, J=10, 3 Hz, 1H), 5.43 (m, 3H), 3.64 (s, 3H), 2.15 (s, 3H), 1.26 (d, J=5 Hz, 3H), 1.17 (s, 6H), 1.00 (s, 9H), 0.20 (s, 3H), 0.15 (s, 3H); MS (APCI) m/e (M+H) ⁺ 492, (MH)' 490.

The silyl ether (intermediate) (0.038 g, 0.077 mmol) was dissolved in THF (3 mL), cooled to 0°C, treated with tetrabutylammonium fluoride (80 mL of 1 M THF, 0.080 mmol), and the mixture was partitioned between ethyl acetate and saturated ammonium chloride. The aqueous layer was extracted with ethyl acetate, the combined organic layers were washed with brine, dried (MgSO ₄ ), and purified by silica gel column chromatography eluting with 25% ethyl acetate in hexanes to give the title compound (0.024 g, 83%).

*H NMR (300 MHz, DMSO-d6) δ 8.71 (s, 1H), 7.93 (d, J=9 Hz, 1H), 6.62 (d, J=9 Hz, 1H), 6.60 (d, J=9 Hz, 1H), 6.47 (d, J=9 Hz, 1H), 6.18 (s, 1H), 5.62 (dd, J=10, 3 Hz, 1H), 5.43 (m, 3H), 3.64 (s, 3H), 2.45-2.18 (m, 2H), 2.15 (s, 3H), 1.30 (d, J=5 Hz, 3H), 1.15 (s, 6H); MS (APCI) m/e calcd for: 377.20. Found; (M+H) ⁺ 378, (MH) + 376.

Example 283

2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-methyl-1-2-butenyl)-1H[1]benzopyrano[3,4-f]quinoline

The aldehyde (intermediate) from Example 282 and isopropyltriphenylphosphonium iodide are treated according to the method of Example 282 to give the desired compound. ¹ H NMR (300 MHz, DMSO-dó) δ 8.65 (s, 1H), 7.91 (d, J=9 Hz, 1H), 6.62 (d, 1=9 Hz, 1H), 6.60 (d, J=9 Hz, 1H), 6.46 (d, J=9 Hz, 1H), 6.14 (s, 1H), 5.60 (dd, J=9, 3 Hz, 1H), 5.43 (s, 1H), 5.15 (m, 1H), 3.64 (s, 3H), 2.45-2.18 (m, 2H), 2.15 (s, 3H), 1.63 (s, 3H), 1.32 (s, 3H), 1.17 (s, 3H), 1.16 (s, 3H); MS (APCI) m/e (M+H) ⁺ 392, (MH)' 390.

Example 284 (+) (5S,3'S) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cyclohexenyl)-1H[1]benzopyrano[3,4-f]quinoline

MS (DCI/NH 3 ) m/z 404 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-do) δ 8.70 (s, 1H), 8.01 (d, 1H), 6.65 (d, 1H), 6.62 (d, 1H), 6.53 (d, 1H), 6.27 (d, 1H), 5.82-5.65 (m, 2H), 5.45 (s, 1H), 5.33 (d, 1H), 3.65 (s, 3H), 2.28 (m, 1H), 2.12 (s, 3H), 1.86 (m, 2H), 1.55 (m, 1H), 1.31 (s, 3H), 1.26-1.14 (m, 3H), 1.03 (s, 3H);

• · * · • · 0 • 0·· • ·

0000 00

211

00 00 ·· < · · 0 0 0 0 1 « 0 0 0 0 0 0’ • 0 000 00 00 ’

0 0 0 0 0 4

00 00 00

C NMR (400 MHz, DMSO-d ₆ ) δ 145.4, 145.0, 144.1, 143.5, 133.6, 130.7, 128.1, 127.9, 127.7, 126.1, 118.4, 117.8, 116.5, 114.4, 113.4, 112.1, 75.9, 59.3, 49.4, 37.2, 29.6, 27.1, 24.7, 24.6, 23.7, 21.2;

[a] _D ²³ - +184° (c 0.33, CHCl ₃ ).

Example 285 (+) (5R,3R) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cyclohexenyl)-1H[1]benzopyrano[3,4-f]quinoline MS (DCI/NH2) m/z 404 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-d ₆ ) δ 8.70 (s, 1H), 7.99 (d, 1H), 6.65 (d, 1H), 6.62 (d, 1H), 6.52 (d, 1H), 6.20 (d, 1H), 5.61 (ddd, 1H), 5.46 (d, 1H), 5.41 (s, 1H), 5.10 (dd, 1H), 3.66 (s, 3H), 2.27 (m, 1H), 2.10 (s, 3H), 1.99-1.72 (m, 2H), 1.70-1.55 (m, 3H), 1.35 (m, 1H), 1.29 (s, 3H), 1.06 (s, 3H);

¹³ C NMR (400 MHz, DMSO-d ₆ ) δ 145.4, 145.0, 143.4, 143.0, 133.5, 131.0, 128.9, 128.1,

126.4, 126.3, 117.9, 116.5, 114.4, 113.5, 112.1, 75.2, 59.3, 49.5, 36.9, 29.7, 27.6, 25.5, 24.6, 24.3,20.0;

[α] _D ²³ = +170° (c 0.23, CHCl 3 ).

Example 286 (+) (5R,3'S) 2,5-(R)-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cyclopentenyl)1H-[1]benzopyrano[3,4-f]quinoline MS (DCI/NH3) m/z 390 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-dg) δ 8.67 (s, 1H), 8.02 (d, 1H), 6.65 (d, 1H), 6.62 (d, 1H), 6.53 (d, 1H), 6.25 (s, 1H), 5.77 (ddd, 1H), 5.69 (ddd, 1H), 5.47 (s, 1H), 5.37 (s, 1H), 3.66 (s, 3H), 2.90 (m, 1H), 2.34-2.13 (m, 2H), 2.10 (s, 3H), 1.55-1.41 (m, 2H), 1.31 (s, 3H), 1.04 (s, 3H); ¹³ C NMR (400 MHz, DMSO-d ₆ ) δ 145.5, 144.9, 144.0, 143.9, 133.6, 132.0, 131.7, 131.5,

127.9, 126.2, 117.7, 117.6, 116.5, 114.4, 113.3, 111.9, 76.1, 59.3, 49.4, 48.6, 31.7, 29.5, 27.1, 24.6,23.7;

[a] _D ²³ = +136° (c 0.355, CHCl ₃ ).

Example 287 (+) (5R,3'R) 2,5(R)-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cyclopentenyl)-1H[ 1 ]benzopyrano[3,4-f]quinoline φ * • ·

212 ·· ·* • · · 9 9 9 9 9

9 9 9 ·'«·

9 999 9 9 99 9 • 9 9 9 9 9 9 9 ·· · 9 9 9 99

MS (DCI/NH ₃ ) m/z 390 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-dg) δ 8.68 (s, 1H), 8.01 (d, 1H), 6.65 (d, 1H), 6.62 (d, 1H), 6.51 (d, 1H), 6.22 (s, 1H), 5.72 (dd, 1H), 5.41 (d, 1H), 5.40 (s, 1H), 5.17 (dd, 1H), 3.63 (s, 3H), 2.90-2.80 (m, 1H), 2.41-2.32 (m, 1H), 2.23-2.10 (m, 1H), 2.06 (s, 3H), 1.89-1.71 (m, 2H),

1.30 (s, 3H), 1.08 (s, 3H);

¹³ C NMR (400 MHz, DMSO-dg) δ 145.5, 145.0, 143.9, 143.4; 133.5, 132.3, 132.2, 130.2,

128.1, 126.4, 117.8, 116.9, 116.4, 114.4, 113.4, 111.9, 75.7, 59.3, 49.5, 48.7, 31.6, 29.8, 27.6, 27.1,24.2;

[a] _D ²³ =+116° (c 0.800, CHCl ₃ ).

Example 288 trans-(5S)-9-hydroxy-5-[(3R)-(1-methoxycarbonyl)cyclohexen-3-yl]-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H-[1]benzopyrano[3,4-f]quinoline

MS (DCI/ _NH3 ) 462 (M+H) ⁺ ;

if NMR (200 MHz, DMSO-dg), δ 8.81 (s, 1H), 8.07 (d, >8.5 Hz, 1H), 6.72 (d, >8.5 Hz, 1H), 6.70 (d, >8.5 Hz, 1H), 6.60 (d, >8.5 Hz, 1H), 6.42-6.41 (m, 1H), 6.21 (d, >1.2 Hz), 5.57 (d, >10.2 Hz, 1H), 1H), 5.45 (s, 1H), 2.71 (s, 2H), 2.58 (s, 2H), 2.56-2.48 (m, 2H), 2.20-2.16 (m, 2H), 2.08 (d, >1.2 Hz), 1.80-1.40 (m, 4H), 1.25 (s, 2H), 1.18 (s, 2H);

HRMS calcd for C28H21NO5 is 461.2202. Found: 461.2212.

Example 289

2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2-methyl-3-propenyl)-1H[ 1 ]benzopyrano[3,4-f]quinoline

The compound from Example 276 (0.040 g, 0.092 mmol) and dichlorobis(triphenylphosphine)palladium(II) complex (0.006 g, 0.009 mmol) were dissolved in dioxane (5 mL), heated to 100°C, and treated with sodium borohydride (0.017 g, 0.460 mmol). The resulting black solution was cooled to room temperature, diluted with water and ethyl acetate, and filtered through celite. The layers were separated, the aqueous layer was extracted with ethyl acetate, the combined organic layers were washed with brine, dried (MgSO 4 ), and concentrated. Purification by column chromatography on silica gel with 25% ethyl acetate in hexanes gave the desired product (0.028 g, 80%) as a colorless foam.

1H NMR (300 MHz, DMSO-dg) δ 8.71 (s, 1H), 7.92 (d, >8 Hz, 1H), 6.62 (d, >8 Hz, 1H),

6.61 (d, >8 Hz, 1H), 6.41 (d, >8 Hz, 1H), 6.18 (d, >1Ηζ, 1H), 5.83 (dd, >3, 10 Hz, 1H),

Φ φ φφφ* φ φ

213 •· *· φφ • φ φ φ * φ · φ φ φ φ φ φ · φ φφφ φ φ φ φ φ φ φ φ φ φ φφ φφ φφ

5.44 (br s, 1Η), 4.75 (br s, 1Η), 4.56 (br s, 1H), 3.65 (s, 3H), 2.50-2.41 (m, 1H), 2.19 (s, 3H), 2.16-2.07 (m, 1H), 1.73 (s, 3H), 1.18 (s, 3H), 1.15 (s, 3H);

¹³ C NMR (125 MHz, DMSO-d _ó ) δ 145.8, 144.9, 143.8, 142.8, 141.6, 133.3, 132.7, 127.5,

126.4, 117.8, 116.3, 116.2, 114.2, 113.6, 112.8, 112.7, 72.0, 59.4, 49.7, 29.2, 28.8, 24.0, 22.4;

MS (DCI/NH3) m/e (M+H) ⁺ 378; Analytical calcd for C24H27NO3: C, 76.36; H, 7.21; N, 3.71. Found: C, 76.06; H, 7.17; N, 3.39.

Example 290

9.10-dimethoxy-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4fquinoline

MS (ESI) m/z 378 (M+H) ⁺ ;

'H NMR (300 MHz, DMSO) δ 7.93 (d, >8.5 Hz, 1H), 6.82 (d, >8.8 Hz, 1H), 6.61 (dd, >4.4, 4.4 Hz, 2 H), 6.22 (d, >1.4 Hz, 1H), 5.83 (ddt, >16.9, 10.3, 3.1 Hz, 1H), 5.70 (dd, >10.3, 3.3 Hz, 1H), 5.44 (s, 1H), 5.44-4.96 (m, 2H), 3.77 (s, 3H), 3.67 (s, 3H), 2.16 (s, 3H), 1.17 (s, 3H), 1.16 (s, 3H);

HRMS calcd for C24H27NO3: 377.1991. Found: 377.2001.

Example 291

9.10-dimethoxy-5-[3-cyclohexenyl]-methoxy-2,2,4-trimethyl-2,5-dihydro-1H[ 1 ]benzopyrano[3,4-f]quinoline

MS (ESI) m/z 418 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO), isomer 1: δ 8.02 (d, >8.8 Hz, 1H), 6.84 (d, >1.7 Hz, 1H), 6.70-6.60 (m, 2H), 6.27 (d, >0.6 Hz, 1H), 5.80-5.60 (m, 2H), 5.16-5.15 (m, 1H), 3.77 (s, 3H), 3.69 (s, 3H), 2.13 (s, 3H), 1.31 (s, 3H), 1.07 (s, 3H); isomer 2: δ 8.01 (d, >8.81Hz, 1H), 6.80 (d, >7 Hz, 1H), 6.64 (m, 2H), 6.26 (d, >0.7Hz, 1H), 5.60 -5.30 (m, 2H), 5.09 (s, 1H), 3.77 (s, 3H), 3.68 (s, 3H), 2.10 (s, 3H), 1.29 (s, 3H), 1.04 (s, 3H);

HRMS calcd for C27H31NO3 417.2304. Found: 417.2299.

Example 292

10-Methoxy-9-ethoxy-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4fquinoline 'H NMR (300 MHz, DMSO) δ 7.94 (d, >8.8 Hz, 1H), 6.79 (d, >8.8 Hz, 1H), 6.60 (d, >8.8 Hz, 1H). 6.55 (d, >8.8, 1H), 6.45 (s, 1H), 5.85 (ddt, >17.3, 10.3, 6.6 Hz, 1H), 5.43 (d, >9.2 • *

214 *· 99 · « · • · · • ··· • · 9999 99

99

9 9

9 9

999

9

99

99 • 9 9 9

9 9 9

9 9 9 9

9 9 9

99

Hz), 5.16 (s, 1H), 5.09 (dd, >10.3, 1.1Hz, 1H), 5.06 (dd, >17.3, 1.1Hz, 1H), 4.91 (s, 1H), 4.06-3.97 (m, 2H), 2.62-2.52 (m, 1H), 2.31-2.15 (m, 1H), 2.24 (s, 3H), 1.35 (t, >7.0 Hz, 3H), 1.26 (s, 3H), 1.07 (s, 3H);

MS (DCI/NH 2 ) m/z 392 (M+H) ⁺ ;

HRMS calcd for C26H27NO3 391.2147. Found: 391.2138.

Example 293

10-Methoxy-9-(3-propenyloxy)-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-f]quinoline

MS (DCI/NH 3 ) m/z 404 (M+H) ⁺ ;

³ Η NMR (300 MHz, DMSO) δ 7.93 (d, >9.0 Hz, 1H), 6.83 (d, >8.8 Hz, 1H), 6.61 (d, J=9.0 Hz, 1H), 6.59 (d, >8.8 Hz, 1H), 6.23 (d, >1.5 Hz, 1H), 6.15-6.02 (m, 1H), 5.81 (ddt, >17.3,

10.3, 6.6 Hz, 1H), 5.67 (dd, >9.8, 3.3 Hz), 5.45 (s, 1H), 5.44 (dd, >16.0, 2.0 Hz, 1H), 5.27 (dd, 10.6, 2.0 Hz, 1H), 5.03 (dd, >10.3, 1.8 Hz, 1H), 4.98 (dd, >17.3, 1.8 Hz, 1H), 4.564.53 (m, 1H), 2.47-2.41 (m, 1H), 2.34-2.27 (m, 1H), 2.16 (s, 3H), 1.17 (s, 3H), 1.16 (s, 3H);

HRMS calcd for C26H29NO3 403.2147. Found: 403.2150.

Example 294

10-Methoxy-9-(3-propynyloxy)-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-f]quinoline

MS (DCI/NH 3 ) m/z 402 (M+H) ⁺ ;

¹ H NMR (300 MHz, DMSO) δ 7.92 (d, J =8.8 Hz, 1H), 6.88 (d, >8.8 Hz, 1H), 6.62 (d, >8.8 Hz, 1 H), 6.61 (d, >8.8, 1H), 6.24 (d, >1.7 Hz, 1H), 5.81 (ddt, >17.3, 10.3, 6.6 Hz, 1H), 5.72 (dd, >9.8, 3.3 Hz), 5.44 (s, 1H), 5.03 (dd, >10.3, 1.8 Hz, 1H), 4.99 (dd, >17.3, 1.8 Hz, 1H), 4.79 (d, >2.3 Hz, 2H), 3.57 (t, >2.3 Hz, 1H), 2.47-2.41 (m, 1H), 2.34-2.27 (m, 1H), 2.16 (s, 3H), 1.17 (s, 3H), 1.16 (s, 3H);

HRMS calcd for C26H27NO3 401.1991. Found: 401.1978.

Example 295

2,5-Dihydro-9-acetoxy-10-methoxy-2,2,4-trimethyl-5-(2-propenyl)-1Η-[1]benzopyrano[3,4fquinoline

215 ··· · · · · · · · · · · • ··· 9 9 · 999 9 9 99 9

9 9 9 9 9 9 9 9

1999 99 99 99 99 99 *H NMR (400 MHz, DMSO-dó) δ 7.78 (d, >8.5, 1H), 6.81 (d, >8.5, 1H), 6.60 (d, J=8.5, 1H), 6.57 (d, >8.9, 1H), 6.18 (d, >1.7, 1H), 5.80-5.70 (m, 2H), 5.39 (s, 1H), 4.99-4.90 (m, 2H), 3.55 (s, 3H), 2.39 (br dd, 2H), 2.23 (s, 3H), 2.10 (d, >0.9, 3H), 1.11 (s, 3H), 1.10 (s, 3H);

¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 169.3, 148.5, 148.0, 146.4, 138.6, 134.1, 133.7, 132.2, 127.4, 126.3, 120.8, 118.3, 117.4, 116.3, 115.1, 113.9, 112.7, 73.7, 60.0, 49.9, 36.7, 29.4, 29.1, 23.9, 20.6;

MS (DCI/NH 3 ) m/e 406(M+H) ⁺ ; Analytical calcd for C ₂₅ H ₂₇ NO ₄ : C 74.05, H 6.71, N 3.45. Found: C 73.91, H 6.79, N 3.31.

Example 296

2,5-dihydro-9-(4-N,N-dimethylamino-4-oxo-butanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2propenyl)-1 H-[ 1 ]benzopyrano[3,4-f|quinoline ’H NMR (300 MHz, DMSO-do) δ 7.86 (d, >8.8, 1H), 6.85 (d, >8.8, 1H). 6.68-6.62 (m, 2H), 6.25 (d, >1.5, 1H), 5.89-5.75 (m, 2H), 5.46 (s, 1H), 5.06-4.96 (m, 2H), 3.62 (s, 3H), 3.00 (s, 3H), 2.85 (s, 3H), 2.83-2.67 (m, 4H), 2.48 (m, 1H), 2.26 (m, 1H), 2.17 (s, 3H), 1.18 (s, 3H), 1.17 (s, 3H);

¹³ C NMR (75 MHz, DMSO-de) δ 171.5, 170.4, 148.3, 148.0, 146.2, 138.5, 134.1, 133.5,

132.1, 127.3, 126.2, 120.8, 118.1, 117.2, 116.2, 115.0, 113.8, 112.5, 73.6, 60.0, 49.8, 36.6, 36.5, 34.9, 29.3, 29.0, 27.6, 23.8;

MS (DCI/NH 3 ) m/e 491 (M+H) ⁺ , 508 (M+NH 3 ) ⁺ ; Analytical calcd for C ₂₉ H ₂₄ N ₂ O ₅ . C 71.00, H 6.99, N 5.71. Found: C 70.88, H 7.10, N 5.49.

The core 9 chemistry procedure described above was used to prepare Examples 297-299.

Example 297

-bromo-5-[3-cyclohexenyl]-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H[1]benzopyrano[3,4-f]quinoline

MS (APCI) m/z 466 (M+H) ⁺ ;

ΪΙ NMR (300 MHz, DMSO), isomer 1: δ 8.03 (d, >8.8 Hz, 1H), 7.33 (d, >9.2 Hz, 1H), 6.65 (dd, >8.8, 1.7 Hz, 2 H), 6.35 (d, >1.3 Hz, 1H), 5.91-5.43 (m, 4 H), 3.86 (s, 3H), 2.14 (s, 3H), 1.99 (s, 3H), 1.31 (s, 3H), 1.06 (s, 3H); isomer 2: δ 8.00 (dd, >8.8 Hz, 1H), 7.33 • «

216 • φ φφ φφφφ φφ φ

• ·* φφ ·· φφ φ φ φ φ

V Φ * Φ • φ φφφ φ φ φφ φφ • Φ φ φ φ φ φ φ • φ φφ (d, J=9.2 Hz, 1Η), 6.65 (dd, J=8.8, 1.7 Hz, 1H), 6.35 (d, J=l.3 Hz, 1H), 6.31 (d, J=l.3 Hz, 1H), 5.91-5.43 (m, 4H), 2.12 (s, 3H), 1.28 (s, 3H), 1.03 (s, 3H);

¹³ C NMR (300 MHz, DMSO) δ 155.5, 145.5, 133.9, 133.7, 129.5, 129.4, 128.5, 127.9, 127.7,

127.2, 127.0, 125.6, 118.1, 115.5, 113.2, 113.1, 106.9, 102.3, 77.2, 76.5, 55.8, 49.4, 37.6, 36.7, 29.6, 29.5, 27.4, 26.9, 25.6, 24.6, 24.2, 23.6, 21.1, 19.8;

^HRMS _calcd for _{C26H28NO279Br} ^465.1303 _. Found: 465.1284; Calcd for _{C26H28NO2881BrNO281Br} : ^467.1283 . Found: 467.1281.

Analytical calcd for _C26H28BrNO2 : C, _66.95 ; H, 6.05; N, 3:00; Found C, 66.77; H,

6.20; N, 2.88.

Example 298

10-Methoxy-7-bromo-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[ljbenzopyrano[3,4fjquinoline

MS (APCI) m/z 426 (M+H) ⁺ ;

³ H NMR (300 MHz, DMSO) δ 7.93 (d, J=8.8 Hz, 1H), 7.33 (d, J =9.2 Hz, 1H), 6.71 (d, J=9.2 Hz, 1H), 6.60 (d, J=8.5 Hz, 1H), 6.25 (d, J=1.5 Hz, 1H), 5.94-5.80 (m, 2H), 5.45 (s, 1H), 5.0 (m, 2H), 3.86 (s, 3H), 2.17 (d, J=1.5 Hz, 3H), 1.17 (s, 6H).

¹³ C NMR (300 MHz, DMSO) 155.3, 147.0, 146.0, 133.8, 133.6, 131.8, 129.5, 127.3, 127.2; 117.4, 116.0, 115.1, 113.2, 107.1, 102.6, 74.8, 55.9, 49.8, 29.0, 23.8.

HRMS calcd for _{C23H2479BrNO2} ^426.3502 . Found: _426.3496 .

Analytical calcd for _C23H24BγN02 : C, 64.79; H, 5.67; N, 3.29; Found C, 65.08; H, 5.73; N, 3.18.

Example 299

7-bromo-5-[1-methyl-3-cyclohexenyl]-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H[1]benzopyrano[3,4-f]quinoline MS (APCI) m/z 480 (M+H) ⁺ ;

³ H NMR (300 MHz, DMSO) isomer 1: δ 8.02 (d, J=8.5 Hz, 1H), 7.55 (d, J=5.9 Hz, 1H), 7.37 (d, J=2.6 Hz, 1H), 7.31 (d, J=1.8 Hz, 1H), 6.67 (dd, J=14.7, 8.8 Hz, 1H), 6.35 (d, J=1.5 Hz, 1H), 5.63 (d, J=5.9 Hz, 1H), 5.56-5.45 (m, 2H), 3.86 (s, 3H), 2.13 (s, 3H), 1.61 (s, 3H), 1.30 (s, 3H), 1.02 (s, 3 H); isomer 2: δ 8.00 (d, J=8.5 Hz, 1H), 7.54 (d, J=5.9 Hz, 1H), 7.35 (d, J=1.8 Hz, 2 H), 6.67 (dd, J=14.7, 8.8 Hz, 2 H), 6.31 (d, J=1.5 Hz, 1H), 5.51 (m, 2 3.86 (s, 3H), 2.08 (s, 3H), 1.50 (s, 3H), 1.09 (s, 3H), 0.92 (s, 3H);

»·

217 *

• ·» and • and «

« • aa »· a· ·· ·· ·· a a a · * a a a a··· · a·· a a *·« a a a a a a a « a · * a · a· aa ·»' aa

HRMS calcd for _{C27H30NO279Br} ^479.1460 . Found: 479.1463;

HRMS calcd for _{C27H30N0281Br} ^481.1439 . Found 481.1456.

Analytical Calcd for _{C27H30NO279Br} ; C, ^61.5 ; H, 6.29; N, 2.92 _; Found C, 67.08; H, 6.38; N, 2.54.

The core 10 chemistry procedure described above is used to prepare the compound of Example 300.

Example 300

10-Methoxy-9-bromo-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4fquinoline

MS (DCl/NH 3 ) m/z 428 (M+H); 426;

’H NMR (300 MHz, DMSO) δ 7.93 (d, J=8.8 Hz, 1H), 7.33 (d, J=8.5 Hz, 1H), 6.67 (d, ,J =8.5 Hz, 1H), 6.65 (d, J=8.5 Hz, 1H), 6.36 (d, >l,lHz, 1H), 5.88-5.74 (m, 2H), 5.46 (s, 1H),

5.05-4.95 (m, 2H), 3.62 (s, 3H), 2.18 (d, >1,1Hz, 3Η), 1.19 (s, 3H), 1.16 (s, 3H) ¹³ C NMR (300 MHz, DMSO) δ 152.7, 150.8, 146.5, 134.0, 133.6, 132.1, 130.0, 127.3, 126.1

119.3, 117.4, 116.2, 115.0, 114.6, 114.0, 109.5, 73.7, 59.6, 49.9, 36.7, 29.4, 29.1, 23.9;

HRMS calcd for _{C23H24NO279Br} ^425.0990 . Found: 425.0998;

HRMS calcd for _{C23H24NO281Br 427.0970} ^. Found: 427.0974.

Analytical calcd for Ο23Η2 ₄ ΒγΝΟ ₂ : C, 64.79; H, 5.67; N, 3.29; Found C, 64.99; H,

5.98; N, 3.13.

The core 11 chemistry procedure described above was used to prepare the compounds of Examples 301-303.

Example 301

7,9-dibromo-10-methoxy-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4fquinoline

MS (ESI) m/z 504 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO) δ 7.57 (d, J=8.9 Hz, 1H), 7.65 (s, 1H), 6.66 (d, >8.8 Hz, 1H), 6.44 (s, 1H), 5.95 (dd, >10.1, 3.1Hz, 1H), 5.97-5.78 (m, 2H), 5.47 (s, 1H), 5.08-4.99 (m, 2H), 3.62 (s, 3H), 2.19 (s, 3H), 1.20 (s, 3H), 1.17 (s, 3H);

ν· ·· • φ · · • · · • >··

218 • Φ ·· • · · · • · · · • · ··· ·· Φ· • · · · * · · · φ · · ·

C NMR (300 MHz, DMSO) δ 152.1, 147.4, 147.0, 133.6, 132.7, 132.0, 131.7, 128.3, 127.1,

126.3, 120.5, 117.6, 115.9, 115.3, 114.0, 113.8, 110.0, 106.6, 75.2, 59.7, 49.9, 36.8, 29.6, 29.2, 23.7;

HRMS calcd for _{C23H2379Br2NO2} ^503.0096 . Found: 503.0086; HRMS calcd for ^{C23H2379Br81BrNO2 505.0075} . Found: 505.0075.

Example 302

7,9-Dibromo-5-[cyclohexen-3-yl]-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H[ 1 ]benzopyrano[3,4-fJquinoline

MS (ESI) m/z 544 (M+H) ⁺ ;

’H NMR (300 MHz, DMSO), first isomer: δ 8.81 (d, 1H, J=8.83 Hz), 7.67 (s, 1H), 6.70 (d, 1H, >8.83 Hz), 6.59 (s, 1H), 5.82-5.59 (m, 4H), 5.50 (s, 1H), 3.61 (s, 3H), 2.49-2.27 (m, 2H), 2.15 (s, 3H), 2.04-1.81 (m, 2H), 1.79-1.41 (m, 2H), 1.32 (s, 3H), 1.08 (s, 3H); second isomer δ 7.9 (d, 1H, J=8.83 Hz), 7.66 (s, 1H), 6.69 (d, 1H, J=8.83 Hz), 6.54 (s, 1H), 5.825.59 (m, 4H), 5.45 (s, 1H), 3.60 (s, 3H), 2.49-2.27 (m, 2H), 2.13 (s, 3H), 2.04-1.81 (m, 2H), 1.79-1.41 (m, 2H), 1.30 (s, 3H), 1.05 (s, 3H);

HRMS calcd for _{C26H2779Br2NO2} ^is _543.0409 . Found: 543.0385;

_HRMS calcd ^for _{C26H2779Br81BrNO2} ^545.0388 . _Found : 545.0396.

Example 303

7,9-dibromo-5-[1-methyl-3-cyclohexenyl]-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H[1]benzopyrano[3,4-1]quinoline MS (ESI) m/z 560 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO), isomer 1: δ 8.83 (d, >8.0 Hz, 1H), 7.37, (s, 1H), 6.70 (d, >8.8 Hz, 1H), 6.58 (s, 1H), 5.58 (d, >9.2 Hz, 1H), 5.49 (s, 1H), 3.61 (s, 3H), 2.51-2.49 (m, 4H), 2.14 (s, 3H), 1.31 (s, 3H), 1.29-1.20 (m, 4H), 1.26 (s, 3H); isomer 2: δ 7.99 (d, J=8.0 Hz, 1H), 7.37 (s, 1H), 6.71 (d, >8.8 Hz, 1H), 6.55 (s, 1H), 5.57 (d, >9.2 Hz, 1H), 5.45 (s, 1H), 3.59 (s, 3H), 2.51-2.49 (m, 4H), 2.09 (s, 3H), 1.30 (s, 3H), 1.29-1.20 (m, 4H), 1.21 (s, 3H);

HRMS calcd for _{C27H29Br2NO2 557.0565} . Found: 557.0548.

The 12 17 core chemistry procedure described above was used to prepare the compounds of Examples 304-310.

• · • · • · • ·

219

Example 304

10-Methoxy-7-(2-ethenyl)-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-f]quinoline

MS (ESI) m/z 373 (M+H) ¹ ;

¹ H NMR (300 MHz, DMSO) δ 7.82 (d, >8.9 Hz, 1H), 7.23 (d, >8.9 Hz, 1H), 6.78 (dd, >11.0, 6.8 Hz, 1H), 6.61 (d, >8.9 Hz, 1H), 6.49 (d, >8.5 Hz, 1H), 5.99 (d, >1.7 Hz, 1H),

5.74 (dd, >7.6, 3.0 Hz, 1H), 5.71-5.63 (m, 1H), 5.57 (dd, >7.6, 1.7 Hz, 1H), 5.32 (s, 1H), 5.00 (dd, >9.3, 1.7 Hz, 1H), 4.92 (dd, >10.2, 1.7 Hz, 1H), 4.83 (dd, >16.9, 1.7 Hz, 1H),

3.75 (s, 3H), 2.06 (s, 3H), 1.53-1.41 (m, 2H), 1.24-1.15 (m, 3H), 1.05 (d, >2.1Hz, 1H); ¹³ C NMR (300 MHz, DMSO) δ 155.66, 147.91, 145.55, 134.17, 133.45, 131.98, 130.77, 127.37, 127.28, 123.88, 119.52, 117.21, 115.99, 115.80, 113.20, 113.18, 112.12, 105.59, 74.01, 55.59, 49.69, 36.40, 29.03, 28.83, 27.67, 26.19, 23.83, 13.5;

HRMS calcd for C25H27NO2 373.2042. Found: 373.2048.

Example 305

10-methoxy-7-methyl-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4fquinoline

MS (ESI) m/z 362 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO) δ 7.92 (d, >8.5 Hz, 1H), 6.93 (d, >8.5 Hz, 1H), 6.59 (dd, >5.5, 2.6 Hz, 1H), 6.10 (s, 1H), 5.90-5.76 (m, 2H), 5.44 (s, 1H), 5.07-4.90 (m, 2H), 3.82 (s, 3H), 2.17 (s, 3H), 2.08 (s, 3H), 1.99 (s, 3H), 1.16 (s, 3H), 1.15 (s, 3H);

¹³ C NMR (300 MHz, DMSO), 154.2, 148.5, 145.4, 134.5, 133.4, 131.9, 127.8, 127.4, 127.1, 118.2, 117.0, 116.3, 116.0, 113.1, 112.9, 104.8, 73.6, 55.5, 49.6, 36.5, 28.9, 28.8, 23.8, 15.0; HRMS calcd for C24H27NO2 361.2042. Found: 361.2045.

Example 306

10-Methoxy-7-acetyl-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4fquinoline

MS (ESI) m/z 390 (M+H) ⁺ .

'H NMR (300 MHz, DMSO), 7.88 (d, >8.8 Hz, 1H), 7.59 (d, >8.8 Hz, 1H), 6.84 (d, >8.8 Hz, 1H), 6.62 (d, >8.8 Hz, 1H), 6.22 (d, >1.5 Hz, 1H), 6.01-5.97 (m, 1H), 5.90-5.69 (m, • ·

1H), 5.46 (s, 1H), 5.03-4.83 (m, 2H), 3.93 (s, 3H), 2.53 (s, 3H), 2.20 (d, J=1.5Hz, 3H), 1.19 (s, 3H), 1.16 (s, 3H).

Example 307 (+/-) 2,5-dihydro-9-methyl-10-methoxy-2,2,4-trimethyl-5-(1-methylcyclohexen-3-yl)-1H[1]benzopyrano[3,4-f]quinoline MS (DCI/NHa) m/z 416 (M+H) ⁺ .

Example 308

10-Methoxy-7-methyl-9-methyl-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-f]quinoline

MS (DCI/NH ₃ ) m/z 376 (M+H) ⁺ ;

Η NMR (300 MHz, DMSO-dé) δ 7.95 (d, J=8.5 Hz, 1H), 6.81 (s, 1H), 6.62 (d, J=8.5 Hz, 1H), 6.17 (d , J=1.5 Hz, 1H), 5.89-5.76 (m, 2H), 5.44 (br s, 1H), 5.04 (dd, J=10.3, 1.8 Hz, 1H), 4.94 (dd, J=17.3, 1.8 Hz, 1H), 3.52 (s, 3 H), 2.46-2.40 (m, 1H), 2.28-2.24 (m, 1H), 2.18 (s, 3 H), 2.17 (s, 3 H), 2.07 (s, 3 H), 1.19 (s, 3H), 1.14 (s, 3H);

HRMS calcd for C25H29NO2 375.2198. Found: 375.2214.

Example 309

10-chloro-5-(3-propenyl)-2,2,4-trimethyl-2,5-dihydro-1H-[1]benzopyrano[3,4-f]quinoline MS (DCI/NH ₃ ) m/z 352 (M+H) ⁺ ;

’H NMR (300 MHz, DMSO) δ 7.93 (d, >8 Hz, 1H), 7.12-7.10 (m, 2 H), 6.90-6.84 (m, 1H), 6.65 (10, 2 Hz, 1H), 4.97 (dd, J=17, 2 Hz, 1H), 2.47-2.26 (m, 2 H), 2.16 (s, 3H), 1.23 (s, 3H), 1.17 (s, 3H);

HRMS (FAB) calcd for C22H22CINO: 351.1390 (M) ⁺ . Found: 351.1385.

Example 310 (+/-) 2,5-dihydro-10-chloro-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano[3,4-f]quinoline MS (DCI/ _NH3 ) m/z 288 (M+H) ⁺ ;

^J H NMR (200 MHz, DMSO) δ 7.98 (d, J=8 Hz, 1H), 7.27-7.14 (m, 5 H), 6.97-6.80 (m, 2 H), 6.81 (br s, 1H), 6.78-6.72 (m, 2 H), 6.44 (br s, 1H), 5.40 (br s, 1H), 1.81 (br s, 2H), 1.26 (s, 2H), 1.16 (s, 2H);

HRMS (FAB) calculated m/z for _C25H23ClNO : 387.1390 (M) ⁺ . Found: 287.1286.

φ φ • ·

221

Example 311

2.5-Dihydro-10-methoxy-5-(3-(N-methyl-N-(carbomethoxymethyl)aminocarbonyloxy)phenyl)2.2.4-trimethyl-1-1H-[1]benzopyrano[3,4-quinoline

The compound of Example 13 and N-methyl-N-(methylglycinate)carbamoyl chloride are treated according to the method of Example 14 to give the desired compound.

MS (DCI/NH ₃ ) m/e 529 (M+H) ⁺ ;

’H NMR (300 MHz, DMSO-d^) δ 8.00(d, 1H), 7.21(m, 1H), 7.03(d, 1H), 6.92(m, 3H), 6.72(m, 3H), 6.55(d, 1H), 6.45(t, 1H), 5.40(s, 1H), 4.15(s, 1H), 4.05(s, 1H), 3.78(s, 3H), 3.65(s, 3H), 3.00(s, 1H), 2.88(s, 2H), 1.84(s, 3H), 1.22(s, 3H), 1.13(s, 3H).

Analytical calcd for _C31H32N2O6 : C, _70.43 ; H, 6.10; N, 5.29. Found: C, 70.98; H, 6.33; N, 4.85.

Example 312

2.5-Dihydro-10-methoxy-5-(3-(N-methyl-N-(N-methylcarbonyl)aminocarbonyloxy)phenyl)2.2.4- trimethyl-1H-[ljbenzopyrano[3,4-fquinoline

The compound of Example 13 and methyl isocyanate are treated according to the method of Example 14 to give the desired compound.

MS (DCI/NH 3 ) m/e 514 (M+H) ⁺ ;

³ H NMR (300 MHz, DMSO-d ₆ ) δ 8.18(q, ΪΗ), 8.01(d, 1H), 7.27(t, 1H), 7.06(t, 2H), 6.98(s, 1H), 6.91(t, 1H), 6.77(s, 1H), 6.70(d, 1H), 6.56(d, 1H), 6.46(d, 1H), 6.19(s, 1H), 5.38(s, 1H), 3.78(s, 3H), 3.19(s, 3H), 2.70(d, 3H), 1.84(s, 3H), 1.22(s, 3H), 1.14(s, 3H).

Analytical calcd for C30H31N3O5 _2H2O : C, 65.55; H, 6.41; N, 7.60. Found: C, 65.71; H, 6.20; N, 7.05.

Example 313

2.5-Dihydro-10-methoxy-5-(3-(N-methylaminocarbonyloxy)phenyl)-2,2,4-trimethyl-1H[ 1 jbenzopyrano [3,4-fj quinoline

The compound of Example 13 and methyl isocyanate were treated according to the method of Example 14 to give the desired compound, MS (DCI/NH3) m/e 457 (M+H) ⁺ ;

222 • · 4 4 · · · · · · · ····· ·· * • · · · Φ «· Φ· ·· ¹ Η NMR (300 MHz, DMSO-dó) δ 8.01(d, 1Η), 7.50(q, 1Η), 7.21(t, 1H), 7.02(d, 1H), 6.92(dd, 2H), 6.80(s, 1H), 6.77(s, 1H), 6.70(dd, 1H), 6.56(d, 1H), 6.46(d, 1H), 6.18(s, 1H), 5.40 (s, 1H), 3.80(s, 3H), 2.60(d, 3H), 1.86(s, 3H), 1.23(s, 3H), 1.15(s, 3H);

Analytical calcd for C28H28N2O4 0.50H2O: C, 72.33; H, 6.27; N, 6.01. Found: C, 72.20; H, 6.38; N, 5.78.

Example 314

2,5-dihydro-10-methoxy-5-(3-(2-hydroxyethyl)phenyl)-2,2,4-trimethyl-1H[ 1 ]benzopyrano[3,4-quinoline

A solution of 3-(2'-methoxymethoxy)ethylphenyl bromide (3.55 g, 14.5 mmol) in THF (150 mL) at -78°C was treated with n-butyllithium (2.5 M in hexanes, 5.80 mL) for 15 min, heated at -30°C, cooled to -78°C, treated with the compound of Example 1F at once, heated to -50°C, quenched with saturated ammonium chloride solution, and allowed to warm to room temperature. The supernatant was decanted and concentrated, and the residue was partitioned between aqueous and ethyl acetate layers. The organic layer was washed sequentially with water and brine, dried ( _Na2SO4 ), and concentrated. The residue was subjected to flash chromatography on a silica gel column with 20-35% ethyl acetate/hexane as the mobile phase to give 0.82 g (56%) of the desired 5-(3'-MOMO-phenyl)hemiketal.

MS (DCI/NH ₃ ) m/e 489 (M+H) ⁺ ;

A solution of the hemiketal prepared above (0.70 g, 1.43 mmol) in methanol (10 mL) was treated with saturated hydrogen chloride in methanol (20 mL) at room temperature, stirred for 18 h, poured into 1:1 ethyl acetate/saturated ammonium chloride. The separated aqueous layer was extracted with ethyl acetate, and the combined acetate layers were washed sequentially with water and brine, dried ( _Na2SO4 ), and concentrated to give 0.52 g (8% yield) of the deprotected hemiketal.

MS (DCI/NH 3 ) m/e 444 (M+H) ⁺ .

A solution of the deprotected hemiketal (0.45 g, 1.00 mmol) and triethylsilane (1.16 g, 10 mmol) in dichloromethane (20 mL) was treated with boron trifluoride etherate (1.42 g, 10 mmol) at room temperature, stirred for 18 h, and poured into a 1:1 ethyl acetate/sat. NaHCO ₃ solution. The separated aqueous layer was extracted with ethyl acetate, and the combined extracts were washed successively with water and brine, dried (Na ₂ SO ₄ ), and concentrated. The residue was flash chromatographed on a silica gel column with 25-45% ethyl acetate in hexanes to give 0.342 g of the desired compound.

• · ♦ · • · • ·

223 ···· ·· ··

MS (DCIZNH3) m/e 428 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-do) δ 8.00(d, IH), 7.00(m, 5H), 6.74(s, IH), 6.70(d, IH), 6.55(d, IH), 6.45(d, IH), 6.16(s, IH), 5.39(s, IH), 4.54(t, IH), 3.79(s, 3H), 3.44(q, 4H), 2.59 (t, 2H), 1.86(s, 3H), 1.22(s, 3H), 1.1 l(s, 3H);

Analytical calcd for C28H29NO3: C, 78.66; H, 6.83; N, 3.27. Found: C, 78.48; H, 6.85; N, 3.29.

Example 315

2.5-Dihydro-10-methoxy-5-(3-(2-methanesulfonyloxyethyl)phenyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline

A solution of Example 314 (200 mg, 0.47 mmol) and triethylamine (94 mg, 0.94 mmol) in CH2Cl2 (6 mL) at 0°C was treated with methanesulfonyl chloride (64 mg, 0.56 mmol), stirred for 30 min, and quenched with sat. NaHCO3. The separated aqueous layer was extracted with CH2Cl2, and the combined organic layers were washed with brine, dried ( _Na2SO4 ), and concentrated. The residue was flash chromatographed on a silica gel column with 10-30% ethyl acetate/hexanes to give 0.30 g (97%) of the desired compound.

MS (DCI/NH 3 ) m/e 506 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-d _ó ) δ 8.00(d, IH), 7.18(s, IH), 7.14(d, IH), 7.09(d, IH), 6.96(d, IH), 6.90(t, IH), 6.75(s, IH), 6.70(d, IH), 6.55(d, IH), 6.45(d, IH), 6.21(s, 1H), 5.39(s, 1H), 4.27(t, 2H), 3.79(s, 3H), 2.88(s, 3H), 2.87(t, 2H), 1.84(s, 3H), 1.24(s, 3H), 1.14(s, 3H) Analytical calculated for C 29 H 31 NO 5 S: C, 68.88; H, 6.17; N, 2.77. Found: C, 69.08; H, 6.14; N, 2.63.

Example 316

2.5-Dihydro-10-methoxy-5-(3-(2-methylthioethyl)phenyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline

A solution of Example 315 (10 mg, 0.02 mmol) in DMF (1 mL) was treated with NaSMe (14 mg, 0.20 mmol) at room temperature, stirred for 2 h, quenched with sat. NaHCO 3 and extracted with ethyl acetate. The organic layer was washed with brine, dried (Na 2 SO ₄ ) and concentrated. The residue was flash chromatographed on a silica gel column with 10-30% ethyl acetate/hexanes to give 9 mg (9% %) of the desired compound.

MS (DCI/NH 3 ) m/e 458 (M+H) ⁺ ;

9 9

9 ·

. 1H0, 6.16(s, 1H), 5.39(s, 1H), 3.77(s, 3H), 2.70(t, 2H), 2.54(t, 2H), 1.91(s, 3H), 1.95(s, 3H), 1.21(s, 3H), 1.15(s, 3H).

Example 317

2,5-dihydro-10-methoxy-5-(3-(2-(N,N-dimethylaminocarbonyloxy)ethyl)phenyl)-2,2,4trimethyl-1H-[1]benzopyrano[3,4-f]quinoline

The compound of Example 314 and N,N-dimethylcarbamoyl chloride are treated according to the method of Example 14 to give the desired compound.

MS (DCI/NH 2 ) m/e 499 (M+H) ⁺ .

’H NMR (300 MHz, DMSO-cL) δ 8.01(d, IH), 7.00(m, 5H), 6.76(s, IH), 6.70(d, IH), 6.55 (s, IH), 6.44(d, IH), 6.15(s, IH), 5.39(s, IH), 4.01(t, 2H), 3.78(s, 3H), 2.79(1, 2H), 2.77(s, 3H), 2.65(s, 3H), 1.84(s, s, 3H), 1.23(s, 3H), 1.15(s, 3H).

Analytical calcd for C31H34N2O4: C, 74.67; H, 6.87; N, 5.61. Found: C, 74.45; H, 6.73; N, 5.45.

Example 318

2,5-dihydro-10-methoxy-5-(3-(2-(N,N-dimethylamino)ethyl)phenyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline

The compound of Example 315 and dimethylamine are treated according to the method of Example 316 to give the desired compound.

MS (DCI/NH 3 ) m/e 455 (M+H) ⁺ ;

*H NMR (300 MHz, DMSO-dé) δ 8.00(d, IH), 7.09(t, IH), 7.01(d, IH), 6.97(m, 2H), 6.90(t, IH), 6.73(s, IH), 6.69(d, IH), 6.55(d, IH), 6.44(d, IH), 6.16(s, IH), 5.39(s, 1H), 3.79(s, 3H), 2.54(t, 2H), 2.25(t, 2H), 2.08(s, 6H), 1.87(s, 3H), 1.22(s, 3H), 1.17(s, 3H).

Example 319

2,5-dihydro-10-methoxy-5-cyclopropyl-2,2,4-trimethyl 1-1H-[1]benzopyrano[3,4-fJ quinoline

Example 319A

A mixture of Example IF (4.43 g, 13.7 mmol), 4-chlorophenol (9.28 g, 72.1 mmol) and MgSO ₄ (8.69 g, 72.1 mmol) in CH ₂ Cl ₂ (100 mL) at room temperature was stirred for 12 h, diluted with ethyl acetate (200 mL), washed (2x) with 1M aqueous NaOH solution and brine, dried

225 ··· · · (Na ₂ SO4) and concentrated. The residue was triturated with hot ethyl acetate (25 mL) to give the desired ethyl acetate (25 mL) to give the desired phenyl acetal.

MS (DCI/NH 2 ) m/e 306 (M-4-Cl-ph) ⁺ .

Example 319B

A solution of Example 319A (131 mg, 0.30 mmol) in toluene (20 mL) at 0°C was treated with cyclopropylmagnesium bromide, prepared by refluxing cyclopropylbromide (363 mg, 3.0 mmol) and Mg (73 mg, 3.0 mmol) in THF (1.5 mL) for 30 min. The final solution was allowed to warm to room temperature and stirred for 12 h, quenched with sat. NH4Cl. The organic layer was washed (2x) with 1M aqueous NaOH and brine, dried ( _Na2SO4 ), and concentrated. The residue was flash chromatographed on silica gel with 5-15% ethyl acetate/hexanes to give 18 mg (17%) of the desired compound.

MS (DCI/NH 3 ) m/e 348 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-d ₆ ) δ 8.01(d, 1H), 7.04(t, 1H), 6.67(d, 1H), 6.60(d, 1H), 6.57(d, 1H), 6.16(s, 1H), 5.44(s, 1H), 5.42(d, 1H), 3.85(s, 3H), 2.12(s, 3H), 1.26(s, 3H), 1.05(s, 3H), 0.28(m, 4H), 0.08(m, 1H).

Example 320

2,5-dihydro-10-methoxy-5-ethenyl-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-fJ quinoline

A solution of Example 2B (34 mg, 0.1 mmol) and tributylvinyltin (96 mg) in CH ₂ Cl ₂ (2 mL) was treated with boron trifluoride etherate (43 mg, 0.3 mmol) at -78°C and allowed to warm to room temperature with stirring over 2 h. The reaction was then quenched with sat. NaHCCl and the organic layer was washed with sat. NaHCO ₃ and brine, dried (Na ₂ SO ₄ ), and concentrated. The residue was flash chromatographed on silica gel with 5-15% ethyl acetate/hexanes to give 27 mg (81%) of the title compound.

MS (DCI/NH 3 ) m/e 334 (M+H) ⁺ ;

^X H NMR (300 MHz, DMSO-d ₆ ) δ 7.93(d, 1H), 7.02(t, 1H), 6.63(dd, 2H), 6.54(d, 1H), 6.19(d, 1H), 6.10(s, 1H), 5.93(m, 1H), 5.42(s, 1H), 5.16(dt, 1H), 4.91(dt, 1H), 3.83(s, 3H), 2.1 L(s, 3H), 1.21(s, 3H), 1.13(s, 3H).

Example 321

Φ· • · · ♦ • · ·

999 ·

9999 99

9 9

226

99

9 9

9 ·

9 ·

9 9 trans 2,5-dihydro-10-methoxy-5-(2-phenylethenyl)-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4f]quinoline

A mixture of Example 320 (13 mg, 0.039 mmol), iodobenzene (12 mg, 0.058 mmol), palladium acetate (18 mg, 0.008 mmol), tri(o-tolyl)phosphine (3.6 mg, 0.012 mmol), triethylamine (12 mg, 0.12 mmol) in CH3CN (1 mL) was heated at 80°C for 4 h in a sealed vessel. After removal of the solvent, the residue was flash chromatographed on a silica gel column with 5-15% ethyl acetate/hexanes to give 7 mg (4% yield) of the desired compound.

MS (DCI/NH 3 ) m/e 410 (M+H) ⁺ ;

'H NMR (300 MHz, DMSO-d _ó ) δ 7.99(d, 1H), 7.22(m, 4H), 7.19(m, 1H), 7.00(t, 1H), 6.67(d, 1H), 6.63(d, 1H), 6.57(d, 1H), 6.38(q, 1H), 6.34(d, 1H), 6.27(d, 1H), 6.14(s, 1H), 5.43(s, 1H), 3.82(s, 1H), 2.12(s, 3H), 1.22(s, 3H), 1.13(s, 3H).

Example 322

2,5-dihydro-10-methoxy-5-(2-phenylethynyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline

The compound of Example 2B and tributylphenylacetylenyltin are treated according to the method of Example 320 to give the desired compound.

MS (DCI/NH3) m/ml 408 (M+H) ⁺ ;

¹ H NMR (300 MHz, DMSO-dg) δ 7.92(d, 1H), 7.29(m, 3H), 7.16(m, 2H), 7.10(d, 1H), 6.78(d, 1H), 6.65(dd, 1H), 6.59(s, 1H), 6.23(s, 1H), 5.45(s, 1H), 3.87(s, 3H), 2.33(s, 3H), 1.28(s, 3H), 1.12(s, 3H).

Example 323 cis 2,5-dihydro-10-methoxy-5-(2-phenylethenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,41] quinoline

A mixture of Example 322 (20 mg, 0.049 mmol), palladium/BaSO ₄ (20 mg) in pyridine (2 mL) was stirred at room temperature for 12 hours, then washed with water and extracted with ethyl acetate. The organic layer was washed with brine, dried (Na 2 SO ₄ ), and concentrated. The residue was subjected to silica gel column chromatography with 5-15% ethyl acetate/hexanes as the mobile phase to give 13 mg (75%) of the desired compound.

MS (DCI/NH3) m/e 410 (M+H) ⁺

227 • ·

9· 99 • · · · • · · · · 999 • 9 · ·· ·· ·· ·· • · · · · · • · · · · · · · · · *

9« 9· 'Η NMR (300 MHz, DMSO-dg) S 7.97(d, 1H), 7.62(d, 2H), 7.48(t, 2H), 7.39(t, 1H), 7.03(t, 1H), 6.72(d, 1H), 6.63(d, 1H), 6.61(d, 1H), 6.52(d, 1H), 6.12(d, 1H), 6.10(s, 1H), 5.70(dd, 1H), 5.27(s, 1H), 3.87(s, 3H), 1.55(s, 3H), 1.17(s, 3H), 1.079s, 3H).

Example 324

2,5-dihydro-10-methoxy-5-(2-methylpropenyl)-2,2,4-trimethyl-1H-[ljbenzopyrano[3,4fjquinoline

The compound of Example 2B and tributyl-(2-methylpropenyl)tin are treated according to the method of Example 320 to give the desired compound.

MS (DCI/NH 2 ) m/e 362 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-dg) δ 7.92(d, 1H), 6.99(t, 1H), 6.65(d, 1H), 6.58(d, 1H), 6.44(d, 1H), 6.24(d, 1H), 6.21(s, 1H), 5.40(s, 1H), 5.18(d, 1H), 3.85(s; 3H), 2.07(s, 3H), 1.84(s, 3H), 1.58(s, 3H), 1.23(s, 3H), 1.10(s, 3H);

Analytical calcd for C24H27NO2: C, 79.74; H, 7.52; N, 3.87. Found: C, 79.34; H, 7.25; N, 3.68.

Example 325 trans 2,5-dihydro-10-methoxy-5-(1-cyclohexenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4]quinoline

The compound of Example 2B and tributyl-(1-cyclohexenyl)tin are treated according to the method of Example 320 to give the desired compound.

MS (DCI/NH 3 ) m/e 388 (M+H) ⁺ ;

’H NMR (300 MHz, DMSO-dg) δ 7.91(d, 1H), 7.00(t, 1H), 6.64(d, 1H), 6.60(d, 1H), 6.49(d, 1H), 6.02(s, 1H), 5.85(s, 1H), 5.39(s, 1H), 5.14(s, 1H), 3.81(s, 3H), 2.18(m, 1H), 2.03(s, 3H), 1.98(m, 1H), 1.8l(m, 1H), 1.64(m, 1H), 1.42(m, 3H), 1.24(m, 1H), 1.22(s, 3H), 1.13(s, 3H); Analytical calcd for C26H29NO2 1.25H2O: C, 76.15; H, 7.74; N, 3.41. Found: C, 76.12; H, 7.34; N, 3.21.

Example 326

2,5-dihydro-10-(2-furans 1)-5-(3-propene 1)-2,2,4-trimethyl-1H-[1jbenzopyrano[3,4-quinoline

A magnetically stirred mixture of triflate 3C [from the original patent application] (196 mg, 0.421 mmol) and 2-(tributylstannyl)furan (0.250 mL, 0.79 mmol) and [1,r-bis(diphenylphosphino)ferrocene]dichloropalladium(II) methylene chloride complex (25 mg, 0.031 mmol)

228 and tetrabutylammonium iodide (25 mg, 0.068 mmol) in dry NMP (6.5 mL) was heated at 70°C under argon. The reaction was allowed to warm to room temperature, diluted with sat. aqueous NaCl, and extracted with ethyl acetate (5 x 20 mL). The combined organic layer was dried (MgSO ₄ ), filtered, and concentrated. The crude material was chromatographed on a silica gel column (16 g) with ethyl acetate-hexanes (10:90) to give a product contaminated with starting material. The material was applied to three 10 x 20 cm, 0.25 mm thick silica gel plates, eluted (4x) with EtOAc-hexanes (5:95). The product was scraped and extracted with ethyl acetate to give 23 mg (0.044 mmol, 14%) of the desired furan as a viscous syrup: 'H NMR δ 7.67 (d, 1H; >1.0 Hz), 7.18 (t, 1H, >7.8Hz), 7.08 (m, 1H), 6.91 (dd, 1H, >8.1 Hz, >1.4Hz), 6.64 (m, 2H), 6.35 (d, 1H, >8.5Hz), 6.25 (d, 1H, J=8.5Hz), 6.14 (m, 1H), 5.82 (m, 2H), 5.43 (s, 1H), 5.05 (dd, 1H, >10.5Hz, J=1.5Hz), 4.99 (dd, 1H, >17.3Hz, >1.5Hz), 2.40 (m, 2H), 2.19 (s, 3H), 1.20 (s, 3H), 1.12 (s, 3H);

MS (DCI) m/z 384 (M+1).

Analytical calcd for C26H25NO2: C, 81.43; H, 6.57; N, 3.65. Found: C, 81.24; H, 6.62; N, 3.66.

Example 327

2,5-dihydro-10-cyano-5-(3-propenyl)-2,2,4-trimethyl-1H-[1Jbenzopyrano[3,4-quinoline

A magnetically stirred mixture of triflate 3C (195 mg, 0.419 mmol), 36 mg (0.031 mmol) tetrakis(triphenylphosphine)palladium) and zinc cyanide (36 mg, 0.31 mmol) in dry dioxane (4.0 mL) and water (1.0 mL) was heated at 80°C for 48 h under argon. The reaction was allowed to cool to room temperature, diluted with ethyl acetate (25 mL) and washed with sat. aq. NaCl. The aqueous layer was extracted with ethyl acetate (2 x 20 mL). The combined organic layer was dried (MgSO ₄ ), filtered and concentrated. The crude material was chromatographed on a silica gel column (20 g) with ethyl acetate-hexanes (10:90) to give the product contaminated with the starting triflate. The partially pure nitrile is applied to two 0.25 mm thick silica gel plates measuring 10 x 20 cm, which are eluted (5x) with a mobile phase of EtOAc-hexanes (5:95). The product was scraped and extracted with ethyl acetate to give 17.3 mg (0.0505 mmol, 12%) of the desired nitrile: 'H NMR δ 7.87 (d, 1H, J=8.5Hz), 7.46 (dd, 1H, J=7.5Hz, >1.5Hz), 7.27 (t, 1H, J=7.8Hz), 7.19 (dd, 1H, >8.1Hz, J=1.4Hz), 6.71 (d, 1H, >8.5Hz), 6.57 (m, 1H), 5.90 (dd, 1H, >10 Hz, >3.6Hz), 5.82 (m, 1H), 5.49 (m, 1H), 5.04 (dm, 1H, >10.5Hz), 4.98 (dm, 1H, >17.3Hz), 2.38 (m, 1H), 2.30 (m, 1H), 2.19 (s, 3H), 1.20 (s, 3H), 1.19 (s, 3H); MS (APCI) m/z 343 (M + 1); Calcd for C23H22N2O: 342.1732. Found: 342.1730.

229

ΦΦ ·· r 3 φ *

Φ Φ ♦ • »»» • * ♦ ··· 99 t 9· • 9 9

Φ · · φ ·»· • · ** • Φ **

Ρ · Φ Φ i φ · φ > φ φ · • 9 9 9

ΦΦ ·*

Example 328

2.5-Dihydro-10-carboxy-5-(3-propenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline

A magnetically stirred mixture of Example 4 (31 mg, 0.082 mmol) and sodium cyanide (51 mg, 0.78 mmol) in dry dimethyl sulfoxide (2.5 mL) was heated at 110°C for 5 h under argon. The reaction was allowed to cool to room temperature, diluted with sat. aqueous NaCl, and extracted with ethyl acetate (5 x 20 mL). The combined organic layer was dried (MgSO 4 ), filtered, and concentrated. The crude material was loaded onto two 0.25 mm thick silica gel plates (10 x 20 cm). These plates were eluted (2x) with EtOAc-hexanes (10:90) and then three times with EtOAc-hexane (50:50). The product was scraped off and extracted with ethyl acetate to give 16 mg (0.044 mmol, 54%) of the desired carboxylic acid as a viscous syrup: ^! Η NMR δ 7.16 (m, 2H), 7.02 (d, 1H, J=8.5Hz), 6.98 (dd, 1H, J=5.5Hz, J=3.7Hz), 6.58 (d, 1H, J=8.5Hz), 6.29 (m, 1H), 5.82 (m, 2H), 5.45 (s, 1H), 5.05 (dd, 1H, J=10.5Hz, J=1.5Hz), 4.98 (dd, 1H, J=17.3Hz, J=1.5Hz), 2.30 (m, 2H), 2.18 (s; 3H), 1.20 (s, 3H), 1.16 (s, 3H); MS (APCI) m/z 362 (M + 1): Analytical calcd for C23H23NO3: C, 76.43; H, 6.41; N, 3.88. Found: C, 76.24; H, 6.46; N, 3.66.

Example 329

2.5-Dihydro-10-(2-hydroxymethyl)-5-(3-propenyl)-2,2,4-trimethyl-1H-[1Jbenzopyrano[3,4fjquinoline

To a magnetically stirred solution of Example 4 (32 mg, 0.085 mmol) in dry methylene chloride (3 mL) cooled to -78° was added dropwise under argon 1.0 M diisobutylaluminum hydride in cyclohexane (0.400 mL, 0.40 mmol). The reaction temperature was raised to 0°C. After 3.5 h, the reaction mixture was quenched by addition to an aqueous solution of Rochelle's salt and the layers were separated. The aqueous layer was extracted with ethyl acetate (3 x 40 mL). The combined organic layer was dried (MgSO ₄ ), filtered and concentrated. The crude material was applied to two 0.25 mm thick silica gel plates measuring 10 x 20 cm. These plates were eluted with hexanes, then EtOAc-hexanes (10:90) (3x). The product was scraped and extracted with ethyl acetate to give 27 mg (0.078 mmol, 91%) of the desired alcohol as a viscous syrup: ^! H NMR δ 7.47 (d, 1H, J=8.5Hz), 7.14 (m, 2H), 6.80 (dd, 1H, J=7.3Hz, J=1.8Hz), 6.64 (d, 1H, J=8.5Hz), 6.17 (m, 1H), 5.81 (ddm, 1H, J=10.5Hz, J=17.1Hz), 5.73 (dd, 1H, J=3.4Hz, J=10.5Hz), 5.46 (m, 1H), 5.32 (dd, 1H, J=6.3Hz, J=4.2Hz), 5.02 (dm, 1H, • ·

230 .............

J=10.5Hz), 4.94 (dm, 1Η, J= 17.1Hz), 4.62 (m, 2H), 2.30 (m, 2H), 2.17 (s, 3H), 1.19 (s, 3H),

1.16 (s, 3H);

MS (ESI) m/z: 348 (Μ + 1); Calcd for C23H25NO2: 347.1885. Found: 347.1897.

Example 330

2.5-Dihydro-10-formyl-5-(3-propenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-quinoline

A magnetically stirred mixture of Example 329 (185 mg, 0.532 mmol) and tetrapropylammonium rutheniumate (205 mg, 0.583 mmol) in dry methylene chloride (10 mL) was stirred for 1.5 h under argon. The reaction was filtered through celite, the filter cake was washed with ethyl acetate, and the filtrate was concentrated. The crude material was chromatographed on a silica gel column (20 g) with EtOAc-hexanes (10:90) to give 144 mg (0.417 mmol, 78%) of the desired aldehyde: *H NMR δ 10.11 (s, 1H), 7.45 (dd, 1H, J=7.8Hz, J=1.2Hz), 7.29 (t,

1H, J=7.8Hz), 7.16 (dd, 1H, J=7.8Hz, J=l.4Hz), 6.84 (d, 1H, J=8.5Hz), 6.70 (d, 1H, J=8.5Hz), 6.53 (m, 1H), 5.91 (dm, 1H, J= 10.0Hz), 5.84 (m, 1H), 5.51 (s, 1H), 5.05 (dm, 1H, J=10.5Hz), 4.97 (dm, 1H, J=17.3Hz), 2.40 (m, 2H), 2.21 (s, 3H), 1.22 (s, 3H), 1.18 (s, 3H);

MS (APCI) m/z 346 (M+1); Calcd for C23H23NO2: 345.1729. Found: 345.1732.

Example 331

2.5-Dihydro-10-aminomethyl-5-(3-propenyl)-2,2,4-trimethyl-1H-[l]benzopyrano[3,4fquinoline

To a magnetically stirred solution of Example 330 (40 mg, 0.116 mmol) and ammonium acetate (77 mg, 1.0 mmol) in dry methanol (10 mL) was added sodium cyanoborohydride (14 mg, 0.23 mmol) under a nitrogen atmosphere. After 5 h, the reaction mixture was quenched with 10% sodium carbonate solution and extracted with ethyl acetate (3 x 40 mL). The combined organic layer was dried (MgSO4), filtered, and concentrated. The crude material was applied to two 0.25 mm thick silica gel plates (10 x 20 cm). These plates were eluted with hexanes, then EtOAc-hexanes (20:80) (4x). The product was scraped and extracted with ethyl acetate to give 8.0 mg (0.023 mmol, 20%) of the desired amine as a viscous syrup: ’H NMR δ 7.55 (d,

1H, J=8.5Hz), 7.14 (m, 2H), 6.80 (dd, 1H, 3=7.3Hz, J=1.8Hz), 6.64 (d, 1H, J=8.5Hz), 6.17 (m, 1H), 5.81 (ddm, 1H, J=10.5Hz, J=I7.1Hz), 5.73 (dd, 1H, J=3.4Hz, J=10.5Hz), 5.46 (m,

1H), 5.02 (dm, 1H, J=10.5Hz), 4.94 (dm, 1H, J=17.1Hz), 4.62 (m, 2H), 3.88 (m, 2H), 2.30 (m, 2H), 2.17 (s, 3H), 1.19 (s, 3H), 1.16 (s, 3H); MS (ESI) m/z: 347 (Μ + 1); Calcd for C23H26N2O: 346.2045. Found: 346.2047.

231 ··· • ·

M· • ·

Example 332

2,5-dihydro-1O-methoxymethyl-5-(3-propenyl)-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4fjquinoline

To a magnetically stirred solution of Example 329 (26 mg, 0.075 mmol) in dry THF (2.0 mL) cooled in an ice bath was added 0.14 mL of 1M potassium hexamethyldisilazide in hexane under argon. Methyl iodide (13.8 mg, 0.097 mmol) was added to the reaction mixture and the reaction mixture was slowly warmed to room temperature. The reaction was quenched with sat. aqueous NH4Cl and extracted with ethyl acetate (3x10 mL). The extracts were dried (MgSO4), filtered, and concentrated. The crude material was applied to three 0.25 mm thick silica gel plates measuring 10 x 20 cm. These plates were eluted (4x) with a mobile phase of EtOAc-hexane (5:95). The product was extracted using EtOAc to give 25 mg (0.069 mmol, 92%) of the desired methyl ether: *H NMR δ 7.34 (d, 1H, J=8.5Hz), 7.11 (m, 2H), 6.85 (dd, 1H, >7.1Hz, >2.4Hz), 6.64 (d, 1H, J=8.5Hz), 6.20 (m, 1H), 5.81 (dm, 1H, >10.2Hz), 5.75 (m, 1H), 5.46 (s, 1H), 5.02 (dm, 1H, >10.2Hz), 4.93 (dm, 1H, J =17.3Hz), 4.61 (d, 1H, >11.2Hz), 4.43 (d, 1H, >11.2Hz), 3.37 (s, 3H), 2.33 (m, 1H), 2.27 (m, 1H), 2.17 (s, 3H), 1.19 (s, 3H), 1.17 (s, 3H); MS (ESI) m/z 362 (M + 1); Calcd for C24H27NO2: 361.2042. Found: 361.2047.

Example 333

2,5-dihydro-10-ethenyl-5-phenyl-2,2,4-trimethyl-1H-[l]benzopyrano[3,4-f]quinoline Example 333A

2,5-dihydro-10-ethenyl-5-phenyl-2,2,4-trimethyl-1 Η- [ 1 J benzopyrano [3,4-f]quinoline

The compound of Example 7 and trifluoromethanesulfonic anhydride are treated according to the method of Example 3C to give the desired triflate.

MS (ESI) m/z 502 (M+H) ⁺ .

Example 333

2,5-dihydro-10-ethenyl-5-phenyl-2,2,4-trimethyl-1Η-[1Jbenzopyrano[3,4-f]quinoline

The compound of Example 333A and vinyltributylstannane are treated according to the method of Example 5 to give the desired compound.

MS (DCI/NH 3 ) m/z 380 (M+H) ⁺ ;

¹ H NMR (300 MHz, CDCl ₃ ) δ 7.30-7.11 (m, 6 H), 7.02-6.89 (m, 3 H), 6.78 (s, 1H), 6.76-6.68 (m, 2 H), 6.32 (br s, 1H), 5.72 (br d, >11.4 Hz, 1H), 5.40 (br s, 1H), 5.30 (br d, >15.9 Hz, 1H), 1.81 (s, 3H), 1.26 (s, 3H), 1.15 (s, 3H);

• · · « • · · · • · · · ·

232 • · · ·« ^I3 C NMR (125 MHz, DMSO) δ 151.3, 145.7, 138.8, 137.3, 133.3, 133.0, 131.2, 128.5 (2), 128.3, 128.2, 128.0 (2), 127.8, 127.4, 126.6, 123.9, 120.8, 118.1, 116.2, 114.5, 113.6, 75.3, 50.0, 30.0, 28.7, 23.2;

HRMS (FAB) calculated m/z for C27H25NO: 379.1936 (M) ⁺ . Found: 379.1924.

Example 334

2,5-dihydro-10-ethynyl-5-phenyl-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline

The compound of Example 333A and (trimethylsilyl)acetylene are treated according to the method of Example 6A and Example 6 to give the desired compound.

MS (DCI/NH 2 ) m/z 378 (M+H) ⁺ ;

1 H NMR (300 MHz, DMSO) δ 8.32 (d, >8.8 Hz, 1H), 7.27-7.16 (m, 5 H), 7.01 (dd, >8.7, 1.8 Hz, 1H), 6.83 (t, >8.6 Hz, 1H), 6.84-6.79 (m, 1H), 6.81 (br s, 1H), 6.74 (d, >8.6 Hz, 1H), 6.42 (br s, 1H), 5.41 (br s, 1H), 4.38 (s, 1H), 2.03 (s, 3H), 1.24 (s, 3H), 1.18 (s, 3H); ¹³ C NMR (125 MHz, DMSO) δ 150.9, 146.4, 138.8, 133.1, 130.7, 128.6, 128.2 (2), 128.0 (2),

127.9, 127.4, 126.6, 126.5, 126.4, 126.3, 118.3, 117.6, 117.5, 115.7, 113.4, 84.3, 75.1, 50.0, 30.0, 28.8, 23.2;

HRMS (FAB) m/z calcd for C27H23NO. 377.1780 (M) ⁺ . Found: 377.1779.

Example 335

Methyl 2,5-dihydro-5-phenyl-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline-10-carboxylate The compound of Example 333 A is processed according to the method of Example 4 to give the desired compound.

Melting point 150-2°C;

MS (DCI/NH ₃ ) m/z 412 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO) δ 7.36-7.30 (m, 2H), 7.28-7.17 (m, 3H), 7.12-7.01 (m, 2H), 6.93-6.88 (m, 2H), 6.84 (d, >8.7Hz, 1H), 6.70 (d, >8.9Hz, 1H). 6.40 (br s, 1H), 5.40 (br s, 1H), 3.79 (s, 3H), 1.81 (s, 3H), 1.26 (s, 3H), 1.17 (s, 3H);

¹³ C NMR (125 MHz, DMSO) δ 169.9, 151.2, 146.1, 138.3, 132.5, 130.3, 128.8 (2), 128.1, 128.0 (2), 127.7, 127.4, 127.0, 126.6, 124.9, 122.9, 119.6, 117.7, 117.5, 114.2, 75.7, 52.2, 50.0, 30.0, 28.6, 23.2;

Analytical calcd for C27H25NO3: C, 78.81; H, 6.12; N, 3.40. Found: C, 78.84; H, 6.25; N, 3.24.

233 •••00 · 0 0 0 ·> 0 0

Example 336

2,5-dihydro-10-(hydroxymethyl)-5-phenyl-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline To a solution of Example 335 (136 mg, 0.330 mmol) in anhydrous CH2Cl2 (12 mL) at -50°C was added Dibal-H (1.65 mL of a 1.0 M solution in heptane, 1.65 mmol). The resulting orange solution was gradually warmed to 0°C over 30 min, then stirred at 0°C for 2 h. EtOAc (5 mL) was added to the solution at 0°C to remove excess Dibal-H (indicated by a color change from orange to light yellow) and the reaction mixture was then treated with saturated aqueous NH4Cl (5 mL). The reaction mixture was partitioned between EtOAc (40 mL) and saturated aqueous Rochelle salts (potassium sodium tartrate; 35 mL) and the resulting mixture was stirred vigorously until the layers were completely separated (approximately 1 hour). The layers were separated and the aqueous layer was extracted with EtOAc (15 mL). The organics were combined and washed with brine (10 mL), then dried ( _Na2SO4 ). Filtration and concentration afforded the title compound (116 mg, 0.302 mmol, 92%) as a colorless foamy solid.

MS (DCI/NH 3 ) m/z 384 (M+H) ⁺ ;

'H NMR (300 MHz, DMSO) δ 7.58 (d, J=8.9 Hz, 1H), 7.23-7.11 (m, 5H), 6.98 (dd, J=8.7,

1.7 Hz, 1H), 6.84 (t, J=8.7 Hz, 1H), 6.76 (br s, 1H), 6.75 (d, J=8.6 Hz, 1H), 6.69 (dd, J=8.7,

1.8 Hz, 1H), 6.26 (br s, 1H), 5.40 (br s, 1H), 5.37 (dd, J=6.0, 4.0 Hz, 1H), 4.65 (dd, J=11.5, 6.0 Hz, 1H), 4.54 (dd, J=11.6, 4.4 Hz, 1H), 1.80 (s, 3H), 1.24 (s, 3H), 1.17 (s, 3H);

¹³ C NMR (125 MHz, DMSO) δ 151.0, 145.6, 139.0, 137.0, 133.1, 131.4, 128.4 (2), 128.1, 128.0 (2), 127.7, 127.6, 126.2, 124.8, 123.7, 118.6, 118.0, 116.0, 113.9, 75.1, 61.9, 49.9,

29.9, 28.7, 23.3;

Analytical calcd for C26H25NO2: C, 81.43; H, 6.57; N, 3.65. Found: C, 81.53; H, 6.86; N, 3.41.

Example 337

2,5-dihydro-10-formyl-5-phenyl-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4-f]quinoline

To a solution of Example 336 (50 mg, 0.130 mmol) in CH2Cl2 (6 mL) at 23°C was added a solution of tetrapropylammonium ruthenium sterate (60 mg, 0.16 mmol) in CH2Cl2 (14 mL). After 15 min, the reaction mixture was filtered through a small pad of silica gel, washing with CH2Cl2, then 1:1 EtOAc-hexanes. The filtrate was concentrated to give a golden syrup which was purified by preparative thin layer chromatography (mobile phase = 3% EtOAc/toluene) to give the desired product (19 mg, 0.050 mmol, 38%) as a pale yellow foam.

• ·

234

MS (DCI/NH 3 ) m/z 382 (M+H) ⁺ ;

’H NMR (300 MHz, DMSO) δ 10.13 (s, 1H), 7.31 (dd, J=8.8, 1.9 Hz, 1H), 7.28-7.16 (m, 5 H), 7.12 (d, 1=8.7 Hz, 1H), 7.05 (dd, J=8.7, 2.0 Hz, 1H), 6.95 (d, J=8.8 Hz, 1H), 6.92 (br s, 1H), 6.81 (d, J=8.8 Hz, 1H), 6.59 (br s, 1H), 5.43 (br s, 1H), 1.85 (s, 3H), 1.27 (s, 3H), 1.18 (s, 3H);

¹³ C NMR (125 MHz, DMSO) δ 191.4, 151.9, 146.8, 138.3, 133.2, 131.5, 131.4, 130.8, 128.6 (2), 128.1 (2), 128.0, 127.2, 126.6, 121.5, 121.4, 118.1, 115.5, 114.2 (2), 75.8, 50.2, 30.1, 29.0, 23.1;

HRMS (FAB) calculated m/z for C26H24NO: 382.1807 (M+H) ⁺ . Found: 382.1816.

Example 338

2,5-dihydro-10-(methoxymethyl)-5-phenyl-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline To a solution of Example 336 (22 mg, 0.057 mmol) in THF (2.0 mL) at 0°C was added KHMDS (110 mL of a 0.5 M solution in toluene, 0.057 mmol). After 15 min, a solution of iodomethane in DMF (100 mL of a solution of 81 mg of iodomethane in 1.0 mL of DMF, 0.057 mmol) was added and the solution was stirred for an additional 30 min at 0°C. The cooling bath was removed and the reaction was stirred for an additional 1.5 h at 23°C. The reaction was then quenched with water (3 mL) and extracted with EtOAc (2 x 20 mL). The combined organic layers were washed with brine (5 mL), then dried (MgSO4) and concentrated in vacuo to give a brown oil. Purification of this residue by preparative thin layer chromatography (mobile phase - 10% EtOAc/hexanes) gave the desired product (15 mg, 0.038 mmol, 66%) as a colorless foam.

MS (DCI/NH ₃ ) m/z 98 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO) δ 7.40 (d, J=8.9 Hz, 1H), 7.19-7.10 (m, 5H), 6.97-6.92 (m, 1H), 6.94 (s, 1H), 6.77-6.70 (m, 3H), 6.29 (br s, 1H), 5.39 (br s, 1H), 4.58 (d, ,J =11,1Hz, 1H), 4.39 (d, J=11,1Hz, 1H), 3.28 (s, 3H), 1.81 (s, 3H), 1.26 (s, 3H), 1.17 (s, 3H);

¹³ C NMR (125 MHz, DMSO) δ 151.0, 145.7, 138.8, 132.9, 132.6, 131.5, 128.4 (2), 127.8 (2), 127.8, 127.7, 127.5, 126.1, 125.7, 124.4, 118.3, 117.9, 116.6, 113.9, 75.2, 72.5, 57.2, 49.9,

29.9, 28.7, 23.3;

HRMS (FAB) calculated m/z for C27H27NO2: 397.2042 (M) ⁺ . Found: 397.2039.

Example 339

2,5-dihydro-10-ethenyl-5-oxo-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-fquinoline ·· ·· ·♦

235 φ » · « · · · « ····» · · * • · · · · · • * · · · · · ·

The compound of Example 3C and vinyltributylstannane are treated according to the method of Example 5 to give the desired compound.

Melting point 218-224°C;

MS (DCI/NH 3 ) m/z 318 (M+H) ⁺ , 335 (M+NH ₄ ) ⁺ ;

1H NMR (300 MHz, DMSO) δ 7.88 (d, >8.8 Hz, 1H), 7.38 (dd, >8.8, 6.6 Hz, 1H), 7.29 (s, 1H), 7.28 (d, >8.6 Hz, 1H), 7.19 (dd, >17.3, 11.1Hz, 1H), 7.13 (d, >8.7 Hz, 1H), 7.03 (br s, 1H), 5.75 (dd, >17.3, 1.2 Hz, 1H), 5.52-5.47 (m, 2H), 1.97 (s, 3H), 1.24 (s, 6H); ⁿ C NMR (125 MHz, CDCl 3 ) δ 160.1, 150.0, 145.4, 138.5, 136.3, 132.2, 131.0, 127.1, 126.7, 126.6, 125.5, 124.1, 119.9, 118.5, 117.2, 115.9, 115.7, 50.0, 27.9(2), 21.0;

Analytical calcd for C21H19NO2. C, 79.47; H, 6.03; N, 4.41. Found: C, 79.28; H, 5.97; N, 4.20.

Example 340

5-(3-cyclohexenyl)-2,5-dihydro-10-ethenyl-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline

To a magnetically stirred solution of Example 339 (100 mg, 0.300 mmol) and 3-(trimethylsilyl)cyclohexene (139 mg, 0.900 mmol) in CH2Cl2 (6 mL) at -78°C was added freshly distilled BF3 _OEt2 (80 mL, 0.600 mmol). The resulting greenish-brown solution was stirred at -78°C for 15 min, then slowly warmed to 23°C with stirring for 1 h. The reaction mixture was poured into 10% NaHCO3 (10 mL) and extracted with EtOAc (2 x 20 mL). The combined organics were washed with brine (8 mL) and dried ( _Na2SO4 ). Filtration and concentration gave a brown residue which was purified by flash chromatography (mobile phase - 5% EtOAc/hexanes) to give the desired product as a tan foam (356 mg, 0.186 mmol, 62%).

MS (DCI/NH 3 ) m/z 384 (M+H) ⁺ ;

¹ H NMR (300 MHz, DMSO) (data for major syn diastereoisomer) δ 7.30 (d, >8.0 Hz, 1H), 7.16-6.97 (m, 3H), 6.95-6.88 (m, 1H), 6.67 (d, >8.0 Hz, 1H), 6.42 (br s, 1H), 5.82-5.60 (m, 3H), 5.52-5.44 (m, 2H), 5.33 (d, >7.6 Hz, 1H), 2.40-2.26 (m, 1H), 2.17 (s, 3H), 2.051.82 (m, 2H), 1.70-1.53 (m, 2H), 1.32 (s, 3H), 1.31-1.07 (m, 2H), 1.05 (s, 3H);

¹³ C NMR (125 MHz, CDCl ₃ ) δ 138.8, 134.2, 129.3 (2), 128.1 (2), 127.9 (2), 126.7, 121.3,

116.4, 114.1, 37.2, 37.0, 34.7, 31.6, 30.2, 27.2, 26.1, 25.2, 24.7, 22.6, 24.1, 21.8 (2), 20.5,

14.1;

• · • ·

236

Analytical calcd for C27H29NO: C, 83.57; H, 7.66; N, 3.60. Found: C, 83.55; H, 7.38; N, 3.45.

Example 341

2,5-dihydro-10-ethenyl-5-[1-methyl-3-cyclohexenyl]-2,2,4-trimethyl-1H[1]benzopyrano[3,4-fquinoline

The compound of Example 339 and 3-(dimethylphenylsilyl)-3-methylcyclohexene are treated according to the method of Example 339 to provide the desired compound.

Melting point 198-201°C;

MS (DCI/NH ₃ ) m/z 398 (M+H) ⁺ ;

*H NMR (300 MHz, DMSO) (data for the major syn diastereoisomer) δ 7.30 (d, J=7.9 Hz, 1H), 7.16-7.00 (m, 3 H), 6.92 (dd, >7.1, 2.6 Hz, 1H), 6.66 (d, >8.0 Hz, 1H), 6.39 (br s, 1 H), 5.73 (d, >12.4 Hz, 1H), 5.52-5.41 (m, 3 H), 5.32 (d, >10.2 Hz, 1H), 2.33-2.22 (m, 1H),

2.14 (s, 3H), 1.91-1.70 (m, 1H), 1.87-1.65 (m, 1H), 1.63-1.51 (m, 1H), 1.60 (s, 3H), 1.341.15 (m, 2H), 1.31 (s, 3H), 1.13-0.98 (m, 1H), 1.04 (s, 3H);

Analytical calcd for C28H31NO: C, 84.59; H, 7.85; N, 3.52. Found: C, 84.46; H, 7.81; N, 3.37.

Example 342

2,5-dihydro-5-(3-propenyl)-10-methylthio-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline To a magnetically stirred solution of Example 3B (120 mg, 0.390 mmol) in anhydrous

Sodium hydride (17 mg of a 60% dispersion in mineral oil, 0.430 mmol) was added to DMF (1.0 mL) at 0°C. The mixture was stirred under nitrogen until nitrogen evolution ceased (1 hour). Solid dimethylthiocarbamoyl chloride (64 mg, 0.520 mmol) was then added all at once and stirring was continued at 0°C for 30 minutes. The cooling bath was removed and the mixture was heated at 80°C for 45 minutes. The reaction mixture was then poured into 1% NaOH (10 mL) and extracted with EtOAc (2 x 25 mL). The combined organics were washed with water (3 x 5 mL) and brine (3 mL), dried (MgSO ₄ ), filtered and concentrated. The resulting brown residue was purified by flash chromatography (mobile phase - 25% EtOAc/hexanes) to afford the resulting thionocarbamate (43 mg, 0.109 mmol, 2δ|%) as a yellow solid.

MS (DCI/NH 3 ) m/z 348 (M+H) ⁺ .

The solid prepared above (113 mg, 0.280 mmol) was placed in an open flask immersed in a Woods metal bath heated at 270-280°C for 6 minutes. The reaction was • ·

237 λ* ^: Cool and the resulting dark brown solution is purified by flash chromatography (gradient elution: 20% - 40% EtOAc/hexanes) to afford the thermally rearranged thiocarbamate product (67 mg, 0.165 mmol, 59%) as a yellow solid.

MS (DCI/NH?) m/z 348 (M+H) ⁺ .

To a solution of the rearranged product (500 mg, 1.26 mmol) in anhydrous toluene (70 mL) at -78°C under _N2 was added dropwise Dibal-H (2.02 mL of a 1.0 M solution in heptane, 2.02 mmol) while maintaining the temperature at -78°C. The resulting red-orange solution was stirred at -78°C for 1.5 h, during which time conversion to the desired product was monitored by TLC of an aliquot (zq/ijc sat. ammonium chloride). A lower Rf compound (diol resulting from greater reduction) was obtained. EtOAc (10 mL) was added to the solution at -78°C to quench excess DIBAL-H (indicated by a color change from orange-red to light yellow), followed by the addition of sat. aqueous NH4Cl (15 mL). The reaction mixture was partitioned between EtOAc (150 mL) and aqueous Rochelle salts (potassium sodium tartrate, 40 mL) and the resulting mixture was stirred vigorously until the layers were completely separated. The layers were separated and the organic layer was washed with brine (20 mL), dried (Na ₂ SO 4 ) and filtered. Removal of the solvent gave the lactol as a pale yellow foam (512 mg) which was used without further purification.

The lactol was dissolved in MeOH (30 mL) at 23° C. and pTsOHH ₂ O (50 mg, 25% w/w) was added as a solid in one portion. The mixture was stirred for 14 h at 23° C., then quenched with saturated aqueous sodium bicarbonate (10 mL) and extracted with EtOAc (2 x 50 mL). The organics were combined and washed with brine (20 mL) and dried (Na ₂ SO 4 ), filtered and concentrated to give a yellow residue which was purified by flash chromatography (mobile phase - 5% EtOAc/CH ₂ Cl ₂ ) to give the methyl acetal (157 mg, 0.416 mmol, 33% yield over two steps) as a yellow foam.

MS (DCI/NH 3 ) m/z 379 (M-OHCH ₃ ) ⁺ .

The lactol and allyltrimethylsilane prepared above are treated according to the method of Example 2 to give allyl at the C5 position.

MS (DCI/NH 3 ) m/z 421 (M+H) ⁺ .

Example 343

2,5-Dihydro-5-(3-propene 1)-10-methylthio-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4-f]quinoline

A suspension of thiocarbamate (249 mg, 0.590 mmol) and KOH (90 mg, 1.20 mmol) in ethylene glycol (6 mL) containing water (1.5 mL) was heated at reflux (homogeneous solution) for 1.5 h. The solution was cooled and poured onto ice (10 g). The mixture was acidified (pH 4) ··

238 • ♦ · · · • · · · · · • · · · · · · · · · · · · · · 9 * · • · » • · ·

9 9

9 9

10% HCl and then extracted with CH2Cl2 (2 x 20 mL). The extracts were dried ( _Na2SO4 ), filtered and concentrated. The resulting residue was purified by flash chromatography (mobile phase - 5% EtOAc/CFGCU) to give an almost homogeneous thiophenol adduct (183 mg) as a yellowish solid, which was used immediately.: ³ H NMR (300 MHz, DMSO-d ₆ ) δ 7.72 (d, J=8.0 Hz, 1H), 7.08 (dd, >7.6, 1.1Hz, 1H), 6.96 (t, >7.5 Hz; 1H), 6.67 (d, >8.1Ηζ, 1H), 6.63 (dd, >7.5, 12 Hz, 1H), 6.28 (br s, 1H), 5.88-5.70 (m, 2H), 5.47 (br s, 1H), 5.41 (s, 1H), 5.03 (dd, >13.2, 1.3 Hz, 1H), 4.98 (dd, >18.4, 1.3 Hz, 1H), 2.48-2.21 (m, 2H), 2.17 (s, 3H), 1.20 (s, 3H), 1.17 (s, 3H); MS (DCI/NH 3 ) m/e 350 (M+H) ⁺ .

A solution of crude thiophenol (183 mg) in DMF (10 mL) at 0°C was treated with cesium carbonate (50 mg, 0.153 mmol). After 10 min, a solution of iodomethane (25 mg, 0.176 mmol) in DMF (0.7 mL) was added and the solution was stirred at 0°C for 30 min, then at 23°C for 2 h. The mixture was diluted with 1:1 EtOAc-hexanes (100 mL) and washed with water (3 x 25 mL), then brine (25 mL). The organics were dried ( _Na2SO4 ), filtered, and concentrated. The resulting residue was purified by flash chromatography (mobile phase - 5% EtOAc/hexanes) to give the thioether (65 mg, 0.179 mmol, 34%) as a yellowish solid: 'H NMR (300 MHz, DMSO-d ₆ ) δ 7.82 (d, > 8.1Hz, 1H), 7.11 (t, >7.6 Hz, 1H), 6.98 (br d, >7.7 Hz, 1H), 6.72 (br d, >7.6 Hz, 1H), 6.62 (d, >8.0 Hz, 1H), 6.27 (br s, 1H), 5.885.70 (m, 2H), 5.47 (br s, 1H), 5.03 (dd, >13.3, 1.1Hz, 1H), 4.99 (dd, >18.3, 1.1Hz, 1H), 2.47 (s, 3H), 2.46-2.33 (m, 1H), 2.32-2.22 (m, 1H), 2.18 (s, 3H), 1.21 (s, 3H), 1.17 (s, 3H); MS (DCI/NH 3 ) m/e 364 (M+H) ⁺ .

Example 344 (+/-) 2,5-dihydro-9-(4-acetamidobutanoyloxy)-10-methoxy-2,2,4-trimethyl-5-allyl-1H[1]benzopyrano[3,4-f]quinoline MS (APCI) m/z 491 (M+H) ⁺ ;

'H NMR (200 MHz, DMSO-dg) δ 7.94 (t, 1H), 7.84 (d, 1H), 6.88 (d, 1H), 6.67 (d, 1H), 6.64 (d, 1H), 6.21 (s, 1H), 5.87-5.78 (m, 2H), 5.46 (s, 1H), 5.06-4.96 (m, 2H), 2.60 (s, 2H), 2.16 (dt, 2H), 2.62 (t, 2H), 2.21-2.27 (m, 2H), 2.18 (s, 2H), 1.82 (s, 2H), 1.79 (m, 2H), 1.18 (s, 2H), 1.17 (s, 2H).

Example 345

10-(difluoromethoxy)-2,5-dihydro-5-phenyl-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline • · ♦ ♦

The compound of Example 7 and bromodifluoromethane are treated according to the method of Example 8A to give the desired compound.

MS (DCI/NH ₃ ) m/z 420 (M+H) ⁺ ;

*H NMR (300 MHz, DMSO-dg) δ 7.80 (s, >8.8 Hz, 1H), 7.26-7.15 (m, 5 H), 7.16-7.13 (m, 1H), 6.97 (t, >8.1Ηζ, 1H), 6.82 (br s, 1H), 6.74 (d, >8.9 Hz, 1H), 6.72-6.67 (m, 1H), 6.38 (br s, 1H), 5.39 (br s, 1H), 1.82 (s, 3H), 1.24 (s, 3H), 1.15 (s, 3H);

HRMS (FAB) calculated m/z for C26H23F2NO2: 419.1697 (M) ⁺ . Found: 419.1714.

Example 346

10-(Bromodifluoromethoxy)-2,5-dihydro-5-phenyl-2,2,4-trimethyl-1H-[1]benzopyrano[3,4f]quinoline

MS (ESI) m/z 498 (M+H) ⁺ .

1H NMR (300 MHz, DMSO-dg) δ 7.68 (s, >8.8 Hz, 1H), 7.25-7.14 (m, 5H), 7.03 (t, >8.2 Hz, 1H), 6.89-6.84 (m, 1H), 6.85 (br s, 1H), 6.83-6.79 (m, 1H), 6.74 (d, >8.6 Hz, 1H), 6.46 (br s, 1H), 5.40 (br s, 1H), 1.81 (s, 3H), 1.25 (s, 3H), 1.15 (s, 3H);

¹³ C-NMR (125 MHz, DMSO-dg) δ 152.34, 146.44, 145.97, 138.38, 133.02, 130.51, 128.61 (2), 128.07, 127.92 (2), 127.33, 126.86 (2), 119.16, 117.82, 116.68, 115.84, 115.32, 114.28, 114.12, 75.60, 49.93, 29.90, 28.72, 23.26;

HRMS (FAB) calculated m/z for _{C26H2279BrF2NO2} : ^497.0802 (M+H) ⁺ . Found: 497.0790. HRMS (FAB) _calculated m/z ^for _{C26H2281BrF2NO2} : _499.0782 (M+ _H ) ⁺ . Found: 499.0793.

Example 347

10-(Bromodifluoromethoxy)-5-phenyl-2,2-dimethyl-4-methylene-2,3,4,5-tetrahydro-1Hchromeno[3,4-f]quinoline

MS (ESI) m/z 498 (M+H).

*H NMR (300 MHz, CDCl ₃ ) δ 7.88 (s, J =8.4 Hz, 1H), 7.31-7.26 (m, 2H), 7.19-7.12 (m, 3H), 6.95 (t, >8.1Ηζ, 1H), 6.86-6.78 (m, 2H), 6.64 (br s, 1H), 6.58 (d, >8.5 Hz, 1H), 4.94 (s, 1H), 4.61 (s, 1H), 4.17 (br s, 1H), 2.45 (br d, J =12.0 Hz, 1H), 2.19 (d, >12.4 Hz, 1H), 1.35 (s, 3H), 1.14 (s, 3H);

HRMS ( _FAB ) _calculated m/z for _{C26H2279BrF2NO2} : ^497.0802 (M+H) ⁺ . Found: 497.0790.

HRMS (FAB) calculated m/z _{for C26H2281BrF2NO2} : ^499.0782 (M+H) ⁺ . Found: 499.0771.

Example 348

0

240

9 00 0 0 ·· • · · 0 0 0 0 0 0 0 0 ·0

0 0 0 0 0 00 • · · · 0 • 90 0 0· 0· ··

2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-((2-fluorophenyl)methyl)-1H[ 1 ]benzopyrano[3,4-f] quinoline

Example 349

10-Methoxy-5-(5-methylisoxazol-3-yl)methyiden-2,5-dihydro-5-phenyl-2,2,4-trimethyl-1H[ 1 ]benzopyrano[3,4-quinoline

The compound of Example 1F and the lithium anion of 3,5-dimethylisoxazole are treated according to the method of Example IB to provide the desired compound.

MS (DCI/NH ₃ ) m/z 401 (M+H) ⁺ ;

^] H NMR (300 MHz, DMSO-dé) δ 8.33 (d, 1H, J=8.83 Hz), 7.7-7.5 (m, 1H), 7.22 (t, 1H, J=8.09), 7.05 (d, 1H, J=1,1Hz), 6.85 (s, 1H), 6.79 (d, 1H, J=8.82 Hz), 5.61 (s, 1H), 5.5 (s, 1H), 3.93 (s, 3H), 2.45 (s, 3H), 1.96 (d, 3H, J=1,1Hz), 1.20-1.30 (s, 6H).

Example 350

10-Methoxy-5-(3-methylisoxazol-5-yl)methyiden-2,5-dihydro-5-phenyl-2,2,4-trimethyl-1H[l]benzopyrano[3,4-f]quinoline

The compound of Example 1F and the lithium anion of 3,5-dimethylisoxazole are treated according to the method of Example IB to provide the desired compound.

MS (DCI/NH 3 ) m/z 401 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-cU), isomer 1: δ 8.38 (d, 1H, J=8.83 Hz), 7.22 (t, 1H,J =8 Hz), 7.09 (s, 1H), 6.87-6.81 (m, 2H), 6.56 (s, 1H), 5.65 (s, 1H), 5.51 (s, 1H), 3.93 (s, 3H), 2.28 (s, 3H), 1.95 (s, 3H), 1.29 (s, 3H), 1.26 (s, 3H); isomer 2: δ 8.16 (d, 1H, J=8.83 Hz), 7.18 (t, 2H, J=8 Hz), 7.06 (s, 1H), 6.80-6.76 (m, 2H), 6.46 (s, 1H), 5.90 (s, 1H), 5.21 (s, 1H), 3.91 (s, 3H), 2.08 (s, 3H), 1.84 (s, 3H), 1.26 (s, 3H), 1.12 (s, 3H).

Example 351

10-Methoxy-5-(4,5-dimethyl-1,3-oxazol-2-yl)methyiden-2,5-dihydro-5-phenyl-2,2,4-trimethyl1Η-[ 1jbenzopyrano[3,4-f]quinoline

The compound of Example 1F and the lithium anion of 3,5-trimethylisoxazole are treated according to the method of Example IB to provide the desired compound.

MS (DCI/NH 3 ) m/z 415 (M+H) ⁺ ;

^X H NMR (300 MHz, DMSO-dé), isomer 1: δ 8.36 (d, 1H, J=8.82 Hz), 7.24-7.20 (m, 1H), 6.82 (m, 3H), 6.25 (s, 1H), 5.49 (s, 1H), 3.92 (s, 3H), 2.31 (s, 3H), 2.09 (s, 3H), 1.28 (s, 3H), • Β ·

241

-Β Β • · • Β ΒΒ ΒΒΒΒ ·

B B B

Β Β Β BBB Β Β • · Β Β

BB BB

BB

B B ·

B B B

B B B

BB

1.2 (m, 6H); isomer 2: δ 8.09 (d, 1Η, >8.82 Hz), 7.16 (m, 1H), 6.78-6.73 (m, 2H), 5.41 (s, 1H), 5.21 (s, 1H), 3.91 (s, 3H), 2.03 (s, 3H), 1.89 (s, 3H), 1.88 (s, 3H), 1.25-1.15 (m, 6H).

Example 352

10-Methoxy-5-(6-chloropyridin-2-yl)methyiden-2,5-dihydro-5-phenyl-2,2,4-trimethyl-1H[1]benzopyrano[3,4-x]quinoline

The compound of Example 1F and the lithium anion of 6-chloro-2-methylpyridine are treated according to Method IB to provide the desired compound.

MS (DCI/NH ₃ ) m/z 431 (M+H) ⁺ ;

^] H NMR (300 MHz, DMSO-d _ó ) δ 8.35 (d, 1H, >4.7 Hz), 8.25 (d, 1H, >8.1Hz), 7.9 (t, 1H, >7.7 Hz), 7.30 (d, 1H, >7.7 Hz), 7.21 (d, 1H, >8 Hz), 7.00 (d, 1H, J =8.1Hz), 6.8 (dd, 2H, >8.4, 2.6 Hz), 6.72 (s, 1H), 5.65 (s, 1H), 5.51 (s, 3H), 3.93 (s, 3H), 1.99 (s, 3H), 1.2 (s, 6H).

Example 353

10-Methoxy-5-(pyridin-2-yl)methyiden-2,5-dihydro-5-phenyl-2,2,4-trimethyl-1H[ 1 jbenzopyrano [3,4-f] quinoline

The compound of Example 1F and 4-picolinyllithium are treated according to the method of Example IB to give the desired compound.

MS (DCI/NH 3 ) m/z 397 (M+H) ⁺ ;

*H NMR (300 MHz, DMSO-d ₆ ), isomer 1: δ 8.52 (d, 2H, >6.1Hz), 8.17 (d, 1H, >8.8 Hz), 7.2 (t, 1H, >8.2 Hz), 6.96 (s, 1H), 6.7 (m, 3H), 6.66 (s, 2H), 5.55 (s, 1H), 4.53 (s, 1H), 3.93 (s, 3H), 1.81 (d, 3H, >1.4 Hz), 1.27 (s, 6H); isomer 2: δ 8.32 (d, 2H,, >6.1Hz), 8.19 (d, 1H, >8.8 Hz), 7.17 (t, 1H, >8.2 Hz), 6.99 (s, 1H), 6.77 (m, 3H), 6.45 (s, 2H), 5.48 (s, 1H), 5.05 (s, 1H), 3.93 (s, 3H), 1.81 (d, 3H, >1.4 Hz), 1.27 (s, 6H).

Example 354

10-Methoxy-5-(but-3-enylidene)-2,5-dihydro-5-phenyl-2,2,4-trimethyl-1H-[ljbenzopyrano[3,4fjquinoline

The compound of Example 1F and the lithium anion of cyclopropylmethyl bromide are treated according to the method of Example IB to give the desired compound.

MS (DCI/NH 3 ) m/z 350 (M+H) ⁺ ;

• ·

242 ·· ·» *· 94 44

4 4 4 4 4 9 4 4 • · · 4 4 8 4 4 8

444 4 4 4 449 9 4 4 4 *

4 4 4 4 4 9 4 4

4444 49 44 44 44 44 ^J H NMR (300 MHz, DMSO-dó) δ 8.16 (d, 1H, J=8.8 Hz), 7.10 (t, 1H, J=7.7 Hz), 6.8-6.6 (m, 4H), 6.47 (s, 1H), 5.89-5.75 (m, 1H), 5.41 (s, 1H), 5.10-4.93 (m, 2H), 4.67 (t, 1H, J =7.5 Hz), 3.88 (s, 3H), 1.97 (d, 3H, J = 1.3 Hz), 1.20 (s, 6H).

Example 355

10-Methoxy-5-(1-methylpropylidene)-2,5-dihydro-5-phenyl-2,2,4-trimethyl-1H[1]benzopyrano[3,4-quinoline

The compound of Example 1F and sec-butyllithium are treated according to the method of Example IB to give the desired compound.

MS (DCI/NH ₃ ) m/z 362 (M+H) ⁺ ;

^! H NMR (300 MHz, DMSO-dó) δ 8.01 (d, 1H,J =8.09 Hz), 7.09 (t, 2H, J=8.09 Hz), 6.7 (dd, 2H, J=8.5, 2.6 Hz), 6.65 (d, 1H, J=8.46 Hz), 6.37 (d, 1H, J=0.8 Hz), 5.4 (s, 1H), 3.87 (s, 3H), 1.86 (d, 3H, J=1,1Hz), 1.48 (s, 3H), 1.33 (s, 3H), 1.08 (s, 3H), 0.9 (t, 3H, J=73 Hz).

Example 356

10-Methoxy-5-(1-butylidene)-2,5-dihydro-5-phenyl-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline

The compound of Example 1F and n-butyllithium are treated according to the method of Example IB to give the desired compound.

MS (DCI/NH ₃ ) m/z 362 (M+H) ⁺ ;

’H NMR (300 MHz, DMSO-dó) δ 8.14 (d, 1H), 7.07 (t, 1H), 6.67 (m, 3H), 6.07 (s, 1H), 5.40 (s, 1H), 4.71 (t, 1H), 3.88 (s, 3H), 2.29 (q, 1H), 2.00 (s, 3H), 1.43-1.36 (m, 2H), 1.21 (s, 6H), 0.88 (t, 3H).

Example 357

2,5-dihydro-10-methoxy-2,2,4-trimethyl-3-oxide-5-phenyl-1Η-[1]benzopyrano[3,4-f]quinoline

Example 357A

8-Amino-7-bromo-1-methoxy-6H-benzo[c]chromen-6-one

A solution of Example 1E (3.0 g, 12.0 mmol) in DMF (100 μΐ) was treated with N-bromosuccinimide (2.2 g, 12.0 mmol), stirred for 40 minutes, poured into 900 mL of water, stirred for 5 minutes, and the resulting solid was collected by filtration and dried to give the desired compound.

*· «φ • φ φ φ φ φ φ φ φφφ φ · φφφφ φφ

243 φ* φφ φφ φφ φφφφ φφφφ φφφφ φφφφ φ φ φφφ φ φ φ φ φ φ φ φφφφ φφ φφ φφ φφ

Example 357Β

7-bromo-1-methoxy-6-phenyl-6H-benzo[c]chromen-8-ylamine

The compound from Example 357A (2.0 g, 6.25 mmol) and phenyllithium were treated according to the method of Examples 1G and 1 to give the desired compound.

Example 357C

-(7-bromo-1-methoxy-6-phenyl-6H-benzo[c]chromen-8-yl)ethan-1-one

Compound from Example 357B (1.23 g, 3.22 mmol), tributyl(1-ethoxyvinyl)tin, (1.4 g,

3.86 mmol) and dichlorobis(triphenylphosphine)palladium(II) complex (263 mg, 0.322 mmol) in NMP (30 mL) were heated at 85°C for 24 h under nitrogen. The mixture was partitioned between EtOAc and saturated aqueous sodium bicarbonate and filtered through Celite. The EtOAc layer was concentrated and the residue was dissolved in acetonitrile, washed with 5 x 20 mL of hexanes and concentrated. The resulting residue was treated with 1:1 IN HCl/THF, stirred for 30 min, poured into cold, sat. sodium bicarbonate solution and extracted with EtOAc (5 x 25 mL). The organic portion was washed with brine, dried ( _Na2SO4 ) and flash chromatographed on a silica gel column (mobile phase -4:1 hexane/EtOAc) to give the title compound.

Example 357D

-(7-Bromo-1-methoxy-6-phenyl-6H-benzo[c]chromen-8-yl)ethan-1-one oxime

A solution of Example 357C (700 mg, 2.03 mmol) and hydroxylamine hydrochloride (2.45 g,

30.4 mmol) in a mixture of EtOH (70 mL) and pyridine (70 mL) was refluxed for 8 h, cooled and concentrated. The residue was dissolved in EtOAc, washed with water, brine, dried ( _Na2SO4 ) and concentrated to give the title compound without purification.

Example 357

2,5-dihydro-10-methoxy-2,2,4-trimethyl-3-oxide-5-phenyl-1Η-[1]benzopyrano[3,4-f]quinoline

Example 357D (700 mg, 1.94 mmol), CuSO ₄ (105 mg) and acetic acid (3 drops) were combined in acetone (30 mL) and refluxed for 8 hours. The mixture was cooled, poured into water and extracted with EtOAc (3 x 50 mL). The organics were combined, washed with brine, dried (Na 2 SO ₄ ) and concentrated. The residue was triturated with EtOAc (30 mL) and the yellow solid was collected by filtration to give the title compound.

MS (DCI/NH 2 ) m/z 401 (M+H) ⁺ ;

* 4 • ·

244 • 4 • · · «

• 4 ·♦ 4Φ * · 4 ·

Φ Φ Φ Φ

Φ Φ ··· Φ »9 Φ ·♦ «Φ • Φ •

Φ

Φ

Φ 'Η NMR (300 MHz, DMSO-dg) δ 8.21 (d, 1Η), 7.30 (s, 1Η), 7.29-7.16 (m, 5H), 7.00-6.92 (m, 2H), 6.61 (d, 1H), 6.57 (s, 1H), 6.44 (d, 1H), 3.72 (s, 3H), 2.01 (s, 3H), 1.55 (s, 3H), 1.28 (s, 3H);

HRMS calculated m/z for C24H27NO2: 400.1787 (M') ⁺ . Found: 400.1786.

Example 358

2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano[3,4-quinoline

A solution of Example 357E (80 mg, 0.2 mmol) in MeOH under 4 atmospheres of hydrogen was treated with Raney nickel and stirred for 24 hours. The mixture was filtered through Celite, concentrated, and the resulting residue was subjected to flash chromatography on a silica gel column (mobile phase - 99:1 EtOAc/MeOH) to afford the title compound.

MS (DCI/NH 3 ) m/z 385 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-d ₆ ) δ 8.22 (d, 1H), 7.26-7.15 (m, 5H), 6.93 (t, 1H), 6.79 (s, 1H), 6.76 (d, 1H), 6.73 (s, 1H), 6.57 (d, 1H), 6.44 (d, 1H), 3.81 (s, 3H), 2.00 (s, 3H), 1.36 (s, 3H), 1.21 (s, 3H).

HRMS calculated m/z for C25H24N2O2: 385.1916 (M+H) ⁺ . Found: 385.1930.

Example 359

2,5-dihydro-10-methoxy-2,2-spiro(tetrahydro-4-pyranyl)]-4-methyl-5-allyl-1H[ljbenzopyrano[3,4-fquinoline

Example 359A

Example 357A (1.3 g, 4.08 mmol), isopropenyltrimethyltin (3.3 g, 16.3 mmol) and dichlorobis(triphenylphosphine)palladium(II) complex (330 mg, 0.40 mmol) in NMP (30 mL) were heated at 85°C for 24 h under nitrogen. The mixture was partitioned between EtOAc and sat. aqueous potassium fluoride, stirred for 3 h and filtered through Celite. The EtOAc layer was washed with 5 x 50 mL water, 5 x 50 mL brine, dried (Na2SO4) and concentrated, then flash chromatographed on silica gel (mobile phase 3:1 hexane/EtOAc) to give the desired product.

Example 359

A mixture of 2-isopropenylaniline (56 mg, 0.2 mmol), tetrahydro-4H-pyran-4-one (160 mg, 1.6 mmol) and iodine (25 mg, 0.1 mmol) in 5 mL toluene in a sealed high-pressure ACE vessel

245 *« ο* ·♦ «♦ ·· ·· «··· ··· · ·· · ««· · » · · · · · . ··· · ··· « · · · · · * «·» ·«··· ··· ·· ·♦ ·· ·· ·· is heated at 80°C for 1 hour, cooled and the mixture is partitioned between EtOAc and 10% aqueous Na ₂ S ₂ O3. The EtOAc layer is washed with water, brine, dried (Na ₂ SO4) and concentrated. Flash chromatography on silica gel (mobile phase 3:2 hexane/EtOAc) gives the desired product as a bright yellow powder. The resulting coumarin is worked up according to the method of Example 2 to give the desired compound. MS (DCI/NH3) m/z 390 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-d ₆ ) δ 7.92 (d, 1H), 7.07 (t, 1H), 6.75 (d, 1H), 6.70 (d, 1H), 6.52 (d, 1H), 6.24 (s, 1H), 5.87-5.73 (m, 2H), 5.71 (s, 1H), 5.01 (dd, 1H), 4.96 (dd, 1H), 3.86 (s, 3H), 3.75-3.39 (m, 4H), 2.51-2.14 (m, 2H), 2.20 (s, 3H), 1.69-1.49 (m, 4H);

_{HRMS calculated m/z for C25H27NO3 : 389.1991} (M) ⁺ . Found: 389.1974.

Analytical calcd for _C25H27NO3 : C, _77.07 ; H, 6.99; N, 3.60. Found: C, 76.92; H, 7.28; _N , 3.64.

Example 360

2.5-Dihydro-10-methoxy-2,2-[spiro(hexyl)]-5-allyl-1H-[1]benzopyrano[3,4-f]quinoline

The compound from Example 357A was reacted sequentially with isopropenyltributyltin and cyclohexanone according to the method of the previous example to give the desired compound. MS (DCI/NH3) m/z 388 (M+H) ⁺ ;

1H NMR (300 MHz, DMSO-d _ó ) δ 7.95 (d, 1H), 7.06 (t, 1H), 6.74 (d, 1H), 6.70 (d, 1H), 6.52 (d, 1H), 6.05 (s, 1H), 5.85-5.72 (m, 2H), 5.58 (s, 1H), 5.02 (dd, 1H), 4.97 (dd, 1H), 3.86 (s, 3H), 2.42 (m, 1H), 2.18 (s, 3H), 2.16 (m, 1H), 1.56-1.25 (m, 10H);

HRMS calculated m/z _{for C20H29NO2} : _387.2198 (M) ⁺ . Found: 387.2196.

Example 361

2.5-Dihydro-10-methoxy-2,2-diethyl-4-methyl-5-allyl-1H-[1]benzopyrano[3,4-quinoline

The compound of Example 357A was reacted sequentially with isopropenyltributyltin and 3-pentanone according to the method of the previous example to give the desired compound.

MS (DCI/NH 3 ) m/z 376 (M+H) ⁺ ;

*H NMR (300 MHz, DMSO-dg) δ 7.92 (d, 1H), 7.05 (t, J-8 Hz, 1H), 6.68 (d, 1H), 6.59 (d, 1H), 6.51 (d, 1H), 5.98 (s, 1H), 5.86-5.77 (m, 2H), 5.27 (s, 1H), 5.04-4.95 (m, 2H), 3.85 (s, 3H), 2.42 (m, 1H), 2.21 (s, 3H), 2.15 (m, 1H), 1.42-1.35 (m, 4H), 0.83 (t, 3H), 0.82 (t, 3H);

Φ« I* Φ* ·· *· ·♦ • · · · φφφφ · · · · φ φ · » · · φ φφφφ

946 ♦ *·* · · · ··* · * · · ·

X» ι\7 Φ φ φ φ φ φ · φ φ φφφφ ·· ·· φφ φφ φφ

HRMS calculated m/z _{for C25H29NO2} : _375.2198 (M') ⁺ . Found: 375.2191.

Analytical _calcd for _C25H29NO2 : C, _79.96 ; H, 7.78; N, 3.73. Found: C, 79.74; H,

7.89; N, 3.54.

Example 362

2.5-Dihydro-10-methoxy-2,2,3,4-tetramethyl-5-allyl-1H-[1]benzopyrano[3,4-f]quinoline

The compound of Example 357A is reacted sequentially with 1-methyl-1-propenyltributyltin and acetone according to the method of the previous example to give the desired compound.

MS (DCl/NH,) m/z 362 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO-d ₆ ) δ 7.97 (d, 1H), 7.07 (t, 1H), 6.70 (d, 1H), 6.62 (d, 1H), 6.53 (d, 1H), 5.90 (s, 1H), 5.76 (m, 1H), 5.61 (dd, 1H), 5.01-4.90 (m, 2H), 3.8.7 (s, 3H), 2.47 (m,

1H), 2.18 (m, 1H), 2.04 (s, 3H), 1.76 (s, 3H), 1.13 (s, 3H), 1.09 (s, 3H);

HRMS calculated m/z _{for C24H27NO2} : _361.2042 (M') ¹ . Found: 361.2055.

Example 363

2.5-Dihydro-10-methoxy-2,2-dimethyl-4-ethyl-5-allyl-2,2,4-trimethyl-1H[ 1 jbenzopyrano [3,4-fquinoline

The compound of Example 357A was reacted sequentially with 1-methylenepropyltributyltin and acetone according to the method of the previous example to give the desired compound.

MS (DCI/NH ₃ ) m/z 362 (M+H) ⁺ ;

³ H NMR (300 MHz, DMSO-de) δ 7.98 (d, 1H), 7.07 (t, 1H), 6.70 (dd, 1H), 6.63 (d, 1H), 6.53 (dd, 1H), 6.12 (bs, 1H), 5.78 (m, 1H), 5.59 (dd, 1H), 5.50 (bs, 1H), 5.03-4.92 (m, 2H), 3.86 (s, 3H), 2.54-2.41 (m, 3H), 2.11 (m, 1H), 1.20 (s, 3H), 1.10 (s, 3H), 1.03 (t; 3H);

HRMS m/z calcd for _C24H27NO2 : _361.2042 ( ^M)+ _. Found: 361.2034.

Example 364

2.5-dihydro-10-methoxy-2,2,3-trimethyl-5-allyl-1Η-[1]benzopyrano[3,4-f]quinoline

The compound of Example 357A was reacted sequentially with (Z)-1-propenyltributyltin and acetone according to the method of the previous example to give the desired compound.

MS (DCI/NH ₃ ) m/z 348 (M+H) ⁺ ;

247 ·* *· · ·· ·* • » · · · · 9 · Φ • · « · · · · » ·

999 99 9 999 9 9 99 9

9 9 9 9 9 9 9 9

9999 99 99 99 99 99

Ή NMR (300 MHz, DMSO-dg) δ 7.89 (d, 1Η), 7.04 (t, 1Η), 6.68 (d, 1H), 6.52 (d, 1H), 6.47 (d, 1H), 6.21 (s, 1H), 5.96 (s, 1H), 5.88 (m, 1H), 5.43 (dd, 1H), 5.03 (m, 1H), 4.96 (m, 1H),

3.84 (s, 3H), 2.35 (m, 1H), 2.08 (m, 1H), 1.83 (s, 3H), 1.23 (s, 6H);

HRMS m/z calcd for C23H25NO2: 347.1885 (M') ⁺ . Found: 347.1879.

Example 365

Z-5-(benzylideneyl)-9-hydroxy-10-methoxy-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-f]quinoline

MS (DCI/NH3) 412 (M+H) ⁺ ;

'Η NMR (300 MHz, DMSO-dg), δ 8.93 (s, 1H), 8.13 (d, >8.8 Hz, 1H), 7.63 (d, >8.8 Hz, 2 H), 7.32-7.15 (m, 3 H), 6.77 (d, 1H), 6.69 (d, 1H), 6.66 (d, 1H), 6.52 (s, 1H), 5.46 (s, 1H), 5.39 (s, 1H), 3.65 (s, 3H), 1.90 (s, 3H), 1.20 (s, 6H);

HRMS calcd for C27H25NO3 is 411.1834. Found: 411.1821.

Example 366

Z-5-(2,5-difluorobenzylideneyl)-9-hydroxy-10-methoxy-2,2,4-trimethyl-1H-2,5-dihydro[l]benzopyrano[3,4-f]quinoline

MS (DCI/NH3) m/e (M+H) ⁺ 448.

Ή NMR (300 MHz, DMSO-dg) δ 9.06 (s, 1H), 8.29 (d, >9 Hz, 1H), 7.96 (m, 1H), 7.24 (m, 1H), 7.11 (m, 1H), 6.86 (d, >9 Hz, 1H), 6.82 (d, >9 Hz, 1H), 6.78 (d, >9 Hz, 1H), 6.72 (br s, 1H), 5.75 (s, 1H), 5.48 (s, 1H), 3.75 (s, 3H), 1.99 (s, 3H), 1.26 (br s, 6H);

Analytical calcd for C27H23NO3F2: C, 72.47; H, 5.18; N, 3.13. Found: C, 72.21; H, 5.31; N, 3.09.

Example 367

Z-5-(3-fluorobenzylideneyl)-10-chloro-9-hydroxy-2,2,4-trimethyl-2,5-dihydro-1H[ 1 ]benzopyrano[3,4-f]quinoline

MS (DCI/NH 3 ) m/z 434 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO) δ 9.86 (br s, 1H), 8.40 (d, >8.5 Hz, 1H), 7.61 (dt, >8.6, 1.8 Hz, 1H), 7.60-7.52 (m, 1H), 7.46-7.38 (m, 1H), 7.15-7.02 (m, 1H), 7.09 (d, >8.4 Hz, 1 H),

6.85 (d, >8.6 Hz, 1H), 6.84 (s, 1H), 6.78 (d, >8.6 Hz, 1H), 5.68 (s, 1H), 5.48 (br s, 1H), 1.97 (br s, 3H), 1.16 (br s, 6H);

248

ΦΦ *· *· φ» φφ φφ

Φ Φ i Φ « Φ

ΦΦΦ ΦΦΦΦ φ·Φ· Φ ΦΦΦΦΦ · ΦΦΦΦΦ ΦΦ ·

ΦΦΦ

ΦΦΦΦ ΦΦ «Φ ΦΦ ΦΦ ΦΦ ¹³ C NMR (125 MHz, DMSO) δ 163.8, 160.6, 149.9, 149.2, 148.2, 146.4, 132.0, 130.3, 128.1, 127.3, 126.2, 125.3 124.5, 118.7, 117.7, 117.3, 116.1, 115.5, 114.6, 114.3, 114.0, 113.7,

62.1,29.8, 28.2,21.2;

HRMS (FAB) calculated m/z for C26H21ClFNO2: 433.1245 (M) ⁺ . Found: 433.1237.

Example 368

Z-10-chloro-9-hydroxy-5-(2-picolinylideneyl)-2,2,4-trimethyl-2,5-dihydro-1H[1]benzopyrano[3,4-f|quinoline

MS (DCI/NH ₃ ) m/z 417 (M+H) ⁺ ;

³ H NMR (300 MHz, DMSO) δ 9.79 (br s, IH), 8.51 (ddd, J-5.9, 1.6, 1.0 Hz, IH), 8.43 (d,

J=8.6 Hz, IH), 8.24 (dt, ,J =7.8, 1.0 Hz, IH), 7.53 (td, J=7.8, 1.7 Hz, IH), 7.22 (ddd, J=7.7,

5.8, 1.2 Hz, IH), 7.00 (d, J=8.5 Hz, IH), 6.88 (d, J=8.6 Hz, IH), 6.81 (d, J=8.5 Hz, IH), 6.63 (br s, IH), 5.71 (s, IH), 5.51 (br s, IH), 2.00 (br s, 3 H), 1.28 (br s, 6H);

¹³ C NMR (125 MHz, DMSO-d ₆ ) δ 153.5, 149.7, 146.4, 145.7, 136.5, 136.1, 132.7, 128.7,

128.2, 123.0, 122.4, 121.5, 118.3, 117.7, 117.6, 116.5, 115.5, 114.8, 114.4, 114.1, 113.9,

49.5, 29.7, 28.1,21.2;

HRMS (FAB) calculated m/z for C25H21CIN2O2. 416.1291 (M) ⁺ . Found: 416.1288.

Example 369

Z-9-Hydroxy-10-methoxy-5-(2-picoylidenyl)-2,2,4-trimethyl-2,5-dihydro-1H[1]benzopyrano[3,4-f]quinoline MS (DCI/NH ₃ ) m/z 413 (M+H) ⁺ ;

Ή NMR (300 MHz, DMSO) δ 9.08 (br s, IH), 8.55 (ddd, J=5.3, 1.4, 1.0 Hz, IH), 8p2 (d, J=8.6 Hz, IH), 8.30 (brt, J=7.7 Hz, IH), 7.83 (td, J=7.8, 1.4 Hz, IH), 7.21 (ddd, J=7.6, 5.3,

1.2 Hz, IH), 6.97 (d, J=8.6 Hz, IH), 6.86 (d, ,J =8.5 Hz, IH), 6.81 (d, J=8.6 Hz, IH), 6.73 (br s, IH), 5.80 (s, IH), 5.54 (br s, IH), 3.78 (s, 3 H), 2.03 (br s, 3 H), 1.31 (br s, 6 H);

¹³ C NMR (125 MHz, DMSO-d ₆ ) δ 158.4, 149.1, 148.2, 146.6, 139.5, 136.0, 133.1, 128.8,

125.7, 124.6, 122.9, 121.0, 119.4, 118.2, 117.3, 116.9, 115.8, 115.1, 114.7, 114.0, 111.5,

73.3,50.2, 29.9, 28.1,22.3;

HRMS (FAB) calcd m/z for C26H25N2O;?: 413.1865 (M+H) ⁺ . Found: 413.1849. Analytical calcd for _{C2όΗ24Ν2 03} : C, 75.71; H, 5.86; N, 6.79. Found: C, 75.61; H, 6.05; N, 6.75.

249 «· ·· *· ·· ·· ** • « · · ···« ···· ··· · · · · · * · · φ ··· 9 · 9 999 99 99 9

999 99999

9*·9 99 99 99 99 99

Example 370

9-hydroxy-10-methoxy-5-(3,5-difluorophenyl)methylidene-2,5-dihydro-5-phenyl-2,2,4-trimethyl1H-[1jbenzopyrano[3,4-fquinoline

Ή NMR (300 MHz, DMSO-dg) δ 9.05 (s, 1H), 8.24 (d, J=9 Hz, 1H), 7.41 (m, 2H), 7.07 (m,

1H), 6.85 (d, J=8 Hz, 1H), 6.80 (d, >9 Hz; 1H), 6.76 (d, J=9 Hz, 1H), 6.70 (br s, 1H), 5.57 (s, 1H), 5.46 (s, 1H), 3.72 (s, 3H), 1.96 (s, 3H), 1.27 (br s, 6H);

¹² C NMR (75 MHz, DMSO-dg) δ 164.0 (d), 160.8 (d), 150.1, 146.2, 146.1, 144.6, 144.4,

132.1, 128.8, 125.2, 125.0, 117.9, 117.8, 115.2, 115.0, 114.8, 112.1, 110.9, 110.8, 110.5, 101.9, 101.6, 101.2, 29.3, 49.5, 21.1 (2xC);

MS (DCI/NH ₃ ) m/e (M+H) ⁺ 448.

Example 371

9-Hydroxy-10-methoxy-5-(3,4-difluorophenyl)methylidene-2,5-dihydro-5-phenyl-2,2,4-trimethyl1H-[1jbenzopyrano[3,4-fquinoline

Ή NMR (300 MHz, DMSO-dg) δ 9.03 (s, 1H), 8.22 (d, >9 Hz, 1H), 7.79 (m, 1H), 7.52 (m, 1H), 7.41 (m, 1H), 6.86 (d, J=9 Hz, 1H), 6.77 (d, J=9 Hz, 1H), 6.74 (d, >9 Hz, 1H), 6.68 (br s, 1H), 5.53 (s, 1H), 5.45 (s, 1H), 3.33 (s, 3H), 1.95 (s, 3H), 1.27 (br s, 6H);

MS (DCI/NH3) m/e (M+H) ⁺ 448. FAB HRMS calcd for C27H23NO3F2.

Example 372 (Z) 9-Hydroxy-10-methoxy-5-((4-fluorophenyl)methylene)-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-f]quinoline ^! H NMR (300 MHz, DMSO-dg) δ 9.01 (s, 1H), 8.19 (d, >9 Hz, 1H), 7.77 ( d, >9 Hz, 1H), 7.76 (d, J =9 Hz, 1H), 7.22 (d, >9 Hz, 1H), 7.18 (d, >9 Hz, 1H), 6.84 (d, >8 Hz, 1H), 6.75 (d, J=9 Hz, 1H), 6.72 (d, >9 Hz, 1H), 6.66 (s, 1H), 5.53 (s, 1H), 5.45 (s, 1H), 3.71 (s, 3H), 1.96 (s, 3H), 1.26 (s, 6H);

¹³ C NMR (75 MHz, DMSO-d ₆ ) δ 161.8, 159.4, 147.4, 146.0, 145.1, 144.4, 132.0, 131.4,

130.2, 130.1, 129.0, 126.2, 125.0, 117.8, 115.4, 115.3, 115.2, 114.6, 114.5, 113.3, 111.0,

59.3.59.2, 49.5,21.0;

MS (DCI/NH3) m/z 430 (M+H) ⁺ ; Analytical calcd for C27H24NO3F: C, 75.51; H, 5.63; N, 3.26. Found: C, 75.64; H, 5.97; N, 3.03.

Example 373 • · · · · • · · · · · · • ·

250 • · · · (Z)-9-hydroxy-10-methoxy-5-([2,3-difluorophenyl]ethylene)-2,2,4-trimethyl-1H-2,5-dihydro[ 1 ]benzopyrano[3,4-f] quinoline 'H NMR (300 MHz, DMSO-dó) δ 9.09 (s, 1H), 8.27 (d, J=9 Hz, 1H). 8.04 ( d, >9 Hz, 1H), 7.33-7.20 (m, 2H), 6.87 (d, >9 Hz, 1H), 6.82 (d, >9 Hz, 1H), 6.76 (s, 1H), 6.75 (d, >9 Hz, 1H), 5.75 (s, 1H), 5.49 (s, 1H), 3.73 (s, 3H), 1.99 (s, 3H), 1.26 (s, 6H);

MS (DCI/NH3) m/z 448 (M+H) ⁺ ; Analytical calcd for C27H23NO3F2: C, 72.47; H, 5.18; N, 3.13. Found: C, 72.17; H, 5.03; N, 2.95.

Example 374

Z-5-(3-Fluorobenzylideneyl)-10-methoxy-9-hydroxy-2,2,4-trimethyl-2,5-dihydro-1H[ 1 ]benzopyrano[3,4-f]quinoline 'H NMR (300 MHz, DMSO-do) δ 9.04 (s, 1H), 8.22 (d, 1H), 7.62-7.37 (m, 3H), 7.10-7.02 (m, 1H), 6.86 (d, 1H), 6.78 (d, 1H), 6.73 (d, 1H), 6.70 (s, 1H), 5.56 (s, 1H), 5.46 (s, 1H), 3.72 (s, 3H), 1.96 (s, 3H), 1.27 (s, 3H).

MS (DCI/NH 3 ) m/z 430 (M+H) ⁺ ;

Analytical calcd for _C27H24NO3F ?0.25H2O: C, 75.51; H, 5.63; N, 3.26. Found: C, 74.84; H, 6.17; N, 2.91.

Example 375 r /-(5S,3'R)-9-hydroxy-5-[1-methoxymethyl-3-cyclohexenyl]-10-methoxy-2,2,4-trimethyl2,5-dihydro-1H-[1jbenzopyrano[3,4-f]quinoline MS (DCI/NH3) m/z 452 (M + H) ⁺ ;

Ή NMR (300 MHz, DMSO) δ 8.02 (d, J = 8.6 Hz, 1H), 6.93 (app s, 2 H), 6.68 (d, J = 8.3 Hz, 1H), 6.48 (br s, 1H), 5.52 (d, J = 10.3 Hz, 1H), 5.42 (br s, 1H), 5.10 (br s, 1H), 4.46 (t, J = 5.5 Hz, 1H), 3.81 (s, 3 H), 3.65 (br d, J = 5.5 Hz, 2 H), 2.26-2.16 (m, 1H), 2.08 (br s, 3 H), 1.951.88 (m, 2 H), 1.77-1.62 (m, 2H), 1.57-1.44 (m, 1H), 1.37-1.28 (m, 1H), 1.30 (s, 3H), 1.11 (s, 3H);

¹³ C NMR (125 MHz, DMSO) δ 150.4, 146.0, 144.9, 140.7, 133.9, 132.7, 127.9, 127.0, 124.3,

119.8, 117.7, 116.7, 115.4, 112.5, 110.7, 75.9, 65.5, 56.4, 49.6, 36.6, 29.7, 27.9, 25.9, 25.0, 24.4, 20.3;

HRMS (FAB) calculated m/z for C27H30CINO3: 451.1915 (M) ⁺ . Found: 451.1922.

Example 376

251

9-hydroxy-10-methoxy- 5 -ethyl-2,2,4-trimethyl-2,5 -dihydro-1 Η- [ 1 Jbenzopyrano [3,4fjquinoline 'H NMR (200 MHz, DMSO-d ₆ ) δ 8.70 (s, 1H), 7.90 (d, J =8 Hz, 1H), 6.61 (m, 2H), 6.51 (d, J=8 Hz, 1H), 6.16 (br s, 1H), 5.52-5.40 (m, 2H), 2.62 (s, 2H), 2.09 (s, 2H), 1.79-1.58 (m, 1H), 1.52-1.27 (m, 1H), 1.17 (s, 2H), 1.15 (s, 2H), 0.89 (t, J=7 Hz, 2H);

¹² C NMR (75 MHz, DMSO-d ₆ ) δ 145.8, 145.0, 142.9, 142.0, 122.5, 122.4, 127.6, 126.4, 118.0, 116.4, 116.1, 114.2, 112.5, 112.2, 75.1,59.2, 49.7,29.2,28.8, 25.5,22.8, 10.4;

MS (DCI/NH3) m/e (M+H) ⁺ 252; Analytical calcd for C22H25NO2 1/ _2H2O : C, 72.94; H, 7.24; N, 2.92. Found: C, 72.78; H, 7.40; N, 2.74.

Example 377 (+/-) 2,5-dihydro-9-cyanomethoxy-10-methoxy-2,2,4-5-allyl-trimethyl-1H[ 1 ]benzopyrano[3,4-f]quinoline *H NMR (200 MHz, DMSO-d ₆ ) δ 7.92 (d, 1H), 6.95 (d, 1H), 6.66 (d, 1H). (d, 1H), 6.26 (d, 1H), 5.86 (m, 2H), 5.45 (s, 1H) 5.12 (s, 2H), 5.00 (m, 2H); 2.69 (s, 2H), 2.42 (m, 1H), 2.26 (m, 1H), 2.17 (s, 2H), 1.18 (s, 2H), 1.17 (s, 2H).

Example 378

2,5-dihydro-9-(4-N,N-diethylamino-4-oxo-butanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2propenyl)-1 H-[ 1 ]benzopyrano[3,4-f]quinoline *H NMR (400 MHz, DMSO-d ₆ ) δ 7.78 (d, >8.5), 6.76 (d, >8.9, 1H). 1H), 6.60-5 6.55 (m, 2H), 6.18 (d, >1.7, 1H), 5.80-5.70 (m, 2H), 5.28 (s, 1H), 4.98-4.90 (m, 2H), 2.55 (s, 2H), 2.28-2.17 (m, 4H), 2.77-2.69 (m, 2H), 2.68-2.57 (m, 2H), 2.29 (m, 1H), 2.19 (m, 1H), 2.10 (s, 2H), 1.11 (s, 2H), 1.10 (s, 2H), 1.06 (t, >7, 2H), 0.95 (t, >7.2, 2H);

¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 171.5; 169.5, 148.2, 148.0, 146.2, 128.5, 124.1, 122.5,

122.1, 127.2, 126.2, 120.8, 118.2, 117.2, 116.2, 115.0, 112.8, 112.5, 72.6, 60.0, 49.8, 41.1,

26.6, 29.2, 29.0, 27.4, 22.8, 14.0, 12.1; MS ₍ ESI/NH3) m/e 519(M+H) ⁺ , 541 (M+Na) ⁺ ; Analytical calcd for _C31H38N2O5 : C 71.79, H 7.28, N 5.40. Found: C 71.50, H 7.28, N 5.28.

Example 379

2,5-Dihydro-9-(4-N -piperidino-4-oxo-butanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2propenyl)-1Η-[1]benzopyrano[3,4-f]quinoline • · · · · • · · · · ·

252

Ή NMR (200 MHz, DMSO-d ₆ ) δ 7.78 (d, >8.4, 1H), 6.76 (d, >8.8, 1H), 6.61-6.55 (m, 2H), 6.17 (d, >1.5, 1H), 5.82-5.68 (m, 2H), 5.28 (s, 1H), 4.99-4.89 (m, 2H), 2.55 (s, 2H), 2.27 (m, 4H), 2.74 (m, 2H), 2.61 (m, 2H), 2.41 (m, 1H), 2.18 (m, 1H), 2.10 (s, 2H), 1.51-1.16 (m, 6H), 1.11 (s, 2H), 1.10 (s, 2H);

¹³ C NMR (75 MHz, DMSO-d ₆ ) δ 171.7, 168.9, 148.5, 148.2, 146.5, 128.7, 124.2, 122.8, 122.2; 127.5, 126.5, 121.0, 118.4, 117.5, 116.4, 115.2, 114.0, 112.8, 72.8, 60.2, 50.0, 45.9,

42.4, 26.8, 29.5, 29.2, 27.7, 26.1, 25.5, 24.2, 24.1; MS (ESI/NH ₃ ) m/e 521(M+H) ⁺ , 552(M+Na) ⁺ ; Analytical calcd for C 32 H 38 N 2 O 5 : C 72.42, H 7.22, N 5.28. Found: C 72.16, H 7.26, N 5.09.

Example 380

2,5-dihydro-9-(4-N-morpholino-4-oxo-butanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2propenyl)-1 Η- [ 1 ] benzopyrano [3,4-f] quinoline *H NMR (400 MHz, DMSO-d ₆ ) δ 7.78 (d, >8.9,1H), 6.77 (d, >8.5,1H). 6.60-6.55 (m, 2H), 6.18 (s, 1H), 5.80-5.70 (m, 2H), 5.28 (s, 1H), 4.98-4.90 (m, 2H), 2.55 (s, 2H), 2.52-2.42 (m, 4H), 2.40 (m, 4H), 2.76 (m, 2H), 2.65 (m, 2H), 2.40 (m, 1H), 2.20 (m, 1H), 2.10 (s, 2H), 1.11 (s, 2H), 1.10 (s, 2H);

¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 171.4, 169.4, 148.2, 148.0, 146.2, 128.5, 124.1, 122.5,

122.1, 127.2, 126.2, 120.8, 118.2, 117.2, 116.2, 115.0, 1 12.8, 112.6, 72.6, 66.1, 60.0, 49.8,

45.1, 41.6, 26.6, 29.2, 29.0, 28.8, 27.2, 22.8; MS (ESI/NH3) m/e 522(M+H) ⁺ , 555(M+Na) ⁺ ; Analytical calcd for C31H36N2O6: C 69.90, H 6.81, N 5.26. Found: C 69.61, H 6.84, N 5.04.

Example 381

2,5-dihydro-9-(4-N,N-dimethylamino-4-oxo-butanoyloxy)-10-methoxy-2,2,4-trimethyl-5(3,4,5 -trifluorophenyl)-1 Η- [ 1 ] benzopyrano [3,4-f] quinoline 'H NMR (400 MHz, DMSO-d ₆ ) δ 7.90 (d, >8.5, 1H), 7.07-7.02 (m, 2H), 6.80-6.70 (m, 2H), 6.62 (d, >8.9, 1H), 6.44 (s, 1H), 5.42 (d, >1.2, 1H), 2.54 (s, 2H), 2.97 (s, 2H), 2.82 (s, 2H), 2.76-2.72 (m, 2H), 2.67-2.64 (m, 2H), 1.84 (s, 2H), 1.25 (s, 2H), 1.15 (s, 2H);

¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 171.4, 170.4, 150.1 (d, >248), 148.4, 147.9, 146.4, 128.7,

128.2 (dd, >251, 49), 126.5, 122.2, 128.2, 127.1, 126.5, 121.0, 118.5, 117.9, 116.1, 114.8, 112.0, 112.8, 112.6, 72.7, 59.7, 49.9, 26.5, 24.9, 29.7, 28.9, 28.6, 27.6, 22.2; MS (ESI/NH3) • ·

253 ............

m/e 581 (M+H) ⁺ , 602 (M+Na) ⁺ ; Analytical calcd for C 32 H 31 F 3 N 2 O 5 : C 66.20, H 5.28, N 4.82. Found: C 66.17, H 5.46, N 4.65.

Example 382

2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-5-difluorophenylmethyl)-1H[ 1 ]benzopyrano [3,4-f]quinoline *H NMR (300 MHz, DMSO-d _ó ) δ 8.81 (s, 1H), 7.95 (d, J = 8 Hz, 1H), 7.10-7.03 (m, 1H),

6.78 (d, J = 9 Hz, 2H), 6.63 (dd, J = 9, 9 Hz, 2H), 6.41 (d, J = 9 Hz, 1H), 6.22 (s, 1H), 5.91 (dd, J = 10, 10 Hz, 1H), 5.40 (s, 1H), 3.69 (s, 3H), 3.06-2.98 (m, 1H), 2.90-2.84 (m, 1H), 2.19 (s, 3H), 1.15 (s, 3H), 1.12 (s, 3H); ¹³ C NMR (75 MHz, DMSO-d ₆ ) δ 163.8, 163.6, 160.6,

160.4, 145.9, 145.2, 144.1, 142.6, 142.4, 142.3, 133.4, 131.7, 127.4, 126.5, 117.8, 116.5,

116.2, 114.5, 113.9, 112.3, 112.2, 111.9, 102.1, 101.7, 101.4, 73.5, 59.5, 49.7, 29.1, 29.0,

24.1;

HRMS calcd for C27H25O3F2N: m/e 449.1803. Found: 449.1801;

Analysis for C27H25O3F2N0.05H20: C, _70.73 ; H, 5.72; N, 3.05; Found: C, 70.52; H, 5.79; N, 2.91.

Example 383

2.5- dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(2-thienyl)-1 H-[ 1 ] benzopyrano [3,4fJ quinoline ’H NMR δ 9.51 (s, 1H), 7.95 (d, 1H, J=8.5Hz), 7.40 (dd, 1H, J=5.1Hz, J=1.4Hz), 6.82 (m, 2H), 6.71 (m, 2H), 6.61 (s, 2H), 6.26 (m, 1H), 5.40 (m, 1H), 1.92 (d, 2H, J=1.4Hz), 1.24 (s, 2H), 1.14 (s, 2H); MS (ESI) m/z: 410 (M + 1); Calculated for C22H20CINO2S: 409.0902. Found: 409.0902.

Example 384

2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-cyclopentyl-1 H-[ 1 ]benzopyrano[3,4fjquinoline 'H NMR (300 MHz, DMSO-d ₆ ) δ 8.70 (s, 1H), 7.99 (d, J = 8 Hz, 1H), 6.63 (d, J = 9 Hz, 1H). 6.61 (d, J = 9 Hz, 1H), 6.18 (d, J = 8 Hz, 1H), 6.27 (br s, 1H), 5.45 (br s, 1H), 5.35 (d, J = 10 Hz, 1H), 3.65 (s, 3H), 2.15 (s, 3H), 2.11 - 1.97 (m, 1H), 1.62 - 1.43 (m, 4H), 1.41-1.26 (m, 2H), 1.30 (s, 3H), 1.21-1.06 (m, 2H), 1.02 (s, 3H); MS (DCl/NH 3 ) (M+H) ⁺ 392.

····· ·· ·

254

Example 385

2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-((2-fluorophenyl)methyl)-1H[ 1 ]benzopyrano[3,4-fquinoline MS (DCI/NH 3 ) m/z 418 (M+H) ⁺ .

Example 386

2,5-dihydro-9-hydroxymethyl-10-methoxy-2,2,4-trimethyl-5-allyl-1H-[1]benzopyrano[3,4fj quinoline

MS (DCI/NH 3 ) m/z 378 (M+H) ⁺ ;

'H NMR (500 MHz, DMSO) δ 7.93 (d, J = 8.2 Hz, 1H), 7.16 (d, J = 8.3 Hz, 1H), 6.67 (d, J =

8, 1Hz, 1H), 6.63 (d, J = 8.3 Hz, 1H), 6.27 (br s, 1H), 5.87-5.75 (m, 2 H), 5.44 (br s, 1H), 5.03 (br d, J = 10.3 Hz, 1H), 4.98 (br d, J = 15.1 Hz, 1H), 4.97-4.93 (m, 1H), 4.57-4.48 (m, 2H), 3.59 (s, 3H), 2.55-2.46 (m, 1H), 2.30-2.22 (m, 1H), 2.19 (s, 3H), 1.19 (s, 3H), 1.16 (s, 3 H);

¹³ C NMR (125 MHz, DMSO) δ 154.0, 150.2, 145.9, 134.2, 133.4, 132.1, 128.9, 127.4, 126.6,

125.9,117.2,116.8,116.3,115.6,113.9,112.6,73.6,60.0,58.1,49.8,36.4,29.4,28.9,23.9; HRMS (FAB) calculated m/z for C24H27NO3: 377.1991 (M) ⁺ . Found: 377.1985.

Example 387

2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(l-pentenyl)-lH-[l]benzopyrano[3,4fjquinoline *H NMR (300 MHz, DMSO-d ₆ ) δ 8.67 (s, 1H), 7.88 (d, J = 9 Hz, 1H), 6.59 (d, J = 9 Hz, 2H). 6.48 (d, J = 8 Hz, 1H), 6.14 (s, 1H), 5.73-5.65 (m, 1H), 5.61-5.57 (m, 1H), 5.43 (s, 1H), 4.944.86 (m, 2H), 3.63 (s, 3H), 2.15 (s, 3H), 1.99-1.93 (m, 2H), 1.73-1.69 (m, 1H), 1.45-1.41 (m, 3H), 1.16 (s, 6H);

¹³ C NMR (75 MHz, DMSO-d ₆ ) δ 145.7, 144.9, 143.9, 143.0, 138.4, 133.4, 133.3, 127.5,

126.4,117.9,116.2,116.1, 114.7,114.2,113.4,112.1,73.5, 59.3,49.7, 32.5,31.7,29.1,28.9,

24.6, 23.8; MS calcd for C25H29O3N: m/e 391.2147. Found: 391.2153; Analysis calcd for C25H29O3N 0.50H ₂ 0: C, 74.97; H, 7.55; N, 3.50; Found: C, 75.20; H, 7.45; N,

3.49.

Example 388

255 ♦ · · · · ·

2,5-dihydro-9-methylcarboxylate-10-methoxy-2,2,4-trimethyl-5-allyl-1H-[1]benzopyrano[3,4fjquinoline

MS (DCI/NH ₃ ) m/z 406 (M+H) ⁺ ;

³ H NMR (125 MHz, DMSO) δ 7.92 (d, J = 8.1Hz, 1H), 6.48 (d, J = 8.3 Hz, 1H), 6.75 (d, J =

8.2 Hz, 1H), 6.65 (d, J = 8.2 Hz, 1H), 6.33 (br s, 1H), 5.90-5.75 (m, 2 H), 5.46 (br s, 1H), 5.04 (dd, J = 10.5, 1.0 Hz, 1H), 4.98 (dd, J = 15.4, 1.0 Hz, 1H), 3.82 (s, 3H), 3.67 (s, 3H), 2.54-2.42 (m, 1H), 2.38-2.27 (m, 1H), 2.18 (s, 3H), 1.19 (s, 3H), 1.16 (s, 3H);

¹³ C NMR (300 MHz, DMSO) δ 166.1, 156.5, 154.6, 146.3, 133.9, 133.5, 131.9, 129.0, 127.2,

126.2, 119.1, 118.1, 117.4, 116.2, 114.5, 114.0, 113.0, 74.0, 60.7, 51.8, 49.8, 36.8, 29.4, 29.0, 23.8;

HRMS (FAB) calculated m/z _{for C25H27NO4 : 405.1940} (M) ⁺ . Found: 405.1939.

Example 389

2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-allenyl-1H-[l]benzopyrano[3,4fjquinoline ^X H NMR (300 MHz, DMSO-d ₆ ) δ 8.67 (s, 1H), 7.93 (d, J = 9 Hz, 1H), 6.57 (dd, J = 10, 9 Hz, 2H). 6.48 (d, J = 9 Hz, 1H), 6.15-6.12 (m, 2H), 5.41 (s, 1H), 5.31 (q, J = 12 Hz, 1H), 4.724.69 (m, 1H), 4.59-4.49 (m, 1H), 3.58 (s, 3H), 2.14 (s, 3H), 1.23 (s, 3H), 1.10 (s, 3H); MS calcd for C 12 H 12 O 3 N: m/e 361.1678. Found: 361.1671; Analysis for C 23 H 23 O 3 N 0.5 H ₂ O: C, 74.58; H, 6.53; N, 3.78; Found: C, 74.98; H, 6.56; N, 3.83.

Example 390 (-) (5S,3'S) 2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-(cyclopenten-3-yl)-1H[1'benzopyrano[3,4-fquinoline ^] H NMR (300 MHz, DMSO-d6) δ 8.05 (d, J = 9 Hz, 1H), 7.09 (ζ J - 8 Hz, 1H), 6.72 (d, J = 8

Hz, 1H), 6.66 (d, J = 9 Hz, 1H), 6.58 (d, J = 8 Hz, 1H), 6.19 (s, 1H), 5.77 (dd, J = 6.3 Hz,

1H), 5.50 (d, J = 10 Hz, 1H), 5.43 (s, 1H), 5.19 (dd, J = 6, 2 Hz, 1H), 3.87 (s, 3H), 2.90 (m, 1H), 2.43-2.15 (m, 2H), 2.09 (s, 3H), 1.97-1.70 (m, 2H), 1.31 (s, 3H), 1.09 (s, 3H);

¹³ C NMR (75 MHz, DMSO-cc) δ 156.2, 151.4, 145.2, 133.7, 132.5, 131.6, 130.0, 128.1,

127.2, 127.1, 117.0, 116.4, 113.4, 113.1, 110.0, 105.3, 75.9, 55.6, 49.5,48.6, 31.6, 29.7, 27.3, 27.2,24.2;

(DCI/NH3) m/z ₃₇₄ ( _M +H) ⁺ ; MS (FAB HRMS) calcd for _C25H27NO2 : m/e 373.2042. Found: 373.2047.

256

Example 391 (-) (5S,3'S) 2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-(cyclohexen-3-yl)-1H[1]benzopyrano[3,4-f]quinoline 1H NMR (300 MHz, DMSO-d6) δ 8.03 (d, J = 9 Hz, 1H), 7.07 (t, J = 8 Hz, 1H), 6.68 (d, J = 8

Hz, 1H), 6.63 (d, J = 9 Hz, 1H), 6.57 (d, J = 8 Hz, 1H), 6.15 (s, 1H), 5.62 (m, 1H), 5.54 (m, 1H), 5.46 (s, 1H), 5.09 (m, 1H), 3.85 (s, 3H), 2.29 (m, 1H), 2.10 (s, 3H), 1.95-1.80 (m, 2H), 1.72-1.50 (m, 2H), 1.38-1.10 (m, 2H), 1.28 (s, 3H), 1.05 (s, 3H); ¹³ C NMR (75 MHz, DMSOd ₆ ) δ 156.2, 151.0, 145.0, 133.7, 130.4, 129.1, 128.1, 127.1, 126.1, 117.9, 116.5, 113.5,

113.1, 110.1, 105.4, 75.3, 55.6, 49.5, 36.8, 29.7, 27.3, 25.5, 24.6, 24.3, 20.0; MS (DCI/NH ₃ ) m/z 388 (M+H) ⁺ ; MS (FAB HRMS) calcd for C ₂₆ H ₂₉ NO ₂ : m/e 387.2198. Found:

387.2204.

[αΓο = -138° (c 0.114, CHCb).

Example 392 (-) (5S,3'R) 2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-cyclohexen-3-yl)-1H[1]benzopyrano[3,4-f]quinoline

Ή NMR (300 MHz, DMSO-d _fi ) δ 8.05 td, J = 9 Hz, 1H), 7.06 (t, J = 8 Hz, 1H), 6.67 (d, J = 8

Hz, 1H), 6.64 (d, J = 9 Hz, 1H), 6.59 (d, J = 8 Hz, 1H), 6.19 (s, 1H), 5.82 (m, 1H), 5.72 (m, 1H), 5.41 (s, 1H), 5.40 (d, J= 10 Hz, 1H), 3.87 (s, 3H), 2.29 (m, 1H), 2.13 (s, 3H), 1.95-1.80 (m, 2H), 1.72-1.50 (m, 2H), 1.38-1.10 (m, 2H), 1.30 (s, 3H), 1.02 (s, 3H);

¹³ C NMR (75 MHz, DMSO-d ₆ ) δ 156.3, 151.4, 145.0, 133.8, 130.0, 128.3, 127.9, 127.5,

127.1, 126.9, 118.5, 116.4, 113.4, 113.0, 110.2, 105.3, 76.1, 55.6, 49.4, 37.1, 29.6, 26.8, 24.7,

23.6, 21.2;; MS (DCI/NH3) m/z 388 (M+H) ⁺ ; MS (FAB HRMS) calcd for C26H29NO2: m/e 387.2198. Found: 387.2206.

[α] ²³ D = -147° (c 0.080, CHCl ₃ ).

Example 393 (-) (5S,3R) 2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-(cyclopenten-3-yl)-1H[l]benzopyrano[3,4-f]quinoline ’H NMR (300 MHz, DMSO-dg) δ 8.07 (d, J= 9 Hz, 1H), 7.08 (t, J= 8 Hz, 1H), 6.70 (d, J = 8 Hz, 1H), 6.66 (d, J = 9 Hz, 1H), 6.61 (d, J = 8 Hz, 1H), 6.22 (s, 1H), 5.82-5.70 (m, 2H), 5.48 (d, J = 13 Hz, 1H), 5.41 (d, J = 10 Hz, 1H), 3.88 (s, 3H), 2.92 (m, 1H), 2.30 (m, 1H), 2.20 • · «0 > 0 0 0 • · · • 0

257

00 ► · 0 0

I 0 0 0 ► 0 0 0 » 0 0 0

0·00 (m, 1H), 2.15 (s, 3H), 1.50-1.40 (m, 2H), 1.33 (s, 3H), 1.05 (s, 3H); ¹³ C NMR (75 MHz, DMSO-dg) δ 156.3, 151.8, 145.1, 133.8, 132.0, 131.8, 130.8, 127.9, 127.0, 117.7, 117.0,

116.5, 113.4, 113.3, 112.9, 109.9, 105.2, 105.0, 76.3, 49.3, 48.4, 32.4, 31.6, 26.7, 24.6, 23.9, 23.6; MS (DCI/NH3) m/z 374 (M+H) ⁺ ; MS (FAB HRMS) calcd for C25H27NO2: m/e 373.2042. Found: 373.2049.

Example 394

2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3(Z)-pentenyl)-1H[ 1 ]benzopyrano[3,4-f)quinoline 'H NMR (300 MHz, DMSO-dg) δ 8.71 (s, 1H), 7.92 (d, J = 9 Hz, 1H), 6.62 (d, J = 9 Hz, 1H). 6.60 (d, 1 = 9 Hz, 1H), 6.47 (d, J = 9 Hz, 1H), 6.18 (br s, 1H); 5.63 (dd, J = 4.9 Hz, 1H), 5.43 (br s, 1H), 5.36 (m, 2H), 3.64 (s, 3H), 2.44 - 2.33 (m, 1H), 2/33 - 2.19 (m, 1H), 2.15 (s, 3H), 1.70 tm, 2H), 1.16 (s, 6H), 0.75 (t, J = 8 Hz, 3H); MS (DCl/NH 3 ) (M+H) ⁺ 392.

Example 395

2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-acetoxyphenyl)-1H[ 1 ]benzopyrano[3,4-quinoline

MS (DCI/NH3) m/z 458(M+H) ⁺ ;

*H NMR (400 MHz, DMSO-cL) 8.62(S, 1H), 7.92(d, 1H), 7.27(t, 1H), 7.12(d, 1H), 6.94(dd, 1H), 6.82(s, 1H), 6.72(d, 1H), 6.67(s, 1H), 6.44(d, 1H), 6.27(d, 1H), 6.20(s, 1H), 5.29(s, 1H), 2.55(s, 2H), 2.18(s, 2H), 1.81 (s, 2H), 1.25(s, 2H), 1.12(s, 2H).

Example 396

10-difluoromethoxy-5-[[3-(methylthio)methoxy]phenyl]-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-fquinoline MS (DCI/NH3) 496 (M+H) ⁺ ;

1H NMR (200 MHz, DMSO-cL), δ 7.80 (d, J=8.5 Hz, 1H), 7.21 (t, JH-F= 56 Hz, 1H), 7.207.12 (m, 2H), 6.99 (t, 1H), 6.82-6.68 (m, 7H), 6.29 (d, J=1,1Hz, 1H), 5.40 (s, 1H), 5.14 (s, 2H), 2.08 (s, 2H), 1.85 (s, 2H), 1.22 (s, 2H), 1.16 (s, 2H);

HRMS calcd for _C28H27NO2F2S is _495.1680 . Found: _495.1682 .

Example 397 • ·

258

99 • 9 9 9 • · · · • · 999

99

99

9 9 9 • 9 9 9

9 9 9

9 9 9

99

2,5-dihydro-7-bromo-9-hydroxy-10-chloro-2,2,4-trimethyl-5-allyl-1H-[1]benzopyrano[3,4fquinoline

MS (DCI/NH ₃ ) m/z 448 (M+H) ⁺ ;

’H NMR (300 MHz, DMSO) δ 10.03 (s, 1H), 7.90 (d, J = 8.5 Hz, 1H), 7.00 (app s, 2 H), 6.63 (d, J = 8.4 Hz, 1H), 6.43 (br s, 1H), 5.92-5.77 (m, 2 H), 5.47 (br s, 1H), 5.11-4.97 (m, 1H), 2.44-2.26 (m, 2H), 2.19 (s, 3H), 1.22 (s, 3H), 1.18 (s, 3H);

¹³ C NMR (125 MHz, DMSO-d ₆ ) δ 156.7, 150.2, 148.6, 144.0, 139.1, 136.3, 135.5, 130.8,

129.2, 124.4, 117.6, 115.9, 115.2, 114.0, 111.6, 75.9, 51.6, 48.3, 35.5, 29.8, 27.9, 24.0;

HRMS (FAB) calculated m/z for _{C22H2i77BrClNO2} : ^445.0444 (M) ⁺ . Found: 445.0436, HRMS (FAB) calculated m/z for ^{C22H2i79BrClNO2} : 447.0424 (M) ⁺ . Found: 447.0413. Analytical calcd for _{C22H2iBrClNO2} : C, 59.15; H, 4.74; _N , 3.14. Found: C, 59.31; H, 4.85; N, 3.22.

Example 398

2,5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-hydroxyphenyl)-1H[ 1 ]benzopyrano[3,4-quinoline

MS (DCI/NH3) m/z 416(M+H) ⁺ ;

1H NMR (400 MHz, DMSO-d ₆ ) 9.22(s, 1H), 8.56(s, 1H), 7.92(d, 1H), 6.98(t, 1H), 6.71(d, 1H), 6.64(d, 1H), 6.58(m, 2H), 6.54(dd, 1H), 6.44(d, 1H), 6.22(d, 1H), 6.22(s, 1H), 5.27(s, 1H), 2.56(s, 2H), 1.82(s, 2H), 1.24(s, 2H), 1.12(s, 2H).

Example 399

2,5-dihydro-9-methylthiomethoxy-10-methoxy-2,2,4-trimethyl-5-(3(methylthio)methoxy phenyl)-1H-[1]benzopyrano[3,4-quinoline

MS (DCI/NH ₃ ) m/z 526(M+H) ⁺ *H NMR (400 MHz, DMSO-cU) 7.94(d, 1H), 7.14(t, 1H), 6.82-6.70(m, 6H), 6.50(d, 1H), 6.24(s, 1H), 5.29(s, 1H), 5.16(s, 2H), 5.14(s, 2H), 2.61(s, 2H), 2.14(s, 2H), 2.08(s, 2H), 1.82(s, 2H), 1.24(s, 2H), 1.16(s, 2H).

Example 400

2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-(methylthiomethophenyl)-1H[ 1 ]benzopyrano[3,4-fquinoline MS (DCI/NH 3 ) m/z 476(M+H) ⁺ ;

• · • ·

259 • · · • * · · *· • · · · · » · · · * ·«* · · 9 9

9 9 9

9999 99 99 9

9 9

9 9

9 9'h NMR (400 MHz, DMSO- _d ) 8.58(s, 1H), 7.92(d, 1H), 7.12(t, 1H), 6.82-6.6.7l(m, 4H), 6.62(s, 1H), 6.42(d, 1H), 6.26(d, 1H), 6.25(s, 1H), 5.28(s, 1H), 5.12(s, 2H), 2.55(s, 2H), 2.07(s, 2H), 1.84(s, 2H), 1.22(s, 2H), 1.15(s, 2H).

Example 401

9-Hydroxy-10-chloro-5-(phenylmethylene)-2,2,4-trimethyl-1H-2,5-dihydro-[ljbenzopyrano[3,4fjquinoline

Ή NMR δ 9.48 (s, 1H), 7.98 (m, 1H), 7.42 (m, 1H), 7.22 (m, 5H), 7.00 (m, 1H), 6.71 (m, 1H), 6.52 (m, 1H), 6.42 (m, 1H), 5.47 (m, 0.5H), 5.12 (m, 0.5H), 1.96 (s, 2H), 1.02 (s, 2H), 0:85 (s, 2H); MS (DCI) m/z: 416 (M + 1); Calcd for C ₂₆ H ₂₂ C1NO ₂ : 415.1229. Found: 415.1229.

Example 402

2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-([2-N,Ndimethylcarbamoyloxy]phenyl)-1H-[ljbenzopyrano[3,4-fquinoline

MS (DCI/NH ₃ ) 504(M+NH}) ⁺ , 487(M+H) ⁺ ;

1H NMR (400 MHz, DMSO-d ₆ ) 8.59(s, 1H), 7.92(d, 1H), 7.22(t, 1H), 7.09(d, 1H), 6.91(dd, 1H), 6.81(t, 1H), 6.72(d, 1H), 6.66(d, 1H), 6.44(d, 1H), 6.24(d, 1H), 6.27(s, 1H), 5.28(s, 1H), 2.55(s, 2H), 2.949s, 2H), 2.82(s, 2H), 1.81(s, 1H), 1.24(s, 2H), 1.12(s, 2H),

Example 403

2.5-Dihydro-9-N,N-dimethylcarbamoyloxy-10-methoxy-2,2,4-trimethyl-5-([2-N,Ndimethylcarbamoyloxy]phenyl)-1H-[1]benzopyrano[3,4-f]quinoline

MS (DCI/NH 3 ) 575 (M+NH ¹ ; 1 H NMR (400 MHz, DMSO-d ₆ ) 7.90(d, 1H), 7.25(t, 1H), 7.11 (d, 1H), 6.95(dd, 1H), 6.85(s, 1H), 6.79(s, 1H); 6.75(d, 1H), 6.71 (d, 1H), 6.52(d, 1H), 6.49(s, 1H), 5.4l(s, 1H), 2.52(s, 2H), 2.02(s, 2H), 2.94(s, 2H), 2.89(s, 2H), 2.85(s, 2H), 1.84(s, 2H), 1.25(s, 2H), 1.15(s, 2H).

Example 404

2.5-Dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-ethyl-1H-[1jbenzopyrano[3,4-fquinoline *H NMR (300 MHz, DMSO-dr,) δ 9.59 (s, 1H), 7.91 (d, J= 8 Hz, 1H), 6.75 (s, 2H), 6.62 (d, J = 8 Hz, 1H), 6.29 (d, J = 2 Hz, 1H), 5.46 (m, 2H), 2.14 (s, 3H), 1.57 (m, 2H), 1.19 (s, 3H), 1, φ · φ · » · φ «

260 φφ φφ φφφ φ

φφ φφφφ φφφφ φ φ φφφ φ φ φ φ φ • · φ φφφφ ·· φφ φφ φφ (s, 3 Η), 0.89 (t, J = 7 Hz, 3H); High resolution MS (APCI) m/e calcd for C 21 H 22 NO 2 Cl: 355.1339. Detected: 355.1353.

Example 405

2.5-Dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-isopropyl-1H-[l]benzopyrano[3,4fjquinoline ^J H NMR (300 MHz, DMSO-de) δ 9.57 (s, 1H), 8.02 (d, > 8 Hz, 1H), 6.76 (s, 2H), 6.65 (d, J = 9 Hz, 1H), 6.45 (s, 1H), 5.45 (s, 1H), 5.32 (d, J = 9 Hz, 1H), 2.17 (s, 3H), 1.70 (m, 1H), 1.30 (s, 3H), 1.02 (s, 3H), 0.92 (d, J = 6 Hz, 3H), 0.67 (d, J = 6 Hz, 3H); HRMS(APCI) m/e calcd for C22H24NO2Cl: 369.1496. Found. 369.1492.

Example 406

9-hydroxy-10-methoxy-5-(phenylmethylene)-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-f]quinoline

MS (DCI/NH3) 412 (M+H) ⁺ ;

¹ H NMR (200 MHz, DMSO-d ₆ ), δ 8.92 (s, 1H), 8.12 (d, >8.8 Hz, 1,H), 7.62 (d, >8.8 Hz, 2 H), 7.22-7.15 (m, 2 H), 6.77 (d, 1H), 6.69 (d, 1H), 6.66 (d, 1H), 6.52 (s, 1H), 5.46 (s, 1H), 5.29 (s, 1H), 2.65 (s, 2H), 1.90 (s, 2H), 1.20 (s, 6H);

HRMS calcd for C27H25NO2 is 411.1824. Found: 411.1821.

Example 407

2.5-Dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-butyl-1H-[1]benzopyrano[3,4-fquinoline 'H NMR (300 MHz, DMSO-d«) δ 9.55 (br s, 1H), 7.91 (d, > 9 Hz, 1H), 6.74 (s, 2H), 6.61 (d, J = 8 Hz, 1H), 6.26 (d, J = 1Hz, 1H), 5.56 (dd, J = 11, 2 Hz, 1H), 5.45 (br s, 1H), 2.15 (m, 3H), 1.64 (m, 1H), 1.46 (m, 1H), 1.31 (m, 4H), 1.19 (s, 3H), 1.15 (s, 3H), 0.78 (t, J = 7 Hz, 3H); MS (DCl/NH 3 ) m/e (M+H) ⁺ 384.

Example 408

2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(1-thiazolyl-2-yl)-1H[ 1 ]benzopyrano[3,4-fquinoline ³ H NMR (300 MHz, DMSO-cL) δ 8.72 (s, 1H), 8.02 (d, J = 8 Hz, IH), 6.88 (s, 1H), 6.70 (d, ,J = 8 Hz, 1H), 6.68 (d, J = 8 Hz, 1H), 6.61 (d, J = 9 Hz, 1H), 6.54 (s, 1H), 6.20 (s, 1H), 5.49 (s, 1H), 3.72 (s, 3H), 2.57 (s, 3H), 2.30 (s, 3H), 1.33 (s, 3H); 1.14 (s, 3H); ¹³ C NMR (75

261 *· ** *» φφ 1» * φ · φ » « · · • φφφ φ « φ «·· φ φ * φφφ φ φ φφφφ φφ φφ φφ φφ φφ

MHz, DMSO-dó) δ 182.9, 182.5, 181.3, 179.8, 169.8, 167.9, 165.5, 163.8, 154.6, 154.4,

153.6, 151.7, 151.3, 150.0, 127.0, 96.8, 87.2, 67.6, 65.7, 60.3; MS (DCI/NH 3 ) (Μ+Η) ⁺ 322.

Example 409

2.5-Dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(2-methylpropyl)-1 Η-[ 1 ]benzopyrano[3,4fjquinoline 'Η NMR (300 MHz, DMSO-do) δ 9.59 (br s, 1H), 7.91 (d, J = 9 Hz, 1H), 6.75 (d, J = 8 Hz, 1H). 6.73 (d, J = 8 Hz, 1H), 6.62 (d, J = 8 Hz, 1H), 6.28 (d, J = 2 Hz, 1H), 5.70 (dd, J= 12, 2 Hz, 1H), 5.45 (br s, 1H), 2.17 (s, 3H), 1.68 (m, 2H), 1.23 (m, 2H), 1.19 (s, 3H), 1.15 (s, 3H), 0.98 (d, J = 6 Hz, 3H), 0.75 (d, J = 7 Hz, 3H); MS (DCl/NH 3 ) m/e (M+H) ⁺ 384.

Example 410

2,5-dihydro-9-hydroxymethyl-10-chloro-2,2,4-trimethyl-5-allyl-1H-[1]benzopyrano[3,4fjquinoline

MS (DCI/NH3) m/z 381 (M) ⁺ ;

’H NMR (500 MHz, DMSO) δ 7.91 (d, J = 8.4 Hz, 1H), 7.30 (d, J = 8.5 Hz, 1H), 6.90 (d, J = 8.4 Hz, 1H), 6.64 (d, ,J = 8.5 Hz, 1H), 6.32 (br s, 1H), 5.90-5.73 (m, 2 H), 5.47 (br s, 1H), 5.28 (t, J = 5.1Hz, 1H), 5.04 (dd, J = 10.2, 1, 1Hz, 1H), 4.97 (dd, J = 10.2, 1.1Hz, 1H), 4.644.50 (m, 2H), 2.46-2.25 (m, 2H), 2.17 (br s, 3H), 1.21 (s, 3H), 1.16 (s, 3H);

HRMS (FAB) calculated m/z for C23H24CINO2: 381.1496 (M) ⁺ . Found: 381.1495.

Example 411

2.5- dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-propyl-1H-[l]benzopyrano[3,4-f]quinoline *H NMR (300 MHz, DMSO-do) δ 9.55 (s, 1H), 7.90 (d, J = 9 Hz, 1H), 6.74 (s, 2H), 6.60 (d, J = 9 Hz, 1H), 6.26 (s, 1H), 5.59 (d, J = 9 Hz, 1H), 5.45 (s, 1H), 2.15 (s, 3H), 1.65 (m, 1H), 1.38 (m, 3H), 1.19 (s, 3H), 1.15 (s, 3H), 0.82 (t, J = 7 Hz, 3H); ¹³ C NMR (75 MHz, DMSOdo) δ 148.6, 146.1, 143.6, 134.8, 133.4, 127.4, 127.0, 123.9, 116.2, 115.9, 115.9, 115.2,

113.9, 112.5, 73.9, 49.8, 33.4, 29.4, 28.8, 23.8, 18.7, 13.4; High Resolution MS (APCI) m/e calcd for C22H24NO2Cl: 369.1496. Found: 369.1504.

Example 412

9-hydroxy-10-methoxy-5-([3-fluorophenyl]methylene)-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-fquinoline

262 »· ** Φ* *· ·· 99 • · » · · · · · « · « φ • · · · « Φ Φ · Φ Φ φ • ’·· · Φ φ φφφ W φ φ φ φ • · · ♦ ΦΦΦΦ* ·»·Φ ΦΦ 99? «φ »φ φ«

Ή NMR (200 MHz, DMSO-de) δ 9.04 (s, 1Η), 8.22 (d, 1Η), 7.62-7.27 (m, 2H), 7.10-7.02 (m, 1H), 6.86 (d, 1H), 6.78 (d, 1H), 6.72 (d, 1H), 6.70 (s, 1H), 5.56 (s, 1H), 5.46 (s, 1H), 2.72 (s, 2H), 1.96 (s, 2H), 1.27 (s, 2H), MS (DCI/NH ₃ ) m/z 420 (M+H) ⁺ ;

Analytical calcd for _C27H24NO2F :0.25H2O: _C , _75.51 ; H, 5.62; N, 2.26. Found: C, 74.84; _H , 6.17; N, 2.91.

Example 413

9-hydroxy-10-chloro-5-([2-pyridyl]methylene)-2,2,4-trimethyl-1H-2,5-dihydro[l]benzopyrano[3,4-f]quinoline

MS (DCI/NH 3 ) m/z 417 (M+H) ⁺ ;

'H NMR (200 MHz, DMSO) δ 9.79 (br s, 1H), 8.51 (ddd, >5.9, 1.6, 1.0 Hz, 1H), 8.42 (d, >8.6 Hz, 1H), 8.24 (dt, >7.8, 1.0 Hz, 1H), 7.52 (td, >7.8, 1.7 Hz, 1H), 7.22 (ddd, >7.7, 5.8, 1.2 Hz, 1H), 7.00 (d, >8.5 Hz, 1H), 6.88 (d, >8.6 Hz, 1H), 6.81 (d, >8.5 Hz, 1H), 6.62 (br s, 1H), 5.71 (s, 1H), 5.51 (br s, 1H), 2.00 (br s, 2 H), 1.28 (br s, 6 H);

¹³ C NMR (125 MHz, DMSO-de) δ 152.5, 149.7, 146.4, 145.7, 126.5, 126.1, 122.7, 128.7,

128.2, 122.0, 122.4, 121.5, 118.2, 117.7, 117.6, 116.5, 115.5, 114.8, 114.4, 114.1, 112.9, 49.5,29.7,28.1,21.2;

HRMS (FAB) calculated m/z for _C25H21C1N2O2 : _416.1291 (M ₎ ⁺ . Found: _416.1288 .

Example 414 re /-(5 S )-9-hydroxy-5-[(3 S )-( l -hydroxymethyl)cyclohexen-3 -yl]-10-methoxy-2,2,4-trimethyl2,5-dihydro-1 H -[ 1 ]benzopyrano[3,4- f ]quinoline ^b H NMR (200 MHz, DMSO-de), δ 8.49 (s, 1H), 7.99 (d, >8.5 Hz, 1H), 6.64 (d, >8.5 Hz, 1H), 6.58 (d, >8.5 Hz, 1H), 6.47 (d, >8.5 Hz, 1H), 6.21 (br s, 1H), 5.99 (br s, 1H), 5.40 (br s, 1H), 5.26-5.21 (m, 1H), 4.81-4.72 (m, 2 H), 4.02-4.02 (m, 1H), 2.61-2.58 (m, 1H), 2.52 (s, 2 H), 2.00-2.95 (m, 1 h), 2.21 (s, 2 H), 1.61-1.40 (m, 4 H), 1.22 (s, 2 H), 1.28-1.24 (m, 2 H), 1.04 (s, 2 H); Analytical calcd for C ₂ 7H ₂ iNO ₄ : C, 74.80; H, 7.21; N, 2.22. Found: C, 74.77; H, 7.15; N, 2.12.

Example 415 rel-(5S)-9-hydroxy-5-[(3S)-(1-methoxycarbonyl)cyclohexen-3-yl]-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H-[1]benzopyrano[3,4-f]quinoline

MS (DCI/NH3) 462 (M+H) ⁺ ;

• · • · • ·

263 *H NMR (200 MHz, DMSO-dó), δ 8.72 (s, IH), 8.04 (d, J=8.5 Hz, IH), 6.90-6.87 (m, IH), 6.67 (d, J =8.5 Hz, IH), 6.64 (d, J =8.5 Hz, IH), 6.52 (d, J=8.5 Hz, IH), 6.25-6.29 (m, IH), 5.50-5.44 (m, 2H), 4.06-4.00 (m, IH), 2.66 (s, 2H), 2.62 (s, 2H), 2.20-2.27 (m, IH), 2.182.05 (m, IH), 2.12 (s, 2H), 1.72-1.60 (m, 2H), 1.25-1.24 (m, 2H), 1.20 (s, 2H), 1.04 (s, 2H);

HRMS calcd for C28H21NO5 is 461.2202. Found: 461.2196,

Analytical calcd for C28H21NO5 0.25^O: C, 72.15; H, 6.81; N, 2.00. Found: C, 72.06; H, 7.06; N, 2.82.

Example 416

2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3,5-dichlorophenyl)-1H[1]benzopyrano[3,4-f]quinoline

MS DCI m/z 468 (M+H);

1H NMR (200 MHz, DMSO), δ 8.69 (s, IH), 7.96 (d, J=8.8 Hz, IH), 7.44 (t, J=1.8 Hz, IH), 7.17 (d, J=1.8 Hz, 2 H), 6.76 (d, J=8.4 Hz, IH), 6.70 (s, IH), 6.48 (d, J=8.8 Hz, IH). 1H), 6.28 (d, J=8.8 Hz, 1H), 6.25 (d, J=1.5 Hz, 1H), 5.41 (s, 1H), 2.57 (s, 2H), 1.82 (s, 2H), 1.25 (s, 2H), 1.14 (s, 2H); ¹³ C NMR (200 MHz, DMSO), δ 145.9, 145.2, 142.6, 142.1, 122.7, 122.0, 128.8, 127.6, 127.2, 127.1, 126.6, 118.2, 117.9, 117.2, 114.5, 112.2, 72.7, 59.0, 49.8, 29.6,

28.2, 22.2.

HRMS calcd for C26H23CIFNO3 is 467.1066. Found: 467.1064.

Example 417 (-) (5S,3'S) 2,5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(1-methylcyclohexen-3-yl)1H-[1]benzopyrano[3,4-f]quinoline MS (DCI/NH3) m/z 422 (M + H) ⁺ ;

'H NMR (300 MHz, DMSO) δ 9.55 (s, IH), 8.02 (d, J = 8.4 Hz, IH), 6.77 (app s, 2 H), 6.68 (d, J = 8.4 Hz, IH), 6.41 (br s, IH), 5.50-5.42 (m, 2 H), 4.88 (br s, IH), 2.23-2.15 (m, IH), 2.07 (br s, 3 H), 1.91-1.80 (m, 2 H), 1.76-1.63 (m, 2 H), 1.60-1.46 (m, IH), 1.50 (br s, 3 H),

1.38-1.28 (m, 1H), 1.30 (s, 3H), 1.09 (s, 3H);

¹³ C NMR (125 MHz, DMSO) δ 148.6, 145.7, 143.7, 135.8, 133.7, 132.6, 128.2, 126.8, 123.7,

120.2, 117.7, 115.9 (2), 115.3, 114.1, 112.4, 75.6, 49.5, 36.3, 29.6, 29.3, 27.5, 25.1, 24.2,

23.7, 20.2;

HRMS (FAB) calculated m/z for C26H28CINO2: 421.1809 (M) ⁺ . Found: 421.1810.

• ·

264

Example 418 (-) (5S,3'R) 2,5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(1-methylcyclohexen-3-yl)1H-[1]benzopyrano[3,4-]quinoline MS (DCI/NH3) m/z 422 (M + H) ⁺ ;

Η NMR (300 MHz, DMSO) δ 9.58 (s, 1H), 8.05 (d, J = 8.4 Hz, 1H), 6.79 (ABq, J = 8.0 Hz,

An _Als = 14.4 Hz, 2 H), 6.67 (d, J = 8.3 Hz, 1H), 6.47 (br s, 1H), 5.49-5.46 (m, 2 H), 5.35 (d, J = 8.9 Hz, 1H), 2.28-2.15 (m, 1H), 2.12 (br s, 3 H), 1.93-1.80 (m, 1H), 1.78-1.63 (m, 2H), 1.64-1.51 (m, 1H), 1.62 (br s, 3H), 1.31 (s, 3H), 1.25-1.13 (m, 2H), 1.04 (s, 3H);

¹³ C NMR (125 MHz, DMSO) δ 148.7, 145.8, 144.2, 135.1, 134.0, 132.1, 127.9, 126.7, 123.7,

121.4, 118.0, 116.0 (2), 115.4, 114.2, 112.4, 103.4, 76.4, 49.5, 37.1, 29.5, 27.2, 24.5, 23.8 (2), 21.6;

HRMS (FAB) calculated m/z for C26H28CINO2: 421.1809 (M) ⁺ . Found. 421.1816.

Example 419 (+) (5R,3'S) 2,5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(1-methylcyclohexen-3-yl)1H-[1]benzopyrano[3,4-f]quinoline [α] _D ²⁵ = +237.8 ^° (c = 0.5, CHCl ₃ ); MS (DCI/NH 3 ) m/z 422 (M + H) ⁺ ;

Ή NMR (300 MHz, DMSO) δ 9.58 (s, 1H), 8.05 (d, J = 8.4 Hz, 1H), 6.79 (ABq, J = 8.0 Hz,

Απαβ = 14.4 Hz, 2 H), 6.67 (d, J = 8.3 Hz, 1H), 6.47 (br s, 1H), 5.49-5.46 (m, 2 H), 5.35 (d, J - 8.9 Hz, 1H), 2.28-2.15 (m, 1H), 2.12 (br s, 3 H), 1.93-1.80 (m, 1H), 1.78-1.63 (m, 2H), 1.64-1.51 (m, 1H), 1.62 (br s, 3H), 1.31 (s, 3H), 1.25-1.13 (m, 2H), 1.04 (s, 3H); ¹³ CNMR(125 MHz, DMSO) δ 148.7, 145.8, 144.2, 135.1, 134.0, 132.1, 127.9, 126.7, 123.7,

121.4, 118.0, 116.0 (2), 115.4, 114.2, 112.4, 103.4, 76.4, 49.5, 37.1, 29.5, 27.2, 24.5, 23.8 (2),

21.6;

HRMS (FAB) calculated m/z for C26H28CINO2: 421.1809 (M) ⁺ . Found: 421.1806.

Example 420 (+) (5R,3R) 2,5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(1-methylcyclohexen-3-yl)1H-[1]benzopyrano[3,4-f]quinoline [a] _D ²⁵ = +147.5 ^° (c = 0.2, CHCl ₃ ); MS (DCI/NH ₃ ) m/z 422 (M + H) ⁺ ;

’Η NMR (300 MHz, DMSO) δ 9.55 (s, 1H), 8.02 (d, J = 8.4 Hz, 1H), 6.77 (app s, 2 H), 6.68 (d, J = 8.4 Hz, 1H), 6.41 (br s, 1H), 5.50-5.42 (m, 2 H), 4.88 (br s, 1H), 2.23-2.15 (m, 1H),

265 • · · · • ·· · • · · · · ·

2.07 (br s, 3 H), 1.91-1.80 (m, 2 H), 1.76-1.63 (m, 2 H), 1.60-1.46 (m, 1H), 1.50 (br s, 3 H), 1.38-1.28 (m, 1H), 1.30 (s, 3 H), 1.09 (s, 3 H);

¹³ CNMR(125 MHz, DMSO) 8 148.6; 145.7, 143.7, 135.8, 133.7, 132.6, 128.2, 126.8, 123.7,

120.2, 117.7, 115.9 (2), 115.3, 114.1, 112.4, 75.6, 49.5, 36.3, 29.6, 29.3, 27.5, 25.1, 24.2,

23.7, 20.2;

HRMS (FAB) calculated m/z for C26H28CINO2: 421.1809 (M) ⁺ . Found: 421.1794.

Example 421 (+/-) 2,5-dihydro-9-(4-N,N-dimethylamino-4-oxo-butanoyloxy)-10-chloro-2,2,4-trimethyl-5-allyl-1H-[1]benzopyrano[3,4-f]quinoline MS (ESI) m/z 495 (M+H) ⁺ ;

'H NMR (200 MHz, DMSO-dó) δ 7.90 (d, 1H), 6.99 (d, 1H), 6.92 (d, 1H), 6.64 (d, 1H), 6.42 (s, 1H), 5.81-5.76 (m, 2H), 5.48 (s, 1H), 5.07-4.94 (m, 2H), 2.99 (s, 2H), 2.84 (s, 2H), 2.822.68 (m, 4H), 2.41-2.27 (m, 2H), 2.18 (s, 2H), 1.20 (s, 2H), 1.17 (s, 2H).

Example 422 (-) 2,5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-cyclopentyl-1H-[1]benzopyrano[3,4]quinoline

MS (DCI/NH3) m/z 296(M+H) ⁺ ;

1 H NMR (400 MHz, DMSO-do) ^! H NMR (200 MHz, DMSO-dó) δ 9.50 (bs, 1H), 8.04 (s, 1H), 6.77 (d, 1H), 6.72 (d, 1H), 6.65 (d, 1H), 6.42 (d, 1H), 5.50 (s, 1H), 5.42 (d, 1H) 2.181.08 (m, 18H).

Example 423

2,5-dihydro-9-(4-N,N-dimethylamino-4-oxo-butanoyloxy)-10-methoxy-2,2,4-trimethyl 1-5-(1 methylethyl)-1 H-[ 1 ]benzopyrano[3,4-fquinoline ^r H NMR (400 MHz, DMSO-do) δ 7.92 (d, J=.8.5, 1H), 6.83 (d, J=8.5, 1H), 6.71-6.65 (m, 2H), 6.31 (d, J=1.7, 1H), 5.46 (br m, 1H), 5.37 (d, 1~.7, 1H), 3.61 (s, 3H), 3.00 (s, 3H), 2.84 (s, 3H), 2.80 (m, 2H), 2.70 (m, 2H), 2.17 (s, 3H), 1.80 (m, 1H), 1.31 (s, 3H), 1.03 (s, 3H), 0.95 (d, J=6.4, 3H), 0.65 (d, J= 6.8, 3H);

¹³ C NMR (125 MHz, DMSO-do) δ 171.5, 170.4, 149.0, 148.0, 145.6, 138.3, 133.6, 131.0,

127.9, 125.8, 120.7, 118.2, 118.2, 115.4, 113.4, 112.1, 78.0, 60.0, 49.4, 36.4, 34.9, 30.9, 29.6, • ·

266 • ····· · · · · · · · · · • · · · · · · · · »···· · · · · · · · · <

28.9, 27.6, 27.3, 23.8, 19.4, 17.8; MS (ESI/NH ₃ ) m/e 493(M+H) ⁺ , 515(M+Na) ⁺ ; HRMS calculated m/z for C 29 H 26 N 2 O 5 : 492.2624. Found: 492.2613.

Example 424

2,5-dihydro-9-(4~N,N-dimethylanuno-4-oxo-butanoyloxy)-10-methoxy-5-(phenylmethyl)2,2,4-trimethyl- 1Η-[ 1 ]benzopyrano[3,4-f]quinoline 'H NMR (500 MHz, DMSO-dg) δ 7.90 (d, >8.8, 1H), 7.29-7.26 (m, 2H). 7.21 (m, 1H), 7.09 (d, >7.0, 2H), 6.89 (d, >8.8, 1H), 6.66 (d, J =8.8, 1H), 6.60 (d, J =8.8, 1H), 6.25 (d, >1.8, 1H), 5.98 (dd, >10.1, 2.5, 1H), 5.42 (s, 1H), 2.67 (s, 2H), 2.01 (s, 2H), 2.97 (m, 1H), 2.85 (s, 2H), 2.84-2.81 (m, 2H), 2.72-2.69 (m, 2H), 2.22 (s, 2H), 1.17 (s, 2H), 1.14 (s, 2H);

¹³ C NMR (125 MHz, DMSO-d _ó ) δ 171.5, 170.4, 148.2, 148.1, 146.2, 128.4, 127.6, 122.4,

121.9, 128.9, 128.2, 127.2, 126.2, 126.2, 120.8, 118.2, 116.2, 115.2, 112.9, 112.6, 74.8, 60.1,

49.7, 28.2, 24.9, 29.2, 29.1, 28.9, 27.6, 24.2; MS (ESI/NH3) m/e 541(M+H) ⁺ , 562(M+Na) ⁺ ; Analytical calcd for C33H36N2O5: C 72.21, H 6.71, N 5.18. Found: C 72.87, H 6.97, N 4.90.

Example 425

2,5-dihydro-9-(4-N,N-dimethylamino-4-oxo-butanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2thieny 1)-1 H-[ 1 jbenzopyrano [3,4-fjquinoline *H NMR (500 MHz, DMSO-dg) δ 7.90 (d, >8.4, 1H), 7.40 (dd, >5.0, 1.3, 1H), 6.96 (s, 1H), 6.86 (m, 1H), 6.80 (m, 1H), 6.4-6.71 (m, 2H), 6.57 (d, >8.4, 1H), 6.32 (d, >1.8, 1H), 5.41 (s, 1H), 3.58 (s, 3H), 2.98 (s, 3H), 2.83 (s, 3H), 2.77-2.74 (m, 2H), 2.68-2.65 (m, 2H), 1.95 (d, >1.1, 3H), 1.23 (s, 3H), 1.15 (s, 3H); ¹³ C NMR (125 MHz, DMSO-dg) δ 171.1, 170.2,

148.6, 147.5, 146.0, 142.8, 138.4, 132.8, 130.1, 128.0, 127.2, 126.3, 126.1, 125.9, 125.8,

120.4, 118.4, 116.8, 115.8, 114.3, 112.3, 70.9, 59.5, 49.7, 36.2, 34.7, 29.5, 28.7, 28.5, 27.4, 22.8; MS (ESVNH3) m/e 533(M+H) ⁺ , 555(M+Na) ⁺ ; Analytical calcd for C20H22N2O5S: C 67.65, H 6.06, N 5.26, Found: C 67.48, H 6.16, N 5.07.

Example 426

2,5-dihydro-9-(4-N,N-dimethylaminobutanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2propenyl)-1H-[ 1 ]benzopyrano[3,4-f]quinoline 'H NMR (500 MHz, DMSO-dg) d 7.85 (d, >8.4, 1H), 6.86 (d, >8.4, 1H). 6.68-6.61 (m, 2H),

6.25 (d, >1.5, 1H), 5.86-5.78 (m, 2H), 5.46 (s, 1H), 5.06-4.98 (m, 2H), 2.61 (s, 2H), 2.62 (t,

267

99 9 9· » · · · · · · < » · · · « 99 99 9 9 >7.1, 2Η), 2.47 (m, 1H), 2.22 (t, >7.0, 2H), 2.25 (m, 1H), 2.18 (s, 2H), 2.16 (s, 6H), 1.80 (m, 2H), 1.18 (s, 2H), 1.17 (s, 2H); ¹³ C NMR (125 MHz, DMSO-d ₆ ) δ 171.8, 148.4, 147.9,

146.2, 128.5, 124.0, 122.5, 122.1, 127.2, 126.2, 120.7, 118.2, 117.2, 116.2, 115.0, 112.8,

112.6, 72.6, 59.9, 58.0, 45.1, 26.6, 21.1, 29.2, 29.0, 22.8, 22.5; MS (ESVNH3) m/e 477(M+H) ⁺ ; Analytical calcd for C29H36N2O4: C 72.08, H 7.61, N 5.88. Found: C 72.77, H 7.74, N 5.64.

Example 427

9-(2-Ethoxy-2-oxo-ethylaminocarbonyl)-oxy-10-methoxy-5-(3-propenyl)-2,2,4-trimethyl-1H2,5-dihydro-[1]benzopyrano[3,4-f]quinol in MS (DCI/NH3) δ 510 (M+NH4) ⁺ , 492 (M+H) ⁺ , 264;

’H NMR (200 MHz, DMSO-dg), δ 8.21 (t, >6.0 Hz, 1H), 7.86 (d >8.5 Hz, 1H), 6.86 (d, >8.5 Hz, 1H), 6.64 (d, >8.5 Hz, 1H), 6.62 (d, >8.5 Hz, 1H), 6.29 (d, >1.1Ηζ, 1H), 5.905.76 (m, 2H), 5.45 (br s, 1H), 5.04 (dd, >10.2, 1.8 Hz, 1H), 4.99 (dd, >17.2, 1.8 Hz, 1H), 4.12 (q, >7.0 Hz, 2H), 2.85 (d, >6.0 Hz, 2 Hz), 2.65 (s, 2 H), 2.20-2.22 (m, 2H), 2.17 (d, >1.1Hz, 2H), 1.21 (t, >7.0Hz, 2H), 1.18 (s, 2H), 1.17 (s, 2H);

Analytical calcd for C28H22N2O6: C, 68.28; H, 6.55; N, 5.69. Found: C, 67.97; H, 6.59; N, 5.62.

Example 428 (+/-) 2,5-dihydro-9-(3-acetamido-propanoyloxy)-10-methoxy-2,2,4-trimethyl-5-allyl-1H[1]benzopyrano[3,4-f]quinoline MS (APCI) m/z 477 (M+H) ⁺ ;

*H NMR (200 MHz, DMSO-dg) δ 8.04 (t, 1H), 7.85 (d, 1H), 6.90 (d, 1H), 6.68 (d, 1H), 6.64 (d, 1H), 6.26 (s, 1H), 5.87-5.77 (m, 2H), 5.46 (s, 1H), 5.04 (dd, 1H), 4.98 (dd, 1H), 2.61 (s, 2H), 2.40 (q, 2H), 2.76 (t, 2H), 2.52-2.44 (m, 1H), 2.20-2.24 (m, 1H), 2.18 (s, 2H), 1.84 (s, 2H), 1.18 (s,2H), 1.17(s,2H).

Example 429 (+/-) 2,5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-benzyl-1H-[1]benzopyrano[3,4]quinoline

MS (DCI/NH3) m/z 418(M+H) ⁺ ;

φ φ φ φ • φ » ♦ ♦ « φ · · «

9AS · ·♦· · · · ··· · · · · · ώνΟ φ <·· · * · Φ ·

ΦΦΦΦ ·Φ «Φ ΦΦ Φ ♦ · · ^! Η NMR (400 MHz, DMSO-dó) ^] Η NMR (200 MHz, DMSO-dó) δ 9.70 (bs, 1H), 7.99 (s,

1H), 7.20-7.08 (m, 5H), 6.79 (d, 1H), 6.67 (d, 1H), 6.62 (d, 1H), 6.19 (d, 1H), 5.86 (dd, 1H),

5.44 (s, 1H) 2.98-2.84 (m, 2H), 2.22 (s, 2H), 1.19 (s, 2H), 1.17 (s, 2H).

Example 430

9-Hydroxy-10-methoxy-5-(phenylmethylene)-2,2,4-trimethyl-1H-2,5-dihydro[1Jbenzopyrano[3,4-f]quinoline (DCI/NH3) 412 (M + H) ⁺ , 'H NMR (300 MHz, DMSO-dó), δ 8.93 (s, 1H), 8.13 (d, > 8.8 Hz, 1H). 7.63 (d, > 8.8 Hz, 2H), 7.32 - 7.15 (m, 3H), 6.77 (d, 1H), 6.69 (d, 1H), 6.66 (d, 1H), 6.52 (s, 1H), 5.46 (s, 1H),

5.39 (s, 1H), 3.65 (s, 3H), 1.90 (s, 3H), 1.20 (s, 6H);

HRMS calcd for _{C27H25NO3 is} 411.1834. Found: _411.1821 .

Example 431

9-(Dimethylaminothiocarbonyl)-oxy-10-methoxy-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5dihydro-[1]benzopyrano[3,4-f]quinoline

MS (DCI/NH3) 451 (M+H) ⁺ ;

¹ H NMR (200 MHz, DMSO-dó), δ 7.84 (d >8.8 Hz, 1H), 6.80 (d, >8.8 Hz, 1H), 6.65 (d, >8.8 Hz, 1H), 6.62 (d, >8.8 Hz, 1H), 6.26 (d, >1.7 Hz, 1H), 5.90-5.76 (m, 2 H), 5.46 (br s,

1H), 5.04 (dd, >10.2, 1.8 Hz, 1H), 4.98 (dd, >17.2, 1.8 Hz, 1H), 2.64 (s, 2H), 2.29 (s, 2H),

2.26 (s, 2H), 2.22-2.22 (m, 2H), 2.18 (d, >1.7 Hz, 2H), 1.18 (s, 2H), 1.16 (s, 2H);

Analytical calcd for _{C26H20N2O2S.0.5H2O :} C, _67.94 ; H, 6.79 _{; N} , 6.09. Found: C,

68.06; H, 6.80; N, 6.12.

Example 432 (+/-) 2,5-dihydro-9-(N-carbamoyl-2-aminoacetoxy)-10-methoxy-2,2,4-trimethyl-5-allyl-1H[1]benzopyrano[3,4-f]quinoline MS (APCI) m/z 464 (M+H) ⁺ ;

^X H NMR (200 MHz, DMSO-dó) δ 7.78 (d, 1H), 6.79 (d, 1H), 6.60 (d, 1H), 6.57 (d, 1H), 6.27 (t, 1H), 6.18 (bs, 1H), 5.80-5.70 (m, 2H), 5.67 (s, 2H), 5.28 (s, 1H), 4.97 (dd, 1H), 4.92 (dd,

1H), 4.01 (d, 2H), 2.55 (s, 2H), 2.42-2.27 (m, 1H), 2.22-2.16 (m, 1H), 2.10 (s, 2H), 1.11 (s,

2H), 1.10 (s,2H).

269 • · · · ·

Example 433 (+/-) 2,5-dihydro-9-(4-ethoxy-4-oxo-butoxy)-10-methoxy-2,2,4-trimethyl-5-allyl-1H[ 1 ]benzopyrano[3,4-fquinoline ¹ H NMR (200 MHz, DMSO-dé) δ 7.92 (d, 1H, J=8Hz), 6.79 (d, 1H), 6.62 (d, 1H, J=8Hz), 6.58 (d, 1H, J=8Hz), 6.18 (d, 1H, >2Hz), 5.82 (m, 1H), 5.72 (dd, 1H, J=2Hz, J=9Hz) 5.45 (s, 1H), 5.05-4.97 (m, 2H), 4.08 (q, 2H, J=5Hz), 4.02-2.91 (m, 2H), 2.70 (s, 2H), 2.50 (t, 2H, J=5Hz), 2.45 (m, 1H), 2.21 (m, 1H), 2.16 (s, 2H), 2.00 (chin, 2H, J=5Hz), 1.19 (t, 2H, J=5Hz), 1.17 (s, 6H).

Example 434 (+/-) 2,5-dihydro-9-(4-oxo-pentanoyloxy)-10-methoxy-2,2,4-trimethyl-5-allyl-1H[1]benzopyrano[3,4-f]quinoline MS (APCI) m/z 462 (M+H) ⁺ ;

1H NMR (200 MHz, DMSO-d ₆ ) δ 7.78 (d, 1H), 6.77 (d, 1H), 6.59 (d, 1H), 6.57 (d, 1H), 6.18 (s, 1H), 5.80-5.68 (m, 2H), 5.28 (s, 1H), 4.96 (dd, 1H), 4.92 (dd, 1H), 2.54 (s, 2H), 2.79 (dd, 2H), 2.70 (dd, 2H), 2.41-2.16 (m, 2H), 2.10 (s, 2H), 2.09 (s, 2H), 1.11 (s, 2H), 1.10 (s, 2H).

Example 435

2.5-Dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(3,4,5-trifluorophenyl)-1H[1]benzopyrano[3,4-fquinoline 'H NMR δ 9.20 (s, 1H), 7.91 (d, 1H, J=8.5Hz), 6.92 (m, 2H), 6.88 (m, 2H), 6.57 (d, 1H, J=8.5Hz), 6.28 (m, 1H), 5.45 (m, 1H), 1.81 (s, 2H), 1.29 (s, 2H), 1.09 (s, 2H); MS (DCI) m/z: 458 (M+-1); Calculated for C25H19CIF2NO2: 457.1056. Found: 457.1054.

Example 436

2.5-Dihydro-9-methylthiomethoxy-10-methoxy-2,2,4-trimethyl-5-allyl-1H[1]benzopyrano[3,4-fquinoline

MS (DCI/NH ₃ ) m/z 424(M+H) ⁺ ;

*H NMR (400 MHz, DMSO-dr,) 7.92(d, 1H), 6.88(d, 1H), 6.62(d, 1H), 6.60(d, 1H), 6.20(s, 1H), 5.81(m, 1H), 5.74(dd, 1H), 5.45(s, 1H), 5.24(s, 1H), 5.02(d, 1H), 4.99(d, 1H), 2.70(s, 2H), 2.45 (m, 2H), 2.22(s, 2H), 2.18(s, 2H), 1.18(s, 2H), 1.17(s, 2H).

Example 437

270 ·· ·♦ » · * * ) · · 9

I» · · * ř · · · · · ·

2.5-dihydro-9-(4-N,N-diethylamino-4-oxo-pentaoyloxy)-10-methoxy-2,2 _? 4-trimethyl-5-(2propenyl)-1H-[1]benzopyrano[3,4-f]quinoline 'Η NMR (400 MHz, DMSO-dg) δ 7.84 (d,J =8.5, 1H), 6.88 (d, >8.9, 1H), 6.68-6.62 (m, 2H),

6.26 (br s, 1H), 5.85-5.77 (m, 2H), 5.45 (br s, 1H), 5.05-4.97 (m, 2H), 3.60 (s, 3H), 3.34-3.21 (m, 4H), 2.65 (t,J =7.4, 2H), 2.45-2.41 (m, 3H), 2.27 (m, 1H), 2.17 (s, 3H), 1.90 (m, 2H),

1.18 (s, 3H), 1.17 (s, 3H), 1.12 (t, >7.0, 3H), 1.02 (t, >7.2, 3H); ¹³ C NMR (100 MHz, DMSO-de) δ 171.7, 170.3, 148.4, 147.9, 146.3, 138.4, 134.0, 133.5, 132.1, 127.3, 126.1,

120.7, 118.2, 117.2, 116.2, 114.9, 113.8, 112.6, 73.6, 59.9, 49.8, 41.2, 36.6, 32.7, 30.9, 29.3, 29.0, 23.8, 20.4, 14.2, 13.1; MS (ESI/NH ₂ ) m/e 533(M+H) ⁺ , 555 (M+Na) ⁺ ; Analytical calcd for C ₂₂ H 40 N ₂ Os: C 72.15, H 7.57, N 5.26. Found: C 72.16, H 7.76, N 5.06.

Example 438

2.5-Dihydro-9-(4-N,N-dimethylamino-4-oxo-pentanoyloxy)-10-methoxy-2,2,4-trimethyl-5(2-propenyl)-1H-[ 1 ]benzopyrano[3,4-f]quinoline ³ H NMR (400 MHz, DMSO-dg) δ 7.77 (d, >8.5, 1H), 6.81 (d, >8.9, 1H), 6.61-6.56 (m, 2H),

6.19 (d, >1.7, 1H), 5.80-5.70 (m, 2H), 5.28 (s, 1H), 4.98-4.90 (m, 2H), 2.71 (s, 2H), 2.90 (s, 2H), 2.76 (s, 2H), 2.58 (t, >7.4, 2H), 2.28-2.25 (m, 2H), 2.20 (m, 1H), 2.10 (s, 2H), 1.84 (m, 2H), 1.11 (s, 2H), 1.10 (s, 2H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 171.7, 171.2, 148.4, 147.9,

146.2, 128.4, 124.1, 122.5, 122.1, 127.2, 126.2, 120.7, 118.2, 117.2, 116.2, 114.9, 112.8,

112.6, 72.6, 59.9, 49.8, 26.6, 24.8, 22.8, 21.2, 29.2, 29.0, 22.8, 20.2; MS (ESI/NH3) m/e 505 (M+H) ⁺ , 527(M+Na) ⁺ ; Analytical calcd for C30H36N2O5 _. C 71.40, H 7.19, N 5.55. Found: C 71.20, H 7.19, N 5.29.

Example 439

2,5-dihydro-9-(4-N-piperidino-4-oxo-pentanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2propenyl)- 1H~[ l]benzopyrano[3,4-fjquinoline ¹ H NMR (400 MHz, DMSO-dg) δ 7.78 (d, >8.9, 1H), 6.81 (d, >8.5, 1H). 6.61-6.55 (m, 2H),

6.19 (d, >1.7, 1H), 5.80-5.70 (m, 2H), 5.28 (s, 1H), 4.98-4.90 (m, 2H), 2.52 (s, 2H), 2.25 (m, 4H), 2.58 (t, >7.2, 2H), 2.29-2.25 (m, 2H), 2.20 (m, 1H), 2.10 (s, 2H), 1.82 (m, 2H), 1.11 (m, 2H), 1.42 (m, 2H), 1.26 (m, 2H), 1.11 (s, 2H), 1.10 (s, 2H); ¹³ C NMR (100 MHz, DMSOd ₆ ) δ 171.7, 169.6, 148.4, 147.9, 146.2, 128.4, 124.0, 122.5, 122.1, 127.2, 126.1, 120.7,

118.2, 117.2, 116.2, 114.9, 112.8, 112.6, 72.6, 59.9, 49.8, 45.8, 41.9, 26.6, 22.8, ,21.2, 29.2,

29.0, 26.0, 25.2, 24.0, 22.8, 20.4; MS (ESI/NH3) m/e 545 (M+H) ⁺ , 567(M+Na) ⁺ ; Analytical calcd for C 13 R 2 R 3 : C 72.77, H 7.40, N 5.14. Found: C 72.50, H 7.42, N 4.99.

Example 440

2,5-dihydro-9-(4-N-morpholino-4-oxo-pentanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2propenyl)-1H-[1]benzopyrano[3,4-fquinoline *H NMR (400 MHz, DMSO-dg) δ 7.77 (d, J =8.5, 1H), 6.81 (d, >8.5, 1H). 6.61-6.56 (m, 2H),

6.19 (s, 1H), 5.78-5.70 (m, 2H), 5.28 (s, 1H), 4.98-4.90 (m, 2H), 2.52 (s, 2H), 2.50 (m, 4H), 2.29 (t, >4.7, 4H), 2.59 (t, >7.4, 2H), 2.41-2.27 (m, 2H), 220 (m, 1H), 2.10 (s, 2H), 1.82 (m, 2H), 1.11 (s, 2H), 1.10 (s, 2H); ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 171.6, 170.2, 148.4, 147.9,

146.2, 128.4, 124.0, 122.5, 122.1, 127.2, 126.1, 120.7, 118.2, 117.2, 116.2, 114.9, 112.8,

112.6, 72.6, 66.1, 60.0, 49.8, 45.2, 41.4, 26.6, 22.7, 21.0, 29.2, 29.0, 22.8, 20.2; MS (ESI/NH3) m/e 547(M+H) ⁺ , 569(M+Na) ⁺ ; Analytical calcd for C32H38N2O6: C 70.21, H 7.01, N 5.12. Found: C 69.99, H 7.06, N 4.91.

Example 441 (-) 2,5-dihydro-9-(4-N,N-dimethylamino-4-oxo-butanoyloxy)-10-methoxy-2,2,4-trimethyl-5(S)-(3(S)-1-cyclopenten-3-yl)-1H-[1]benzopyrano[3,4-f]quinoline MS (APCI) m/z 517 (M+H) ⁺ ;

’H NMR (200 MHz, DMSO-cL) δ 7.94 (d, 1H), 6.84 (d, 1H), 6.69 (d, 1H), 6.67 (d, 1H), 6.22 (s, 1H), 5.75 (dd, 1H), 5.52 (d, 1H), 5.42 (s, 1H), 5.17 (dd, 1H), 2.62 (s, 2H), 2.99 (s, 2H), 2.90-2.85 (m, 1H), 2.84 (s, 2H), 2.80 (t, 2H), 2.68 (t, 2H), 2.29-2.21 (m, 1H), 2.25-2.12 (m, 1H), 2.08 (s, 2H), 1.92-1.74 (m, 2H), 1.20 (s, 2H), 1.08 (s, 2H).

Example 442

10-Methoxy-9-(allylaminocarbonyl)oxy-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-quinoline

MS (DCI/NH 3 ) 464 (M+NR) ⁺ , 447 (M+H) ⁺ , 264.

^X H NMR (200 MHz, DMSO-cL), δ 7.96 (t, >5.9 Hz, 1H), 7.86 (d,J =8.5 Hz, 1H), 6.86 (d, >8.5 Hz, 1H), 6.62 (d, >8.5 Hz, 2H), 6.28 (d, >1.5 Hz, 1H), 5.90-5.76 (m, 2 H), 5.45 (br s, i H), 5.27-4.97 (m, 4 H), 2.71 (m, 1H), 2.64 (s, 2 H), 2.41-2.22 (m, 2 H), 2.17 (d, >1.5 Hz, 2 H), 1.18 (s, 2 H), 1.17 (s, 2 H);

φ φ φ φ φ φ φ φ φ φ φ

272

ΦΦ ·* φφ φφ • φ φ φ ♦ ♦ · · φ φ φ φ φ φ · • φφφφφ φ φφφ • φφφφ • ΦΦΦ ·Φ φφ · φ φφ φφ

Analytical calcd for C27H20N2O4.0.25H2O: C, 71.89; H, 6.81; N, 6.21. Found: C, 72.18; H, 7.08; N, 5.98.

Example 443

10-Methoxy-9-(cyclohexylaminocarbonyl)-oxy-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5dihydro- [ 1 jbenzopyrano [3,4-fj quinoline MS (DCI/NH 3 ) 506 (M+NH ₄ ) ⁺ , 489 (M+H) ⁺ , 264.

1H NMR (200 MHz, DMSO-d ₆ ), δ 7.86 (d J=8.8 Hz, 1H), 7.67 (d, J =7.8 Hz, 1H), 6.84 (d, J=8.8 Hz, 1H), 6.62 (d, J=8.8 Hz, 1H), 6.61 (d, J=8.8 Hz, 1H), 6.25 (d, J=1.0 Hz, 1H), 5.905.76 (m, 2 H), 5.45 (br s, 1H), 5.04 (dd, J=10.2, 1.8 Hz, 1H), 4.99 (dd, J=17.2, 1.8 Hz, 1H), 4.02 (br s, 1H), 2.62 (s, 2 H), 2.20-2.22 (m, 2 H), 2.17 (d, J=1.0 Hz, 2 H), 1.86-1.52 (m, 5 H), 1.21-1.22 (m, 5 H), 1.18 (s, 2 H), 1.17 (s, 2 H); HRMS calcd for C20H26N2O is 488.2675. Found: 488.2670.

Example 444

2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-thienyl)-1 H-[ 1 jbenzopyrano[3,4fjquinoline *H NMR (300 MHz, DMSO-d ₆ ) δ 8.57 (s, 1H), 7.91 (d, J = 9 Hz, 1H), 7.35 (dd, J = 5, 5 Hz, 1H), 6.99 (d, J = 5 Hz, 1H), 6.92 (s, 1H), 6.68 (d, J = 9 Hz, 1H), 6.64 (s, 1H), 6.44 (d, J = 9 Hz, 1H), 6.34 (d, 1 = 9 Hz, 1H), 6.21 (s, 1H), 5.38 (s, 1H), 3.57 (s, 3H), 1.87 (s, 3H), 1.23 (s, 3H), 1.13 (s, 3H); ^,3 C NMR (125 MHz, DMSO-d ₆ ) δ 183.2, 182.4, 181.4, 181.1, 170.3,

168.8, 165.3, 165.2, 164.1, 163.1, 163.5, 163.4, 162.6, 155.8, 154.7, 151.6, 149.6, 108.9,

96.6, 87.3, 67.3, 66.0, 60.6; MS (DCl/NH 3 ) (M+H) ⁺ 406.

Example 445

2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(4-(fluorophenyl)methyl)-1H[ 1 jbenzopyrano[3,4-fquinoline *H NMR (300 MHz, DMSO-d ₆ ) δ 8.47 (s, 1H), 7.94 (d, J = 8 Hz, 1H), 7.33-7.31 (m, 1H). 7.13-7.04 (m, 3H), 6.62 (dd, J = 9, 8 Hz, 2H), 6.41 (d, J = 9 Hz, 1H), 6.41 (s, 1H), 5.82 (dd, J = 10, 9 Hz, 1H), 5.40 (s, 1H), 3.69 (s, 3H), 3.01-2.93 (m, 1H), 2.81-2.76 (m, 1H), 2.20 (s, 1H), 1.15 (s, 3H), 1.13 (s, 3H); ¹³ C NMR (75 MHz, DMSO-d ₆ ) δ 162.5, 159.2, 145.8, 145.1, 144.0, 142.8, 134.1, 133.4, 132.2, 130.8, 130.7, 127.4, 126.4, 117.9, 116.4, 116.2, 115.0, 1

14.7, 114.4, 113.8, 112.5, 74.4, 59.5, 49.7, 37.1, 29.2, 29.0, 24.3;

MS calcd for C27H26O3NF: m/e 431.1897. Found: 431.1905;

Analysis calculated for _{C27H26O3NF.0.30H2O} : C, _74.23 ; H, 6.14; N, 3.21; Found: C, 74.16; H, 6.44; N, 2.96.

Claims (36)

00 00 anti(5R, 2'S) 2,5-dihydro-10-methoxy-5-(2-oxo-3-tetrahydropyranyl)-2,2,4-trimethyl-1H[ 1 ]benzopyrano[3,4-f]quinoline, 00 00 • 0 00 0 * 0 0 0 0 0 0 0 0 0 0 0 0 0 «000 00 325 • 0 »0 0 0 0 0 0 0 0 0 · 0 0 0 * 0 • 0 0 00 ·0 :::: 0 0 0 · 0 0 0 0 • 0 00 00 00 00 90 0 0 0 0 0 0 0 0 0 0 0 0 0 PATENT CLAIMS 1-(3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f)quinolin-5-yl)-5methylphenylethanone, 1-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1Η-[ 1 ]benzopyrano[3,4-f]quinolin-5-yl)-2propanone, methyl 2,5-dihydro-10-methoxy-2,2,4-trimethyl-1Η-[ 1 ]benzopyrano[3,4-f]quinolin-5-acetate, 1-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolin-5-yl)-3,3dimethyl-2-butanone, 1 -[3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolin-5-yl)-5methylphenylethanone, • 0 · · • · 0 0 • * · • · ·· · • · • · · · · · 294 ·· 1-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolin-5-yl)-2propanone, methyl 2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolin-5-acetate, 1-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1Η- [ 1 ]benzopyrano[3,4-fJquinolin-5-yl)-3,3 dimethyl-2-butanone, 1». (1) -NR ₇ NR _X -, (m) -co ₂ r/ (n) -CmNR ₈ R ₉ · (0) =NA)Rio, (P) from Rio, (q) _/ /-S(0)tRio, ω/ -X'C(X)R ₁₀ , —(ξΧΧ(t) -O-(CH ₂ ) _q -Z-R 10 , (u) -OC(X)NR 8 -R ₉ , (v) -L b R 50 , (w) alkanoyloxy groups, where the alkyl group has one to twelve carbon atoms, (x) -OSO 2 R 11 , and (y) -NR ₇ (X)NR 8 R ₉ ; the substituent Rg is a hydrogen atom or an alkyl having one to twelve carbon atoms; or -L2-R5 and Rg together are selected from (1) =0, 1. A compound having formula I or pharmaceutically acceptable salts or prodrugs thereof, wherein the substituent R1 is -Lj-Ra, wherein Li is selected from (1) a covalent bond, (2) -O-, (3) -S(O)t-, wherein the index t is 0, 1 or 2, (4) -C(X)-, (5) -NR7-, wherein the substituent R7 is selected from (a) hydrogen, (b) aryl, (c) cycloalkyl having three to twelve carbon atoms, (d) alkanoyl wherein the alkyl moiety has one to twelve carbon atoms, (e) alkoxycarbonyl wherein the alkyl moiety has one to twelve carbon atoms, (f) alkoxycarbonyl wherein the alkyl moiety has one to twelve carbon atoms and is substituted with 1 or 2 aryl groups, (g) alkyl having one to twelve carbon atoms, (h) alkyl having one to twelve carbon atoms substituted with 1 or 2 substituents independently selected from (i) aryl and (ii) cycloalkyl having three to twelve carbon atoms, (i) alkenyl having three to twelve carbon atoms, with the proviso that the carbon of the carbon-carbon double bond is not directly attached to the nitrogen, * 9 274 • 999 • · 9 · · · • · · · 9 • 9 9 9 9 9 • «···« ·· · • · 9 9 9 9 9 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(4-(fluorophenyl)methyl)-1H[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-thienyl)-1H-[1Jbenzopyrano[3,4fquinoline, and 2.5-Dihydro-9-(4-N-morpholino-4-oxo-pentanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2propenyl)-1 H-[ 1 Jbenzopyrano[3,4-fquinoline, (-) 2,5-dihydro-9-(4-N,N-dimethylamino-4-oxo-butanoyloxy)-10-methoxy-2,2,4-trimethyl 15(S)-(3(S)-1 -cyclopenten-3-yl)-1Η-[ 1 ]benzopyrano[3,4-f]quinoline, 10-methoxy-9-(allylaminocarbonyl)oxy-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro[ 1 ]benzopyrano[3,4-f]quinoline, 2.5-Dihydro-9-(4-N-piperidino-4-oxo-pentanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2propenyl)-1H-[1Jbenzopyrano[3,4-fquinoline, 2.5-Dihydro-9-(4-N,N-dimethylamino-4-oxo-pentanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2propenyl)-1Η-[1]benzopyrano[3,4-f|quinoline, 2.5-Dihydro-9-(4-N,N-diethylamino-4-oxo-pentanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2-propenyl)-1H-[1Jbenzopyrano[3,4-fJquinoline, 2.5-dihydro-9-methylthiomethoxy-10-methoxy-2,2,4-trimethyl-5-allyl-1H[1]benzopyrano[3,4-f| quinoline, 2.5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-[3,4,5-trifluorophenyl)-1H[1]benzopyrano[3,4-f]quinoline, 2.5-Dihydro-9-(4-N,N-dimethylaminobutanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2propenyl)-1Η-[1]benzopyrano[3,4-f]quinoline, 2.5-Dihydro-9-(4-N,N-dimethylamino-4-oxo-butanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2thienyl)-1Η-[1]benzopyrano[3,4-f]quinoline, 2,5-dihydro-9-(4-N,N-dimethylamino-4-oxo-butanoyloxy)-10-methoxy-5-(phenylmethyl)2,2,4-trimethyl-1H-[1]benzopyrano[3,4-fquinoline, 2.5-Dihydro-9-(4-N,N-dimethylamino-4-oxo-butanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(1methylethyl)-1H-[1]benzopyrano[3,4-fquinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3,5-dichlorophenyl)-1H[ 1 Jbenzopyrano [3,4-fJquinoline, ♦ · • · φ • 999 9 2.5-Dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-propyl-1H-[1]benzopyrano[3,4-f)quinoline, 9-hydroxy-10-methoxy-5-([3~fluorophenyl]methylene)-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-f]quinoline, 2.5-Dihydro-9-hydroxymethyl-10-chloro-2,2,4-trimethyl-5-allyl-1H-[1Jbenzopyrano[3,4fJquinoline, 2.5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(2-methylpropyl)-1H-[1]benzopyrano[3,4fjquinoline, 2.5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(1-thiazol-2-yl)-1Η-[1]benzopyrano[3,4fquinoline, 2.5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-butyl-1H-[1]benzopyrano[3,4-f]quinoline, 2.5-Dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-isopropyl-1Η-[1Jbenzopyrano[3,4fjquinoline, 2.5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-ethyl-1Η-[1]benzopyrano[3,4-fJquinoline, 2.5-Dihydro-9-N,N-dimethylcarbamoyloxy-10-methoxy-2,2,4-trimethyl-5-([2-N,Ndimethylcarbamoyloxyphenyl)-1Η-[1]benzopyrano[3,4-fJquinoline, 2.5- dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-([2-N,N-dimethylcarbamoyloxyJphenyl)1 Η- [ 1 ]benzopyrano[3,4-fJquinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-(methylthiomethoxy)phenyl-1H[1Jbenzopyrano[3,4-fJquinoline, 2.5-Dihydro-9-methylthiomethoxy-10-methoxy-2,2,4-trimethyl-5-(3(methylthio)methoxyphenyl)-1H-[1]benzopyrano[3,4-f]quinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-hydroxyphenyl)-1H[1]benzopyrano[3,4-quinoline, 340 2.5-dihydro-7-bromo-9-hydroxy-10-chloro-2,2,4-trimethyl-5-allyl-1Η-[1jbenzopyrano[3,4fjquinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-acetoxyphenyl)-1H[1jbenzopyrano[3,4-fjquinoline, 2.5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-(Z-pentenyl)-1H[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-allenyl-1H-[ljbenzopyrano[3,4fjquinoline, (-) (5S,3'S) 2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-(cyclopenten-3-yl)-1H[ 1jbenzopyrano[3,4fjquinoline, (-)-(5S,3'S) 2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-(cyclohexen-3-yl)-1H[1]benzopyrano[3,4-fquinoline,, (-) (5S, 3'R) 2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-(cyclohexen-3-yl)-1H[ 1 ]benzopyrano[3,4-fquinoline, (-) (5S, 3'R) 3'R) 2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-(cyclopenten-3-yl)-1H[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-9-methylcarboxylate-10-methoxy-2,2,4-trimethyl-5-allyl-1Η-[1jbenzopyrano[3,4fjquinoline, 2.5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(1-pentenyl)-1Η-[1jbenzopyrano[3,4fjquinoline, 2.5-Dihydro-9-hydroxymethyl-10-methoxy-2,2,4-trimethyl-5-allyl-1Η-[1]benzopyrano[3,4fjquinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-((2-fluorophenyl)methyl)-1H[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-cyclopentyl-1H-[1]benzopyrano[3,4l]quinoline, 2.5-dihydroxy-9-hydroxy-10-chloro-2,2,4-trimethyl 1-5-(2-thienyl)-1H-[1]benzopyrano[3,4fquinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-5-difluorophenylmethyl)-1H[ 1 jbenzopyrano[3,4-fquinoline, φφ • φ φ • · • · • · • φ φ • φφ · · 339 •··· φ φ ·· φφ φφ φφφ φ φφφ · • φφφ φ · • · φ φ ·· φφ φ* 2.5-Dihydro-9-(4-N,N-dimethylamino-4-oxo-butanoyloxy)-10-methoxy-2,2,4-trimethyl-5(3,4,5-trifluorophenyl)-1H-[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-9-(4-N-morpholino-4-oxo-butanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2propenyl)-1H-[1jbenzopyrano[3,4-fquinoline, 2.5-Dihydro-9-(4-N-piperidino-4-oxo-butanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2propenyl)-1Η-[1jbenzopyrano[3,4-fquinoline, 2.5-Dihydro-9-(4-N,N-diethylamino-4-oxo-butanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2propenyl)-1 Η- [ 1 jbenzopyrano [3,4-fquinoline, 2.5-Dihydro-10-methoxy-2,2,3-trimethyl-5-allyl-1Η-[1Jbenzopyrano[3,4-fquinoline, Z 5-(benzylideneyl)-9-hydroxy-10-methoxy-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-x]quinoline, Z 5-(2,5-difluorobenzylideneyl)-9-hydroxy-10-methoxy-2,2,4-trimethyl-1H-2,5-dihydro[ 1 ]benzopyrano[3,4-fjquinoline, φφ φφ ' φ φ φ • φ · φ φφφφ « · • · • · 338 From 5-(3-fluorobenzylideneyl)-10-chloro-9-hydroxy-2,2,4-trimethyl-2,5-dihydro-1H[ 1 ]benzopyrano[3,4-quinoline, Z-10-chloro-9-hydroxy-5-(2-picolinylideneyl)-2,2,4-trimethyl-2,5-dihydro-1H[ 1 jbenzopyrano [3,4-fquinoline, From 9-hydroxy-10-methoxy-5-(2-picolinylideneyl)-2,2,4-trimethyl-2,5-dihydro-1H[ 1 jbenzopyrano [3,4-fquinoline, 2.5-Dihydro-10-methoxy-2,2-dimethyl-4-ethyl-5-allyl-1H-[1Jbenzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-2,2,3,4-tetramethyl-5-αHyl-1H-[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-2,2-diethyl-4-methyl-5-allyl-1H-[1]benzopyrano[3,4-quinoline, 2.5-dihydro-10-methoxy-2,2-[spiro(hexyl)]-5-allyl-1Η-[1]benzopyrano[3,4-fquinoline, 2.5-Dihydro-10-methoxy-2,2-[spiro(tetrahydro-4-pyranyl)-4-methyl-5-allyl-1H[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-phenyl-1H-[1Jbenzopyrano[3,4-quinazoline, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-3-oxide-5-phenyl-1Η-[1Jbenzopyrano[3,4-fquinazoline, 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-((2-fluorophenyl)methyl)-1H[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-5-(3-propenyl)-10-methylthio-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline, (+/-) 2,5-dihydro-9-(4-acetamidobutanoyloxy)-10-methoxy-2,2,4-trimethyl-5-allyl-1H[1]benzopyrano[3,4-f|quinoline, 2.5-dihydro-5-(3-propenyl)-10-methylthio-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f|quinoline, 2.5-Dihydro-10-ethenyl-5-[1-methyl-3-cyclohexenyl]-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline, 2.5- dihydro-10-ethenyl-5-oxo-2,2,4-trimethyl-NH-[1]benzopyrano[3,4-f]quinoline, 2.5-Dihydro-10-(methoxymethyl)-5-phenyl-2,2,4-trimethyl-1 Η- [ 1 jbenzopyrano[3,4-fquinoline, 2.5-Dihydro-10-formyl-5-phenyl-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-10-(hydroxymethyl)-5-phenyl-2,2,4-trimethyl-1Η-[1jbenzopyrano[3,4-fquinoline, 2.5-Dihydro-10-ethynyl-5-phenyl-2,2,4-trimethyl-1H-[1jbenzopyrano[3,4-fquinoline, methyl 2,5-dihydro-5-phenyl-2,2,4-trimethyl-1H-[l]benzopyrano[3,4-f)quinoline-10-carboxylate, 2.5-dihydro-10-ethenyl-5-phenyl-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-x]quinoline, 2.5-Dihydro-10-methoxymethyl-5-(3-propenyl)-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4fquinoline, 2.5-dihydro-10-aminomethyl-5-(3-propenyl)-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4fjquinoline, 2.5-dihydro-10-formyl-5-(3-propenyl)-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4-f]quinoline, 2.5-Dihydro-10-(2-hydroxymethyl)-5-(3-propenyl)-2,2,4-trimethyl 1-1H-[1jbenzopyrano[3,4fjquinoline, 2.5-Dihydro-10-carboxy-5-(3-propenyl)-2,2,4-trimethyl-1H-[1jbenzopyrano[3,4-quinoline, 2.5-Dihydro-10-cyano-5-(3-propenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-10-(2-furanyl)-5-(3-propenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-5-(2-methylpropenyl)-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4fjquinoline, trans 2,5-dihydro-10-methoxy-5-(1-cyclohexenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fjquinoline, 2.5-Dihydro-10-methoxy-5-(2-phenylethynyl)-2,2,4-trimethyl-1Η-[ 1Jbenzopyrano[3,4fjquinoline, • ·· · · 336 ·« ·· • · · · • · ♦ » • · · · • · · · ·· ·· cis 2,5-dihydro-10-methoxy-5-(2-phenylethenyl)-2,2,4-trimethyl- 1Η-[ 1 jbenzopyrano [3,4fjquinoline, 2.5-dihydro-10-methoxy-5-ethenyl-2,2,4-trimethyl-1Η-[ I ]benzopyrano[3,4-fquinoline, trans 2,5-dihydro-10-methoxy-5-(2-phenylethenyl)-2,2,4-trimethyl-1Η-[ 1 ]benzopyrano[3,4fquinoline, 2.5-Dihydro-10-methoxy-5-cyclopropyl-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-5-(3-(2-(N,N-dimethylamino)ethyl)phenyl)-2,2,4-trimethyl-1H[ 1 Jbenzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-5-(3-(2-(N,N-dimethylaminocarbonyloxy)ethyl)phenyl)-2,2,4trimethyl-1H-[1Jbenzopyrano[3,4-quinoline, 2.5-dihydro-10-methoxy-5-(3-(2-methylthioethyl)phenyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline, 2.5-Dihydro-10-methoxy-5-(3-(2-methanesulfonyloxyethyl)phenyl)-2,2,4-trimethyl-1H[ 1 Jbenzopyrano[3,4-fj quinoline, 2.5-dihydro-10-methoxy-5-(3-(2-hydroxyethyl)phenyl)-2,2,4-trimethyl-1H[1Jbenzopyrano[3,4-f]quinoline, 2.5-Dihydro-10~methoxy-5-(3-(N-methylaminocarbonyloxy)phenyl)-2,2,4-trimethyl-1H[1 Jbenzopyrano[3,4-quinoline, 2,5-Dihydro-10-methoxy-5-(3-(N-methyl-N-(N-methylcarbonyl)aminocarbonyloxy)phenyl)2.2.4-trimethyl-1H-[ljbenzopyrano[3,4-fquinoline, 2.5- dihydro-10-methoxy-5-(3-(N-methyl-N-(carbomethoxymethyl)aminocarbonyloxy)phenyl)2.2.4- trimethyl-1H[ 1Jbenzopyrano[3,4-fquinoline, 2.5-Dihydro-9-(4-N,N-dimethylamino-4-oxo-butanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2-propenyl)-1H-[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-9-acetoxy-10-methoxy-2,2,4-trimethyl-5~(2-propenyl)-1H[ljbenzopyrano[3,4fjquinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2-methyl-3-propenyl)-1H[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-methyl-2-butenyl)-1H[1]benzopyrano[3,4-quinoline, (+)(5S,3'S) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cyclohexenyl)-1H[1 Jbenzopyrano[3,4-fJquinoline, (+) (5R,3'R) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cyclohexenyl)-1H[ 1 Jbenzopyrano j3,4-fJquinoline, (+) (5R,3'S) 2,5(R)-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cyclopentenyl)-1H[ 1 ]benzopyrano[3,4-f]quinoline, (+) (5R,3'R) 2,5(R)-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cyclopentenyl)-1 H[ 1 ]benzopyrano[3,4-f]quinoline, rel-(5 S )-9-hydroxy-5-[(3R)-( 1 -methoxycarbonylcyclohexen-3-yl N-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1Η-[1]benzopyrano[3,4-fquinoline, 0 0 • 0 0 · 334 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2-hydroxymethyl-3-propenyl)-1H[1Jbenzopyrano[3,4-fjquinoline, methyl 2-[2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-1H[1Jbenzopyrano[3,4-fJ-quinolinyl]acetate, (Z) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2-butenyl)-1H[1]benzopyrano[3,4-f]quinoline, 2.5.5-trihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-quinoline, 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-cyclohexy i-1H-[1]benzopyrano[3,4fjquinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2-acetoxymethyl-3-propenyl)-1H[ 1 Jbenzopyrano[3,4-fquinoline, (+) (5R,3'S) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-[1-ethyl-3-cyclohexenyl]1Η-[ 1 jbenzopyrano[3,4-f]quinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2-thienyl)-1H-[1Jbenzopyrano[3,4fquinoline, (±) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2-methylphenyl)-1H[1]benzopyrano[3,4fquinoline, 2.5- dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(5-methoxy-2-thienyl)-1H[ 1 ]benzopyrano[3,4-fquinoline, (±) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2,3,4,5,6-pentafluorophenyl)-1H[ 1 jbenzopyrano[3,4-fjquinoline, (+/-) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5(S)-(3(S)-lhydroxymethylcyclopenten-3-yl)- 1H-[1 jbenzopyrano[3,4-fjquinoline, (+/-) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5(S)-(3 (S)-1methylcarboxylate cyclopenten-3-yl)-1H-[1jbenzopyrano[3,4-quinoline, 333 .......... 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2-propyl)-1H-[ljbenzopyrano[3,4fjquinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-5-(3-propynyl)-2,2,4-trimethyl-1Η-[1jbenzopyrano[3,4fjquinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-5-(phenylmethyl)-2,2,4-trimethyl-1H-[ljbenzopyrano[3,4fquinoline, (-) (5 S,3*R) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-[ 1 -ethyl-3-cyclohexenyl j1 H-[ 1 jbenzopyrano[3,4-fquinoline, (-) (S) 5-cyclopentyl-2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-1H[ 1 jbenzopyrano[3,4-fjquinoline, (+) (R) 5-cyclopentyl-2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-1H[ 1 jbenzopyrano[3,4-fjquinoline, 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-butenyl)-1H-[1jbenzopyrano[3,4fjquinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-fluoro-4-chlorophenyl)-1H[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2-methylpropyl)-1H[1jbenzopyrano[3,4-quinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-trifluoromethyl-4-chlorophenyl)-1H[1]benzopyrano[3,4-quinoline, 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-5-bisdifluoromethylphenyl)-1H[1]benzopyrano[3,4-fquinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-trifluoromethylphenyl)-1H[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(4-fluorophenyl)-1Η-[1]benzopyrano[3,4fjquinoline, 2.5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-[3,4-difluorophenyl]-1H[ 1 ]benzopyrano[3,4-fquinoline, ·· ·· • · · · • · · · • φ · · 332 • · ·· 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3,4,5-trifluorophenyl)-1H[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3,5-difluorophenyl)-1H[ 1 Jbenzopyrano[3,4-f]quinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano[3,4fquinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-5-propyl-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline, (-) (5S,3'S) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cycloheptenyl)-1H[ 1 ]benzopyrano[3,4fquinoline, (-) (5S,3'R) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl 1-5-(3-cycloheptenyl)-1H[1]benzopyrano[3,4-quinoline, (-) 2,5(S)-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(3S-cyclopentenyl)-lH[ 1 ]benzopyrano[3,4-fjquinoline, (-) 2,5(S)-dihydro-9-hydroxy-10-ehloro-2,2,4-trimethyl-5-(3R-cyclopentenyl)-lH[ 1 Jbenzopyrano[3,4-f] quinoline, 2.5-Dihydro-10-methoxy-5-(4-pyridyl)-2,2,4-trimethyl-1Η-[ 1Jbenzopyrano[3,4-f]quinoline, (10-chloro-9-hydroxy-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro[l]benzopyrano[3,4f]quinoline, 2.5-Dihydro-10-methoxy-5-(3-pyridyl)-2,2,4-trimethyl-1H-[1Jbenzopyrano[3,4-fJquinoline, 2.5-dihydro-10-methoxy-5-(2-pyridyl)-2,2,4-trimethyl-1H-[1Jbenzopyrano[3,4-f]quinoline, 2.5-Dihydro-10-methoxy-5-(cyclohexyl)-2,2,4-trimethyl-1Η-[1Jbenzopyrano[3,4-fJquinoline, 2.5-Dihydro-10-methoxy-5-)3,4,5-trifluorophenyl)-2,2,4-triniethyl-1Η-[1Jbenzopyrano[3,4fJquinoline, 2.5-Dihydro-10-methoxy-5-(1-methylpropa-1,2-dienyl)-2,2,4-trimethyl-1H[1Jbenzopyrano[3,4-fJquinoline, 2.5-dihydro-10-methoxy-5-(cyclopentyl)-2,2,4-trimethyl-1H-[1Jbenzopyrano[3,4-f]quinoline, 2.5-Dihydro-10-methoxy-5-(carboethoxy)-2,2,4-trimethyl-1H-[1Jbenzopyrano[3,4-fJquinoline, 2.5-dihydro-10-methoxy-5-(ethoxycarbonylamino)methyl-2,2,4-trimethyl-1H[1Jbenzopyrano[3,4-fJquinoline, 2.5-Dihydro-10-methoxy-5-(aminomethyl)-2,2,4-trimethyl-1H-[1]benzopyrano-[3,4fquinoline, 2.5-Dihydro-10-methoxy-5-(2,2-dimethylethoxycarbonylamino)methyl)-2,2,4-trimethyl-1H[ 1 Jbenzopyrano[3,4-fJquinoline, 2.5-Dihydro-10-methoxy-5-(2-methoxymethoxy ethyl)-2,2,4-trimethyl 1-1 Hifi ]benzopyrano[3,4-f]quinoline, 2.5-Dihydro-10-methoxy-5-(2-(N,N-dimethylaminocarbonyloxy)ethyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline, 2.5-Dihydro-10-methoxy-5-(2-(N-methylaminocarbonyloxy)ethyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-fJquinoline, 2.5-dihydro-10-tnethoxy-5-(2-(N-(2-methoxyethyl)aminocarbonyloxy)ethyl)-2,2,4-trimethylΙΗ-f 1 Jbenzopyrano[3,4-f Jquinoline, 2.5-Dihydro-10-methoxy-5-(2-(N-morpholinocarbonyloxy)ethyl)-2,2,4-trimethyl-1H[ 1 Jbenzopyrano[3,4-fquinoline, • · • · 2.5-dihydro-10-methoxy-5-(2-(N-benzylcarbonyloxy)ethyl)-2,2,4-trimethyl-1H[1Jbenzopyranoj]3,4-quinoline, 2.5-Dihydro-10-methoxy-5-(2-hydroxyethyl)-2,2,4-trimethyl-1H-[1Jbenzopyrano[3,4fjquinoline, 2.5-Dihydro-10-methoxy-5-(1,1-difluoro-1-propen-3 y 1 )-2,2,4-trimethyl-1H[ 1 Jbenzopyrano[3,4-fJquinoline, (E) methyl 2-(2,5-dihydro-10-methoxy-2,2,4-trimethyl- 1Η-[ 1 ]benzopyrano[3,4-f]quinolin-5yl)-2-butenoate, (E) 2,5-dihydro-10-methoxy-5-(4-hydroxy-2-buten-1 -yl)-2,2,4-trimethyl-1-lithium Jbenzopyrano[3,4-f]quinoline, (E)2,5-dihydro-10-methoxy-5-(4-(N,N-dimethylaminocarbonyloxy)-2-buten-1-yl)-2,2,4trimethyl-1H-[ 1 Jbenzopyrano[3,4-fjquinoline, (E)2,5-dihydro-10-methoxy-5-(4-(N-methylaminocarbonyloxy)-2-buten-l-yl)-2,2,4trimethyl-1Η-[ 1 ]benzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-5-(3-methyl-2-butenyl)-2,2,4-trimethyl-1H-[1Jbenzopyrano[3,4jquinoline, trans 2,5-dihydro-10-methoxy-5-(2-penten-1-yl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline, 2.5-Dihydro-10-methoxy-5-(2-cycloheptylideneylethyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-5-(2-cyclopentylideneylethyl)-2,2,4-trimethyl-1H[1Jbenzopyrano[3,4-fJquinoline, 2.5-Dihydro-10-methoxy-5-(2-cyclohexylideneylethyl)-2,2,4-trimethyl-1H[1Jbenzopyrano[3,4-fJquinoline, 2-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-fJquinolin-5yl)acetaldehyde, 2.5-Dihydro-10-methoxy-5-(3-hydroxy-3-propenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline, • · 2.5-Dihydro-10-methoxy~5-(1-(hydrazinocarbonylamino)-3-propyl)-2,2,4-trimethyl-1H[ 1 ]benzopyrano[3,4-quinoline, (E) 2,5-dihydro-10-methoxy-5-(2-carbomethoxy-1-ethenyl)-2,2,4-trimethyl-1H[ 1 ]benzopyrano[3,4-quinoline, (Z)-2,5-dihydro-10-methoxy-5-( 1 -propenyl)-2,2,4-trimethyl- 1Η-[ 1 ]benzopyrano[3,4fjquinoline, (E) 2,5-dihydro-10-methoxy-5-(3-hydroxy-1-propenyl)-2,2,4-trimethyl-1H[ 1 ]benzopyrano[3,4-f]quinoline, (E) 2,5-dihydro-10-methoxy-5-(3-(N,N-dimethylaminocarbonyloxy)-1-propenyl)-2,2,4trimethyl-1Η-[ 1 ]benzopyrano[3,4-f]quinoline, (E) 2,5-dihydro-10-methoxy-5-(3 -methoxy methoxy-1 -propenyl)-2,2,4-trimethyl-1H[ 1 ]benzopyrano[3,4-f]quinoline, 2.5-Dihydro-10-methoxy-5-(1-amino-3-propyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline, 2.5-Dihydro-10-methoxy-5-(1-(N-phthalimido)-3-propyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-fJquinoline, 2,5-dihydro-10-methoxy-5-(1,2-epoxy-3-propenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline, 2.5-dihydro-10-methoxy-5-(1,2-dihydroxy-3-propyl)-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4fquinoline, 2.5-Dihydro-10-methoxy-5-(2-carbomethoxy-3-propenyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-5-(1,3-butadiene-2-yl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fJquinoline, 2.5-Dihydro-10-methoxy-5-(2-methyl-3-propenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline, 2,5-dihydro-10-methoxy-5-(1-chloromethy 1-3-cyclohexene 1)-2,2,4-trimethyl 1-1H[ 1 jbenzopyrano [3,4-fquinoline, re/(5R,3'R) 2,5-dihydro-10-methoxy-5-(1-methoxymethyl-3-cyclohexenyl)-2,2,4-trimethyl-1Η-[ 1 ]benzopyrano[3,4-fquinoline, rel (5R, 3'R) 2,5-dihydro-10-methoxy-5-(1-methylthiomethyl-3-cyclohexenyl)2,2,4trimethyl- 1Η-[ 1jbenzopyrano[3,4-fquinoline, rel (5R, 3'S) 2,5-dihydro-10-methoxy-5-(1-acetoxymethyl-3-cyclohexenyl)-2,2,4-trimethyl1 H-[ 1 jbenzopyrano[3,4-fquinoline, rel (5R,3'R) 2,5-dihydro-10-methoxy-5-( 1 -acetoxymethyl-3-cyclohexenyl)-2,2,4-trimethyl1 H-[ 1 ]benzopyrano[3,4-quinoline, rel (5R, 3'R) 2,5-dihydro-10-methoxy-5-(1-methoxymethyl-3-cyclohexenyl)-2,2,4-trimethyl1Η-[ 1jbenzopyrano[3,4-quinoline, rel (5R, 3'R) 2,5-dihydro-10-methoxy-5-(1-(N,N-dimethylamino)methyl-3-cyclohexenyl)2,2,4-trimethyl-1 H-[ 1 jbenzopyrano[3,4-fquinoline, rel (5R, 3'S) 2,5-dihydro-10-methoxy-5-(1-methylthiomethyl-3-cyclohexenyl)-2,2,4-trimethyl-1H-[ 1 jbenzopyrano[3,4-fquinoline, rel (5R,3'R) 2,5-dihydro-10-methoxy-5-(1-(N-morpholino)methyl-3-cyclohexenyl)-2,2,4trimethyl- 1Η-[ 1 ]benzopyrano[3,4-fquinoline, rel (5R,3'R) 2,5-dihydro-10-methoxy-5-(1 -(N-methyl-N-methylsulfonylamino)methyl-3 cyclohexenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-quinoline, 327 ·· ·· ·· ·· ·· ·· φ · * · · · · · ···· • · · ···· · · · · • ··· · · · ··· · · · · · • · φ · · · · · · ···· ·· ·· ·· »· ·· rel (5R, 3'S) 2,5-dihydro- 10-Methoxy-5-(1-(N,N-ditnethylamino)methyl-3-cyclohexenyl)2,2,4-trimethyl-1 H-[ 1 ]benzopyrano[3,4-fJquinoline, rel(5R, 3'R) 2,5-dihydro-10-methoxy-5-(1-(N-methylamino)methyl-3-cyclohexenyl)-2,2,4-trimethyl-1H-[ 1 ]benzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-5-(3-indolyl)-2,2,4-trimethyl-1H-[ljbenzopyrano[3,4-fquinoline, rel (5S,3'S) 2,5-dihydro-10-methoxy-5-(1-methyl-3-cyclohexenyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-fquinoline, 326: -cyclohexenyl)-2,2,4-trimethyl-1H[1jbenzopyrano[3,4-fjquinoline, (-) (5S,3'S) 2,5-dihydro-10-methoxy-5-(1-methyl-3-cyclohexenyl)-2,2,4-trimethyl-1H[1jbenzopyrano[3,4-fjquinoline, (-) (5S,3'R) 2,5-dihydro-10-methoxy-5-(1-hydroxymethyl-3-cyclohexenyl)-2,2,4-trimethyl1H-(1jbenzopyrano[3,4-fjquinoline, (+) (5R, 3'S) 2,5-dihydro-10-methoxy-5-(1-hydroxymethyl-3-cyclohexenyl)-2,2,4-trimethyl1H-[1jbenzopyrano[3,4-j]quinoline, (-)-(5S,3'R)2,5-dihydro-10-methoxy-5-(1-methyl-3-cyclohexenyl)-2,2,4-trimethyl-1H[1 jbenzopyrano[3,4-quinoline, (+)-(5R,3'S)2,5-dihydro-10-methoxy-5-(1-methyl-3-cyclohexenyl)-2,2,4-trimethyl-1H[1 jbenzopyrano[3,4-f]quinoline, 2.5-Dihydro-10-methoxy-5-(3-hydroxymethyl-3-cyclohexenyl)-2,2,4-trimethyl-1H[1jbenzopyrano[3,4-fquinoline, 2.5-Dihydro-10-methoxy-5-(2-bromo-3-propenyl)-2,2,4-trimethyl-1H-[l]benzopyrano[3,4fquinoline, re/(5R,3'R) 2,5-dihydro-10-methoxy-5-(1-hydroxymethyl-3-cyclohexenyl)-2,2,4-trimethyl1 Η- [ 1 ]benzopyrano[3,4-fquinoline, r<?/(5R,3'S)2,5-dihydro-10-methoxy-5-(1-hydroxymethyl-3-cyclohexenyl)-2,2,4-trimethyl1Η-[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-5-(3,3-dimethyl-6-cyclohexenyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-5-(1-cyclohexenylmethyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fjquinoline, 2.5-Dihydro-10-methoxy-5-(3-cycloheptenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline, 2.5-Dihydro-10-methoxy-5-(3-cyclooctenyl)-2,2,4-trimethyl-1H-[ljbenzopyrano[3,4fjquinoline, 2.5-Dihydro-10-methoxy-5-(1-oxo-2-cyclohexyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline, 2.5-dihydro-10-methoxy 5-(1-methylene-2-cyclohexyl)-2,2,4-triniethy 1-1H[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-5-(4,4-dimethyl-3-cyclohexenyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-5-(1-ethenyl-1-cyclohexyl)-2,2,4-trimethyl-1-1H-[1jbenzopyrano[3,4fjquinoline, 2.5-Dihydro-10-methoxy-5-(3-butenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-fquinoline, 2.5-Dihydro-10-methoxy-5-(3-cyclohexene 1)-2,2,4-trimethyl-1 Η-[ 1 jbenzopyrano [3,4fjquinoline, 2.5-Dihydro-10-methoxy-5-(3-cyclopentenyl)-2,2,4-trimethyl-1H-[ljbenzopyrano[3,4fjquinoline, 2.5-Dihydro-10-methoxy-5-(5,5-dimethyl-3-cyclohexenyl)-2,2,4-trimethyl-1H[ 1 ]benzopyrano[3,4-fJquinoline, rel (5R,2'R) 2,5-dihydro-10-methoxy-5-(2-oxo-3-tetrahydropyranyl)-2,2,4-trimethyl-1H[ 1 Jbenzopyrano[3,4-fJquinoline, «0 00 0 0 0 · • 0 0 0 » 0 0 0 · 0 0 0 0 2.5-Dihydro-10-methoxy-5-(3-methyl-3-butenyl-2,2,4-trimethyl-1H-[1Jbenzopyrano[3,4fquinoline, 2.5-Dihydro-9,10-dimethoxy-2,2,4-trimethyl-5-(2-propenyl)-1Η-[1]benzopyrano[3,4fjquinoline, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(2-thienyl)-1Η-[1Jbenzopyrano[3,4-fJquinoline, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(2-pyridinylmethylene)-1H-[1Jbenzopyrano[3,4fquinoline, 2.5-dihydro-10-methoxy-2,2,4-trimethyl-5-[(4,5-dihydro-4,4-dimethyl-2-oxazolyl)methyleneJ1H~[1]benzopyrano[3,4-fJquinoline, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[[3(trifluoromethyl)phenyl-methylene-1H-[1-benzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(3-methyl-5-(1H-pyrrolidin-1-yl)phenyl]-1H[1]benzopyrano[3,4-quinoline, 2.5-dihydro-10-methoxy-2,2,4-trimethyl-5-[3-methyl-5-(2-propenyl)phenylj-1H[ 1 ]benzopyrano[3,4-fj-quinoline, 2.5-dihydro-10-methoxy-2,2,4-trimethyl-5-[3-(methylthio)phenyl j-1Η-[1]benzopyrano[3,4fjquinoline, O-[3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-£1]benzopyrano[3,4-f]quinolin-5yl)phenyljmethylcarbonothioate, [3-(2,5-dihydro-10-methoxy-2,2,4-trimethylj-1Η-[1]benzopyrano[3,4-f)quinolin-5yl)phenyljtrifluoromethanesulfonate, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[3-[(methylsulfinyl)methoxyjphenyl]-1H[ 1 jbenzopyrano[3,4-fquinoline, ·· ♦ * • « 323 • «»· • · ···· ·· *· ·· • · · • · · · · ·♦ 0-(3-(2,5-dihydro- ί 0-methoxy-2,2,4-trimethyl-1 Η-[ 1 ]bezopyrano[3,4-f}quinolin-5yl)phenyl]ester, 2.5- dihydro-10-methoxy-2,2,4-trimethyl-5-[3-(methoxymethoxy)phenyl)- 1H[ 1 ]benzopyrano[3,4-quinoline, [(2,5-dihydro-10-methoxy-2,2,4-trimethyl- 1Η-[ 1 ]benzopyrano[3,4-quinolin-5yl)phenyl j-1 morpholinecarboxylate, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[4-(phenylmethoxy)phenylj-1H-[1]benzopyrano[3,4fquinoline, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[[4-(methylthio)methoxyjphenylj-1H[ 1jbenzopyrano[3,4-quinoline, [4-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[ljbenzopyrano[3,4-jquinolin-5yl)phenyljdimethylcarbamate, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[3-(2-propynyloxy)phenyl]-1H-[1]benzopyrano[3,4fquinoline, 2.5-dihydro-10-methoxy-2,2,4-trimethyl-5-[3-[2-(1-piperidinyl)ethoxy)phenylj-1H[1jbenzopyrano[3,4-fjquinoline, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[3-(phenylmethoxy)pheny-1j-1H-[1jbenzopyrano[3,4fjquinoline, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[3-(2-propenyloxy)phenyl)-1H-[ljbenzopyrano[3,4fquinoline, 2,5-dihydro-10-methoxy-5-(3-methoxyphen1)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline, 2.5-Dihydro-2,2,4-trimethyl-5-(2-propenyl)-1H-[1]benzopyrano[3,4-f]quinolin-10-ol, 10-(bromodifluoromethoxy)-2,5-dihydro-2,2,4-trimethyl-5-(2-propenyl)-1H[1]benzopyrano[3,4-f]quinoline, [3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1Η-[ 1 ]benzopyrano[3,4-f]quinolin-5yl)phenyl]methylcarbonate, ♦ · • · * · 322 • · · · «··· * • « · · · · · · « • ··· # » · ·♦· » · • « · · · · ·«·* ·· ·· *· 2.5-Dihydro-2,2,4-trimethyl-5-(2-propenyl)-1H-[1]benzopyrano[3,4-f]quinoline-10carboxylic acid, 2.5-dihydro-2,2,4-trimethyl-5-(2-propenyl)-1Η-[1]benzopyrano[3,4-quinoline-10-methanol, 2.5-dihydro-2,2,4-trimethyl-5-phenyl-10-(2-propenyloxy)-1H-[1]benzopyrano[3,4-f)quinoline, 2.5-Dihydro-2,2,4-trimethyl-5-phenyl-10-(2-propynyloxy)-1H-[1]benzopyrano[3,4-f]quinoline, 2.5-dihydro-2,2,4,10-tetramethyl-5-phenyl-1H-[1]benzopyrano[3,4-quinoline, 2.5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline-5-propanol, 2.5-dihydro-10-methoxy-2,2,4-trimethyl-5-(2-propynyl)-1H-[1]benzopyrano[3,4-f]quinoline, 2.5-dihydro-10-methoxy-2,2,4,N,N-pentamethyl-1H-[1]benzopyrano[3,4-f]quinoline-5ethanamine, N-cyclopropyl-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline-5acetamide, 2.5-Dihydro-10-methoxy-2,2,4,Ν,Ν-pentamethyl-1Η-[1]benzopyrano[3,4-f]quinoline-5acetamide, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-(-methylene-1H-[1Jbenzopyrano[3,4-fJquinoline-5propanol, 321 ΦΦΦΦ ·* φ* φ· φφ ♦ · φ φ φφφφ φφφφ • φφ φφφφ φφφφ • φφφφφ φ φ φ φ φ φφ · φ φφφ φφφφφ φφφφ φφφφφ φφφφ 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(2-methylpropyl)-1H-[1]benzopyrano[3,4fquinoline, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(1-methylethyl)-1H-[1]benzopyrano[3,4fquinoline, 2.5-dihydro-10-methoxy-2,2,4,5-tetramethyl-1H-[1]benzopyrano[3,4-f]quinoline, 2.5-dihydro-10-methoxy-2,2,4-trimethyl-5-propyl-1H-[1]benzopyrano[3,4-f)quinoline, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(phenylmethyl)-1H-[1Jbenzopyrano[3,4-fJquinoline, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(4-methylphenyl)-1H-[1Jbenzopyrano[3,4fjquinoline, 2-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1Η-[1Jbenzopyrano[3,4-fJquinolin-5-yl)-1phenylethanone, 2.5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline-5-carbonitrile, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[4-(]-norphylmyl)phenyl]-1H~[1Jbenzopyrano[3,4fquinoline, 2.5- dihydro-10-methoxy-2,2,4-trimethyl-5-(5-propyl-2-thienyl)- 1Η-[ 1 jbenzopyrano[3,4fjquinoline, «·«· · * 9 · W * · * ·«· · · t · · · · • ··· · * «♦··<· · 0 * __ 9 9 9 9 9 9 9 9 320 ...» ·» ·· ·· ·« ♦» 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(5-methoxy-2-thienyl)-1H-[1]benzopyrano[3,4fquinoline, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-1H-[ljbenzopyrano[3,4-fquinoline, 2.5- dihydro-10-methoxy-2,2,4,N-tetramethyl-N-phenyl-1H-[l]benzopyrano[3,4-f|quinoline-5amine, (-)2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-(2-propenyl)-1H-[l]benzopyrano[3,4-f]quinoline, (+)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-(2-propenyl)-1Η-[1jbenzopyrano[3,4fjquinoline, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(3-methylphenyl)-1H-[1]benzopyrano[3,4fquinoline, (±)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-phenyl-1H-[1jbenzopyrano[3,4-fquinoline, (±)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-phenyl-1H-[1jbenzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-5-(4-methoxyphenyl)-2,2,4-trimethyl-1H-[1jbenzopyrano[3,4fjquinoline, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[3-(trifluoromethyl)phenyl)-1H-[1]benzopyrano[3,4fquinoline, 319 ·« ·« ** ** ♦· « > « · ··«« · · φ » ♦ · « ♦ · · ' • «·· · « · ··« · · · « · · · · « · ···· ·♦ ·« tt ·· 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(phenylmethylene)-1Η-[1jbenzopyrano[3,4fjquinoline, 2.5-dihydro-10-methoxy-2,2,4-trimethyl-5-[3-methyl-5-(1-morpholinyl)phenylj-1H[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[[3-(methylthio)methoxyjphenylJ-1H[ 1 ]benzopyrano[3,4-quinoline, [3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]-benzopyrano[3,4-quinolin-5yl)phenyljdimethylcarbamate, 2.5-Dihydro-2,2,4-trimethyl-5-phenyl-1H-[1Jbenzopyrano[3,4-quinolin-10-ol, 2.5- dihydro-2,2,4,N-tetramethyl-5-(2-propenyl)-1Η-[ 1 Jbenzopyrano[3,4-fquinoline-10-amine, methyl 2,5-dihydro-2,2,4-trimethyl-5-(2-propenyl)- 1Η-[ 1 Jbenzopyrano[3,4-fquinoline-10-carboxylate, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(2-propenyl)-1H-[1]benzopyrano[3,4-fquinoline, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano[3,4-f|quinoline-1H[ 1 Jbenzopyrano[3,4-f|quinoline, 2.5-Dihydro-10-methoxy-2,2,3-trimethyl-5-allyl-1H-[1]benzopyrano[3,4-f]quinoline. 2.5-dihydro-10-methoxy-2,2-dimethyl-4-ethyl-5-allyl-1H-[1]benzopyrano[3,4-f]quinoline, and 2.5-dihydro-10-methoxy-2,2,3,4-tetramethyl-5-allyl-1Η-[1]benzopyrano[3,4-f]quinoline, 2.5-dihydro-10-methoxy-2,2-diethyl-4-methyl-5-allyl-1H-[l]benzopyrano[3,4-f]quinoline, 2.5-dihydro-10-methoxy-2,2-[spiro(hexyl)]-5-allyl-1H-[1]benzopyrano[3,4-f]quinoline, 2.5-dihydro-10-methoxy-2,2-[spiro(tetrahydro-4-pyranyl)]-4-methyl-5-allyl-1H[1]benzopyrano[3,4-f]quinoline, 2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-phenyl-1H-[1jbenzopyrano[3,4-quinazoline. 2.5-dihydro-10-methoxy-2,2,4-trimethyl-3-oxide-5-phenyl-1H-[1]benzopyrano[3,4-f]quinazoline and 2,5-dihydro-2,2,4-trimethyl-5-phenyl-10-(2-propynyloxy)-1Η-[1jbenzopyrano[3,4-f]quinoline. 2,5-Dihydro-2,2,4-trimethyl-5-phenyl-10-(2-propenyloxy)-1H-[1]benzopyrano[3,4-f]quinoline. 315 • φ · · • · ♦ · φ φ φ • · φ φ • φ ♦· • φ φ φ • φ φ φ • φ φφφ φφ φφ φφ φφ Φ Φ Φ 9 Φ · Φ · Φ Φ Φ · « Φ Φ Φ 2.5-Dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-propyl"1H-[1Jbenzopyrano[3,4-f]quinoline, 9-hydroxy-10-chloro-5-([2-pyridyl]methylene)-2,2,4-trimethyl-1H-2,5-dihydro[1Jbenzopyrano[3,4-f]quinoline, rel-{5 S)-9-hydroxy-5 -[(3 S )-( 1 -hydroxy methyl lcyclohexen-3 -yl] -10-chloro-2,2,4-trimethyl-2,5dihydro- 1Η-[ 1 ]benzopyrano[3,4-fquinoline, (-) (5S,3'S) 2,5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(1-methylcyclohexen-3-yl)-1 H-[ 1 ]benzopyrano[3,4-f]quinoline, (-) (5S,3'R) 2,5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-( 1 -methylcyclohexen-3 -yl)1Η-[ 1 ]benzopyrano[3,4-f]quinoline, (+) (5R,3'S) 2,5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(l-methylcyclohexen-3-yl)1Η-[ 1 ]benzopyrano[3,4-f]quinoline, (+) (5R,3'R) 2,5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(1-methylcyclohexen-3-yl)1H-[ 1 ]benzopyrano[3,4-quinoline, (+/-) 2,5-dihydro-9-(4-N,N-dimethylamino-4-oxo-butanoyloxy)-10-chloro-2,2,4-trimethyl-5allyl-1 H-[ 1 ]benzopyrano[3,4-f|quinoline, (-) 2,5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-cyclopentyl-1H-[ 1 ]benzopyrano[3,4-f|quinoline, and (+/-) 2,5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-benzyl-1Η-[1Jbenzopyrano[3,4fjquinoline. you* 2.5- dihydro-9-hydroxymethyl-10-chloro-2,2,4-trimethyl-5-allyl-1H-[1]benzopyrano[3,4f] quinoline, 2.5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(2-methylpropyl)-1H~[1Jbenzopyrano[3,4fjquinoline, 2.5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(1-thiazol-2-yl)-1Η[1]benzopyrano[3,4-quinoline, 2.5- dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-butyl-1H-[1]benzopyrano[3,4-f|quinolm, ΦΦΦ · φ 314 • · · · φφ φφ φ · φ φ φ · * • φ · φ · · · • φφφφφ φφ φ • · φ · φ · φφ «φ φφ φφ 2.5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-isopropyl-1H-[1]benzopyrano[3,4f]quinoline, 2.5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-ethyl-1H-[1]benzopyrano[3,4-x]quinoline, 2.5-Dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-([2-N,N-dimethylcarbamoyloxy3phenyl)1H-[1]benzopyrano[3,4-fquinoline, 2.5-dihydro-7-bromo-9-hydroxy-10-chloro-2,2,4-trimethyl-5-allyl-1Η-[1]benzopyrano[3,4fjquinoline, 2.5-Dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(3,4,5-trifluorophenyl)-1H[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(2-thienyl)-1H-[1]benzopyrano[3,4fquinoline, 2.5-dihydro-10-formyl-5-phenyl-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4-f]quinoline, From 5-(3-fluorobenzylideneyl)-10-chloro-9-hydroxy-2,2,4-trimethyl-2,5-dihydro-1H[1]benzopyrano[3,4-f]quinoline, Z-10-chloro-9-hydroxy-5-(2-picolinylideneyl)-2,2,4-trimethyl-2,5-dihydro-1H[ 1 ]benzopyrano[3,4-fquinoline, rel (5S,3'R)-9-hydroxy-5-[1-methoxymethyl-3-cyclohexenyl]-10-chloro-2,2,4-trimethyl-2,5-dihydro-1H[ 1 ]benzopyrano[3,4-quinoline, 2.5-Dihydro-10-formyl-5-(3-propenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline, 2.5-dihydro-10-carboxy-5-(3-propenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline, 2.5-Dihydro-10-cyano-5-(3-propenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline, 2.5-Dihydro-10-(2-furanyl)-5-(3-propenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f)quinoline, 2.5-Dihydro-2,2,4-trimethyl-5-(2-propenyl)-1H-[1]benzopyrano[3,4-fquinolin-10-ol, (10-chloro-9-hydroxy-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4-fquinolin-10-ol, 2.5-Dihydro-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano[3,4-quinolin-10-ol, 2,5-dihydro-10-ethynyl-5-phenyl-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-quinoline. 2.5- dihydro-10-ethenyl-5-[1 j-methyl-3-cyclohexenyl j-2,2,4-trimethyl-1H[ 1 jbenzopyrano [3,4-fjquinoline, ·· ·· ·· • « * » » • ě · · · · · · · •«· · · · · · · · · · · · · · · · • · · · · · · · · · · · · · · »· 99 312 2.5-Dihydro-10-ethenyl-5-oxo-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4-f]quinoline, 5-(3-cyclohexenyl)-2,5-dihydro-10-ethenyl-2,2,4-trimethyl-1H-[l]benzopyrano[3,4f]quinoline, and 2.5-dihydro-10-ethenyl-5-phenyl-2,2,4-trimethyl-1Η-[1jbenzopyrano[3,4-f]quinoline, 2.5-Dihydro-10-(methoxymethyl)-5-phenyl-2,2,4-trimethyl-1Η-[1jbenzopyrano[3,4-fquinoline, 2.5-Dihydro-10-(hydroxymethyl)-5-phenyl-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4-quinoline, and 2.5-Dihydro-10-methoxymethyl-5-(3-propenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline, 2.5-Dihydro-10-aminomethyl-5-(3-propenyl)-2,2,4-trimethyl-1H-[1jbenzopyrano[3,4fquinoline, 2.5-Dihydro-10-(2-hydroxymethyl)-5-(3-propenyl)-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4fquinoline, 2.5-Dihydro-2,2,4-trimethyl-5-(2-propenyl)-1H-[1jbenzopyrano[3,4-quinoline-10-methanol, 2,5-dihydro-2,2,4,10-tetramethyl 1-5-pheny 1-1H-[1jbenzopyrano[3,4-f]quinoline, 5-(3,5-dichlorophenyl)-10-ethyl-2,5-dihydro-2,2,4-trimethyl-1H-[ljbenzopyrano[3,4-f]quinoline, 2.5-Dihydro-2,2,4-trimethyl-5-(2-propenyl)-1Η-[1jbenzopyrano[3,4-quinoline-10carboxylic acid. 2.5-Dihydro-2,2,4,N-tetramethyl-5-(2-propenyl)-1Η-[1jbenzopyrano[3,4-quinoline-10-amine, 5-(3,5-dichlorophenyl)-2,5-dihydro-2,2,4,N-tetramethyl-1H-[l]benzopyrano[3,4-quinoline-10-amine, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(4-(fluorophenyl)methyl)-1H[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-thienyl)-1H-[1]benzopyrano[3,4fjquinoline, and 2.5-Dihydro-9-(4-N-morpholino-4-oxo-pentanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2propenyl)-1Η-[1]benzopyrano[3,4-fquinoline, (-) 2,5-dihydro-9-(4-N,N-dimethylamino-4-oxo-butanoyloxy)-10-methoxy-2,2,4-trimethyl5(S)-(3(S)-1-cyclopenten-3-yl)-1H-[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-9-(4-N-piperidino-4-oxo-pentanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2propenyl)-1Η-[1]benzopyrano[3,4-f]quinoline, 2.5-Dihydro-9-(4-N,N-dimethylamino-4-oxo-pentanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2-propenyl)-1H-[1]benzopyrano[3,4-fquinoline, 2.5-Dihydro-9-(4-N,N-diethylamino-4-oxo-pentanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2propenyl)-1H-[1]benzopyrano[3,4-fquinoline, 2,5-dihydro-9-methylthiomethoxy-10-methoxy-2,2,4-trimethyl-5-allyl 1 -1H[1]benzopyrano[3,4-f]quinoline, 2.5-Dihydro-9-(4-N,N-dimethylaminobutanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2-propenyl)-1H-[1]benzopyrano[3,4-fquinoline, 2.5-Dihydro-9-(4-N,N-dimethylamino-4-oxo-butanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2thienyl)-1H-[1]benzopyrano[3,4-fquinoline, 2.5-Dihydro-9-(4-N,N-dimethylamino-4-oxo-butanoyloxy)-10-methoxy-5-(phenylmethyl)2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f|quinoline, 2.5-Dihydro-9-(4-N,N-dimethylamino-4-oxo-butanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(1 methylethyl)-1H-[1]benzopyrano[3,4-quinoline, 2.5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3,5-dichlorophenyl)-1H[1]benzopyrano[3,4-f]quinoline, 2.5- dihydro-9-N,N-dimethylcarbamoyloxy-10-methoxy-2,2,4-trimethyl-5-([2-N,Ndimethylcarbamoyloxy]phenyl)-1H-[1]benzopyrano[3,4-f]quinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-(methylthiomethoxy)phenyl)-1H[1]benzopyrano[3,4-quinoline, 2.5-dihydro-9-methylthiomethoxy-10-methoxy-2,2,4-trimethyl-5-(3(methylthio)methoxyphenyl)-1H-[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-hydroxyphenyl)-1H(1]benzopyrano[3,4-quinoline, 2.5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-acetoxyphenyl)-1H[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3(Z)-pentenyl)-1H[1]benzopyrano[3,4-quinoline, 308 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-allenyl-1H-[1jbenzopyrano[3,4fjquinoline, (-) (5S, 3'S) 2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-(cyclopenten-3-yl)-1H[ 1jbenzopyrano[3,4fjquinoline, (-) (5S, 3'S) 2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-(cyclohexen-3-yl)-1H[ 1 ]benzopyrano[3,4-quinoline, (-) (5S, 3'R) 2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-(cyclohexen-3-yl)-1H[ 1 ]benzopyrano[3,4-quinoline, (-) (5S, 3'R) 2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-(cyclopenten-3-yl)-1H[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-9-methylcarboxylate-10-methoxy-2,2,4-trimethyl-5-allyl-1H-[ljbenzopyrano[3,4fjquinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(1-pentenyl)-1H-[1-benzopyrano[3,4-quinoline, 2.5-dihydro-9-hydroxymethyl-10-methoxy-2,2,4-trimethyl-5-allyl-1H-[1]benzopyrano[3,4fjquinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-((2-fluorophenyl)methyl)-1H[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-cyclopentyl-1H-[1]benzopyrano[3,4fquinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-5-difluorophenylmethyl)-1H[1]benzopyrano[3,4-fquinoline, 2.5-Dihydro-9-(4-N,N-dimethylamino-4-oxo-butanoyloxy)-10-methoxy-2,2,4-trimethyl-5(3,4,5-trifluorophenyl)-1Η-[1]benzopyrano[3,4-f]quinoline, 2.5-Dihydro-9-(4-N-morpholino-4~oxo-butanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2propenyl)-1H-[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-9-(4-N-piperidino-4-oxo-butanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2propenyl)-1H-[1]benzopyrano[3,4-fquinoline, 2.5-Dihydro-9-(4-N,N-diethylamino-4-oxo-butanoyloxy)-10-methoxy-2,2,4~trimethyl-5-(2propenyl)-1H-[1jbenzopyrano[3,4-fquinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-((2-fluorophenyl)methyl)-1H[ 1 ]benzopyrano[3,4-quinoline, 306 2.5-Dihydro-5-(3-propenyl)-10-methylthio-2,2,4-trimethyl-1Η-[ 1 Jbenzopyrano[3,4-fquinoline, (+/-) 2,5-dihydro-9-(4-acetamidobutanoyloxy)-10-methoxy-2,2,4-trimethyl-5-ally 1-1H[ 1 Jbenzopyrano[3,4-fquinoline, 2.5-Dihydro-5-(3-propenyl)-10-methylthio-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-5-(2-methylpropenyl)-2,2,4-trimethyl-1H-[ljbenzopyrano(3,4fjquinoline, trans 2,5-dihydro-10-methoxy-5-( 1 -cyclohexenyl)-2,2,4-trimethyl- 1Η-[ 1Jbenzopyrano[3,4fjquinoline, 2.5-Dihydro-10-methoxy-5-(2-phenylethynyl)-2,2,4-trimethyl-1H-[1jbenzopyrano[3,4fjquinoline, cis 2,5-dihydro-10-methoxy-5-(2-phenylethenyl)-2,2,4-trimethyl-1H-[l]benzopyrano[3,4fjquinoline, 2.5- dihydro-10-methoxy-5-ethenyl-2,2,4-trimethyl-1H-[ljbenzopyrano[3,4-fjquinoline, trans 2,5-dihydro-10-methoxy-5-(2-phenylethenyl)-2,2,4-trimethyl-1H-[l]benzopyrano[3,4fjquinoline, 2.5-Dihydro-10-methoxy-5-cyclopropyl-2,2,4-trimethyl-1Η-[1Jbenzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-5-(3-(2-(N,N-dimethylamino)ethyl)phenyl)-2,2,4-trimethyl-1H[ 1 Jbenzopyrano [3,4-quinoline, 2.5-Dihydro-10-methoxy-5-(3-(2-(N,N-dimethylaminocarbonyloxy)ethyl)phenyl)-2,2,4trimethyl-1H-[ljbenzopyrano[3,4-fquinoline, 2,5-dihydro-10-methoxy-5-(3-(2-methylthioethyl)phenyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-5-(3-(2-methanesulfonyloxyethyl)phenyl)-2,2,4-trimethyl-1H[ 1 Jbenzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-5-(3-(2-hydroxyethyl)phenyl)-2,2,4-trimethyl-1H[1jbenzopyrano[3,4-quinoline, 2.5-dihydro-10-methoxy-5-(3-(N-methylaminocarbonyloxy)phenyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-quinoline, 2.5- dihydro-10-methoxy-5-(3-(N-methyl-N-(N-methylcarbonyl)aminocarbonyloxy)phenyl)2.2.4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline, 99 99 • · · · • · · • ··· · • · ···· 99 305 ·* ·· • · · 9 • · · · · • · ··· · • · · 2.5- dihydro-10-methoxy-5-(3-(N-methyl-N-(carbomethoxymethyl)aminocarbonyloxy)phenyl)2.2.4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline, 2.5-Dihydro-9-(4-N,N-dimethylamino-4-oxo-butanoyloxy)-10-methoxy-2,2,4-trimethyl-5-(2propenyl)-1Η-[1]benzopyrano[3,4-f]quinoline, 2.5-dihydro-9-acetoxy-10-methoxy-2,2,4-trimethyl-5-(2-propenyl)-1H-[1]benzopyrano[3,4f]quinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2-methyl-3-propenyl)-1H[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-methyl-2-butenyl)-1H[1]benzopyrano[3,4-f]quinoline, (+) (5S,3'S) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cyclohexenyl)-1H[1 ]benzopyrano[3,4-fquinoline, (+) (5R,3'R) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cyclohexenyl)-1H[ 1 ]benzopyrano[3,4-fquinoline, (+) (5R,3'S) 2,5(R)-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cyclopentenyl)-1H[ 1 ]benzopyrano[3,4-fquinoline, (+) (5R,3'R) 2,5(R)-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cyclopentenyl)- 1H[ 1 ]benzopyrano[3,4-fquinoline, rel-(5S)-9-hydroxy-5-[(3R)-(1 -methoxycarbonyl)cyclohexen-3-yl]-10-methoxy-2,2,4trimethyl-2,5-dihydro-1H-[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2-hydroxymethyl-3-propenyl)-1H[1]benzopyrano[3,4-fjquinoline, methyl 2-[2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-1H-[l]benzopyrano[3,4-fj-5quinolinyl] acetate, (Z) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2-butenyl)-1H[1]benzopyrano[3,4-f]quinoline, 2,5,5-trihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-1H-[1]b enzopyrano[3,4-fquinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-cyclohexyl-1H-[1]benzopyrano[3,4fjquinoline, 2.5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2-acetoxymethyl-3-propenyl)-1H[ 1 ]benzopyrano[3,4-f]quinoline, 303 ·» ·* ·» ·· *· 94 **»· · · · · ··«« ··· · » · ě · · · · 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2-thienyl)-1H-[l]benzopyrano[3,4fjquinoline, (±) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2-methylphenyl)-lH[1Jbenzopyrano[3,4-f]quinoline, 2.5- dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(5-methoxy-2-thienyl)- 1H[ 1 ]benzopyrano[3,4-f]quinoline, (±) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2,3,4,5,6-pentafluorophenyl)- 1H[ 1 ]benzopyrano[3,4-f]quinoline, (+/-) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5(S)-(3(S)-1-hydroxy methylcyclopenten-3-yl)-1H-[l ]benzopyrano[3,4-f]quinoline, (+/-) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5(S)-(3 (S)-1 methylcarboxylate cyclopenten-3 -yl)-1 Η- [ 1 J benzopyrano [3,4-f]quinoline, (-) (5 S,3 'S) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3 -cyclohexene 1)-1H[ 1 ]benzopyrano[3,4-f]quinoline, (-) (5 S,3 'R) 2,5 -dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl 1-5-(3-cyclohexene 1)-1H[1]benzopyrano[3,4-fJquinoline, 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2-propyl)-1H-[1Jbenzopyrano[3,4fjquinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-5-(3-propynyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline, 2.5- dihydro-9-hydroxy-10-methoxy-5-(phenylmethyl)-2,2,4-trimethyl-1H-[ 1 ]benzopyrano[3,4f]quinoline, (-) (5S,3'R) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-[-1-ethyl-3-cyclohexenyl]1Η-[ 1 ]benzopyrano[3,4-f]quinoline, (-) (S) 5-cyclopentyl-2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl 1-1H[ 1 Jbenzopyrano[3,4-fJquinoline, (+) (R) 5-cyclopentyl-2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-1H[ 1 ]benzopyrano[3,4-f]quinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-butenyl)-1H-[1]benzopyrano[3,4fquinoline, 2.5- dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-fluoro-4-chlorophenyl)-lH[ 1 ]benzopyrano[3,4-fjquinoline, φφ «* φφ φφ • * » * · · φ • · · φ * · • ··· · φ φφφ • · φφφφφφ* φφφφφφ ΦΦ • · φ φ φ φ φ φ ΦΦ AND 302 ΦΦ φ 2.5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(2-methylpropyl)-1H[1]benzopyrano[3,4-quinoline, 2.5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-trifluoromethyl-4-chlorophenyl)-1H[1]benzopyrano[3,4-f]quinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-5-bistrifluoromethylphenyl)-1H[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-trifluoromethylphenyl)-1H[1]benzopyrano[3,4-quinoline, 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(4-fluorophenyl)-1Η-[1]benzopyrano[3,4fjquinoline, 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3,4-difluorophenyl)-1H[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3,4,5-trifluorophenyl)-1H[1]benzopyrano[3,4-fquinoline, 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3,5-difluorophenyl)-1H[1]benzopyrano[3,4-quinoline, 2.5- dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-phenyl- 1Η-[ 1jbenzopyrano [3,4fjquinoline, 2.5-Dihydro-9-hydroxy-10-methoxy-5-propyl-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline, (-) (5S,3'S) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cycloheptenyl)-1H[ 1 ]benzopyrano[3,4fquinoline, (-) (5S,3'R) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cycloheptenyl)-1H[1]benzopyrano[3,4-f]quinoline, 2.5-dihydro-10-methoxy-5-(4-pyridyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline, 2.5-Dihydro-10-methoxy-5-(3-pyridyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline, 2.5-Dihydro-10-methoxy-5-(2-pyridyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline, « Β * · B · « B B 300 • B ·· B B B B B B B B BBB B B B ·· B B BB BB B B B B • B B * B · B B B • B · B BB BB 2.5-Dihydro-10-methoxy-5-(cyclohexyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline, 2.5-Dihydro-10-methoxy-5-(3,4,5-trifluorophenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline, 2.5-Dihydro-10-methoxy-5-(1-methylpropa-1,2-diene 1)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-fquinoline, 2.5-dihydro-10-methoxy-5-(cyclopentyl)-2,2,4-trimethyl-1H-[1Jbenzopyrano[3,4-f]quinoline, 2.5-dihydro-10-methoxy-5-(carboethoxy)-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-5-(ethoxycarbonylamino)methyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-5-(aminomethyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-5-(2,2-dimethylethoxycarbonylamino)methyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-5-(2-methoxymethoxyethyl)-2,2,4-trimethyl-1H[ 1 Jbenzopyrano[3,4-f]quinoline, 2.5-Dihydro-10-methoxy-5-(2-(N,N-dimethylaminocarbonyloxy)ethyl)-2,2,4-trimethyl-1H[ 1 Jbenzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-5-(2-(N-methylaminocarbonyloxy)ethyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-5-(2-(N-(2-methoxyethyl)aminocarbonyloxy)ethyl)-2,2,4-trimethyl1Η-[ 1 Jbenzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-5-(2-(N-morpholinocarbonyloxy)ethyl)-2,2,4-trimethyl-1H[1Jbenzopyrano[3,4-fJquinoline, 2.5-dihydro-10-methoxy-5-(2-(N-benzylcarbonyloxy)ethyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline, 2.5-Dihydro-10-methoxy-5-(2-hydroxyethyl)-2,2,4-trimethyl-1H-[1Jbenzopyrano[3,4fjquinoline, 2.5-Dihydro-10-methoxy-5-(1,1-difluoro-1-propen-3-yl)-2,2,4-trimethyl-1H[ 1 ]benzopyrano[3,4-f]quinoline, (E) methyl 2-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1E[-[l]benzopyrano[3,4~f]quinolin-5yl)-2-butenoate, • » • · 299. 1 ]benzopyrano[3,4~f|quinoline, (E) 2,5-dihydro-10-methoxy-5-(4-(N,N-dimethylaminocarbonyloxy)-2-buten-1-yl)-2,2,4trimethyl- 1Η-[ 1 ]benzopyrano[3,4-f|quinoline, (E) 2,5-dihydro-10-methoxy-5-(4-(N-methylaminocarbonyloxy)-2-buten-1 -yl)-2,2,4trimethyl-1H-[1H-benzopyrano[3,4-fJquinoline, (E) 2,5-dihydro-10-methoxy-5-(2-butenyl)-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4-f]quinoline, 2.5-Dihydro-10-methoxy-5-(3-methyl-2-butenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4f]quinoline, trans 2,5-dihydro-10-methoxy-5-(2-penten-1-yl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline, 2.5-Dihydro-10-methoxy-5-(2-cycloheptylideneylethyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-fJquinoline, 2.5-dihydro-10-methoxy-5-(2-cyclopentylideneylethyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline, 2.5-Dihydro-10-methoxy-5-(2-cyclohexylideneylethyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-fJquinoline, 2-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-x]quinolin-5yl)acetaldehyde, 2.5-Dihydro-10-methoxy-5-(3-hydroxy-3-propenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4f]quinoline, methyl 2-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolin-5yl)acetylhydroxamate, 2.5- dihydro-10-methoxy-5-( 1 -(hydrazinocarbonylamino)3-propyl)-2,2,4-trimethyl-1H[ 1 ]benzopyrano[3,4-f]quinoline, (E)- 2,5-dihydro-10-methoxy-5-(2-carbomethoxy-1-ethenyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline, (Z)-2,5-dihydro-10-methoxy-5-( 1 -propenyl)-2,2,4-trimethyl- 1Η-[ 1 ]benzopyrano[3,4f]quinoline, (E) 2,5-trihydro-10-methoxy-5-(3-hydroxy-l-propenyl)-2,2,4-trimethyl-1H[ 1 ]benzopyrano[3,4-f]quinoline, (E) 2,5-dihydro-10-methoxy-5-(3-(N,N-dimethylaminocarbonyloxy)-1-propenyl)-2,2,4trimethyl-1H-[1]benzopyrano[3,4-f]quinoline, (E)2,5-dihydro-10-methoxy-5-(3-methoxymethoxy-1-propenyl)-2,2,4-trimethyl-1H[1 ]benzopyrano[3,4-f}quinoline, 2,5-dihydro-10-methoxy-5-(1-amino-3-propyl)-2,2,4-trimethyl-1H-[1jbenzopyrano(3,4fjquinoline, • 0 • 0 298 0 «0 0 0 0 0 0 000 0 0 0 0000 00 ·« 00 0 0 0 0 0 0 0 0 0 0 0 00 0 0 0 • 0 «♦ • 0 0 0 0 0 0 0 0 0 0 0 2.5-Dihydro-10-methoxy-5-(1-(N-phthalimido)-3-propyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-5-(1,2-epoxy-3-propenyl)-2,2,4-trimethyl-1H-[ljbenzopyrano[3,4fquinoline, 2.5-Dihydro-10-methoxy-5-(1,2-dihydroxy-3-propyl)-2,2,4-trimethyl-1Η-[1jbenzopyrano[3,4fjquinoline, 2.5-dihydro-10-methoxy-5-(2-carbomethoxy-3-propenyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline, 2.5-Dihydro-10-methoxy-5-(1,3-butadiene-2-yl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline, 2.5-Dihydro-10-methoxy-5-(2-methyl-3-propenyl)-2,2,4-trimethyl-1H-[1jbenzopyrano[3,4fjquinoline, 2.5- dihydro-10-methoxy-5-( 1 -chloromethyl-3-cyclohexenyl)-2,2,4-trimethyl- 1H[ 1 jbenzopyrano[3,4-f]quinoline, rel (5R, 3'R) 2,5-dihydro-10-methoxy-5-(1-methoxymethyl-3-cyclohexenyl)-2,2,4-trimethyl-1H[ 1 ]benzopyrano[3,4-fjquinoline, φ φ • φ 297 φφφφ φ φφφ φ φ φφφ φ φ φ φ φφφ φφφφ φφ φφ φ φφ φφ φφφφφ • · « · · φφφφ φ φ φ φφφφ rel (5R, 3'R) 2,5-dihydro-10-methoxy-5-(l-methylthiomethyl-3-cyclohexenyl)-2,2,4-trimethyl-1H-[ ]benzopyrano[3,4-f]quinoline, rel (5R, 3'S) 2,5-dihydro-10-methoxy-5-(1-acetoxymethyl-3-cyclohexenyl)-2,2,4-trimethyl1H-[l]benzopyrano[3,4-f]quinoline, rel (5R, 3'R) 2,5-dihydro-10-methoxy-5-(1-acetoxymethyl-3-cyclohexenyl)-2,2,4-trimethyl1 H-[ 1 jbenzopyrano [3,4-fjquinoline, rel (5R, 3'R) 2,5-dihydro-10-methoxy-5-(1-methoxymethyl-3-cyclohexenyl)-2,2,4-trimethyl1 H-[ 1 jbenzopyrano [3,4-fj quinoline, rel (5R, 3'R) 2,5-dihydro-10-methoxy-5-(1-(N,N-dimethylamino)methyl-3-cyclohexenyl)2,2,4-trimethyl-1 H-[ 1 jbenzopyrano[3,4-fquinoline, rel (5R,3'S) 2,5-dihydro-10-methoxy-5-(l-methylthiomethyl-3-cyclohexenyl)-2,2,4-trimethyl-1H-[ljbenzopyrano[3,4-fquinoline, rel (5R, 3'R) 2,5-dihydro-10-methoxy-5-(l-(N-morpholino)methyl-3-cyclohexenyl)-2,2,4-trimethyl- 1H-[l]benzopyrano[3,4-fquinoline, rel (5R, 3'R) 2,5-dihydro-10-methoxy-5-(1-(N-methyl-N-methylsulfonylamino)methyl-3cyclohexenyl)-2,2,4-trimethyl- 1Η-[ 1jbenzopyrano[3,4-fquinoline, rel (5R, 3'S) 2,5-dihydro-10-methoxy-5-(1-(N,N-dimethylamino)methyl-3-cyclohexenyl)2,2,4-trimethyl-1 H-[ 1 jbenzopyrano[3,4-fquinoline, rel (5R, 3'R) 2,5-dihydro-10-methoxy-5-(1-(N-methylamino)methyl-3-cyclohexenyl)-2,2,4-trimethyl-1 H-[ 1 jbenzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-5-(3-indolyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline, rel (5S,3'S) 2,5-dihydro-10-methoxy-5-(1-methyl-3-cyclohexenyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline, rel (5R,3'S) 2,5-dihydro-10-methoxy-5-( 1 -methyl-3 -cyclohexenyl)-2,2,4-trimethyl- 1H[ 1 jbenzopyrano[3,4-f]quinoline, (-) (5S,3'S) 2,5-dihydro-10-methoxy-5-( 1 -methyl-3 -cyclohexenyl)-2,2,4-trimethyl- 1H[ 1 ]benzopyrano[3,4-f]quinoline, (-) (5S,3'R) 2,5-dihydro-10-methoxy-5-( 1 -hydroxymethyl-3-cyclohexenyl)-2,2,4-trimethyl1Η-[ 1 ]benzopyrano[3,4-f]quinoline, (+) (5R,3'S) 2,5-dihydro-10-methoxy-5-(1-hydroxymethyl-3-cyclohexenyl)-2,2,4-trimethyl1Η-[ 1 ]benzopyrano[3,4-fquinoline, (-)-(5S,3'R) 2,5-dihydro-10-methoxy-5-(1-methyl-3-cyclohexenyl)-2,2,4-trimethyl-1H[ 1 jbenzopyrano[3,4-fquinoline, (+)-(5R, 3'S) 2,5-dihydro-10-methoxy-5-(1 -methyl-3-cyclohexenyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-quinoline, 2.5-dihydro-10-methoxy-5-(3-hydroxymethyl-3-cyclohexenyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline, 2.5-Dihydro-10-methoxy-5-(2-bromo-3-propene 1)-2,2,4-trimethyl-1H-[ 1 ]benzopyrano[3,4fquinoline, rel (5R,3'R) 2,5-dihydro-10-methoxy-5-( 1 -hydroxymethyl-3-cyclohexenyl)-2,2,4-trimethyl-1Η-[ 1 ]benzopyrano]3,4-f]quinoline, rel (5R,3'S) 2,5-dihydro-10-methoxy-5-(1-hydroxymethyl-3-cyclohexenyl)-2,2,4-trimethyl1H-[1jbenzopyrano[3,4-f]quinoline, 2.5-dihydro-10-methoxy-5-(3,3-dimethyl-6-cyclohexenyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-5-(1-cyclohexenylmethyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4ljquinoline, 2.5-Dihydro-10-methoxy-5-(3-cycloheptenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline, 2.5- dihydro-10-methoxy-5-(3 -cyclooctenyl)-2,2,4-trimethyl- 1Η-[ 1 ]benzopyrano[3,4fjquinoline, • · φφ φφ φφ ♦ ·* φ * ♦ · φ • · Φ Φ 9 9 9 • 99999 9999 2.5-Dihydro-10-methoxy-5-(1-oxo-2-cyclohexyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline, 2.5-Dihydro-10-methoxy-5-(1-methylene-2-cyclohexyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-5-(4,4-dimethyl-3-cyclohexenyl)-2,2,4-trimethyl-1H[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-5-(1-ethenyl-1-cyclohexyl)-2,2,4-trimethyl-1H-[1Jbenzopyrano[3,4fquinoline, 2,5-dihydro-10-methoxy-5-(3-butenyl)-2,2,4-trimethyl-1H-[1Jbenzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-5-(3-cyclohexenyl)-2,2,4-trimethyl-1H-[1Jbenzopyrano[3,4fquinoline, 2.5-Dihydro-10-methoxy-5-(3-cyclopentenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline, 2.5-Dihydro-10-methoxy-5-(5,5-dimethyl-3-cyclohexenyl)-2,2,4-trimethyl-1H[ 1 Jbenzopyrano [3,4-fquinoline, rel (5R,2'R) 2,5-dihydro-10-methoxy-5-(2-oxo-3-tetrahydropyranyl)-2,2,4-trimethyl-1H[ 1 ]benzopyrano[3,4-quinoline, anti (5R, 2'S) 2,5-dihydro-10-methoxy-5-(2-oxo-3-tetrahydropyranyl)-2,2,4-trimethyl-1H[ 1 ]benzopyrano[3,4-quinoline, 2,5-dihydro-10-methoxy-5-(3-methyl-3-butenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline, 2,5-dihydroxy-9,10-dimethoxy-2,2,4-trimethyl 1-5-(2-propenyl)-1H-[1jbenzopyrano[3,4fjquinoline, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(2-thienyl)-1Η-[1]benzopyrano[3,4-quinoline, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(2-pyridinylmethylene)-1H-[1]benzopyrano[3,4fquinoline, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[(4,5-dihydro-4,4-dimethyl-2-oxazolyl)methylene]1H-[1jbenzopyrano[3,4-fquinoline, 2.5- dihydro-10-methoxy-2,2,4-trimethyl-5-[[3-(trifluoromethyl)phenyl jmethylenej-1 Η- [ 1 ] benzopyrano[3,4-f]quinoline, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[3-methyl-5-(1H-pyrrolidin-1-yl)phenyl]-1H[1]benzopyrano[3,4-f]quinoline, 2.5-dihydro-10-methoxy-2,2,4-trimethyl-5-[3-methyl-5-(2-propenyl)phenyl]-1H[ 1 ]benzopyrano[3,4-f]quinoline, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[3-(methylthio)phenyl]-1H-[1]benzopyrano[3,4fquinoline, O-[3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolin-5yl)phenyl]methylcarbonothioate, [3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl]-1H-[1Jbenzopyrano[3,4-f]quinolin-5yl)phenyl]trifluoromethanesulfonate, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[3-[(methylsulfinyl)methoxy]phenyl]-1H[ 1 Jbenzopyrano[3,4-fquinoline, O-[3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-α-quinolin-5yl)phenyl]ester, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[3-(methoxymethoxy)phenyl]-1H[1]benzopyrano[3,4-f]quinoline, [(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1Jbenzopyrano[3,4-f]quinolin-5-yl)phenyl]-1morpholinecarboxylate, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[4-(phenylmethoxy)phenyl]-1H-[1]benzopyrano[3,4fquinoline, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[[4-(methylthio)methoxy]phenyl]-1H[ 1 Jbenzopyrano[3,4-f]quinoline, [4-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f|quinolin-5yl)phenyl]dimethylcarbamate, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[3-(2-propynyloxy)phenyl J-1H-[1]benzopyrano[3,4fquinoline, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[3-[2-(1-piperidinyl)ethoxy]phenyl-1H[1]benzopyrano[3,4-f]quinoline, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[3-(phenylmethoxy)phenyl]-1H-[1]benzopyrano[3,4fquinoline, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[3-(2-propenyloxy)phenyl]-1H-[1]benzopyrano[3,4fquinoline, 2.5-Dihydro-10-methoxy-5-(3-methoxyphenyl)-2,2,4-trimethyl-1H-[l}benzopyrano[3,4fquinoline, 2.5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1Jbenzopyrano[3,4-f]quinoline-5-propanol, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(2-propynyl)-1Η-[1Jbenzopyrano[3,4-fJquinoline, 5-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolin-5-yl)-2(5H)furanone, 2.5-Dihydro-10-methoxy-2,2,4,N,N-pentamethyl-1Η-[1Jbenzopyrano[3,4-f]quinoline-5ethanamine, N-cyclopropyl-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1Jbenzopyrano[3,4-fJquinoline-5acetamide, 2.5-Dihydro-10-methoxy-2,2,4,N,N-pentamethyl-1H-[1]benzopyrano[3,4-f]quinoline-5acetamide, • · « · < · · · φ · · φ φφφ « · φφφφ · · φ φ «φ · * 292 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-(-methylene-1H-[1]benzopyrano[3,4-f]quinoline-5propanol, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(2-methylpropyl)-1H-[1]benzopyrano[3,4fquinoline, 2.5-dihydro-10-methoxy-2,2,4-trimethyl-5-(1-methylethyl)-1H-[1]benzopyrano[3,4f]quinoline, 2.5-dihydro-10-methoxy-2,2,4,5-tetramethyl-1Η-[1]benzopyrano[3,4-f]quinoline, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-propyl-1H-[1]benzopyrano[3,4-f|chmoline, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(phenylmethyl)-1H-[1]benzopyrano[3,4-f]quinoline, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(4-methylphenyl)-1H-[1]benzopyrano[3,4fquinoline, 2-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4-f]quinolin-5-yl)-1 phenylethanone, 2.5-dihydro-10-methoxy-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4-f]quinoline-5-carbonitrile, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[4-(1-morpholinyl)phenyl]-1H-[1]benzopyrano[3,4fjquinoline, • · • ··· · · · «φφφφ · φ · • · · · ···· 291 .............. 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(5-propyl-2-thienyl)-1H-[1]benzopyrano[3,4fquinoline, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(5-methoxy-2-thienyl)-1H-benzopyrano[3,4fquinoline, 2.5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f|quinolm, 2.5- dihydro-10-methoxy-2,2,4,N-tetramethyl-N-phenyl-1H-[1]benzopyrano[3,4-f]quinoline-5amine, (-)2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-(2-propenyl)- 1Η-[ 1 ]benzopyrano[3,4-f]quinoline, (+)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-(2-propenyl)-1Η-[1]benzopyrano[3,4fquinoline, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(3-methylphenyl)-1H-[1]benzopyrano[3,4-quinoline, (±)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano[3,4-quinoline, (±)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano[3,4-f]quinoline, 2.5-Dihydro-10-methoxy-5-(4-methoxyphenyl)-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline, • · • · • · · · • · 4 > · · 4 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[3-(trifluoromethyl)phenylj-1H-[ljbenzopyrano[3,4fjquinoline, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(phenylmethylene)-1H-[1]benzopyrano[3,4fquinoline, 2.5-dihydro-10-methoxy-2,2,4-trimethyl-5-[3-methyl-5-(1-morpholinyl)phenyl]-1H[ 1 ]benzopyrano[3,4-f|quinoline, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-[[3-(methylthio)methoxyphenyl]-1H[1]benzopyrano[3,4-f]quinoline, [3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f|quinolin-5-yl)phenyl]dimethylcarbamate, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-(2-propenyl)-1Η-[1]benzopyrano[3,4-f]quinoline, 10-(difluoromethoxy)-2,5-dihydro-2,2,4-trimethyl-5-(2-propenyl)-1H-[1]benzopyrano[3,4f]quinoline, 2.5-Dihydro-10-methoxy-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano[3,4-f]quinoline-1H[1]benzopyrano[3,4-f)quinoline, 2. A compound according to claim 1 of formula II or pharmaceutically acceptable salts or prodrugs thereof, wherein the substituents R 1 , R ₂ , R 3 , R 4 , R 5 , R 6 and L ₂ are as defined above. • · · · in in 289 • 4 94 4 9 4 • · · · · • · · · 9 4 4 4 ·· (2) , where δ is 1, 2, 3 or 4 and A is selected from (a) -CH ₂ -, (b) -O-, (c) -S(O>, and (d) -NR?-, and (3) , where the carbon-carbon double bond may have an E or Z configuration and the substituents R ₂ g and R ₂ g- are independently selected from (a) hydrogen, (b) alkenyl having three to twelve carbon atoms, (c) aryl, (d) heterocycle, 287 (e) alkyl having one to twelve carbon atoms, (f) cycloalkyl having three to twelve carbon atoms, (g) cycloalkenyl having four to twelve carbon atoms, and (h) cycloalkenyl having four to twelve carbon atoms, wherein (a) - (f) may be optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from (i) alkoxy having one to twelve carbon atoms, (ii) -OH, with the proviso that no two -OH groups are attached to the same carbon atom, (iii) -SH, with the proviso that no two -SH groups are attached to the same carbon atom, (iv) -CN, (v) halogen, (vi) -CHO, (vii) -NO ₂ , (viii) haloalkoxy having one to twelve carbon atoms, (ix) perfluoroalkoxy having one to twelve carbon atoms, (x) -NR8-R9, (xi) -NNR8-R9-, (xíí) -NR7NR8R9-, (xiii) -C0 ₂ R10, (xiv) -C(X)NR _x R ₉ , (xv) =N-OR10, (xvi) =NR10, (xvii) -S(0)tR10, (xviii) -X'C(X)R10, (xix) (=X), (xx) -0-(CH ₂ ) _q -Z-R10, (xxi) -OC(X)NR8-R9, (xxii) -L _b R ₃ 0, (xxiii) alkanoyloxy groups, where the alkyl group has one to twelve carbon atoms, (xxiv) -OSO2R11, and •ř 288 • · · · ·· · · ·· « • ····· · · · · · · ·· · • ··· · · · · · ·« · · ·9 · · ·· · · ·· (xxv) -NR ₇ (X)NRs-R ₉ -; the substituents R 1 , and R 1 , are independently hydrogen or alkyl having one to six carbon atoms; or the substituents R 16 and R 16 - together are alkenyl having two carbon atoms; the dashed line represents an optionally present double bond, with the proviso that if the substituents R 16 and R 17 together are alkenyl having two carbon atoms, then no double bond is present; Y is selected from carbon, nitrogen and IST(=0); the substituent R17 is absent or is hydrogen or alkyl having one to six carbon atoms, with the proviso that if a double bond is present and Y is nitrogen or NT(=0'), then the substituent R17 is absent; and the substituents Rig and Rix are independently hydrogen or alkyl having one to six carbon atoms; or the substituents Rig and Rig' together are a cycloheteroalkyl ring or a cycloalkyl ring having three to eight carbon atoms. 2 substituents independently selected from aryl or cycloalkyl having three to twelve carbon atoms, (ix) alkenyl having three to twelve carbon atoms, with the proviso that the carbon-carbon double bond is not directly attached to the nitrogen, and (x) alkynyl having three to twelve carbon atoms, with the proviso that the carbon-carbon triple bond is not directly attached to the nitrogen, (n) -CO2R10, wherein the substituent R10 is selected from (i) (ii) (iii) aryl, aryl substituted with 1, 2 or 3 alkyls having one to twelve carbon substituents, cycloalkyl having three to twelve carbon atoms, alkyl having one to twelve carbon atoms, and alkyl having one to twelve carbon atoms substituted with aryl or cycloalkyl having three to twelve carbon atoms, (iv) (v) (0) -C(X)NRgR ₉ , (P) =N-ORio, (q) =NRio, (r) -S(0)tRio, (s) -X'C(X)Rio, (t) (=X), and (u) -OSO ₂ Ru, (17) cycloalkyl having three to twelve carbon atoms, (18) cycloalkenyl having four to twelve carbon atoms, with the proviso that the carbon of the carbon-carbon double bond is not directly attached to Li if Li is other than a covalent bond, wherein (17) and (18) may be optionally substituted with 1, 2, 3 or 4 substituents independently selected from (a) alkyl having one to twelve carbon atoms, (b) aryl, ·* ·♦ ·* ·· 99 • 9 9 · · · · · · · · 9 3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[ljbenzopyrano[3,4-fJquinolin-5-yl)-N-(2propenyl)benzenamine, • Φ ♦ · ··» ·9 ♦ · • « · · » « · · ·«·· ·«· · · · · «· · * «I» » · · ·« » » ·· · _Λ · »··«···· 324 ···· ·' ·♦ ♦* ·· ♦· Ν'-[3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1 Η-[ 1 ]benzopyrano[3,4-f]chmolin-5-yl)-5methylphenyl]-N,N-dimethylurea, N-[3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1Jbenzopyrano[3,4-f]quinolin-5yl)phenyl]benzenemethanamine, 3-(2,5-Dihydro-10-methoxy-2,2,4-trimethyl-1H-[1-benzopyrano[3,4-quinol-5-yl)-N-(2-methoxyethyl)-5-methylbenzenamine, 3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-h]quinolin-5-yl)-5methyl-N-(2-propenyl)benzamide, 3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1-benzopyrano[3,4-quinoline-5-methyl)5,N-dimethylbenzenamine, 3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolin-5-yl)-5trimethylbenzenemethanol, 3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1Η-[1jbenzopyrano[3,4-quinolin-5-yl)benzoic acid, 3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1jbenzopyrano[3,4-hquinolin-5-yl)phenol, 3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1Η-[1jbenzopyrano[3,4-quinolin-5-yl)-N-(2propenyl)benzenamine, N'“[3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolin-5-yl)-5methylphenyl]-N,N-dimethylurea, N-[3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1jbenzopyrano[3,4-hquinolin-5yl)phenyl]benzenemethanamine, 3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[ljbenzopyrano[3,4-f]quinolin-5-yl)-N-(2methoxyethyl)-5-methylbenzenamine, 3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-quinolin-5-yl)-5methyl-N-(2-propenyl)benzamide, 3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[ljbenzopyrano[3,4-f]quinoline-5-methyl-5,Ndimethylbenzenamine, 3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-quinolin-5-yl)-5-trimethylbenzenemethanol, 3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-fJquinolin-5yl)benzoic acid, 3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1Jbenzopyrano[3,4-f}quinolin-5-yl)phenol-4methylbenzenesulfonate (ester), ♦ · « « • · · · • · · • · · · 293 ·· 99 99 • * · 9 9 9 9 3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolin-5-yl)phenol, 3. A compound according to claim 2, wherein the substituent R1 is -Li-Ra, Li is -O- or -S- and the substituent R2 is alkyl having one to twelve carbon atoms which may be optionally substituted or the substituents R1 and _R2 together are 4-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-quinolin-5-yl)phenol, 4-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-quinolin-5yl)phenol acetate (ester), 3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[ljbenzopyrano[3,4fquinolin-5-yl)phenol 4-methylbenzenesulfonate (ester), 4-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-quinolin-5-yl)-N,Ndimethylbenzenamine, 4-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1Η-[1Jbenzopyrano[3,4-f|quinolin-5-y1)phenol, 4-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-fJquinolin-5yl)acetate phenol (ester), 4-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-fJquinolin-5-yl)-N,Ndimethylbenzenamine, 4 · ♦ I 290 4. A compound according to claim 3 selected from: 5-(3-cyclohexenes 1)-2,5-dihydro-10-ethenes 1-2,2,4-trimethyl-1H-[1jbenzopyrano[3,4fquinoline, (-) (5S,3'S) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cyldohexene 1)- 1H[ 1 ]benzopyrano[3,4-f]quinoline, (-)(5S,3'R)2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cyclohexenyl)-1H[ 1 Jbenzopyrano[3,4-fJquinoline, 5-Butyl-2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-1H-[ 1Jbenzopyrano[3,4fjquinoline, (-) (5S,3'S) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3 -cyclopentenyl)-1H[ 1Jbenzopyrano[3,4fjquinoline, (-) (5S,3'R) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cyclopentenyl)-1H[1]benzopyrano[3,4-quinoline, 5-(3-propenyl)-9-chloro-10-difluoromethoxy-2,2,4-trimethyl-2,5-dihydro-1H[1]benzopyrano[3,4-quinoline, 5-(2-cyclohexen-1-yl)-2,5-dihydro-9,10-dimethoxy-2,2,4-trimethyl-1H-[1Jbenzopyrano[3,4fquinoline, 5-[(2-Fluorophenyl)methyleneJ-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1Jbenzopyrano[3,4fquinoline, 5-[(2,6-dichlorophenyl)methylene]-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H[ 1 Jbenzopyrano[3,4-fJquinoline, 5-[(2-chlorophenyl)methyleneJ-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1Η-[ 1Jbenzopyrano[3,4fjquinoline, 5-[(2,6-difluorophenyl)methyleneJ-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H[1]benzopyrano[3,4-fJquinoline, 5-[(4-chlorophenyl)methylene-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline, 5-[(3,5-dichlorophenyl)methyleneJ-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H[1]benzopyrano[3,4-fJquinoline, 5-[3-(2-furanyl)phenyl]-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline, 5-(3-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)phenylj-2,5-dihydro-10-methoxy-2,2,4-trimethyl1H-[1jbenzopyrano[3,4-f]quinoline, ethyl 3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1jbenzopyrano[3,4-f]quinolin-5yl)benzoate, 5-[3-(2,4-dinitrophenoxy)phenyl j-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H[1jbenzopyrano[3,4-quinoline, 5-(3-hexyloxyphenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline, 5-[3-(cyclopropylmethoxy)phenyl j-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H[1jbenzopyrano[3,4-quinoline, 5-(3,5-dichlorophenyl)-2,5-dihydro-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4-f]quinolin-10yl]methylcarbonate, 5-(3,5-dichlorophenyl)-2,5-dihydro-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolin-10-ol, 5-(3,5-dichlorophenyl)-10-ethoxy-2,5-dihydro-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline, 5-(3,5-dichlorophenyl)-2,5-dihydro-2,2,4-trimethyl-N-(2-propenyl)-1H-[1]benzopyrano[3,4fquinolin-10-amine, 5-(3,5-dichlorophenyl)-2,5-dihydro-2,2,4,N-tetramethyl-1H-[1]benzopyrano[3,4-quinoline-10amine, 5-(3,5-dichlorophenyl)-10-ethyl-2,5-dihydro-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-fJquinoline, 5-(3-butenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f|quinoline, 5-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f|quinolin-5-yl)-2(5H)furanone, 5-Ethyl-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1Η-[ 1 ]benzopyrano[3,4-fjquinoline, 2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1Jbenzopyrano[3,4-fJquinoline-5-carboximidic acid ethyl ester, 5-(3-fluorophenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4-quinoline, 5-(4-fluorophenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline, 5-(3-bromophenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4-x]quinoline, 5-(3-Fluoro-4-methylphenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1Jbenzopyrano[3,4fquinoline, 5-[2-(Chloromethyl)-2-propenyl]-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H[1Jbenzopyrano[3,4-fjquinoline, 2,5-dihydro-10-methoxy-2,2,4-trimethyl-(-methylene-1Η-[ 1Jbenzopyrano[3,4ftJquinoline-5-propanol acetate, (ester) 5-(3,5-difluorophenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[ljbenzopyrano[3,4fjquinoline, 5-(4-fluorophenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[ljbenzopyrano[3,4-fquinoline, 5-[3,5-bis(trifluoromethyl)phenylj-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H[ 1 ]benzopyrano[3,4-fquinoline, (-)-5-(3,5-dichlorophenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[ljbenzopyrano[3,4fjquinoline, (+)-5-(3,5-dichloropheny 1)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1-1H-[l]benzopyrano[3,4fjquinoline, 5-(3,4-dimethylphenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[ljbenzopyrano[3,4fjquinoline, 5-(4-chlorophenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1Η-[1jbenzopyrano[3,4-quinoline, 5-(3,5-dimethylphenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1Η-[1jbenzopyrano[3,4fjquinoline, 5-(3-chlorophenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-quinoline, 5-Butyl-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-fquinoline, 5-(3,5-dichlorophenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[ljbenzopyrano[3,4fjquinoline, 5-[3-(2-furanyl)-5-methylphenyl]-2 _J 5-dihydro-10-methoxy-2,2,4-trimethyl-1H[ 1 ]benzopyrano[3,4-quinoline, 5-(3-Bromo-5-methylphenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1Η-[1Jbenzopyrano[3,4fjquinoline, acetate 3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1Η-[1Jbenzopyrano[3,4-rijno li n-5yl)phenol (ester), 5-(3,5-Dichlorophenyl)-2,5-dihydro-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolin-10yl]methylcarbonate. 5-(3,5-Dichlorophenyl)-2,5-dihydro-2,2,4-trimethyl-1H-[1-benzopyrano[3,4-1-quinolin-10-ol, 5-(3,5-dichlorophenyl)-2,5-dihydro-2,2,4-trimethyl-N-(2-propenyl)-1H-[1]benzopyrano[3,4fquinolin-10-amine and 5. The compound of claim 2, wherein the substituent R1 is -Lj-Ra, Lj is a covalent bond and the substituent Ra is -NR7R7'. 310 • ··· φ φ φφφφ φ φ φ φ φ φ φφ φ · · · · φ φφ φ φ φφ * φ · ΦΦΦΦΦ · · · φ φ φφφφ φφ φφ φφ φφ 5-Butyl-2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fjquinoline, (-) (5S,3'S) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl 1-5-(3-cyclopentenyl)-1H[1jbenzopyrano[3,4-f]quinoline, (-) (5 S,3'R)2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cyclopentenyl)-1H[1]benzopyrano[3,4-quinoline, 5-(2-cyclohexen-1-yl)-2,5-dihydro-9,10-dimethoxy-2,2,4-trimethyl-1Η-[1jbenzopyrano[3,4fjquinoline, 5-[(2-fluorophenyl)methylene)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[ljbenzopyrano[3,4fjquinoline, • · 0 0 • 0 0 0 0 · 0 0 0 0 0 • 0 «000 00 295 0 0 0 · 0 0 0 0 0 0 0 0 0 W 0 0 000 0 0 • · 0 0 «0 «0 5-[(2,6-dichlorophenyl)methylene)-2,5-dihydro-10-triethoxy-2,2,4-trimethyl-1H[1]benzopyrano[3,4-quinoline, 5-[(2-chlorophenyl)methylene]-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline, 5-[(2,6-difluorophenyl)methylene j-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H[1]benzopyrano[3,4-quinoline, 5-[(4-chlorophenyl)methylene]-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1jbenzopyrano[3,4fjquinoline, 5-[(3,5-dichlorophenyl)methylene]-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H[1]benzopyrano[3,4-quinoline, 5-[3-(2-furanyl)phenyl-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline, 5-(3-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)phenyl]-2,5-dihydro-10-methoxy-2,2,4-trimethyl1Η-[ 1 ]benzopyrano[3,4-fquinoline, ethyl 3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolin-5yl)benzoate, 5-[3-(2,4-dinitrophenoxy)phenyl-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f)quinoline, 5-(3-hexyloxyphenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1Jbenzopyrano[3,4fquinoline, 5-[3-(cyclopropylmethoxy)phenyl-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline, 5-(3,5-dichlorophenyl)-10-ethoxy-2,5-dihydro-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline, 5-(3-butenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1Jbenzopyrano[3,4-fJquinoline, 5-ethyl-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline, 2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline-5-carboximidic acid ethyl ester, 5-(3-fluorophenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline, 5-(4-Fluorophenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-flquinoline,, 5-(3-bromophenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-x]quinoline, 5-(3-Fluoro-4-methylphenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline, 5-[2-(chloromethyl)-2-propenyl]-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H[ 1 ]benzopyrano[3,4-f]quinoline, 2,5-dihydro-10-methoxy-2,2,4-trimethyl-(-methylene- 1Η-[ 1 ]benzopyrano[3,4f]quinoline-5-propanol acetate (ester), 5-(3,5-difluorophenyl)-2,5-dihydro-10-triethoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline, 5-(3,4-Dimethylphenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline, 5_(4_fl _UO rphenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline, 5-[3,5-bis(trifluoromethyl)phenyl]-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H[1]benzopyrano[3,4-f]quinoline, (-)-5-(3,5-dichlorophenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl- 1Η-[ 1 ]benzopyrano[3,4f]quinoline, (+)-5-( _3j 5-dichlorophenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4f]quinoline, 5-(4-chlorophenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline, 5-(3,5-dimethylphenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4f]quinoline, 5-(3-chlorophenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4-quinoline, 5-butyl-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-quinoline, 5-(3,5-dichlorophenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[ljbenzopyrano[3,4fjquinoline, 5-[3-(2-furanyl)-5-methylphenyl-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H[1]benzopyrano[3,4-quinoline, 5-(3-bromo-5-methylphenyl)-2,5-dihydro-10-methoxy-2,2,4-trimethyl-1Η-[ 1 ]benzopyrano[3,4fquinoline, 3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[ 1 ]benzopyrano[3,4-fquinolin-5yl)phenol acetate (ester), 6. A compound according to claim 5 selected from: 7.9- Dibromo-5-[1-methyl-3-cyclohexenyl]-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H[ 1 jbenzopyrano [3,4-fquinoline, 7.9-Dibromo-5-[cyclohexen-3-yl-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H[1]benzopyrano[3,4-1]quinoline, 7.9- Dibromo-10-methoxy-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4]quinoline, 7-bromo-5-[1-methyl-3-cyclohexenyl-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H[1]benzopyrano[3,4-quinoline, 7-bromo-5-[3-cyclohexenyl]-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1-H[ 1 jbenzopyrano[3,4-fquinoline, 7. The compound of claim 2, wherein the substituent R1 is -Li-Ra, L2 is -C(X)X'-, X and X' are -O-, and the substituent R2 is alkyl having one to twelve carbon atoms which may be optionally substituted. 7.9-Dibromo-5-[1-methyl-3-cyclohexenyl]-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H[1]benzopyrano[3,4-f]quinoline, 7.9- Dibromo-5-[cyclohexen-3-yl]-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H[ 1 ]benzopyrano[3,4-quinoline, 7.9-dibromo-10-methoxy-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4-quinoline, 7-bromo-5-[1-methyl-1-3-cyclohexenyl]-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H[1]benzopyrano[3,4-f]quinoline, 7-bromo-5-[3-cyclohexenyl]-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H-[1]benzopyrano[3,4fquinoline, 8-fluoro-10-methoxy-5-phenyl-2,2,4-trimethyl-2,5-dihydro-1H-[1Jbenzopyrano[3,4-f]quinoline, 5-(3-propenyl)-8-fluoro-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H-[1]benzopyrano[3,4-f]quinoline, (10-methoxy-9-fluoro-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4fquinoline, 8. A compound according to claim 7 selected from: methyl 2,5-dihydro-2,2,4-trimethyl-5-(2-propenyl)-1H-[1]benzopyrano[3,4-quinoline-10carboxylate and methyl 2,5-dihydro-5-phenyl-2,2,4-trimethyl-1Η-[1jbenzopyrano[3,4-quinoline-10-carboxylate. 8-fluoro-10-methoxy-5-phenyl-2,2,4-trimethyl-2,5-dihydro-1 H-[ 1 ]benzopyrano[3,4-fjquinoline, 5-(3-propenyl)-8-fluoro-10-methoxy-2,2,4-trimethyl-2,5-dihydro- 1Η-[ 1 ]benzopyrano[3,4-fjquinoline, (10-methoxy-9-fluoro-5-(3 -propenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4f]quinoline, 9-(Dimethylaminothiocarbonyl)-oxy-10-methoxy-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5dihydro-[ 1 ]benzopyrano[3,4-f]quinoline, (+/-) 2,5-dihydro-9-(N-carbamoyl-2-aminoacetoxy)-10-methoxy-2,2,4-trimethyl-5-allyl-1H[1 ]benzopyrano[3,4-f]quinoline, (+/-) 2,5 -dihydro-9-(4-ethoxy-4-oxo-butoxy)-10-methoxy-2,2,4-trimethyl-5 -allyl-1H[ 1 ]benzopyrano[3,4-f]quinoline, φφ φφ » · · ' • Φ 4 342 (+/-) 2,5-Dihydro-9-(4-oxo-pentanoyloxy)-10-methoxy-2,2,4-trimethyl-5-allyl-1H[ljbenzopyrano[3,4-fquinoline, 9-hydroxy-10-methoxy-5-(phenylmethylene)-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-quinoline, 9-(2-ethoxy-2-oxo-ethylaminocarbonyl)-oxy-10-methoxy-5-(3-propenyl)-2,2,4-trimethyl-1H2.5-dihydro-[1]benzopyrano[3,4-fquinoline, (+/-) 2,5-dihydro-9-(3-acetamido-propanoyloxy)-10-methoxy-2,2,4-trimethyl-5-allyl-1H[1 ]benzopyrano[3,4-fquinoline, (+/-) 2,5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-benzyl-1H-[l]benzopyrano[3,4fquinoline, 9 9 9 · • Φ Φ 9 99 φ* (-) (5 S,3 'S) 2,5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-( 1 -methylcyclohexen-3 -yl)1 H-[ 1 ]benzopyrano[3,4-fjquinoline, (-) (5S,3'R) 2,5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-( 1 -methylcyclohexen-3-yl) -yl)1 H-[ 1 ]benzopyrano[3,4-f]quinoline, (+) (5R,3'S) 2,5 -dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-( 1 -methylcyclohexen-3 -yl)1 Η-[ 1Jbenzopyrano[3,4-f]quinoline, (+) (5R,3'R) 2,5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-( 1 -methylcyclohexen-3-yl)1 H-[ 1 Jbenzopyrano[3,4-f]quinoline, (+/-) 2,5-dihydro-9-(4-N,N-dimethylamino-4-oxo-butanoyloxy)-10-chloro-2,2,4-trimethyl-5allyl- 1Η-[ 1 ]benzopyrano[3,4-f]quinoline, (-) 2,5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-cyclopentyl-1Η-[1]benzopyrano[3,4fjquinoline, 9 9 9999 99 341 ·· 99 • · 9 9 • 9 9 9 9-hydroxy-10-chloro-5-([2-pyridyl)methylene)-2,2,4-trimethyl-1H-2,5-dihydro[ 1 ]benzopyrano[3,4-fJquinoline, re/-(5S)-9-hydroxy-5-[(3S)-(1-hydroxymethyl)cyclohexen-3-ylJ-10-chloro-2,2,4-trimethyl-1H-2,5-dihydro[1] ]benzopyrano[3,4-f]quinoline, r/-(5S)-9-hydroxy-5-[(3S)-(1-methoxycarbonyl)cyclohexen-3-yl]-10-methoxy-2,2,4trimethyl-2,5-dihydro-1H-[l]benzopyrano[3,4-f]quinoline, 9-hydroxy-10-methoxy-5-(phenylmethylene)-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-f]quinoline, 9-hydroxy-10-chloro-5-(phenylmethylene)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4fquinoline, 9-hydroxy-10-methoxy-5-ethyl-2,2,4-trimethyl-2,5-dihydro-lH-[ljbenzopyrano[3,4fjquinoline, (+/-) 2,5-dihydro-9-cyanomethoxy-10-methoxy-2,2,4-trimethyl-5-allyl-lH[ 1jbenzopyrano[3,4-fjquinoline, 9-hydroxy-10-methoxy-5-(3,4-difluorophenyl)methylidene-2,5-dihydro-5-phenyl-2,2,4-trimethyl1Η-[ 1 jbenzopyrano[3,4-fjquinoline, (Z) 9-hydroxy-10-methoxy-5-((4-fluorophenyl)methylene)-2,2,4-trimethyl-lH-2,5-dihydro[ 1 ]benzopyrano[3,4-fjquinoline, [Z]-9-hydroxy-10-methoxy-5-([2,3-difluorophenyljmethylene)-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-quinoline, Z-5-(3-fluorobenzylideneyl)-10-methoxy-9-hydroxy-2,2,4-trimethyl-2,5-dihydro-1H[ 1 jbenzopyrano[3,4-fquinoline, rc/-(5S,3 ^, R )-9-hydroxy-5-[1-methoxymethyl-3-cyclohexenyl]-10-chloro-2,2,4-trimethyl-2,5-dihydro-1H[ 1 ]benzopyrano[3,4-quinoline, 9-hydroxy-10-methoxy-5-(3,5-difluorophenyl)niethylidene-2,5-dihydro-5-phenyl-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-quinoline, 9.10-dimethoxy-5-[3-cyclohexenyl-methoxy-2,2,4-trimethyl-2,5-dihydro-1H[1]benzopyrano[3,4-fj quinoline, 9.10-dimethoxy-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4fquinoline, 9-chloro-10-difluoromethoxy-5-phenyl-2,2,4-trimethyl-2,5-dihydro-1Η-[1Jbenzopyrano[3,4fjquinoline, 9-chloro-10-methoxy-5-phenyl-2,2,4-trimethyl-2,5-dihydro-1H-[1]benzopyrano[3,4-f]quinoline, 9-10-methylenedioxy-5-phenyl-2,2,4-trimethyl-1H-2,5-dihydro-[1Jbenzopyrano[3,4-fJquinoline, 5-(3-propenyl)-9-chloro-10-ethenyl-2,2,4-trimethyl-2,5-dihydro-1H-[1Jbenzopyrano[3,4-fjquinoline, 9 9 328 .......... methyl 2-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1Η-[1Jbenzopyrano[3,4-f|quinolin-5yl)acetylhydroxamate, 9 9 * ♦ • 9 9 « ♦ Β · · « • Β · · • Β ΒΒΒ or pharmaceutically acceptable salts or prodrugs thereof, wherein the substituents R ₁ , R 2 , R ₃ , R 4 R 5 , R 6 and L ₂ are as defined above. R16 and R17 are independently hydrogen or alkyl having one to six carbon atoms; and R17 and R18 are independently hydrogen or alkyl having one to six hydrogen atoms; or R18 and R19 together are a cycloheteroalkyl ring or a cycloalkyl ring having three to eight carbon atoms; 9 B · 9 9 • ♦ B B-· · · 99 99 9 * •··· ·9 9-hydroxy-10-chloro-5-(phenylmethylene)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4fjquinoline, and 9. The compound of claim 2, wherein the substituent R1 is -Li-Ra, Li is -X'(C)X-, X and X are -O-, and the substituent R2 is alkyl having one to twelve carbon atoms which may be optionally substituted. 9-(Dimethylaminothiocarbonyl)-oxy-10-methoxy-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5dihydro-[1]benzopyrano[3,4-fquinoline, (+/-) 2,5-dihydro-9-(N-carbamoyl-2-aminoacetoxy)-10-methoxy-2,2,4-trimethyl-5-allyl-1H[ 1 ]benzopyrano[3,4-f]quinoline, (+/-) 2,5-dihydro-9-(4-ethoxy-4-oxo-butoxy)-10-methoxy-2,2,4-trimethyl-5-allyl-1H[ 1 ]benzopyrano[3,4-f]quinoline, (+/-) 2,5-dihydro-9-(4-oxo-pentanoyloxy)-10-methoxy-2,2,4-trimethyl-5-allyl-1H[1]benzopyrano[3,4-f]quinoline, 9-hydroxy-10-methoxy-5-(phenylmethylene)-2,2,4-trimethyl-1H-2,5-dihydro[l]benzopyrano[3,4-f]quinoline, • · • · ♦ · • · · • ·« · · 309 9-(2-ethoxy-2-oxo-ethylaminocarbonyl)-oxy-10-methoxy-5-(3-propenyl)-2,2,4-trimethyl-1H2.5-dihydro-[1]benzopyrano[3,4-fjquinoline, (+/-) 2,5-dihydro-9-(3-acetamido-propanoyloxy)-10-methoxy-2,2,4-trimethyl-5-allyl-1H[ 1]benzopyrano[3,4-quinoline, 9-hydroxy-10-methoxy-5-([3-fluorophenyl]methylene)-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-quinoline, r /-(5S)-9-hydroxy-5-](3S)-(1-methoxycarbonyl)cyclohexen-3-yl]-10-methoxy-2,2,4trimethyl-2,5-dihydro-1H-[1]benzopyrano[3,4-f]quinoline, 9-hydroxy-10-methoxy-5-(phenylmethylene)-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-x]quinoline, 9-hydroxy-10-methoxy-5-ethyl-2,2,4-trimethyl-2,5-dihydro-1H-[1Jbenzopyrano[3,4fjquinoline, 307 (+/-) 2,5-dihydro-9-cyanomethoxy-10-methoxy-2,2,4-trimethyl-5-allyl-1H[ 1 jbenzopyrano[3,4-fquinoline, 9-hydroxy-10-methoxy-5-(3,4-difluorophenyl)methylidene-2,5-dihydro-5-phenyl-2,2,4-trimethyl1Η-[ 1 ]benzopyrano[3,4-fjquinoline, (Z) 9-hydroxy-10-methoxy-5-((4-fluorophenyl)methylene)-2,2,4-trimethyl-lH-2,5-dihydro[ 1 Jbenzopyrano[3,4-f] quinoline, (Z)-9-hydroxy-10-methoxy-5-([2,3-difluorophenyl Jmethylene)-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-fJquinoline, Z-5-(3-fluorobenzylideneyl)-10-methoxy-9-hydroxy-2,2,4-trimethyl-2,5-dihydro-1H[1]benzopyrano[3,4-quinoline, 9-hydroxy-10-methoxy-5-(3,5-difluorophenyl)methylidene-2,5-dihydro-5-phenyl-2,2,4-trimethyl1Η-[ 1 Jbenzopyrano[3,4-fJquinoline, 9 9 · • · · • · · 9 9 9 9* 99 9.10-Dimethoxy-5-[3-cyclohexenyl]-methoxy-2,2,4-trimethyl-2,5-dihydro-1H[1]benzopyrano[3,4-quinoline, 9.10-dimethoxy-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4fquinoline, 9 ··* · · «·»·»« ·« « • « · · ····< ··*· ♦♦ ·· ♦ · «· «· (+) (5R,3’S) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-[ 1 -ethyl-3-cyclohexenylJ1 H-[ 1 ]benzopyrano[3,4-f]quinoline, 9-chloro-10-difluoromethoxy-5-phenyl-2,2,4-trimethyl-2,5-dihydro-1H-[1]benzopyrano[3,4fquinoline, 9-chloro-10-methoxy-5-phenyl-2,2,4-trimethyl-2,5-dihydro-lH-[l]benzopyrano[3,4-f]quinoline, 5-(3-propenyl)-9-chloro-10-difluoromethoxy-2,2,4-trimethyl-2,5-dihydro-lH[ 1 ]benzopyrano[3,4-f]quinoline, 9-10-methylenedioxy-5-phenyl-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4-fjquinoline, 5-(3-propenyl)-9-chloro-10-ethenyl-2,2,4-trimethyl-2,5-dihydro-1H-[1]benzopyrano[3,4f]quinoline, 9 9 · · > ΦΦΦΦ ΦΦ ΦΦ ΦΦ 296 ·· ΦΦ Φ ♦ Φ Φ « · Φ Φ • 9 φ Φ Φ Φ Φ Φ 9 9 9 9 9 9 •9 99 99 9 999 9 9 99 9 9 9 9 9 9 9 9 9 99 · · · ····· <$· · • · · 9 9 9 9 9 99 99 99 99 99 (xxv) -NR7(X)NRs R9- or the substituents R20 and R21 together are selected from (a) cycloalkyl having three to twelve carbon atoms, (b) cycloalkenyl having four to twelve carbon atoms, and (c) &23 (allen), wherein the substituents R22 and R23 are independently hydrogen or alkyl having one to twelve carbon atoms, and (11) cycloalkenyl having four to twelve carbon atoms, wherein together the cycloalkenyl group or the ring formed by the substituents _R2 and R21 may be substituted with one or two substituents independently selected from (a) alkoxy having one to twelve carbon atoms, (b) -OH, with the proviso that no two -OH groups are attached to the same carbon atom (c) -SH, with the proviso that no two -OH groups are attached to the same carbon atom -SH groups, (d) -CN, (e) halogen, (f) -CHO, (g) -NO2, (h) haloalkoxy groups having one to twelve carbon atoms, (i) perfluoroalkoxy groups having one to twelve carbon atoms, 0) -NR8- _R9 , (to) =NNRgR ₉ , (O -NR7NR.8 R ₉ ·, (m) -CO2R10, (n) -C(X)NR8R ₉ - (0) =N-OR ₁₀ , (P) =NR ₁₀ , (q) ~S(0)tRio, (r) -X'C(X)Rio, (s) (=X), • · 9 4 4 4 4 4 8 4 4 4 9 » *»· » » · ·»· · · *· · • « » 9 9 9 8 4 9 4944 44 44 4 4 94 44 (a) -OH, with the proviso that no two -OH groups are attached to the same carbon atom, (b) -SH, with the proviso that no two -SH groups are attached to the same carbon atom, (c) -CN, (d) halogen, (e) -CHO, (t) -no ₂ , (g) haloalkoxy groups having one to twelve carbon atoms, (h) perfluoroalkoxy groups having one to twelve carbon atoms, In (i) -NRg Rs»', where the substituents Rg and R<r are selected from (i) a hydrogen atom, (ii) alkanoyl, where the alkyl moiety has one to twelve carbon atoms, (iii) alkoxycarbonyl, where the alkyl moiety has one to twelve carbon atoms, (iv) alkoxycarbonyl, where the alkyl moiety has one to twelve carbon atoms and is substituted with 1 or 2 phenyl substituents, (v) cycloalkyl having three to twelve carbon atoms, (vi) alkyl having one to twelve carbon atoms, (vii) alkyl having one to twelve carbon atoms substituted with 1, 2 or 3 substituents independently selected from alkoxy having one to twelve carbon atoms, cycloalkyl having three to twelve carbon atoms, aryl and alkoxycarbonyl, where the alkyl moiety has one to twelve carbon atoms, (viii) alkenyl having three to twelve carbon atoms, with with the proviso that the carbon of the carbon-carbon double bond is not directly attached to the nitrogen, (ix) alkynyl having three to twelve carbon atoms, with the proviso that the carbon of the carbon-carbon triple bond is not directly attached to the nitrogen, (x) -C(O)NRxRy, where the substituents Rx and Ry are independently selected from hydrogen and alkyl having one to twelve carbon atoms, (xi) alkoxy groups having one to twelve carbon atoms, (c) (d) (e) (t) (g) (h) (0 SH-groupZ....... ..... ......'------CN, halogen, -CHO, -no ₂ , haloalkoxy groups having one to twelve carbon atoms, perfluoroalkoxy groups having one to twelve carbon atoms, -NRg-Ry·, where the substituents Rg and R9- are represented by (i) a hydrogen atom, (ii) (iii) (iv) / alkanoyl, where the alkyl part has one to twelve carbon atoms, / alkoxycarbonyl, where the alkyl moiety has one to twelve carbon atoms, alkoxycarbonyl, where the alkyl moiety has one to twelve carbon atoms and is substituted with 1 or 2 phenyl substituents, / (v) cycloalkyl having three to twelve carbon atoms, / (vi) alkyl having one to twelve carbon atoms, (vii) alkyl having one to twelve carbon atoms substituted with 1, 2 Z or 3 substituents independently selected from alkoxy groups having one/ to twelve carbon atoms, cycloalkyl having three to twelve carbon atoms / carbon, arylalkoxycarbonyl, where the alkyl group has one to twelve carbon atoms, / (viii) alkenyl having three to twelve carbon atoms, with the proviso that the carbon of the carbon-carbon double bond is not directly attached to the nitrogen, (ix) alkynyl having three to twelve carbon atoms, / with the proviso that the carbon of the carbon-carbon triple bond is not ^directly attached to the nitrogen, -C(O)NRxRy, where the substituents Rx and Ry are independently selected from hydrogen and alkyl having one to twelve carbon atoms, -'(xi)·--a-phenyloxy groups having one to twelve carbon atoms, (xii) aryl, and (xiii) aryl substituted with 1, 2, 3, 4 or 5 substituents independently selected from alkyl having one to twelve carbon atoms, alkanoyloxy groups, where the alkyl portion has one to twelve carbon atoms, alkoxycarbonyl, where the alkyl portion has one to twelve carbon atoms, alkoxy groups having one to twelve carbon atoms, halogen, -OH with the proviso that two -OH groups are not attached to the same carbon atom, thioalkoxy groups having one to twelve carbon atoms, perfluoroalkyl having one to twelve carbon atoms, -NR7R7', -co ₂ r _I0 , -OSO2R11, and (=X) or the substituents R«· and R9- together with the nitrogen atom to which they are attached form a ring selected from (i) aziridine, (ii) azetidine, (iii) pyrrolidine, (iv) piperidine, (v) pyrazine, (vi) morpholine, (vii) phthalimide, (viii) thiomorpholine, and (ix) thiomorpholine sulfone wherein (i) - (ix) may be optionally substituted with 1, 2 or 3 alkyls having one to twelve carbon substituents, (j) =nnr ₈ -r ₉ ·, (k) -NRzNRs-Rs»·, (l) -CO2R8, (m) -C(X)NRsR ₉ -, (n) =N-ORs, (o) =NR«, (p) -StOjtRw, (q) -X'C(X)R ₈ , (=X), « · 4 4 4 ···*« · « « V 4 · · » • * * · *« (r) (s) (t) (u) (v) (w) -O-(CH ₂ ) _q -ZR _I0 , where the substituent R 10 is as defined above, the index q is 1, 2 or 3 and Z is O or -S(O\-, -OC(X)NR8-R ₉ ·, -oso ₂ r„, alkanoyloxy groups, where the alkyl group has one to twelve carbon atoms, -LbRbo, where L _B is selected from (i) a covalent bond, (ii) -O-, (iii) -S(O>, and (iv) -C(X)-, and the substituent R30 is selected from (i) alkyl having one to twelve carbon atoms, (ii) alkenyl having one to twelve carbon atoms, with the proviso that the carbon of the carbon-carbon double bond is not directly attached to L _B , if L _B is other than a covalent bond, (iii) alkynyl having one to twelve carbon atoms, with the proviso that the carbon of the carbon-carbon triple bond is not directly attached to L _B , if L _B is other than a covalent bond, where (i), (ii) and (iii) may be optionally substituted with cycloalkyl having three to twelve carbon atoms, -OH with the proviso that no two -OH groups are attached to the same carbon atom, a carbon atom, a halogen, an alkoxy group having one to twelve carbon atoms, a thioalkoxy group having one to twelve carbon atoms, -NR8R9', -O-(CH ₂ ) _q -Z-R 10 , alkoxycarbonyl, where the alkyl group has one to twelve carbon atoms, alkanoyloxy groups, where the alkyl group has one to twelve carbon atoms, ^3 » 0 000 -NR ₇ SO ₂ -(alkyl having one to twelve carbon atoms), -OSO ₂ -(alkyl having one to twelve carbon atoms), aryl, and heterocycles, (iv) aryl, (v) aryl substituted with 1, 2, 3, 4 or 5 substituents independently selected from alkyl having one to twelve carbon atoms, halogen, -NO ₂ , and -OH, with the proviso that no two -OH groups are attached to the same carbon atom, (vi) heterocycles, and (vii) heterocycles substituted with 1, 2, 3, 4, or 5 substituents independently selected from alkyl having one to twelve carbon atoms, halogen, -NO ₂ , and -OH with the proviso that two -OH groups are not attached to the same carbon atom, (x) -X'C(X)XRio, (y) -NHC(O)NHNH ₂ , (z) an alkenyl having two carbon atoms, (aa) -C(=NR ₇ )ORio, and (bb) -NR ₇ (X)NRs-R ₉ ', ^20 IN" Rj ₉ with the proviso that when the substituent Rs is (9), then L ₃ is other than -NR ₇ - or -O-, wherein the carbon-carbon double bond has the Z or E configuration and the substituents R19, R20 and R ₂ i are independently selected from (a) hydrogen, (10) 'Ví f « « · · · « · - ···· ·« *· ·· »· A*V (b) halogen, (c) alkoxycarbonyl, where the alkyl group has one or twelve carbon atoms, (d) alkyl having one to twelve carbon atoms, and (e) alkyl having one to twelve carbon atoms substituted with (i) alkoxy having one to twelve carbon atoms, (ii) -OH, with the proviso that no two -OH groups are attached to the same carbon atom, (iii) -SH, with the proviso that no two -SH groups are attached to the same carbon atom, (iv) -CN, (v) halogen, (vi) -CHO, (vii) -NO2, (viii) haloalkoxy groups having one to twelve carbon atoms, (ix) perfluoroalkoxy groups having one to twelve carbon atoms, (x) -NRb'R9', (xi) =NNR ₈ -R ₉ -, (xii) -NRvNRA·, (xiii) -CO2R10, (xiv) -C(X)NR«R ₉ , (xv) =N-ORio, (xvi) =NRio, (xvii) -S(0)tRio, (xviii) -X'C(X)Rio, (xix) (=X), (xx) -O-(CH ₂ ) _q -ZR ₁₀ , (xxi) -OC(X)NRs-R ₉ -, (xxii) -LsRao, (xxiii) alkanoyloxy groups, where the alkyl group has one or twelve carbon atoms, (xxiv) -OSO2R11, and 9 4 9 9 4 9 4 4 9 4 4 8 9 9 9 9 9 9 9 9 9 278 ····........ ·· (c) alkoxy groups having one to twelve carbon atoms, (d) halogen, (e) alkoxycarbonyl, where the alkyl group has one to twelve carbon atoms, and (f) -OH, with the proviso that two -OH groups are not attached to the same carbon atom, (19) perfluoroalkyl having one to twelve carbon atoms, (20) aryl, and (21) heterocycles, where (20) and (21) may be optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from (a) alkyl having one to twelve carbon atoms, (b) alkanoyloxy groups, where the alkyl portion has one to twelve carbon atoms, (c) alkoxycarbonyl, where the alkyl portion has one to twelve carbon atoms, (d) alkoxy groups having one to twelve carbon atoms, (e) halogen, (f) -OH, with the proviso that no two -OH groups are attached to the same carbon atom, (g) thioalkoxy groups having one to twelve carbon atoms, (h) perfluoroalkyl having one to twelve carbon atoms, (i) -NR7R7', (j) -CO2R10, (k) -OSO2R11, and (0 (=x); the substituents R ₂ , R ₃ and R 4 are independently hydrogen or R 8 or the substituents R 1 and R ₂ together are -X -Y -Z -, where X is -O- or -CH ₂ ~, Y is -C(O)- or (C(R ₁ )(R ₃ )) _v -, where the substituents R 12 and R 1n are independently hydrogen or alkyl having one to twelve carbon atoms and the index v is 1, 2 or 3 and Z is selected from -CH ₂ -, -CH ₂ S(O) t -, -CH ₂ O-, -CH ₂ NR ₇ -, -NR ₇ - and -O-; • · · 0 279 • · » 0 · 0 « « · · · L ₂ is selected from (1) a covalent bond, (2) alkylene having one to twelve carbon atoms, (3) alkylene having one to twelve carbon atoms substituted with 1 or 2 substituents independently selected from (a) spiroalkyl having three to eight carbon atoms, (b) spiroalkenyl having five or eight carbon atoms, (c) oxo, (d) halogen, and (e) -OH, with the proviso that no two -OH groups are attached to the same carbon atom, (4) alkynylene having two to twelve carbon atoms, (5) -NR ₇ -, (6) -C(X)-, (7) -O-, and (8) -S(O)r; and R5 is selected from (1) halogen, (2) hydrogen, (3) -C(= _NR7 ) _OR10 , (4) -CN, with the proviso that if R5 is (1), (2) or (3) then L2 is a covalent bond, (5) alkyl having one to twelve carbon atoms, (6) alkynyl having up to twelve carbon atoms, with the proviso that the carbon of the carbon-carbon triple bond is not directly attached to L3 if L3 is other than a covalent bond, (7) cycloalkyl having three to twelve carbon atoms, (8) heterocycle, (9) aryl wherein (5) - (9) may be optionally substituted with 1,2, 3, 4 or 5 substituents independently selected from 280 r« »· »♦ *· »· ·* 9 999 9 9 9 999 9 9 99 · 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 99 99 (j) alkynyl having three to twelve carbon atoms, with the proviso that the carbon of the carbon-carbon triple bond is not directly attached to the nitrogen (6) -NRsC(X)NR9-, where X is O or S and Rs and Rg are independently selected from (a) hydrogen, (b) aryl, (c) cycloalkyl having three to twelve carbon atoms, (d) alkyl having one to twelve carbon atoms, (e) alkyl having one to twelve carbon atoms substituted with 1 or 2 substituents independently selected from aryl or cycloalkyl having three to twelve carbon atoms, (f) alkenyl having three to twelve carbon atoms, with the proviso that the carbon of the carbon-carbon double bond is not directly attached to the nitrogen (g) alkynyl having three to twelve carbon atoms, with the proviso that the carbon the carbon-carbon triple bond is not directly attached to the nitrogen (7) -X'C(X)-, where X is as defined above and X' is O or S, (8) -C(X)X'-, (9) -X'C(X)X-, where X and X' are as defined above and X is O or S, with the proviso that if X is O, then at least one of X' or X is O, (10) -NRsC(X)-, (11) -C(X)NRs-, (12) -NRsC(X)X'-, (13) -X'C(X)NR8-, (14) -SO ₂ NR8-, (15) -NRsSOi- and (16) -NRgSOiNRgwhere (6) - (16) are drawn with their right ends attached to a substituent Ra selected from (1) -OH, (2) -OG, where G is an -OH protecting group, (3) -SH, • Φ φφ φ « φ φ φ φ φ φ φ φ φ φφφ φ φ φ φφ φ* 275 φφ • Φ φ · · · φ φ φ φφφ φ φφφφ φφφ φ* φφ φ · φ φ φ φ * φ φ φ φ φ φ φ φ φ φ φφ φφ φφ (4) -CO2R20, where R20 is hydrogen or alkyl having one to twelve carbon atoms, (5) alkoxycarbonyl, (6) -CN, (7) halogen, (8) haloalkoxy group having one to twelve carbon atoms, (9) perfluoroalkoxy group having one to twelve carbon atoms, (10) -CHO, (11) -NR7R7, where R7 is as defined above and R7 is selected from (a) hydrogen, (b) aryl, (c) cycloalkyl having three to twelve carbon atoms, (d) alkanoyl, where the alkyl moiety has one to twelve carbon atoms, (e) alkoxycarbonyl, where the alkyl moiety has one to twelve carbon atoms carbon atoms (f) alkoxycarbonyl, where the alkyl portion has one to twelve carbon atoms and is substituted with 1 or 2 aryl groups, (g) alkyl having one to twelve carbon atoms, (h) alkyl having one to twelve carbon atoms substituted with 1 or 2 substituents independently selected from (i) aryl and (ii) cycloalkyl having three to twelve carbon atoms, (i) alkenyl having three to twelve carbon atoms, with the proviso that the carbon of the carbon-carbon double bond is not directly attached to the nitrogen (j) alkynyl having three to twelve carbon atoms, with the proviso that the carbon of the carbon-carbon triple bond is not directly attached to the nitrogen (12) -C(X)NR ₈ R ₉ , (13) -OSO2R11, where the substituent R 1 is selected from (a) aryl, (b) cycloalkyl having three to twelve carbon atoms carbon, (c) alkyl having one to twelve carbon atoms, (d) alkyl having one to twelve carbon atoms substituted with 1, 2, 3 or 4 halogen substituents and 276 φφφ •φφφ ·· »* φφ ·· ♦ · • · · · * * φ · • Φ · · Φ Φ Φ · • · ΦΦΦΦΦ * · · • Φ Φ ΦΦΦΦ ΦΦ «Φ ΦΦ ΦΦ (e) perfluoroalkyl having one to twelve carbon atoms, (14) alkyl having one to twelve carbon atoms, (15) alkenyl having two to twelve carbon atoms, with the proviso that the carbon of the carbon-carbon double bond is not directly attached to Li if Li is other than a covalent bond, (16) alkynyl having two to twelve carbon atoms, with the proviso that the carbon of the carbon-carbon triple bond is not directly attached to Li if Li is other than a covalent bond, wherein (14), (15) and (16) may be optionally substituted with 1, 2 or 3 substituents independently selected from (a) alkoxy having one to twelve carbon atoms, (b) -OH, with the proviso that two -OH groups are not attached to the same carbon atom, (c) -SH, (d) thioalkoxy having one to twelve carbon atoms, with the proviso that no two -SH groups, (e) -CN, (f) halogen, (g) -CHO, (h) -NO ₂ , (i) haloalkoxy groups having one to twelve carbon atoms, (j) perfluoroalkoxy groups having one to twelve carbon atoms, (k) -NR7R7', (l) =nnr ₇ r ₇ ·, (m) -NR7NR7 R7, where R7 and R7 are as defined above and R7 is selected from (i) hydrogen, (ii) aryl, (iii) cycloalkyl having three to twelve carbon atoms, (iv) alkanoyl, where the alkyl portion has one to twelve carbon atoms, (v) alkoxycarbonyl, where the alkyl portion has one to twelve carbon atoms, (vii) alkoxycarbonyl, where the alkyl portion has one to twelve carbon atoms ΦΦ φφ φφ φφ φφ φ φφφφ φφφφ φ φφφφ φφφφ φ φφφ φ φ φ φφφ φ · φ· φ φ φφφ φφφφφ φφφφ φφ φφ φφ φφ 277 substituted with 1 or 2 aryl groups, (vii) alkyl having one to twelve carbon atoms, (viii) alkyl having one to twelve carbon atoms substituted with 1 or 10-Methoxy-9-(cyclohexylaminocarbonyl)-oxy-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5dihydro-[1 Jbenzopyrano[3,4-quinoline, 10-difluoromethoxy-5-[[3-(methylthio)methoxyphenyl]-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-quinoline, 10-Methoxy-5-(1-butylidene)-2,5-dihydro-5-phenyl-2,2,4-trimethyl-1Η-[1]benzopyrano[3,4fjquinoline, 10-Methoxy-5-(1-methylpropylidene)-2,5-dihydro-5-phenyl-2,2,4-trimethyl-1H[1]benzopyrano[3,4-quinoline, 10-Methoxy-5-(but-3-enylidene)-2,5-dihydro-5-phenyl-1-2,2,4-trimethyl-1H-[1Jbenzopyrano[3,4fquinoline, 10-Methoxy-5-(pyridin-2-yl)methylidene-2,5-dihydro-5-phenyl-2,2,4-trimethyl-1H[1Jbenzopyrano[3,4-quinoline, 10-Methoxy-5-(6-chloropyridin-2-yl)methylidene-2,5-dihydro-5-phenyl-2,2,4-trimethyl-1H[ 1 jbenzopyrano[3,4-fquinoline, 10-Methoxy-5-(4,5-dimethyl-1,3-oxazol-2-yl)methylidene-2,5-dihydro-5-phenyl-2,2,4trimethyl-1Η-[1jbenzopyrano[3,4-quinoline, 10-Methoxy-5-(3-methylisoxazol-5-yl)methylidene-2,5-dihydro-5-phenyl-2,2,4-trimethyl-1H[1Jbenzopyrano[3,4-quinoline, 10-Methoxy-5-(5-methylisoxazol-3-yl)methylidene-2,5-dihydro-5-phenyl-2,2,4-trimethyl-1H[ 1 Jbenzopyrano [3,4-fquinoline, 10-(bromodifluoromethoxy)-5-phenyl-2,2-dimethyl-4-methylene-2,3,4,5-tetrahydro-1Hchromo[3,4-quinoline, 10-(bromodifluoromethoxy)-2,5-dihydro-5-phenyl-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fquinoline, 337 10-(difluoromethoxy)-2,5-dihydro-5-phenyl-2,2,4-trimethyl-1H-[1jbenzopyrano[3,4-quinoline, 10-Chloro-5-(3-propenyl)-2,2,4-trimethyl-2,5-dihydro-1H-[lJbenzopyrano[3,4-fquinoline, (+/-) 2,5-dihydro-10-chloro-2,2,4-trimethyl-5-phenyl-1H-[lJbenzopyrano[3,4-fquinoline, 10-methoxy-7-methyl-9-methyl-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano [3,4-fj quinoline, 10-Methoxy-7-acetyl-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[ljbenzopyrano[3,4fjquinoline, (+/-) 2,5-dihydro-9-methyl-10-methoxy-2,2,4-trimethyl-5-( 1 -methylcyclohexen-3 -y 1)-1H[ 1 Jbenzopyrano[3,4-fjquinoline, 10-methoxy-7-methyl-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4fquinoline, 10-Methoxy-7-(2-ethenyl)-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-quinoline, 335 .......... 10-methoxy-9-bromo-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4fquinoline, 10-methoxy-7-bromo-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4fquinoline, 10-Methoxy-9-(3-propynyloxy)-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-quinoline, 10-Methoxy-9-(3-propenyloxy)-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-f]quinoline, 10-methoxy-9-ethoxy-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1jbenzopyrano[3,4fjquinoline, 10-Methoxy-9-hydroxy-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1Jbenzopyrano[3,4f]quinoline, (+/-) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cyclohexenyl)-1H[1Jbenzopyrano[3,4-f]quinoline, (+/-) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(l-methylcyclohexen-3-yl)-1H[ 1 Jbenzopyrano[3,4-f]quinoline, (-) (5S,3'S)-9-hydroxy-5-[l-methyl-3-cyclohexenylJ-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H[ 1 Jbenzopyrano[3,4-fquinoline, • · · · · * · 331 (+) (5R,3'R)-9-hydroxy-5-[1-methyl-3-cyclohexenyl]-10-methoxy-2,2,4-trimethyl-2,5dihydro-1Η-[1]benzopyrano[3,4-f]quinoline, (+) (5R,3'S)-9-hydroxy-5-[1-methyl-3-cyclohexenyl)-10-methoxy-2,2,4-trimethyl-2,5dihydro-1 H-[ 1 ]benzopyrano[3,4-fquinoline, (-) (5S,3'R)-9-hydroxy-5-[ 1 -methyl-3-cyclohexenyl]-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H-[ 1]Benzopyrano[3,4-f]quinoline, rel-(5S,3'R)-9-hydroxy-5-[1-hydroxymethyl-3 -cyclohexenyl]-10-methoxy-2,2,4-trimethyl2,5 -dihydro-1 Η- [ 1 J benzopyrano [3,4-f | quinoline, (+/-) (5 S,3 'R) 2,5 -dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5 -(1 -methylcyclohexen-3 yl)- 1Η-[ 1 ]benzopyrano[3,4-f]quinoline, rel-(5 S,3 'R)-9-hydroxy-5-[I-methoxymethyl-3 -cyclohexenyl]-10-methoxy-2,2,4-trimethyl2,5-dihydro-1Η-[1]benzopyrano[3,4-quinoline, 10-chloro-9-hydroxy-5-(3,4-difluorophenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1Jbenzopyrano[3,4fquinoline, 10-Chloro-9-hydroxy-5-(3,5-dichlorophenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[l]benzopyrano[3,4fjquinoline, (+)-(5R,3'S) 2,5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(3-cyclopentenyl)-lH[1Jbenzopyrano[3,4-fjquinoline, (+)-(5R,3'R)2,5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(3-cyclopentenyl)-1H[1]benzopyrano[3,4-f]quinoline, 10-chloro-9-hydroxy-5-(3,5-dimethylphenyl)-2,2,4-trimethyl-1H-2,5-dihydro[ 1 ]benzopyrano[3,4-fJquinoline, n?/-(5S,3'R)-9-hydroxy-10-methoxy-5-[1-hydroxymethyl-3-cyclohexenylJ-2,2,4-trimethyl-2,5-dihydro-1H-[ 1 ]benzopyrano[3,4-fJquinoline, • · 330 .......... 10-chloro-9-hydroxy-5-phenyl-2,2,4-trimethyl-1H-2,5-dihydro-[ 1 Jbenzopyrano[3,4-f]quinoline, 10-chloro-9-hydroxy-5-(3-trifluoromethylphenyl)-2,2,4-trimethyl-1H-2,5-dihydro[ 1 Jbenzopyrano[3,4-f]quinoline, 10-ethyl-2,5-dihydro-2,2,4-trimethyl-5-phenyl-1Η-[1]benzopyrano[3,4-f]quinoline, 10-ethoxy-2,5-dihydro-2,2,-trimethyl-5-phenyl-1H-[1]benzopyrano[3,4-quinoline, 2,5-dihydro-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano[3,4-quinolin-10-ol acetate (ester), 10-(difluoromethoxy)-2,5-dihydro-2,2,4-trimethyl-5-(2-propenyl)-1H[ljbenzopyrano[3,4fjquinoline, 10-ethynyl-2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-(2-propenyl)-1H-[1Jbenzopyrano[3,4fjquinoline, 10-ethenyl-2,5-dihydro-2,2,4-trimethyl-5-(2-propenyl)-1H-[1]benzopyrano[3,4-quinoline, 10-chloro-5-(3-propenyl)-2,2,4-trimethyl-2,5-dihydro- lyl-[l]benzopyrano[3,4-f]quinoline, (+/-) 2,5-dihydro-10-chloro-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano[3,4-f]quinoline, 10-chloro-9-hydroxy-5-(3,4-difluorophenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4fquinoline, 10-chloro-9-hydroxy-5-(3,5-dichlorophenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4fjquinoline, • · 99 • » 313 « » · · (+)-(5R, 3'S) 2,5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(3-cyclopentenyl)-1H[ 1 ]benzopyrano[3,4-f]quinoline, (+)-(5R, 3'R) 2,5-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(3-cyclopentenyl)-1H[1]benzopyrano[3,4-quinoline, 10-chloro-9-hydroxy-5-(3,5-dimethylpheny1)-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-fquinoline, rel (5S,3'R)-9-hydroxy-10-methoxy-5-[l-hydroxymethyl-3-cyclohexenyl]-2,2,4-trimethyl2,5-dihydro-1H-[1jbenzopyrano [3,4-fquinoline, (-) 2,5 (S)-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(3S-cyclopentenyl)-1H[ 1 ]benzopyrano[3,4-fquinoline, (-) 2,5(S)-dihydro-9-hydroxy-10-chloro-2,2,4-trimethyl-5-(3R-cyclopentenyl)-1H[ 1 jbenzopyrano[3,4-quinoline, 10-chloro-9-hydroxy-5-phenyl-2,2,4-trimethyl-1H-2,5-dihydro-[ljbenzopyrano[3,4-fjquinoline, 10-chloro-9-hydroxy-5-(3-trifluoromethylphenyl)-2,2,4-trimethyl-1H-2,5-dihydro[ 1 ]benzopyrano[3,4-fjquinoline, 10-ethynyl-2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-(2-propenyl)-1H-[1]benzopyrano[3,4fquinoline and 10-ethyl-2,5-dihydro-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano[3,4-quinoline, 10. A compound according to claim 9 having the formula 2,5-dihydro-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano[3,4-f]quinolin-10-ol acetate (ester), 10-methoxy-9-(cyclohexylaminocarbonyl)-oxy-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5dihydro-[1]benzopyrano[3,4-f]quinoline, 10-Methoxy-9-(allylaminocarbonyl)oxy-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-f]quinoline, 10-difluoromethoxy-5-[[3-(methylthio)methoxy]phenyl]-2,2,4-trimethyl-1H-2,5dihydro[1]benzopyrano[3,4-quinoline, 10-Methoxy-5-(1-butylidene)-2,5-dihydro-5-phenyl-2,2,4-trimethyl-1H-[1Jbenzopyrano[3,4fquinoline, Z 5-(benzylideneyl)-9-hydroxy-10-methoxy-2,2,4-trimethyl-1-1H-2,5-dihydro[1]benzopyrano[3,4-x]quinoline, Z 5-(2,5-difluorobenzylideneyl)-9-hydroxy-10-methoxy-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-f]quinoline, From 9-hydroxy-10-methoxy-5-(2-picolinylideneyl)-2,2,4-trimethyl-2,5-dihydro-1H[1]benzopyrano[3,4-f]quinoline, 10-Methoxy-5-(1-methylpropylidene)-2,5-dihydro-5-phenyl-2,2,4-trimethyl-1H[ 1 Jbenzopyrano [3,4-fJquinoline, 10-Methoxy-5-(but-3-enylidene)-2,5-dihydro-5-phenyl-2,2,4-trimethyl-1H-[1]benzopyrano[3,4fJquinoline, 10-methoxy-5-(pyridin-2-yl)methylidene-2,5-dihydro-5-phenyl-2,2,4-trimethyl-1H[l]benzopyrano[3,4-f]quinoline, 10-Methoxy-5-(6-chloropyridin-2-yl)methylidene-2,5-dihydro-5-phenyl-2,2,4-trimethyl-1H[ 1 Jbenzopyrano [3,4-fJquinoline, 10-Methoxy-5-(4,5-dimethyl-1,3-oxazol-2-yl)methylidene-2,5-dihydro-5-phenyl-2,2,4-trimethyl1Η-[1]benzopyrano[3,4-quinoline, 10-Methoxy-5-(3-methylisoxazol-5-yl)methylidene-2,5-dihydro-5-phenyl-2,2,4-trimethyl-1H[ 1 Jbenzopyrano [3,4-fJquinoline, 10-methoxy-5-(5-methylisoxazol-3-yl)methylidene-2,5-dihydro-5-phenyl-2,2,4-trimethyl-1H[ 1 ]benzopyrano[3,4-f]quinoline, 10-(bromodifluoromethoxy)-2,5-dihydro-5-phenyl-2,2,4-trimethyl-1H-[1Jbenzopyrano[3,4fquinoline, 10-(Difluoromethoxy)-2,5-dihydro-5-phenyl-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline, 10-methoxy-7-methyl-9-methyl-5-(3-propenyl)-2,2,4-tri,methyl-1H-2,5-dihydro[1]benzopyrano[3,4-f]quinoline, 10-Methoxy-7-acetyl-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4f]quinoline, (+/-) 2,5-dihydro-9-methyl-10-methoxy-2,2,4-trimethyl-5-(1-methylcyclohexen-3-yl)-1H[1]benzopyrano[3,4-f]quinoline, 10-methoxy-7-methyl-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4fj quinoline, 10-methoxy-7-(2-ethenyl)-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-f]quinoline, 10-Methoxy-9-bromo-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4fquinoline, 10-methoxy-7-bromo-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4f]quinoline, 10-methoxy-9-(3-propynyloxy)-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-f]quinoline, 10-methoxy-9-(3-propenyloxy)-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro[1]benzopyrano[3,4-quinoline, ΦΦ • * * t φ φ • ·«<» 304 ·· φ • ΦΦ · ♦ φ ** φφ • φ φ « • * φ φ • · · » φ « · · ·»* φφ φφ Φ· • * φ φ φ φ φ φ • » φ · φ « φ φ · At ΦΦ 10-methoxy-9-ethoxy-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4fquinoline, 10-Methoxy-9-hydroxy-5-(3-propenyl)-2,2,4-trimethyl-1H-2,5-dihydro-[1]benzopyrano[3,4fquinoline, (+/-) 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(3-cyclohexenyl)-1H[ 1 ]benzopyrano[3,4fquinoline, (+/-) 2,5 -dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(1-methylcyclohexen-3-yl)-1H[1]benzopyrano[3,4-f]quinoline, (-) (5S,3'S)-9-hydroxy-5-[1-methyl-3-cyclohexenyl]-10-methoxy-2,2,4-trimethyl-2,5-dihydro- 1H-[1]benzopyrano[3,4-f|quinoline, (+) (5R,3'R)-9-hydroxy-5-[1-methyl-3-cyclohexenyl]-10-methoxy-2,2,4-trimethyl-2,5 dihydro-1H-[1]benzopyrano[3,4-f|quinoline, (+) (5R,3'S)-9-hydroxy-5-[1"methyl-3-cyclohexenyl]-10-methoxy-2,2,4-trimethyl-2,5dihydro-1H-[1]benzopyrano[3,4-fquinoline, (-) (5S,3'R)-9-hydroxy-5-[1 -methyl-3-cyclohexenyl]-10-methoxy-2,2,4-trimethyl-2,5dihydro-1H-[1] ]benzopyrano[3,4-f]quinoline, r /-(5S,3'R)-9-hydroxy-5-[1]-hydroxymethyl-3-cyclohexenyl]-10-methoxy-2,2,4-trimethyl2,5-dihydro-1H-[1]benzopyrano[3,4-f]quinoline, (+/-) (5S,3'R) 2,5-Dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(1-methylcyclohexen-3yl)-1Η-[1Jbenzopyrano[3,4-f]quinoline, 301 φ φ · φ φ · · • · · φφφφ φ φφφ φ φ φ φ φ φ φ φφφφ ·· φφ φφ φφ re/-(5S,3'R)-9-hydroxy-5-[l-methoxymethyl-3-cyclohexenyl]-10-methoxy-2,2,4-trimethyl2.5-dihydro-1 Η-[ 1 ]benzopyrano[3,4-quinoline] 10-(Bromodifluoromethoxy)-2,5-dihydro-2,2,4-trimethyl-5-(2-propenyl)-1H[ 1 Jbenzopyrano[3,4-fJ quinoline, [3-(2,5-dihydro-10-methoxy-2,2,4-trimethyl-1 H-[ 1 Jbenzopyrano[3,4-fJquinolin-5-yl)phenyl]methylcarbonate, 10-ethoxy-2,5-dihydro-2,2,4-trimethyl-5-phenyl-1H-[1]benzopyrano[3,4-f]quinoline, 11. The compound of claim 2, wherein the substituent R1 is -Li- _Ra , Li is a covalent bond, and the substituent R2 is an alkyl having two to twelve carbon atoms, which may be optionally substituted. 311 12. A compound according to claim 11 selected from: 13. The compound of claim 2, wherein the substituent R1 is -Li-Ra, Li is a covalent bond, and the substituent R2 is an alkenyl having two to twelve carbon atoms, which may be optionally substituted. 14. A compound according to claim 13 selected from: 10-ethenyl-2,5-dihydro-2,2,4-trimethyl-5-(2-propenyl)-1H-[1]benzopyrano[3,4-f]quinoline, 15. The compound of claim 2, wherein the substituent R1 is -Li-Ra, Li is a covalent bond, and the substituent R2 is an alkynyl having two to twelve carbon atoms, which may be optionally substituted. 16. A compound according to claim 15 selected from: 17. The compound of claim 2, wherein the substituent R1 is -Li-Ra, Li is a covalent bond, and the substituent R2 is -OH, halogen, heterocycle, -CN, -CO2H, or -CHO. 18. A compound according to claim 17 selected from: 19. The compound of claim 2, wherein the substituent R1 is -Li-Ra, Li/Ό and the substituent R2 is an alkenyl having three to twelve carbon atoms which may be optionally substituted. 20. A compound according to claim 19 of the formula 21. The compound of claim 2, wherein the substituent R1 is -Li-Ra, Li is O, and the substituent Ra is an alkynyl having three to twelve carbon atoms, which may be optionally substituted. 22. A compound according to claim 21 of the formula 23. The compound of claim 2, wherein the substituent R1 is -Li-Ra, Li is -X'C(X)X''-, X, X', and X are O. 24. A compound according to claim 23 of the formula 25. A compound according to claim 1 of formula III or pharmaceutically acceptable salts or prodrugs thereof, wherein the substituents R 1 , R ₂ , R 3 , R 4 , R 5 , R 6 and L ₂ are as defined above. 26. A compound according to claim 25, wherein the substituent R1 is -Li-Ra, Li is -O- and the substituent _R2 is an alkyl having one to twelve carbon atoms which may be optionally substituted. 316 27. A compound according to claim 26 of the formula 10-(bromodifluoromethoxy)-5-phenyl-2,2-dimethyl-4-methylene-2,3,4,5-tetrahydro-1H-chromeno[3,4-f]quinoline. 28. A compound of claim 1 of formula IV or pharmaceutically acceptable salts or prodrugs thereof, wherein Y is nitrogen or (I) (O') and the substituents R 1 , R ₂ , R ₃ , R 4 , R 5 , R 6 and U are as defined above. 29. A compound according to claim 28, wherein the substituent R 1 is -Li-R _a , Li is -O- and the substituent R _A is alkyl having one to twelve carbon atoms which may be optionally substituted. 30. A compound according to claim 29 selected from: 31. A compound according to claim 1 of formula V « · 317 ΒΒ «· « · · Β • 9 99 9 32. The compound of claim 31, wherein the substituent R1 is -Li-Ra, Li is -O-, and the substituent Ra is alkyl having one to twelve carbon atoms, which may be optionally substituted. 33. A compound according to claim 32 selected from: 34. A compound selected from: 0· 00 0 0 0 · • 0 0 · 0 0 0 · 0 0 >0 0 0· 0« • · • * • 0 0 · 318 • 000 • 00 • 0 • 0 0 0 • · · 0 0 0 0 00 • 0 0 ♦ · ·♦ 35. A method of selectively modulating activating, repressing, agonistic and antagonistic effects of glucocorticoid receptors in mammals, characterized in that it comprises administering an effective amount of a compound according to claim 1. 36. A method of treating inflammation and immune, autoimmune and inflammatory diseases in mammals, comprising administering an effective amount of a compound according to claim 1.