CA1089859A - Obtention de 2-azabicyclo [2.2.2]-oct-5-enes - Google Patents

Obtention de 2-azabicyclo [2.2.2]-oct-5-enes

Info

Publication number: CA1089859A
Authority: CA; Canada
Prior art keywords: alkyl; formula; acid; ethyl; methyl
Prior art date: 1974-05-20
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired

Application number

CA314,868A

Other languages

English (en)

Inventor

William F. Michne

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

STWB Inc

Original Assignee

Sterling Drug Inc

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1974-05-20

Filing date

1978-10-30

Publication date

1980-11-18

1974-05-20 Priority claimed from US05/471,571 external-priority patent/US3932422A/en

1975-05-20 Priority claimed from CA227,350A external-priority patent/CA1052785A/fr

1978-10-30 Application filed by Sterling Drug Inc filed Critical Sterling Drug Inc

1978-10-30 Priority to CA314,868A priority Critical patent/CA1089859A/fr

1980-11-18 Application granted granted Critical

1980-11-18 Publication of CA1089859A publication Critical patent/CA1089859A/fr

Status Expired legal-status Critical Current

Links

238000002360 preparation method Methods 0.000 title description 14
MSSNLHVTCZSIKB-UHFFFAOYSA-N 5-azabicyclo[2.2.2]oct-2-ene Chemical class N1CC2CCC1C=C2 MSSNLHVTCZSIKB-UHFFFAOYSA-N 0.000 title 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 248
150000001875 compounds Chemical class 0.000 claims description 141
229910052739 hydrogen Inorganic materials 0.000 claims description 87
239000001257 hydrogen Substances 0.000 claims description 86
238000000034 method Methods 0.000 claims description 73
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 53
-1 3-furylmethyl Chemical group 0.000 claims description 47
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 23
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 18
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
125000004432 carbon atom Chemical group C* 0.000 claims description 10
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
125000004093 cyano group Chemical group *C#N 0.000 claims description 8
229910052736 halogen Inorganic materials 0.000 claims description 6
150000002367 halogens Chemical class 0.000 claims description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
125000000753 cycloalkyl group Chemical group 0.000 claims description 5
239000000126 substance Substances 0.000 claims description 5
JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 claims description 4
125000000217 alkyl group Chemical group 0.000 claims description 4
125000001589 carboacyl group Chemical group 0.000 claims description 4
PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 3
NURQLCJSMXZBPC-UHFFFAOYSA-N 3,4-dimethylpyridine Chemical compound CC1=CC=NC=C1C NURQLCJSMXZBPC-UHFFFAOYSA-N 0.000 claims 3
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
UDWJEJINASVQGJ-UHFFFAOYSA-M magnesium;1-methanidyl-4-methoxybenzene;chloride Chemical compound [Mg+2].[Cl-].COC1=CC=C([CH2-])C=C1 UDWJEJINASVQGJ-UHFFFAOYSA-M 0.000 claims 2
239000002253 acid Substances 0.000 abstract description 40
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 abstract description 40
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 abstract description 20
235000019253 formic acid Nutrition 0.000 abstract description 20
239000000730 antalgic agent Substances 0.000 abstract description 15
239000003960 organic solvent Substances 0.000 abstract description 15
229940111121 antirheumatic drug quinolines Drugs 0.000 abstract description 12
150000003248 quinolines Chemical class 0.000 abstract description 12
238000007363 ring formation reaction Methods 0.000 abstract description 12
239000002904 solvent Substances 0.000 abstract description 12
230000000202 analgesic effect Effects 0.000 abstract description 11
238000010438 heat treatment Methods 0.000 abstract description 11
239000003887 narcotic antagonist Substances 0.000 abstract description 3
ZAPGVTRGSVGMKY-UHFFFAOYSA-N 2-benzyl-3-azabicyclo[2.2.2]oct-5-ene Chemical compound N1C(C=C2)CCC2C1CC1=CC=CC=C1 ZAPGVTRGSVGMKY-UHFFFAOYSA-N 0.000 abstract 1
VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical class [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 abstract 1
RFQDDXWZZVRLKO-UHFFFAOYSA-N benzo[g]quinoline Chemical class N1=CC=CC2=CC3=CC=CC=C3C=C21 RFQDDXWZZVRLKO-UHFFFAOYSA-N 0.000 abstract 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 303
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 293
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 66
239000000243 solution Substances 0.000 description 66
239000002585 base Substances 0.000 description 65
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 63
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 54
239000000047 product Substances 0.000 description 53
238000006243 chemical reaction Methods 0.000 description 49
239000000203 mixture Substances 0.000 description 43
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 37
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 36
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 30
229910000041 hydrogen chloride Inorganic materials 0.000 description 30
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
238000012360 testing method Methods 0.000 description 25
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 23
239000012458 free base Substances 0.000 description 23
238000007792 addition Methods 0.000 description 22
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 20
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 19
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 18
101100134922 Gallus gallus COR5 gene Proteins 0.000 description 18
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
150000003839 salts Chemical group 0.000 description 18
239000007787 solid Substances 0.000 description 17
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 16
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
238000010992 reflux Methods 0.000 description 16
230000000875 corresponding effect Effects 0.000 description 15
239000000543 intermediate Substances 0.000 description 15
229940093499 ethyl acetate Drugs 0.000 description 14
235000019439 ethyl acetate Nutrition 0.000 description 14
150000002431 hydrogen Chemical class 0.000 description 14
PSXRWZBTVAZNSF-UHFFFAOYSA-N hydron;quinoline;chloride Chemical compound Cl.N1=CC=CC2=CC=CC=C21 PSXRWZBTVAZNSF-UHFFFAOYSA-N 0.000 description 14
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
230000009467 reduction Effects 0.000 description 13
238000006722 reduction reaction Methods 0.000 description 13
239000007858 starting material Substances 0.000 description 13
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 12
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
238000002844 melting Methods 0.000 description 12
230000008018 melting Effects 0.000 description 12
230000002829 reductive effect Effects 0.000 description 12
241000894007 species Species 0.000 description 12
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 11
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 11
239000000460 chlorine Substances 0.000 description 11
229940035676 analgesics Drugs 0.000 description 10
150000002148 esters Chemical class 0.000 description 10
AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 10
125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 description 10
239000003921 oil Substances 0.000 description 10
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
239000000706 filtrate Substances 0.000 description 9
239000010410 layer Substances 0.000 description 9
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
238000001914 filtration Methods 0.000 description 8
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 8
DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 8
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 7
OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 7
AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 7
YKGMKSIHIVVYKY-UHFFFAOYSA-N dabrafenib mesylate Chemical compound CS(O)(=O)=O.S1C(C(C)(C)C)=NC(C=2C(=C(NS(=O)(=O)C=3C(=CC=CC=3F)F)C=CC=2)F)=C1C1=CC=NC(N)=N1 YKGMKSIHIVVYKY-UHFFFAOYSA-N 0.000 description 7
DZGCGKFAPXFTNM-UHFFFAOYSA-N ethanol;hydron;chloride Chemical compound Cl.CCO DZGCGKFAPXFTNM-UHFFFAOYSA-N 0.000 description 7
239000000284 extract Substances 0.000 description 7
235000011167 hydrochloric acid Nutrition 0.000 description 7
229960000443 hydrochloric acid Drugs 0.000 description 7
125000004356 hydroxy functional group Chemical group O* 0.000 description 7
239000000463 material Substances 0.000 description 7
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 6
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
230000003187 abdominal effect Effects 0.000 description 6
229960000583 acetic acid Drugs 0.000 description 6
239000002168 alkylating agent Substances 0.000 description 6
229940100198 alkylating agent Drugs 0.000 description 6
229960001040 ammonium chloride Drugs 0.000 description 6
235000019270 ammonium chloride Nutrition 0.000 description 6
150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 6
238000002955 isolation Methods 0.000 description 6
238000007127 saponification reaction Methods 0.000 description 6
238000012216 screening Methods 0.000 description 6
229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
235000017557 sodium bicarbonate Nutrition 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 5
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 5
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 5
229960004373 acetylcholine Drugs 0.000 description 5
239000000908 ammonium hydroxide Substances 0.000 description 5
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 5
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
239000003054 catalyst Substances 0.000 description 5
239000003795 chemical substances by application Substances 0.000 description 5
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 5
239000012259 ether extract Substances 0.000 description 5
238000001704 evaporation Methods 0.000 description 5
230000008020 evaporation Effects 0.000 description 5
239000012362 glacial acetic acid Substances 0.000 description 5
125000001979 organolithium group Chemical group 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
238000001953 recrystallisation Methods 0.000 description 5
238000003756 stirring Methods 0.000 description 5
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
QSLPNSWXUQHVLP-UHFFFAOYSA-N $l^{1}-sulfanylmethane Chemical compound [S]C QSLPNSWXUQHVLP-UHFFFAOYSA-N 0.000 description 4
241001535291 Analges Species 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
241000906446 Theraps Species 0.000 description 4
239000003513 alkali Substances 0.000 description 4
229910052783 alkali metal Inorganic materials 0.000 description 4
239000005557 antagonist Substances 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
239000012043 crude product Substances 0.000 description 4
238000001035 drying Methods 0.000 description 4
238000005886 esterification reaction Methods 0.000 description 4
238000000605 extraction Methods 0.000 description 4
150000004820 halides Chemical class 0.000 description 4
150000003840 hydrochlorides Chemical class 0.000 description 4
230000007062 hydrolysis Effects 0.000 description 4
238000006460 hydrolysis reaction Methods 0.000 description 4
229910052500 inorganic mineral Inorganic materials 0.000 description 4
229910052744 lithium Inorganic materials 0.000 description 4
239000012280 lithium aluminium hydride Substances 0.000 description 4
GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 4
235000010755 mineral Nutrition 0.000 description 4
239000011707 mineral Substances 0.000 description 4
BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 4
229910052757 nitrogen Inorganic materials 0.000 description 4
239000012044 organic layer Substances 0.000 description 4
230000000144 pharmacologic effect Effects 0.000 description 4
SUVIGLJNEAMWEG-UHFFFAOYSA-N propane-1-thiol Chemical compound CCCS SUVIGLJNEAMWEG-UHFFFAOYSA-N 0.000 description 4
238000005932 reductive alkylation reaction Methods 0.000 description 4
229920006395 saturated elastomer Polymers 0.000 description 4
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
238000010998 test method Methods 0.000 description 4
238000005406 washing Methods 0.000 description 4
239000008096 xylene Substances 0.000 description 4
150000003970 1-benzazocines Chemical class 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
239000000556 agonist Substances 0.000 description 3
229910000288 alkali metal carbonate Inorganic materials 0.000 description 3
150000008041 alkali metal carbonates Chemical class 0.000 description 3
230000029936 alkylation Effects 0.000 description 3
238000005804 alkylation reaction Methods 0.000 description 3
229910000147 aluminium phosphate Inorganic materials 0.000 description 3
150000001450 anions Chemical class 0.000 description 3
125000005605 benzo group Chemical group 0.000 description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
238000009835 boiling Methods 0.000 description 3
239000012267 brine Substances 0.000 description 3
150000007942 carboxylates Chemical class 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
230000000694 effects Effects 0.000 description 3
230000032050 esterification Effects 0.000 description 3
125000001033 ether group Chemical group 0.000 description 3
125000004494 ethyl ester group Chemical group 0.000 description 3
239000011737 fluorine Substances 0.000 description 3
229910052731 fluorine Inorganic materials 0.000 description 3
238000005755 formation reaction Methods 0.000 description 3
150000002576 ketones Chemical class 0.000 description 3
229910003002 lithium salt Inorganic materials 0.000 description 3
159000000002 lithium salts Chemical class 0.000 description 3
230000003647 oxidation Effects 0.000 description 3
238000007254 oxidation reaction Methods 0.000 description 3
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 3
ZQHYKVKNPWDQSL-KNXBSLHKSA-N phenazocine Chemical compound C([C@@]1(C)C2=CC(O)=CC=C2C[C@@H]2[C@@H]1C)CN2CCC1=CC=CC=C1 ZQHYKVKNPWDQSL-KNXBSLHKSA-N 0.000 description 3
229960000897 phenazocine Drugs 0.000 description 3
238000000746 purification Methods 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
229910052708 sodium Inorganic materials 0.000 description 3
239000011734 sodium Substances 0.000 description 3
XVSFHIIADLZQJP-UHFFFAOYSA-M sodium;propane-1-thiolate Chemical compound [Na+].CCC[S-] XVSFHIIADLZQJP-UHFFFAOYSA-M 0.000 description 3
239000000725 suspension Substances 0.000 description 3
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
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QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 1
RUEKPBLTWGFBOD-UHFFFAOYSA-N bromoethyne Chemical group BrC#C RUEKPBLTWGFBOD-UHFFFAOYSA-N 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000002775 capsule Substances 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
235000011089 carbon dioxide Nutrition 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
238000010531 catalytic reduction reaction Methods 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
229960002471 cholic acid Drugs 0.000 description 1
235000019416 cholic acid Nutrition 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 1
239000002178 crystalline material Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
PYRZPBDTPRQYKG-UHFFFAOYSA-N cyclopentene-1-carboxylic acid Chemical compound OC(=O)C1=CCCC1 PYRZPBDTPRQYKG-UHFFFAOYSA-N 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 1
229960002069 diamorphine Drugs 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
238000006345 epimerization reaction Methods 0.000 description 1
125000004185 ester group Chemical group 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
FZTNKBUGLYHIJK-UHFFFAOYSA-N ethyl 5,6-dibenzyl-2-methyl-5-azabicyclo[2.2.2]oct-2-ene-8-carboxylate;hydrochloride Chemical compound Cl.C=1C=CC=CC=1CN1C(C=C2C)C(C(=O)OCC)CC2C1CC1=CC=CC=C1 FZTNKBUGLYHIJK-UHFFFAOYSA-N 0.000 description 1
SQJXYJYDTREEKT-UHFFFAOYSA-N ethyl 6-benzyl-2-methyl-5-azabicyclo[2.2.2]oct-2-ene-8-carboxylate Chemical compound N1C(C=C2C)C(C(=O)OCC)CC2C1CC1=CC=CC=C1 SQJXYJYDTREEKT-UHFFFAOYSA-N 0.000 description 1
NKEPPYBBBAYJDH-UHFFFAOYSA-N ethyl N-(15,16-dimethyl-10-azatetracyclo[10.2.2.02,7.09,14]hexadeca-2(7),3,5,15-tetraen-4-yl)carbamate Chemical compound CC1=C(C2CNC3CC4=C(C1C3C2)C=C(C=C4)NC(=O)OCC)C NKEPPYBBBAYJDH-UHFFFAOYSA-N 0.000 description 1
BLHLJVCOVBYQQS-UHFFFAOYSA-N ethyllithium Chemical compound [Li]CC BLHLJVCOVBYQQS-UHFFFAOYSA-N 0.000 description 1
239000012065 filter cake Substances 0.000 description 1
239000012467 final product Substances 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
LRBQNJMCXXYXIU-QWKBTXIPSA-N gallotannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@H]2[C@@H]([C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-QWKBTXIPSA-N 0.000 description 1
239000011491 glass wool Substances 0.000 description 1
239000000174 gluconic acid Substances 0.000 description 1
235000012208 gluconic acid Nutrition 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
229910000039 hydrogen halide Inorganic materials 0.000 description 1
239000012433 hydrogen halide Substances 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
230000033444 hydroxylation Effects 0.000 description 1
238000005805 hydroxylation reaction Methods 0.000 description 1
ZQDWXGKKHFNSQK-UHFFFAOYSA-N hydroxyzine Chemical compound C1CN(CCOCCO)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZQDWXGKKHFNSQK-UHFFFAOYSA-N 0.000 description 1
239000005457 ice water Substances 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000001361 intraarterial administration Methods 0.000 description 1
229910052742 iron Inorganic materials 0.000 description 1
229940045996 isethionic acid Drugs 0.000 description 1
125000000654 isopropylidene group Chemical group C(C)(C)=* 0.000 description 1
150000003951 lactams Chemical class 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
239000007788 liquid Substances 0.000 description 1
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 1
XBEREOHJDYAKDA-UHFFFAOYSA-N lithium;propane Chemical compound [Li+].CC[CH2-] XBEREOHJDYAKDA-UHFFFAOYSA-N 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 1
125000004372 methylthioethyl group Chemical group [H]C([H])([H])SC([H])([H])C([H])([H])* 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
150000004682 monohydrates Chemical class 0.000 description 1
LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
ASZOJFWNMZRJLI-UHFFFAOYSA-N n,n-dimethyl-1-phenylmethanamine;formic acid Chemical compound [O-]C=O.C[NH+](C)CC1=CC=CC=C1 ASZOJFWNMZRJLI-UHFFFAOYSA-N 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
230000003533 narcotic effect Effects 0.000 description 1
150000002828 nitro derivatives Chemical class 0.000 description 1
RAMJGUDCAOCTHF-UHFFFAOYSA-N non-6-en-4-one Chemical compound CCCC(=O)CC=CCC RAMJGUDCAOCTHF-UHFFFAOYSA-N 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
239000008188 pellet Substances 0.000 description 1
229940049954 penicillin Drugs 0.000 description 1
229960000482 pethidine Drugs 0.000 description 1
150000002989 phenols Chemical class 0.000 description 1
OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
DJXNJVFEFSWHLY-UHFFFAOYSA-N quinoline-3-carboxylic acid Chemical compound C1=CC=CC2=CC(C(=O)O)=CN=C21 DJXNJVFEFSWHLY-UHFFFAOYSA-N 0.000 description 1
230000036647 reaction Effects 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
230000004044 response Effects 0.000 description 1
230000007017 scission Effects 0.000 description 1
239000002002 slurry Substances 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
239000011343 solid material Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
JDVPQXZIJDEHAN-UHFFFAOYSA-N succinamic acid Chemical compound NC(=O)CCC(O)=O JDVPQXZIJDEHAN-UHFFFAOYSA-N 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000003826 tablet Substances 0.000 description 1
229940033123 tannic acid Drugs 0.000 description 1
235000015523 tannic acid Nutrition 0.000 description 1
229920002258 tannic acid Polymers 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
IRFHMTUHTBSEBK-QGZVFWFLSA-N tert-butyl n-[(2s)-2-(2,5-difluorophenyl)-3-quinolin-3-ylpropyl]carbamate Chemical compound C1([C@H](CC=2C=C3C=CC=CC3=NC=2)CNC(=O)OC(C)(C)C)=CC(F)=CC=C1F IRFHMTUHTBSEBK-QGZVFWFLSA-N 0.000 description 1
VXKWYPOMXBVZSJ-UHFFFAOYSA-N tetramethyltin Chemical compound C[Sn](C)(C)C VXKWYPOMXBVZSJ-UHFFFAOYSA-N 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
PTMFUWGXPRYYMC-UHFFFAOYSA-N triethylazanium;formate Chemical compound OC=O.CCN(CC)CC PTMFUWGXPRYYMC-UHFFFAOYSA-N 0.000 description 1
UPVCRZBVVOXMDA-UHFFFAOYSA-N trimethylazanium;formate Chemical compound OC=O.CN(C)C UPVCRZBVVOXMDA-UHFFFAOYSA-N 0.000 description 1

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Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

CA314,868A 1974-05-20 1978-10-30 Obtention de 2-azabicyclo [2.2.2]-oct-5-enes Expired CA1089859A (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA314,868A CA1089859A (fr)	1974-05-20	1978-10-30	Obtention de 2-azabicyclo [2.2.2]-oct-5-enes

Applications Claiming Priority (6)

Application Number	Priority Date	Filing Date	Title
US471,571		1974-05-20
US05/471,571 US3932422A (en)	1974-05-20	1974-05-20	8-Methylene-3-azabicyclo[3.3.1]non-6-en-4-ones
US57631375A	1975-05-12	1975-05-12
US576,313		1975-05-12
CA227,350A CA1052785A (fr)	1974-05-20	1975-05-20	Synthese de methane -2,6 benzazocines
CA314,868A CA1089859A (fr)	1974-05-20	1978-10-30	Obtention de 2-azabicyclo [2.2.2]-oct-5-enes

Publications (1)

Publication Number	Publication Date
CA1089859A true CA1089859A (fr)	1980-11-18

Family

ID=27425844

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA314,868A Expired CA1089859A (fr)	1974-05-20	1978-10-30	Obtention de 2-azabicyclo [2.2.2]-oct-5-enes

Country Status (1)

Country	Link
CA (1)	CA1089859A (fr)

1978
- 1978-10-30 CA CA314,868A patent/CA1089859A/fr not_active Expired

Legal Events

Date	Code	Title	Description
1997-11-18	MKEX	Expiry

Publication	Publication Date	Title
US3932422A (en)	1976-01-13	8-Methylene-3-azabicyclo[3.3.1]non-6-en-4-ones
DE69612003T2 (de)	2001-06-21	Substituierte benzolaktamverbindungen als substanz-p-antagonisten
US5869672A (en)	1999-02-09	Huperzine A and analogs thereof
US4929731A (en)	1990-05-29	Method for the synthesis of huperzine A and analogs thereof and compounds useful therein
EP0626949A1 (fr)	1994-12-07	Composes neuroleptiques bicycliques contenant de l'azote
US3639407A (en)	1972-02-01	Novel 1 2 3 4 5 6-hexahydro-6-phenyl-2 6-methano-3-benzazocines
US4228169A (en)	1980-10-14	1,9-Dihydroxyoctahydrobenzo[c]quinolines and 1-hydroxyhexahydrobenzo[c]quinoline-9(8H)-ones as antiemetic agents
CA1291759C (fr)	1991-11-05	Antidepresseur de type 2-(4,5-dihydro-1h-imagazolyl)- dihydro-1h-indoles,-tetrahydroquinolines et 1h-indoles
CA1136130A (fr)	1982-11-23	Composes a base de 14-methoxymorphinan-6-one
NO137694B (no)	1977-12-27	Analogifremgangsm}te for fremstilling av terapeutisk aktive benzomorfaner
US4255579A (en)	1981-03-10	11-Substituted hexahydro-2,6-methano-3-benzazocines
US3131191A (en)	1964-04-28	Process for the preparation of noraporphines
US4100164A (en)	1978-07-11	2,6-Methano-3-benzazocines
US4239890A (en)	1980-12-16	Octahydro-3,5-etheno- and 3,5-ethanobenzo[g]quinolines
CA1090796A (fr)	1980-12-02	Obtention de 2,6-methano-benzazocines
CA1079273A (fr)	1980-06-10	Preparation de 3-methanobenzazocines
US4335243A (en)	1982-06-15	Oximes of 11-(3-oxooctyl)-hexahydro-2,6-methano-3-benzazocines
US3810899A (en)	1974-05-14	2-hydroxy-n-substituted-morphinan derivatives
US4180667A (en)	1979-12-25	2-Azabicyclo[2.2.2]oct-5-enes
CA1052785A (fr)	1979-04-17	Synthese de methane -2,6 benzazocines
US4139534A (en)	1979-02-13	Process for the preparation of 14-hydroxymorphinan derivatives
JPS6237034B2 (fr)	1987-08-10
US4296238A (en)	1981-10-20	2,6-Methano-3-benzazocines
US6288225B1 (en)	2001-09-11	Substituted benzolactam compounds as substance P antagonists
Smula et al.	1973	The Synthesis of (±)-Cordrastine. A New Route to the Phthalideisoquinoline System