SU1246894A3 - Method of producing 9-oxy-benzo(c)-quinolines - Google Patents

Description

WITH/

The invention relates to a method of the new 9-hydroxy-benzo (C) -quinoline gitluchemins of the general formula

where r r

one

R, R

hydrogen or acetyl, acetyl 5

hydrogen or methyl hydrogen or alkyl with 1-4 carbon atoms

Z alkyleneoxy from 1-7 atom of 1Cool of carbon;

W is hydrogen or phenyl, suitable for use as compounds for action on the central nervous system (CNS), especially as anesthetic drugs and transient sensitizers J as blood pressure lowering drugs, drugs for glaucoma and as dietics,

The purpose of the invention is the synthesis of new compounds possessing valuable properties.

Example 1, d ,, f-5j6j6a, 7.0, I Oa-taxhydro-1 hydroxy-6 5-metsh-3. (2-heptranshoxy) -benzo (C) X1 gnapin-9 (8H) Ok,

Suspension of d, 1-5,6,6a, U-tetrahydro 1 - hydroxy-6 p-methyl-3 (2-heptylox with -:) - beiso (C) quinoline-9 (8H) -one (1 , 0 g, 2p91 mmol) in tetrahydrofur ne (20 ml) is added dropwise, via an additional funnel, to a vigorously stirred solution of lithium (0.1 g) in liquid (75 ml), distilled-H1-1J through potassium hydroxide tablets ) An additional funnel was washed with tetrahydrofuran (10 np). The mixture was mixed with 10 # 1H and then solid chloride a 4 min was added to destroy the blue color. The amount of ammonium given is allowed to evaporate and the residue is discharged into water (100 rin) and ethyl acetate (50 ml). The ethyl acetate layer is separated and the suitable phase is extracted with ethyl acetate (2 x 30 ml), the United extracts are washed with a salt of mtiH solution, dried (MgSO4) and concentrated under reduced levels until a brown semi-liquid is obtained.

product (1j85 g). A careful raster; 1 semi-solid product in a mixture of gallons / ref (1: 1) results in a light brown solid {0.884 g), t, mp 130-138 ° C.

The above procedure is repeated using 1. 84 g (5.36 mmol) of the following: - dc (C) - quinoline-9 he reagent, 0.184 g lithium, | 40 ml of liquid ammonium and 45 glp. tetrahydrofuran, Residue (2.1 g), left after evaporation of ammonium., dissolved in benzene and introduced into a chromatographic column (3.8 x 61 cm) with silica gel (280 g),

5 The column is washed with a degassed volume (5 benzene, equal to the column volume, and then 1700 ml. Of the degassed Bengol / EF Ir mixture (9: 1). Continuation of the eluorum and (1 10t) ml) results in red eluent, which is concentrated to a light purple solid compound (580 mg) under reduced pressure and triturated with cHect benzene / ether (1: 1) to give

5,370 mg of solid compound ,, t, al.154-156C. It is stored under a nitrogen atmosphere in the dark. Selected vevstostoy; is a mixture and trans-isomers of the compound specified

0 to rg / e - 345 (ra / l H NMR

(100 mz), (h, per million,) 5.85 k

49 (; n, perm. OH),., 5.35, 5.93 (d, I - 2HZ, 2K POLY, aromatic .. hydrogens 3 mixtures of cis / trans 0., 90 (t, 3N, terminal CH ), | „12--4.43 (m, the rest of the H e N).

PREMIER 2, 6.5a, 7.10, - 10a Texahydro-1-acetoxy-3- (2-heptylox) benzo (C) -quinoline-9- (3N) -one „

Solution, 6p5 7-tetrahydro-1-- oxy-3- (2 heptyloxy) -benzo (C) -chymol-S (8H) - eye (9.0 g) in tetrahydrofuram (too ml ) add dropwise to Ci: c 1 tro stirred solution of lithium (0.1 g) in liquid ammonia (75 ° C), E 0, an additional 0.1 g lithium is added dropwise in parts to preserve blue color. The mixture is stirred; 1 pass 10 minutes, then the blue is decolorized; an excess is added: - Loric acid a1 € U1oni, Beat the amber; ionia are allowed to evaporate and the residue is placed in a mixture of water and ethyl acetate. The organic layer is separated: and the water is extracted twice with ethyl acetate, the combined extracts are taken up in water, saline

0

45

50

55

thief, dried () and evaporated to give 8.45 g of crude product as a brown solid

The crude product (8.0 g) is suspended in methylene chloride (48 ml) at 0 ° C and treated with N, N- -dimetsh1-4-aminopyrid 1 (3.24 g) and triethylamine (3.72 ml). Acetic anhydride (2.52 ml) is then added and the resulting mixture is stirred for 30 minutes under OC. It is diluted with methylene chloride (300 g-w) and the methylene chloride layer is separated, washed with water (3 x 150 ml), saturated sodium bicarbonate (1 x 100 ml), salted with bore (1 x 100 ml) and dried (MgSOi, ), After evaporation of methylene chloride, 13.7 of a dark oil is obtained, which is purified on a chromatography column with silica gel (480 g), the column is washed successively with ether / hexane (1: 1), ether / hexane (2: 1) and ether. Collect 18 ml fractions. Fractions 176-224 are combined and concentrated

 TO, oil, which is recrystallized from hexane, is obtained 3.24 g (32%). The yield of the trans-isomer, indicated in the title of the compound, in the form of light yellow crystals, t, piece 63.5 68 C, / e - 373 (tO.

IR (KBr): 5.82 (ketone C 0), 5.75 (ester C 0), 2.95 (NH) f.

Fractions 246-290 were combined and concentrated to give 0.56 g (5%) of the crude cis isomer of the compound, indicated in the title, as an oil. It is further purified on a chromatographic column as described above, and a pure cis isomer is obtained in the form of an oil, t / e - 373 (t).

IR (CHCtj): 5.82 (keto, C 0), 5.67 (elephant ester C 0), 2.92 (NH),

N

Calculated

3.75. Found

3.69.

%: C 70.75, H 3.37;

%: C, 70.90; H 8.54;

The 4, -Fractions 226-245 are combined and evaporated to give 2.69 g (26%) of a 50 mixture of cis and trans isomers, which

1 was isolated according to the procedure described previously from D, -5,6,6a, 7-tetrahydro-1-hydroxy-3- (5-phenyl-2-pentyloxy) benzo (C) -quinoline-9 (8H) - in the same way 55 the following compounds are obtained,

 d, T-trans-5,6,6a ,, 7,10,10ao1, -Hag-sacdro-1-acetoxy-3- (5-phenyl-2-pen246894

-

Q tyloxy) -benzo (C) -hinap in-9 (8a) -one in the form of oil, t / e - 42 Km),

Z: C 74.08; H 7.41;

N

Calculated, 3.32, C26Hj, 0, N Navdo,%:

C, 74.16; H 7.59; N 3.20,

e, bcis-5 „6.6a, 7, 10, Yua-Hexa-hydro-1-acetoxy-3- (5-phenyl-2-pentyloxy) -benzo (C) -quinolin-9 (8H) -one in the form of oil, t / e - 421 (t).

Calculated: 5%: C, 74.08; H 7.41; N 3.32,

t5

20

Q

°

50

25

five

0

five

Ci6H ,, 0, N

Found,%: C 74.04; H 7.49; N 8.54,

d, -5,6,6a, 7-tetrahydro-1-hydroxy-6 l-methyl-3- (5-phen-2-pentyl-oxy) -benzo (C) -quinoline-9 (8H) -one is converted to d, j -TpaHC-5,6, 10,10a-L-hexa-hydro-1-acetoxy-6 (/, methyl 3- (5-phenyl-2-pentyloxy) benzo ( C) -quinoline-9 (8H) -one, and: d, e-cis-5,6,6a, 7,10, 1 Oar-hexahydro-1-acetoxy-bl-methyl-3- (5-phenyl -2-pentyloxy) -benzo (C) -quinoline-9 (8H) -one.

The isomeric products are converted to their hydrochloric acid salts according to method 5 described in the general salt preparation procedure.

Characteristics of the salts obtained are given in table. one"

Primer, d, trans-5,6,6a, 7,8,9, 10, 10 al-Octagidro-1,9-diacetoxy-b; methyl 3- (2-heptyloxy) -benzo (C) -quinoline.

1.2 g of the non-chromatographed reduction product d, f-TpaHC- -5.6, tOj 10a (6-Hexahydro-1-acetoxy-6 | -methyl-3- (2-heptyloxy) benzo (C) - quinoline-9 (8H) -one is stirred with excess acetic anhydride and pyridine overnight at room temperature. The mixture is poured into ice-water, the aqueous mixture is extracted with ether (3 X 100 ml), the combined extracts are washed with water, brine and then dried ( MgSO4) and extrude. The residue is chromatographed on a column (40 g of silica gel, benzene / ether mixture (9: 1) as an eluting solvent, and 680 mg of the desired d is obtained; s-5,6a, 7,8,9,10, 10ar-octagidro-1,9-diacetoxy-6 | -methyl-3- (2-hegyloxy) benzo (C) -quinoline, which crystallizes from an additional amount of hexane and ethyl acetate, t, mp, 86-87 C, t / e - 431 (t),

IR (KBG) -. : i, 73ju (carb) nile: s

ester)

Tms

 and NMR (60 MHz) (h on NUIH)

(/ Ij

5.88 (BS, H2,), 2.28 and 2.05 (2 siglets from three protons, CHj-C) O (-) and 0.8-5.0 (multiplet, the remaining protons).

Imported,%: C 69.57, H 8.64, N 3.25 „

, 0, n.

Found 5%: C 69.51; H 8.54; N 3.14

After a similar treatment, 60 mg d, f-TpaHC-5,6,6a, 7,8,9, 10, 10a "(octacro 1 acetoxy-9 -oxy-5-methyl-3 - (4-phenylbutyloxy a) -benzo (C) -quinoline in pyridine (1 ml) and acetic anhydri7;, e (1 ml) for 1 h at room temperature, take the necessary d, 1, -trans-5, 6, bar, 7,8,9,10,1 OA 1-octa-hydro 1 "9 | -diacetoxy-6-methyl-3- (4-phenylbutyloxy) -benzo (C) quinoline; t, 1SH 146- 147 ° C after recrystallization from ethyl acetate / hexane (1: 1), t / e 462 (t).

%, C: 72.23; H 7.58; N 3,, 01.

1% 5%; C 72.15., H 7.61 C N

By repeating this procedure: 1 ry5 using equivalent amounts of acetyl chloride instead of benzoyl chloride 1 and corresponding to P T benzo (C) -quinoline, we obtain the following compound: d, f-TpaHC 5,6,6rt, fe 7 j 10 , (Oao1-hexahydro 1-acetoxy-3- (2 Heptipoxy) -5-acetyl-6-methylbenzo (C) - shnolin-9 (8H) - he. N; / e - 433 (ha)

Pr and measures 4. d, -trans-5, b5ba 7, 10 ,, YuL-gek sagidro-1-acetoxy-5-methyl-6Y-Utetil-3 (2-heptyloxy) -ben 30 (c) quinoline- 9 (8H) -one „

To a stirred solution of 387 mg d 5 f-TpaHC 5s 6, 6a-7,10,1 Oa1 hexohydro-1 -ai, etoxy-6, -methyl- (2 heptyloxy) benzo (C) -quinolin-9 (8H) -one in 3 ml of acetonitrile5 cooled to 15 Cj, 0.5 n formaldehyde is added, and then 100 mg of cyanoborohydride. Acetic acid is added to maintain the pH until the reaction is complete, which is monitored by the disappearance of the starting material on a thin layer chromatogram. The product is added in the following way.

To the reaction mixture is added water and byproduct: nfir, an unnumbered layer

0

five

divide, and the aqueous once again extracted with ether. The ether extracts of the compound are HNH1T, dried and evaporated to give the desired d, J -TpaHC-5.6, 6a, 7.10, 10a and -g hexahydro-acetoxy-5-methyl-6p-methyl-3- (2- heptyloxy) benzo (C) -quinolin-9 (8H) -one in the form of 4L NMZ oil (60 MHz) (SDSH) shows a characteristic absorption of 2.35 (h, per million) for X N-CH.

Similarly, the following compounds are obtained from the corresponding reagents.

d, trans-5,6,6a, 7, 10, 10a-Hexagid1 o-1 - acetoxy-5-methyl-3- (2-heptichyux) -benzo (C) -quinoline-9 (8H -It is in the form of oil.

d, -trans-5,6,6a /, 7,8,9,10, 10 avb; Octagidro - 1,9-diacetoxy-5-methyl-6ji-MeTRn-3- (2-heptyloxy) benzo ( C) - quinoline in the form of oil, ha / e - 445 (t),

In addition, the following compounds are prepared in a similar manner.

ABOUT

thirty

which are given in

components table 2,

Example 5 „d, -trans-5,6, 6a | , 7,6,9,10, YuavS-Oktagidro-Yatsetoksi-9-hydroxy-5-methyl-3- (5-fvnil-2-pentypoksk) -benzo (s) -quinoline.

Formaldehyde (1.1 ml, 57% aqueous solution) is added to solution d, - trans-5.6, 7, 10, Yue-hexahydro-1-acetoxy-3- (5-phenyl-2-pentyloxy) - -benzo (C) -quinolin-9 (8H) -one in acetonitripe.

Calculated Z: C 74.11; H 8.06; N3520.

C, H, jO, M

Knipe, enO; %; N 3.21.

C, 73.56; H 7.86;

Similarly, d, -trans-5,6, ba ,, 7, 10 ,. 1 Oaog-hexahydro-acetoxy-3- (2-heptyloxy) -benzo (C) -hipolin-9 (8H) -one is treated with sodium cyanoborohydride, resulting in d, F-trans-5,6,6a /, 75 10 ,, 10a111-hexahydro-1-acetoxy-5 methyl-3- (2-heptyloxy) -ben-30 (C) -quinolin-9 (8H) -one in the form of oil, ha / e - 337 (w), IR (SNS e): 5.80 (ke

tone c 0), 5.65 (C O in ester).

%, C: C, 29.29; H, 3.53; N 3.61.

.N

Found,%: C 70.78; H 8.71; N 3.27.

d, t-trac-5,6,6ap, 7,8,9,10,10a ": - Octohydro-1-acetoxy-9 -hydroxy-5- -methyl-3- (2-heptyloxy) -beiso (C ) -hi nolin in the form of oil, t / e - 389 (t). IR (CHCej): 2.80 (0-H), 5.70 (, ester).

Calculated,%: C, 70.92; H 9.05; N 3.60.

,,,OK

Found,%: C 70.56; H 8.95; N 3.56,

and d, -trans-5,6,6a /, 7,10, Yual-hexa-hydro-1-acetoxy-6 | -methyl-3- (6-fesh1p -2-pentyloxy) -benzo (C) -quinoline-9 (8H) -one is converted into d, -trans-5,6,6a, 7, 10,10a (1 -hexahydro-1-acetoxy-5-methyl-6-methyl-3- (5-phenyl-2- -pentyloxy) benzo (C) -quinoline-9 (8H) -one;

d, € -TpaHC-5,6,6.a, 7,8,9, 10, tOa-- -octagidro-1-acetoxy-9 -hydroxy-5-methyl-6-methyl-3- (5-phenyl 2-pentyl-oxy) benzo (C) -quinoline, which is isolated in the form of hydrochloride, m.p. 1663-le S C, m / e - 451 (m).

Example 6. d, -trans-5,6,6a 7,8,9,10,10a1.-Octagidro-1-acetoxy-9-hydroxy-5-isobutyr-3- (phenyl-2-pentyloxy) - benzo (C) quinoline.

Sodium borohydride (38 mg, 10 mmol, is added to the solution of d, F- -trans-5,6,6af, 7,10,10a-hexahydro-1-acetoxy-5-isobutyryl-3- (5-phenyl- -2-PentioIoxy) -benzo (C) -quinoline-) -on (260 mg, 0.529 mmol) in absolute ethanol (20 ml) and a temperature of 5-10 C in nitrogen atmosphere. The reaction mixture was stirred for 1 hour and then acidified with 10% hydrochloric acid. Ethanol is removed by concentration under reduced pressure. 10 ml of water are added to the remaining thief, which is then extracted

ethyl acetate (2 x 50 ml). The extracts were combined, washed with a sap solution, and then dried (MgSO4). After concentration in vacuo, the title compound is obtained in the form of a solid amorphous substance (213 mg) which is used without further purification.

15

five

.

five

0

0

five

PRI me R 7, d, f-TpaHC-5,6,6a ,. 7,8,9,10, 10ai-Octagidro-1, 9 -diacetoxy-5-isobutyryl-3- (5-fenkl-2-pentyloxy) benzo (C) -quinoline.

Under nitrogen, the solution is d, C- -trans-5,6,6a, 8., 7,8,9, 10, Yu.-octahydro-1-acetoxy-9-hydroxy-5-isobutyryl. 3- (5-phenyl-2-pentyloxy) -benzo (C) -quinoline (213 mg, 0.432 mmol) in tetrahydrofuran (5 ml) is added to a suspension of lithium aluminum hydrideX 100 mg, 2.6 nmol) in tetrahydrofuran (5 ml ) at room temperature. The mixture was stirred overnight and then water (0.1 ml), 15% sodium hydroxide solution (O, 1 ml) and water (0.3 ml) were added. It is then filtered under nitrogen and the remaining filtrate is washed with tetrahydrophl / wound (2 x 5 ml). The combined filtrate and washed solution was concentrated to a reddish oil (0.174 g). The oil was dissolved under nitrogen in pyridine (1 ml) and the resulting solution was cooled to 0 ° C. Acetic anhydride (1 ml) was added with stirring to the pyridine solution and the reaction mixture was stirred for 30 minutes at 0 ° C. Then pour it into water (25 ml) and extract with ethyl acetate (3x25 ml). The extracts were combined, washed with brine, dried (MgSO4) n, concentrated to a brown oil (184 mg), the oil was quickly washed with nitrogen, and chromatographed on silica gel (40 g) using benzene / ether (6: 1 as eluting solvent). ). Collect fractions of 10 ml each. Fraction 2-10 is combined and concentrated to an oil (109 mg). m / e - 52 Km).

Calculated,%: C 73.67; H 8.3G, N 2.68.

C ,, H ,, OfN

Found,%: C 74.33; H 8, C9, N2.23.

 n NMR (60 MHz), r (h, on

 - Dv Cv

min): 7.22 (C, 5H, aromatics), 6.05 (d, 1H, aromatics), 5.90 (D, 1H, aromatics), 4.90 (bs, 1H), 4.30 (bs , 1H) 8.10 (d, 2H, N-CH,), 2.90 (d, 2H, N-CHj); 2.70 (bs, 2H); 2.40 n 2.15 (s, 6H, 2-CH5-COO-); 1.85 (bs, 2H,

SI

n, and Id), 1.15 (m) 1.05 (d, bN.

L.n

1 at 0-3, O (perm, other protons).

),

Data on the obtained compounds are summarized in Table. 3

The analgesic properties of the proposed compounds were determined by tests of thermal nioceptive irritation, for example cauterization of the tail in the male, or by chemical nociceptive irritation, for example, by measuring the ability of the compounds to suppress the pain in mlsi, induced by phenylbenzene stimulant. Test methods are given below.

Tests using thermal nociceptive irritation.

Test the analgesic effect on mice using a hot plate.

An aluminum plate with a thickness of 1/8 (3.1 mm) is applied to the paws of the mice, which is adjustable by the heat source. An infrared reflector (250 W) is placed on the bottom of the aluminum plate. The thermostat in the form of a thermister located on the plate surface regulates the heating of the pump so as to supply (keep the plate at a constant temperature. Each wean is placed in a glass cylinder (6 mm) in diameter, the base of which is an aluminum plate, and the timing starts from the moment when the paws touch the plate. 5 and 2 hours after the test compound has been processed, observe the first convulsive movements of one or both hind paws and until an interval of 10 seconds between these movements is established. The dose of morphine is MPE, d 4-4.5 mg / kg, PE ffBG is the maximum possible effect.

Testing the Analgesic Effect on Mice by Tail Swings. The caudal method is more convulsive: the movements are modified and use a regulated, intensive heat supply to the mouse tail. Every mouse is placed in

ten

15

124689D 10

lindra so that her tail is high

vals from one end of the cylinder. This c1: -1 cylinder is set so that the tail lies flat above the shielded lamp, which is the source of heat. At the beginning of the test, the aluminum screen above the lamp is removed, allowing the beam of light to pass through the target and focusing it on the tip of the tail. At the same time include a timer. The time of occurrence of the convulsive movement of the bone is determined. Mice that have not been pretreated usually respond 3-4 seconds after exposure to lamp light. The maximum period for protection is 10 Co Each target is tested after 0.5 and 2 hours after treatment with morphine and test compound 2D | nor eat it. The dose of morphine is MB3f, 3.2-5.6 mg / kg.

Tests of chemical conceptual irritation. Suppression of phenylbenzoquinone pain syndrome.

A group of 5 moles (Carworth Tarms CF-1) is pretreated by subcutaneous or oral administration with morphine, codeine, or a test compound saline. After 20 (for subcutaneous administration) or 50 (for oral administration), each group is subjected to intraperitoneal injection of phenylbenzoquinone, which causes abdominal contractions. After 5 minutes after the excitator is observed, 5 minutes HJL is observed regarding the presence or absence of convulsive contractions. The effect of the previously administered drug in the dose of MVE on the suppression of convulsive contractions is determined.

The results of the tests described are expressed as a percentage of the maximum possible effect (% MPE). The% MVE for each group is statistically, c. The% MIi3 of the control and pre-test (5from; an animal.% Of MBE is calculated as follows;

25

t

415

conveniently fitted metal qi% MVE test BpeMH-KOH rpoJibHije time x cut-off time - control time

100,

In Table 4, analgesic activity is expressed in units of MVE, i.e. the dose at which in this test reach half the maximum effect possible.

The compounds of the present invention are active analgesic 100,

ffitHMH by means of both oral and parenteral administration, and their Eshodt usually consists of 55- Such compositors include

pharmacentric carriers selected on the basis of the method of administration and on the basis of the generally accepted pharmaceutical

practice. For example, they can be administered in the form of tablets, pills, powders, or pellets containing such additives as starch, milk sugar, some varieties of clay, etc. They can be administered in the form of capsules in a mixture with the same or equivalent additives. They can also be administered in the form of suspensions, solutions, emulsions, dp syrups, oral administration and elixirs, which may contain fragrances and coloring agents. Tablets and capsules containing from about 0.01-100 Mg are suitable for oral administration of therapeutic agents of the invention.

The doctor must prescribe the dose that is most appropriate for the particular patient, and it depends on the age, weight and susceptibility of the particular patient and on the method of administration. Typically, the initial analgesic dose for adults is in the range of 0.01-500 mg per day for a single dose, or divided into parts. In many cases, it is not necessary to exceed a dose of 100 mg per day. A dose in the range of 0.01-300 mg / day is most suitable, and a dose in the range of 0.10-50 mg / day is preferred. P1 is most appropriate when administered parenterally, a dose of 0.01-100 mg / day is preferred, and a dose of 0.01-20 mg / day is most preferred.

Using the methods described, the analgesic activities of some compounds of the invention and some previously known compounds were determined (Table 4, where the following abbreviations are accepted: PBO-phenyl benzoquinone is the causative agent of pain synchrome, TF is the needle convulsion method

HP - hot plate method).

Inhibited The effects of N-dihydromorphine on formulations that are sensitive to drugs, benzo (C) quinoline at the concentration given in Table. 5, where the following notation is used: a Z-W OCH (CHj) (SND

Sat

; b Z-W -o (cHj)

five

five

 Z-W O (CHj), - CgH ,,, and the diasteromer isomer A, Z-W A; and diastereoisomer B, Z-W a.

Data on acute toxicity were obtained only for two compounds according to the invention. The first product is D-trans-5,6,6a, 7,8,9, 10, 10a "b-octahydro-1-acetoxy-9JB-oxy-6-methyl-3- (5-phenes I-2-pen -; thi.poxy) -benzo (C) -quinoline. It corresponds to the compound of example 7. The second compound, for which

0 there is evidence of acute toxicity, is the twisting enantiomer of the above named compound.

In tab. 6 for each of these two compounds are given the values

5 LDjp (lethal dose), which is defined on mice and rats.

LD5p is much higher than the effective dosages at which these compounds are used as analgesics in experiments on mice and rats. For maximal mice, a possible effect with subcutaneous injection of the first soybean, the expression is achieved at the dosage of O, A mg / kg, for rats - at 1.0 mg / kg. For the second compound, for subcutaneous administration, the corresponding values are 0, 1 and 0.3 mg / kg. The maximum effect as a percentage is interpreted as the average degree of analgesic effect. Thus, the dosages with which these compounds are used as analgesics are significantly lower than

0

five

 Thin layer chromatography, benzene / ether mixture (1: 1). Calculated for HCl: C 68.71; H 7.26, N 2.96.

I

table 2

CH,

SI,

CH,

H N

1) - Calculated,% g C 69.19, H 7.47, 2.88.

-NS1

Found,%: C 68.72; And 7.18, 2.74.

2) Calculated,%: C, 74.80; 7.35; 3.12. C ,, H ,, 0, N.

CHjk 94-97 s

449

CH. H Butter

44 Oe

CH, H 102-103 С

J)

435

 Found ,, Z: C 74.66; H 8.05; 2.66.

69-75 ° C.

3) Calculated,%: C, 74.45; H 7.64 3.22.

C, H., 0, N.

Found 7: C 73.89; H 7.5G, 3.04.

g

cho

f o

about

CSI

but;

X

EV

az

but:

but:

but:

(3k

U

az

U

a: o

a: and

but:

U

§

about

az

oh oh

U

as about and

g

a and o and

but:

a: and o and

but:

g

but; and oh oh

but:

but:

but:

U

oh oh

Fli,

 Rs

Re

ORi

Re

Concentration is 10 M.

Rat mice

427 347

Editor E. Papp

Compiled by G.Zhukova

Tehred I.Popovich Proofreader V. But ha

Order 4029/59 Circulation 379 Subscription VNIIPI USSR State Committee

for inventions and discoveries 113035, Moscow, Zh-35, Raushsk nab., 4/5

Production and printing company, Uzhgorod, st. Project, 4

Table 6

262 210

Undefined 147

231 Undefined

Claims (1)

METHOD FOR PRODUCING 9-OXY-BEN '30 (C) -QINOLINES of the general formula n OH where R is hydrogen or acetyl, R ^ is acetyl, Rj is hydrogen or methyl, R ₃ is hydrogen or alkyl with 1-4 at- mami carbon ’, Z - alkyleneoxy with 1-7 carbon atoms; * W - hydrogen or phenyl, l and seething from I'm that with * the unity of the General formula where R _t , Rj ZW have the indicated meanings; R _# - hydrogen or acetyl, is acetylated. SU _1I> 1246894 AZ