SU535034A3 - The method of obtaining quinoline derivatives, their salts or their isomers - Google Patents

Description

This invention relates to a process for the preparation of quinoline derivatives of the general formula 1 2, where A is a group of the general formula -CH. is hydrogen or Cj alkyl, RX is hydrogen or halogen, hydroxy or carboxy group, unbranched or carried C-Se-alkyl; C5-C-cycloalkyl, C -Cj-alkoxy, which may be substituted by phenyl or C-Ccnc-barboxy, C2-C, -carbalkoxy, oxymethyl, phenyl, phenox -, amino, pyrrolidine residue or morpholine; Rj-Ky is the same or different, hydrogen or halogen, methyl, hydroxy, methoxy, cyanoamine, nitro, trifluoromethyl, carboxy, acetyl, C-C -carbalkoksil or two radicals from R, R. or R together form methylenedioxy; - hydrogen, straight-chained or branched C-C-alkyl, which may be substituted by hydroxy, methoxy, carboxy, cyano, dimethylaminocarbonyl, morpholinocarbonyl or Cj-C-carboxy alkoxy, unsubstituted or substituted by a methoxy group of unbranched or branched aliphatic C-acyl, unsubstituted or substituted by halogen benzoyl, C-C -carbalkoxy, C C -carbicycloalkoxy, unsubstituted or substituted by methyl benzyl, substituted by methyl or halogen, phenylsulfonyl, C-C -alkenylphenyl trifluorocetyl.amidine residue, amido -, tioami ogruppa, phenoxycarbonyl, or benzyloxycarbonyl, or methylsulfonyl; 1 hydrogen or together means a double bond, their salts or their isomers, which have biological activity. Based on the known condensation reaction of aromatic O-aminocarbonyl compounds with carbonyl compounds, the proposed method for the preparation of compounds of formula (I) is that the compounds of the general formula T2 Ri in, where R and R have the above-mentioned meanings; - lower C.-C.-alkoxy B and D in and D together - oxygen and U and U2 are hydrogen, or B is lower C-C-alkoxy, D and Hz together are double-Y and Y are hydrogen, or D and Y together is a double bond and Y is hydrogen, is treated with a compound of the general formula (III) where Rj is Ry as described above; 2, is a cyano group or a group of the general formula K-f -CO-, in which R has the meanings indicated above for R and a mono or disubstituted amino group, under water-dissolving conditions, followed by isolation of the desired product in free form, in the form of a salt or individual isomers. The process is usually carried out using a solvent, such as water, benzene or toluene, in the presence of water-leaving agents such as sodium hydroxide solution, hydrochloric acid, sulfuric acid or phosphoric acid, phosphorus oxychloride, polyphosphoric acid or toluenesulfonic acid, at O - 200 ° WITH. In addition, the process can be carried out with a constant azeotropic distillation, forming water from the reaction mixture. When using compounds of formula 11 in which R is inorganic acyl, the reaction 11 is carried out in the presence of an acidic condensation agent in an anhydrous solvent. If in a compound of formula P1 R is roxy, the reaction is carried out in the presence of phosphorus oxyhalide and an isomeric mixture of compounds of formula 1 is obtained, where R2 is halogen. When polyphosphoric acid is used, an isomeric mixture of compounds of Form 1 is obtained, where Rj is hydroxyl.

The resulting isomeric mixture containing compounds of the general formula -Bb is separated by base chromatography, extraction or fractional crystallization of bases or salts. Synthesized compounds of the formula I, in which at least one of the radicals is a reactive hydrogen atom, can be converted into corresponding derivatives by alkylation, acylation and / or vinylation. From compounds of formula I. where R, is alkyl or aralkyl, by reacting with chloroformate in a solvent, for example, methylene chloride, chloroform, ethylene chloride or tetrachlorethylene, at O-12 ° C, you can obtain the compounds of formula I, in which is alkoxycarbonyl cycloalkoxycarbonyl or phenyloxycarbonir. When reducing compounds of formula I, where R is acyl and / or R2-carboxyl, complex metal hydrides, such as lithium aluminum hydride in a solvent, such as ether, ether-dioxane or tetrahydrofuran (THF), at O - 70 ° C, preferably at a temperature boiling of the solvent, to obtain compounds of formula 1, where R is apkyl and / or Rn is oxymethyl. By oxidizing compounds of formula I, where R is acyl or carbalkoxy, for example, hydrogen peroxide or perbenzoic acid, the corresponding 6-N-oxides are obtained. From the 6-N-oxides of the formula 1, where R is non-hydrogen and R2 is methyl, compounds of formula I, where Rg is oximetry, can be obtained, preferably conducting the reaction in a solvent such as benzene, dioxane or THF, in the presence of reactive acid derivative , such as acetic anhydride, acetyl chloride, propionic anhydride or chormyate ester, with o - Anhydrides, Kispot halides or corresponding acids are usually used for acidification in the presence of a dehydrating agent, such as hydrochloride Reed or N, N-dicyclohexylcarboimide, preferably in a solvent such as water, ethanol, benzene, dioxane, chloroform or dimethylformamide, if necessary in the presence of a base, such as triethylamine, pyridine or sodium carbonate, at 0 -. Among the compounds of formula I or their isomeric mixtures, which can be separated into individual isomers, it is possible to obtain their salts with inorganic or organic acids, such as hydrochloric, methyl bromide, sulfuric, phosphoric, lactic, citric, tartaric or maleic. The compounds of the formula I can be obtained by condensation on Dickman of N-substituted ethyl 4- (2-ethoxycarbonylethyl) amino-acid ethyl ester in the presence of potassium t-butylate, followed by saponification and decarboxylation of the resulting intermediates in the presence of acids. Derivatives of N-acylhexahydroazepinone- (4) are obtained by acylation of hexahydroazepinone- (4), 4-Alkoxyazepines of formula 11 are obtained by reacting the corresponding azepinone- (4) with ortruminic acid ether, followed by cleavage of the alcohol T forming 4,4-dialkoxyacetate, forming 4,4-dialkoxyacetate, and 4 Example 1. Dihydrochlorides 1,2, 4,5, tetrahydro-11-methyl-3H-azepino-4 5-bl-quinoline and 2,3,4,5-tetrahydro-11-methyl-1H-azepino-4, 3-b 3 -quinoline. 222 g (1.48 mol) of hexahydroazepinone- (4) B hydrochloride; 2.8 l 2 n. hydrochloric acid and 20O g (1.48 mol) of 2-aminoacid of tofenone are heated to boiling for 72 hours, cooled, alkalized with concentrated sodium hydroxide solution, extracted with chloroform, the extract is dried over sodium sulfate, the solvent is distilled off and a 312 g (1OO%) of a mixture of 4.5-1) 1 and 4,3-b3 isomers (4: b). The mixture of isomers is dissolved in 300 ml of methanol and chromatographed in a thin layer on a column of silica gel {d 10 cm; h. 160 cm; grain size 0.05-0.2 mm), eluted with methanol, methanol was distilled off from the homogeneous fractions and 95 g (30%) of the 4,5-LC-isomer were obtained, m.p. 103 ° C, and 1O4 g (33%) of 4,3-b-isomer, mp, 123 ° C. The resulting bases are dissolved in hot isopropanol, an isopropanol solution of hydrochloric acid is added, cooled, and the 4,5-b-isomer dihydrochloride is isolated, yield 90%, m.p. 296 ° C (decomp.), And dihydrochloride 4, 3 - 1 -isomer, yield 96%, so pl. 284 ° C (dec,). Examples 2-9. Analogously to example 1, receive 1 lR-1,2., 4, 5-tetrahydro-ZN-azepino-4, -quinoline and 11-R-2, 3,4,5-tetrahydro-1H-azepino 4, 3-b -quinoline using hexahydroazepinone hydrochloride- (4) and the corresponding ketones or aldehydes. The properties of the isomers are given in table. 1. Example 10. 1,2,4,5-Tetrahydro-3H-11-azepino-4, 5-N-quinolinecarboxylic acid and 2,3,4,5-tetrahydro-1H-ll-azepino-4,3 - B - quinoline carboxylic acid. 5 g (33.5 mmol) of hexahydroazepinone-14 hydrochloride) and 4.9 g (33.5 mol) of isatin in 27 ml Yun, sodium hydroxide and 27 ml of ethanol are heated to boiling for 16 hours, cooled, neutralized with hydrochloric acid, evaporated dry, extract the residue with ethanol under heating, chromatograph on a column of silica gel, elute with methanol, and obtain 4,5-I) -isomer, yield 6%, mp. 233-C (dec), and 4, 3- | isomer, yield 10%, t, pl. 269 ° C. (res.) Example 11. 11-Chloro-2,3,4, 5-tetrahydro-1H-azepino-4, 3-b-quinoline. 48 g (0.35 mol) of anthranilic acid and 52.4 g (0.35 mol) of hexahydroazepinone hydrochloride- (4) are heated with an excess of phosphorus oxychloride, cooled, decomposed with ice water, extracted with chloroform, evaporated and chromatographed the residue on a column of silica gel eluting with ethanol. Yield 4%, m.p. 1270C. Example 12. 3-Benzyl-1, 2,4,5-tetrahydro-11-methyl-3H-azepino-4, 5-1) -quinoline dihydrochlorides and 2-benzyl-2, 3,4, 5-tetrahydro-11 -methyl-1 H-azepino-4,3-oZ-quinoline. 11 g (54 mmol) of 1-benzylhexahydroazepinone- (4) is dissolved in 10 O ml of toluene, 18.6 g (1O8 mmol) of toluenesulfonic acid and 7.3 g (54 mmol) of 2-aminoacetophenone are added, heated for 6 hours to boil with gradual azeotropic distillation of water, cooled, the precipitate is filtered off with suction, dissolved in 2N. caustic soda and extracted with chloroform. After drying over sodium sulfate and distilling off chloroform, 15 g (92%) of a mixture of 4 and 4,3-tl-isomers (4: 6) are obtained in the form of an oil, which is dissolved in 20 ml of ethyl acetate, chromatographed on a thin layer on a column of silica gel (d 3.5 cm; h 12O cm; grain size O, O 5-2 mm)

l

2 o

§. Ф 2 о со

S

J P)

9

The oil is eluted with ethyl acetate from the homogeneous fractions and the solvent is distilled off to obtain 4 g (24.5%) of 4.5- & isomers, so pl. 110 ° C, and 6 g (36.8%) of 4,3-b isomer, so pl. 126 ° C.

For the preparation of dihydrochlorides, bases are dissolved in isopropanol with heating and mixed with an isopropanol solution of hydrochloric acid. The output of the dihydrochloride 4,5-1} -isomer 90-95%, so pl.255OS

Examples io-20. 1,2,4,5-tetrahydro 3-R 11 -methyl-3115-azepino-4,5-b-hknopn and 2; 0,4.5-te5 rahydro-2-R-11-methyl -1M-yzepino- 4, 3-L-quinoline is obtained from 1-R-hexahydroazepiccock- (4) hydrochloride (2) to 2 aN: i HO acetophenone in the same way as upii.vsepy 1.

JO The properties of the synthesis of BrOb1 &x; soyneiky are given in Table 2.

Dihydrochloride I-i, 3- b-isomer

i (different)

3 Jr 10 18 60 12 8

Acetone is used for chromatography.

K: S

Ethyl acetate is taken for chromatography.

The mixture of isomers without chromatographic separation is converted into the dihydrochloride. The dihydrochloride of the 4,3-b isomer is extracted in a Soxhlet apparatus, nojiyi, i; i and the residue is undissolved 4.5-6 isomer. A DL-isomeric mixture was obtained using azepinone- (4). Example21. 1,2,4,5-tetrahydro-5, 11-dimethyl-3N-azepino-4-, 5-b1 -azepine dihydrochloride. Using 3-methyl-hexahydroazepinone- (4) hydrochloride and 2-aminoacetophenone, as in Example 1, the target Dihydrochloride is obtained in a yield of 36%, mp, 250 ° С (decomp.). Example 22, 3-Benzyl-1, 2.4., 5-tetrahydro-ZN-azepino-4,5-11-quinopine dihydrochloride and 2-benzyl-2,3,4,5-tetrahydro-1H-azepino-4 , 3-b-quinoline, 15 g (124 mmol) of 2-aminobenzaldehyde and 29.6 g (124 mmol) of 1-benzylhexahydroazepinone hydrochloride- (4) solution 50 55 60 60 DL -terbuthexagydroxy in 360 ml of methanol, 2.95 (124 mmol) of sodium hydroxide solution are added and stirred in the dark for 24 hours at room temperature. After distillation. Etar, ol, the residue is dissolved in chloroform, filtered, evaporated, recrystallized from isopropanol and ethanol to give 4,3-b isomer, yield 21%, t, pl. . When treating the stock solution with an nsopropanol solution of hydrochloric acid and subsequent recrystallization from ethanol, the dihydrochloride 4.5-1) 1-isomer is obtained, yield 10%, mp, 252 ° С (decomp.). Example 23, 1,2, 4,5-tetrahydro-3- (4-methylbenzyl) dihydrochloride 1,212

pino-4,5-z-quinoline and 2,3,4,5-tetrahydide. chloride 4,5-b-isomer, yield 43%, mp.

(4-methylbenzyl) -1H-azepino-4.3-278 ° C (decomp.,), And G4,3-δ gbl-quinoline dihydrochloride, isomer 34%, m.p.

From hydrochloride of 1- (4-methylbenzyl) -hec-Example 28. 3-Ethyl-11-cyclohexahydroazepinone- (4) and 2-aminobenzalde-5sil-1,2,4,5-tetrahydro-3N-azepino-4,5gida as in Example 22, a mixture of isomers, cohexyl-2,3,4,5-tetrahydro-1H-azepino-4, is obtained in a mixture of methanol-b3-quinoline and 2-ethylcyclo-water dihydrochloride (1: 1) 3 copy is treated in isopropanol with isopro-3H-quinoline.

hydrochloric acid solution. At 1.77 g (10 mmol) of 1-crystalline hydrochloride crystallization from methanol by crystallization of ethyl hexahydroazepinone- (4) and 2 g (10

only dihydrochloride 4,5-b-mol) 2-aminophenylcyclohexyl ketone appears in

isomer, yield 7%, so pl. 263 ° C. The mother-40 ml of phosphorus oxychloride is heated for 2.5 hours

The solid solution is evaporated to dryness, processed to boiling, phosphorus oxychloride is distilled off, it is covered with ethanol, and the dihydrochloride is prepared with ice water, substitute L4, 3- b - isomer, yield 19%, mp. 208 p. 15 poured with caustic soda, extracted with chloro Example 24. The dihydrochlorides are 3-roform, the extracts are dried over sulfate

-ethyl-9-хХЛО-1,2,4,5-tetrahydro-11-phenyl-sodium, the solvent is distilled off, dissolved

-ZH-azepino-4,3-b-quinoline and 2-ethyl-residue in methanol and chromatographed on

-9-chloro-2,3,4,5-tetrahydro-11-phenyl-1H-column with silica gel (d 2 cm; h 80 cm;

-azepino- 4,3-b-quinoline. 20 grain size 0.05-0.2 mm), eluting methane Using hydrochloride with 1-ethylhexahydride. The preparation of the dihydrochloride is carried out

roazepinone- (4) and 2-amino-5-chlorodiphenyl-acetone in acetone using an isopropanol rasteron, analogously to example 1 in a mixture of 2 N. yard of hydrochloric acid. The yield of 4,5-b-isosulfuric acid and dioxane (2: 1) gives 15%, m.p. 10 ° C. The output of the dihydrochloride mixture of isomers, during chromatography of which 25 is the 4,3-b -isomer 45%, so pl. 255 ° C. acetone is used as eluent. You are Example 29. Dihydrochlorides 3-

the progress of the dihydrochloride is 4,5-bj-isomer 26%, - ethyl-11-chloro-1,2,4,5-tetrahydro-ZN-azet. mp. 2800С (decomp.). The output of dihydrochloridapine-4,5-quinoline and 2-ethyl-11-chloro 4, 3-1 isomer 44%, so pl. 278 ° C (decomp.). - 2,3,4,5-tetrahydro-1H-azepino-4,3-b Example 25. H-these dihydrochlorides - α-quinoline.

-1,2,4,5-tetrahydro-11-phenyl-3H-azepino-OO g (0.563 mol) of hydrochloride, 5-b-quinoline and 2-ethyl-2,3,4,5-tet-ethylhexahydroazepinone- (4) v 500ml chlorohydro-11-phenyl-1H-azepino-4.3-1) -hi-oxide of phosphorus is boiled with 72.5 g (0.5 63 mol)

nolina. - anthranilic acid for 4 hours,

From hydrochloride, 1-ethylhexahydroazepi is cooled, decomposed by ice, podschelanone- (4) and 2-aminobenzophenone are analogous and extracted with chloroform. For

Example 24: 4,5-isomer dihydrochloride is obtained; chromatography is carried out with is-g

- b-isomer, yield 28%, so pl. 280 ° Cage on silica gel column, eluting

(decomp.), and dihydrochloride 4,3-b-isomer, methanol. When processing ethanol solution of 5O%, so pl. 2730C (decomp.). Hydrochloric acid is obtained by digesting dihydro Example 26. Dihydrochlorides of 3-ben-chloride of 4,3-b-isomer, yield 45%, m.p.

Zyl-1,2,4,5-tetrahydro-11-phenyl-3N-azepi-267 ° C (decomp.), and dihydrochloride 4,

, 5-b-quinoline and 2-benzyl-2, 3,4,5 - isomer, yield 16%, so pl. 233-236 ° C

-tetrahydro-11-phenyl-1H-azepino-4,3-L1-45P - quinoline. Example 30. 3-benzo dihydrochloride 1-benzylhexahydro-azazyl-11-chloro-1,2,4,5-tetrahydro hydrochloride -ZN-azepipinone- (4) and 2-aminobenzophenone, as in pri-but-4,5-b-quinoline and 2-benzyl-11-chlorine

at least 24, get dihydrochloride 4, 3,4,5-tetrahydro-1H-azepino-4.3-1) isomer, yield 26%, so pl. 250 ° C (decomp.), Gg-quinoline.

and 4,3-Y-isomer dihydrochloride, yield 135 g (0.563 mol) of hydrochloride 149%, so pl. 2480C-benzylhexahydrozepinone- (4) and 77.5 g

Example 27. Dihydrochloride 9- (0.563 mol) anthranilic acid in 5OO

-chloro-1,2,4,5-tetrahydro-11-phenyl-3H-aze-ml of phosphorus oxychloride is boiled for 3 hours, the mixture is pinot-4, 5-b-quinoline and 9-chloro-2,3, 4.5- 55 g of ice water, alkalinized, extra-tetrahydro-11-phenyl-1H-azepino-4.3-1) 1 -gased with chloroform, the extracts evaporated,

-quinoline. The residue was recrystallized from the isoproduct from hexahydroazepi-hydrochloride hydrochloride and the 4,3-b isomer was isolated, yield

nona- (4) and 2-amino-5-chlorodiphenylketone, 33%, so pl. 148 ° C. analogously to example 24, dihydro-60 is obtained From the mother liquor during the treatment

535034

13 An isopropanolic solution of hydrochloric acid gives dihydrochporid 4,5 b -isomer, yield 31%, mp. 220 ° C (dec.). Example 31. 3-Ethyl-11-hydroxy-1, 2,4,5-tetrahydro-3H-aza-pino-4,5-β-quinoline and 2-atyl-11-oxy-2,3,4,5 dihydrochlorides tetrahydro 1H-azepino-4, 3-bli-quinoline, 6.85 g {50 mmol) anthranilic acid and 8.9 g (50 mmol) of 1-ethylhexahydroazepinone hydrochloride- (4) are stirred in 300 g of polyphosphoric acid for 3 hours at 16 ° C, poured on ice, alkalinized, extracted with chloroform, and the residue is chromatographed on a silica gel column in a chloroform-methanol system (1: 1). In this zero, by adding an ethanolic solution of hydrochloric acid, the 4,5-S-isomer dihydrochloride is obtained, yield 13%, m.p. 295 ° C (decomp.), And dihydrochloride 4,3-I} -isomer, yield 6%, so pl. 294 ° C {section). Example 32. 3-Benzyl-11 hydroxy-1, 2,4,5-tetrahydro-3H-azepino-4,5-b1 -quinoline and 2-benzyl-11-hydroxy-2, 3,4,5-tetrahydro ro -1H-azepino- {4.3-1) 1 -quinoline. 135 g {0.563 mol) of 1-benzylhexahydroazepinone {4} to 77.5 g {0.563 mol) anthranilic acid hydrochloride is stirred for 5 hours with 1200 g of polyphosphoric acid at 160 ° C, drank on ice, basified, extracted; sloroform, condensed extracts and the residue is recrystallized from ethanol. Output 4, 5-1) of the 5-isomer of 10.4%, so pl. . From the one stripped off mother liquor, the G4, 3-TS3 isomer was isolated by repeated recrystallization from methanol, yield 2O%, m.p. 258 ° C, Example 33. 1,2,4, 5-tetrahydro-11-methyl-3H-azepino-4,5-bl-quinoline dihydrochloride and 2,3,4,5-tetrahydro-11-methyl-1 H -azepino- 4,3-L-quinoline. 25 mmol of hexahydroazepinone {4) and 2-aminoacetophenone hydrochlorides are thoroughly crushed, mixed and heated to 120 ° C, the formation of a melt is observed, kept for 120 minutes at 120 140-C {melt crystallizes), cooled, dissolved in water, alkalized with caustic soda and extracted with chloroform. The yield of the mixture of isomers is 98%. The isomers are separated as in Example 1. The yield of dihydrochloride is 4,5-O isomer 43%, m.p. 296ОС. The output of 4.3-13 isomer 32%, so pl. . Example 34. Dihydrochlorides 9-bromo-1, 2,4,5 - tetrahydro 11-methyl-3N azepino-4, quinoline and 9-bromo-2,3, 4,5-tetrahydro-11 methyl-1H-- azepino-4,3-y-quinoline. From hexahydroazepinone- {4 and 2-amino-5-bromoacetophenone hydrochloride, similarly

14, example 1, dihydrochloride is obtained 14, b of the L isomer, yield 21%, mp, 313 ° C {decomp. and 4.3-1 dihydrochloride - isomer €, yield 22%, so pl. 307 ° C (res.). Example 35: D-hydrochloride 9-chloro-1, 2,4.5-tetrahydro-11-methyl 3N-zepino-4, 5-TDl-XHHOHHHa and 9-chloro-2, 3,4,5-tetrahydro-11-methyl 1 H-azepino-4,3-) 1-quinoline. From hexahydro-aaepinone- {4) hydrochloride and 2-amino-5-chloro-petophenone. as in example 1, dihydrochloride 4 5-131-isomer is obtained, yield 19%, mp, (decomp.), and dihydrochloride 4, 3-t) isomer, yield 30%, pl. 288 ° C (decomp.). Example 36. Hydrochlorides 1,2, 4,5-tetragndro-11.-yekkp-9-.nigro-3N azepi, 5-b-chi nol and 2,3,4,5-t e tr agidro-11- methyl 9-nitro-1H azepn-4, 3-b3-quinoline. 4.5 g (25 dmmol) 2-a: yno-5 gatroats9tophenone and 3.8 g {25 mmol) hexahydroazepinone hydrochloride {4) and 50 m, p phosphorus oxychloride is heated to boiling for 3 hours, phosphorus oxychloride is distilled h vacuum created by water jet. -v; pump, dissolve the residue 3 in water, basify with caustic and extract with chloroform. The extracts are dried over sodium sulfate, filtered, and evaporated to a thin layer on a silica gel column with: 3 cm; methanol - ;. One of the hydrogen fraction of the fractions was distilled off methanopane and, in acetone, a mixture of isopropanol and 1 st solution of hydrochloric acid was collected. Output dt1gtdrohpor1; yes. B - iso ome% g. 30S ° C (decomp.,), The output of the dihydrochloride 4,3-Ij -: {zomera 15%, so pl. 308 ° C (decomp.). PRI me R 37 Digadrochloride .1,2. 4,5-tetrahydro-11-methyl-8-nctro ZK-azepino-4j5-1 quinopine and 2, 3, 4, 5-Getrahydro-11-metip-8-kitro - 1 H-azepk-no-4 quinoline From hexahydroazepinone- {4) and 2-amino-4-1 -t-tsetofenok hydrochloride analogously to example 36, the dihydrochloride 4, 5-Ь J-isomer is recalled, yield 20%, m.p. {different). and dihydrochloride 4,3-bj-isomer, yield 22%. m.p. 300 ° C (decomp.). Example 38 1,2,4: 5-Tetrahydro-11-methyl-7-th1Tro-ZN-azepino-4, 5---quinoline and 2,3,4,5-tetragandpo-ll-methyl-7-nitPO 1 H-azepino-4,3 L-hanolin. From hexahyd1 hydrochloride: azepinone- {4) and 2-amino-3-W4Troa1tetofenon5, as in Example 36, the 4,5-b3 isomer is obtained. yield 15%, so pl. 1300C, and 4.3 b isomer, yield 18%, m.p. 127 ° C 39. DKHYDROCHLORIDES EXAMPLE 4,5-tetrahydro-11-metip-10-kyrc-3H-aze of pino-4,5-b-hymn and 2,3,4,5-tetrahydro O-mecl-10-nitro -1 H azepino-4.3 and 1-quinoline. From hexahydroazepinone- (4 and 2-amino-6-W1tro-acetophenone hydrochloride as in Example 36, the 4,5- isomer dihydrochloride is obtained, yield 18%, mp. 190 ° C (decomp.), And dihydrochloride 4,3-1) isomer, yield 19% m.p. 210 ° C (times). Example 4O. 1,2, 4,5-tetrahydro-9-hydroxy-11-methyl-3H-azepE (, 5-b-quinopine and 2,3,4,5-tetrahydro-9-hydroxy-11-methyl-1H- azepino-14,3-Yquinoline. Using hexahydroazepinone- (4) and 2-amino-5 hydroxyacetophenone hydrochloride, analogously to Example 1, the 4,5-b-isomer dihydrochloride is obtained, yield 10%, mp (decomp.), and dihydrochporid 4,3-b-isomer, yield 2O%, mp 250 ° C (decomp.). Example 41. Dihydrochlorides 1,2, 4, 5-tetrahydro-7-hydroxy-11-methyl-3Н- azepino-4,5-b-quinoline and 2,3,4,5-tetrahydro-7-hydroxy-11-methyl-1H-azeshga-4,3-b1-quinoline. From hexahydroazepinone- (4) hydrochloride and 2- amino-3-oxyacetophenone anal according to Example 1, a 4,5-b-isomer dihydrochloride is obtained, yield 19.5%, mp (decomp.), and 4.3-b3 isomer dihydrochloride, 23.5% yield, mp 3170C ( ex.). Example 42. 3-benzyl-1, 2,4,5-tetrahydro-9-OXI-11-methyl-3H-azepino-4, 5-1) dihydrochlorides; 1-quinoline and 2-benzyl-2, 3,4,5-tetrahydro-9-OXI-11-methyl-1H-azepico-4, 3-L-quinoline. From 1-benzylhexahydroazepinone- (4) and 2-amino-5-hydroxyacetophenone hydrochloride, as in Example 1, the 4,5-b-isomer dihydrochloride is obtained, yield 10%, mp.278 ° C (section), and dihydrochloride 4,3-111-isomer, yield 2O%, so pl. 210 ° C (decomp.), Example 43. Dihydrochlorides 1,2, 4,5-tetrahydro-11-methyl-9-methoxy-3H-azepk-4, 5-1) 1-quinoline and 2,3,4, 5-tetrahydro-11-methyl-9-methoxy-1 H-azepino-4, 5-b-quinoline. From hexahydroazepinone- (4) and 2-amino-5-methoxyacetophenone hydrochloride, similarly to Example 1, 4,5-L1-isomer dihydrochloride is obtained, yield 10%, m.p. (decomp.), and dihydrochloride 4,3-t) -isomer, yield 29%, so pl. 2740C (decomp.) Example 44. 1,2, 4,5-tetrahydro-11-methyl-7-methoxy-3H-azepino-4, 5-b-quinopine dihydrochlorides and 2, 3.4. 5-tetrahydro-11-methyl-7 -methoxy-1H-azepino- | 4, 3-b1 -quinoline. 53 4 From hexahydroazepinoc- (4) hydrochloride and 2-amino-3-methoxyaceto8none analogously to example 1, dihydrochloride 4, 5-ti-isomer is obtained, yield 19%, mp. 26 ° C (dec.), And dihydrochloride 4, 3 b1-isomer, yield 35%, m.p. 224 ° C (decomp.). Example 45. 1,2,4,5-tetrahydro-11-methyP-3-azepino-4,5-b1 -quinolinecarboxylic acid ethyl ester hydrochloride, Solution 146 g (1.08 mol), 2-aminoacetophenone 2.5 l of toluene is mixed with 186 g (0.98 mol) of toluene sulfonic acid hydrate, heated to boiling with simultaneous azeotropic distillation of water, 200 g (1.08 mol) of hexahydroazepinone ethyl ester (4) -1- is added dropwise over 45 minutes carboxylic acid, heated to boiling for 6 hours, cooled, and a mixture of 1,2,4,5-tetrahydro-11-methyl-3-azepino-G4,5-b3-quinoline-carboxylic acid ethyl esters and 2, is isolated 3,4,5-ones ragidro- 11-methyl-1 H-2-azepino- 4,3-1) -quinolinecarboxylic acid (6: 4) as a p-toluenesulfonate. To the mixture was added 5% sodium hydroxide solution and extracted with 4x5OO ml of chloroform, dried over sodium sulfate, and chloroform was distilled off to obtain 270 g (88%) of a mixture of 4, 3-131 isomers (6: 4), which recrystallized from ether (2 O ml / g of mixture) or ethyl acetate. The yield of the pure 4,5-b3 isomer is 43.5%, mp. 124 ° C. 96 g of 1,2,4,5-tetrahydro-11-m9-ethyl-3H-azn-epino-4,5-b1-quinoline-carboxylic acid ethyl ester is dissolved in 550 ml of isopropanol with heat, filtered, 1oo ml of isopropanol hydrochloric acid solution is added. acids and hydrochloride are separated, yield 93.5%, m.p. 247 ° C (decomp.). Example 46. Ethyl esters of 1,2,4,5-tetrahydro-11-methyl-3-azepino-4,5-b 1 -quinolinecarboxylic acid hydrochlorides and 2,3,4,5-tetrahydro-11-methyl-1H- 2-azepino-4,3-1) 1-quinolinecarboxylic acid. 1.2 g. Of a mixture of 4.5-1) 1- and 4,3-b-isomers (6: 4), prepared as in Example 43, is dissolved by heating in 20 ml of isopropanol, acidified with an isopropanol solution hydrochlorically Acids and crystallize out 4,5-TEZ isomer in pure form. After distilling off the solvent and transferring to the base from the mother liquor, the 4, 3-bj-isomer is isolated with ether. The yield of hydrochloride 4,5-b-isomer 70%, mp, 247-C (decomp.). The yield of hydrochloride 4,3-N-isomer of 8%, so pl. 219oc pazr.). Example 47, 1,2, 4,5-tetrahydro-8-hydroxy-11-me-hyp-3-zepp ethyl esters (: 1U-4, 5- | J-quinolish sarbokova tp-gslot ii 2,3,4 , 5 "letrahydro-8-.oxy-11-methyl-1H -azepino-4,3-1) -hinopis-1carboxylic acid. Starting from 1 ethoxycarbonylhexahydroazepinone- (4) and 2-amino-4 oxyacetophenol, analogously to example 12, 4,5-tjl-isomer is obtained, yield 12%, mp. 263 C (times and 4.3-1) -isomer, yield 8%, mp. 254 ° C (decomp). Example 48. Dihydrochlorides 1,2, 4,5-tetrahydro-9,11-dimethyl-3H-azepino 4, 5-L-quinoline and 2,3,4,5-tetrahydro-9, 11-dimethyl-1 H- azepino-4,3-bl-quinoline. 6.6g (44.4 mmol) of hexahydroazepinone- (4) hydrochloride (50 ml) in 2 ml. oolic acid and 6.6 g of 2-amino 5-methylacetophenone are heated to boiling for 72 hours, cooled, alkalinized with concentrated sodium hydroxide solution, extracted with chloroform, dried over sodium sulfate, the solvent is distilled off and a mixture of 4.5 and 4.3 is distilled - ti - isomers (2: 3), which is dissolved in 15 ml of methanol and chromatographed on a silica gel column in a thin layer (d 3-4 cm; h. 120-140 cm; grain size 0.05-0.2 mm), eluting with methanol. Methanol is distilled off from the homogeneous fractions to obtain 2.7 g (27%) of the 4,5-LC-isomer, m.p. 68-70 ° C and 4.2 g (42% of the 4,3-Ij isomer, mp 15 ° C. To convert to the base dihydrochloride, it is dissolved in acetone by heating and mixed with an isopropanol hydrochloric acid solution. dihydrochlorides 4,5-b and 4,3-1 -isomers ZOO ° C (decomp.) and 293295 ° C (decomp.), respectively. Example 49. Dihydrochlorides 1,2, 4,5-tetrahydro-11-methyl- 3-phenyl-3H-azepino-4, 5-bl-quinopine and 2,3,4,5-tetrahydro-11-methyl-2-phenyl-1 H-azepino 4,3-b-quinoline. 2.7g (14 , 3 mmol) of 1-phenylhexahydroazepinone- (4) and 1.95 g (14.3 mmol) of 2-aminoacetophecon were dissolved in 30 g of polyphosphoric acid, heated for 4 hours to 120-140 ° С, oh It is causticized, alkalized with caustic soda, extracted with ether, dried over sodium sulfate and 4 g of mixture 4 is obtained, and 4,3-b isomers are present as reddish oil. Isomer separation is carried out in the same way as in example 27 in the benzene-ether system (7: 3 4, and 4,3-b-isomer, 0.4 g each (10%), T. pl. Of dihydrochlorides 4, and 4,3-1-isomer 239 and 196 ° C, respectively. Example 5 O. 3-allip dihydrochlorides 1, 2,4,5-tetrahydro-11, methkl-3N-azepino-4, 5-153-quinoline and 2-allyl-2.3 4.5-tetrahydro-11-methyl-1H -azepinoI - 4.3-6 - quinoline. 5 g (27.6 mmop) of 1-allyl-4-ethoxy2, 3,6,7-tetrahydroazepine in 10 O ml of toluene, 5.3 g of T-toluenesulfonic acid and 3.75 g (27.6 mmol) of 3-aminoacetophenone heated for 2 hours with a water separator until boiling, decanted toluene from P-toluenesulfonate, alkalinized, extracted with chloroform, dissolved over sodium sulfate, evaporated and get 6.5 g of a mixture of 4,5-Tz - and 4,3-1 3 -isomers, which solution 50 ml of methanol and chromatographed on a column of silica gel (d 3 ml; tl 12O cm; grain size 0.05-0.2 mm), eluting with methanol. From the homogeneous fractions, 0.2 g (3%) of the 4,5-b isomer and 1.4 g (2O%) of the T4,3-b isomer are obtained in the form of a colorless oil. The bases are dissolved in isopropanol with heating, an isopropanol solution of hydrochloric acid is added, cooled and the dihydrochloride is separated. M.p. 4,5-b and 4,3-b1-isomer 278 and 270 ° С, respectively. Example 51. 1,2, 4,5-tetrahydro-8,11-dimethyl-3N-azepino-4, 5-b-quinoline and 2,3,4,5-tetrahydro-8, 11-dimethyl-1 H dihydrochlorides -azepino-4,3-bI-quinoline. From hydrochloride hexahydroazepinone-14) and 2-amino-4-methylacetophenone analogously to example 48, G4,5-b dihydrochloride isomer is obtained, yield 17%, mp, 290292 ° С (decomp.), To G4.3 dihydrochloride isomer, yield 32%, so pl. 305-ЗО7ОС (decomp.). Note 52. 8-chloro-1, 2,4,3-tetrahydro-11-methyl-3N-azepino-4, 5-b-quinoline dihydrochlorides and 8-chloro-2,3, 4,5-tetrahydro-11 -methyl-1H-azepino-4,3-1z -quinoline. From hexahydroazepinone- (4) and 2-amino-4-chloroacetophenone hydrochloride as in Example 48, the 4,5-b-isomer dihydrochloride is obtained, yield 24%, mp. 287 ° C (decomp.), And dihydrochloride 4, 3-b-isomer, yield 16%. m.p. 304 ° C. Example 53. Dihydrochlorides 9fluoro-1, 2,4,5-tetrahydro-11-methyl-3N-azepino-4, 5-b-quinoline and 9-fluoro-2,3, 4,5 - tetrahydro-11 - methyl 1H - azepino4, 3-133 -quinoline. From hexahydroazepinone- (4) and 2-amino-5-fluoro-acetophenone hydrochloride, as in Example 48, the 4,5-tl I -isomer dihydrochloride is obtained, yield 18%, mp. (decomp.), and 4,3-b dihydrochloride isomer, yield 24%, so pl. 285 ° C (decomp.). Example 54. Ethyl esters hydrochlorides of 8,9-dimethoxy-1,2,4,5-tetrahydro-11-methyl-3H-azepi-4,5-b-quinolinecarboxylic acid and 8,9-dimethoxy-2, 3, 4,5-tetrahydro-11-methyl-1H-2-azepino-4, 3-N-quinopicarboxylic acid. From 1-ethoxycarbonylhexahydroazepinone- (4) and 2-amino-4,5-dimethoxyaethopheno, by analogy with Example 50, the expected product is obtained, which is chromatographed on a column of silica gel in the ethyl acetate-methanol system (95: 5). The yield of hydrochloride 4,5-b-isomer 15%, so pl. 246 ° C (decomp. The yield of dihydrochloride 4,3 -) - isomer 22%, so pl. 202 ° C (decomp.). Example 55. 8-hydroxy-1, 2,4,5-tetrahydro-11-methyl-9-methoxy-3 H-azepino-4,5-1-quinoline and 8-hydroxy-2,3,4,5 dihydrochlorides -tetrahydro-11-methyl-9-meTOXI-1H-azepino-E4, 3-b-quinolcn. From hexahydroazepinone- (4) hydrochloride and 2-amino-4,5-dimethoxy-adetophenone, as in Example 48, a 4,5-1) -isomer dihydrochloride is obtained, yield 5%, mp. 3250C (decomp.), And 4,3-b dihydrochloride isomer, yield 4%, m.p. 294 ° C (decomp.). Example 56. 1,2, 4,5-tetrahydro-8,9-methylenedioxy-11-methyl-3H-azepino-4, 5-b-quinoline and 2,3, 4,5-tetrahydro-8,9- dihydrochlorides methylenedioxy-11-methyl-1H-azepino-4,3-b quinoline. From hexahydroazepinone- (4) hydrochloride and 2-amino-4,5-methylenedioxyacetophenone, as in Example 48, the 4,5-b-isomer dihydrochloride is obtained, yield 8%, m.p. ZOO (decomp.), And dihydrochloride 4,3-b-isomer, yield 10%, so pl. ZOOOS (decomp.). Example 57 Dihydrochlorides 1,2, 4,5-tetrahydro-11-methyl-8-trifluoromethyl-3N-azepino-4, 5-b1-quinoline and 2,3,4, 5-tetrahydro-11-methyl-8- trifluoromethyl-1H-azepino-4,3-b -quinoline. From 2-amino-4-trifluoromethylacetophenone and hexahydroazepinone- (4) hydrochloride (analogously to Example 49), the 4,5-b-isomer dihydrochloride is obtained, yield 38, m.p. 275 ° C, and dihydrochloride 4,3-t) -isomer, yield 38.2%, so pl. 270 ° C. Example 58. Dihydrochlorides 1,2 4,5-tetrahydro-11-methyl-9-trifluoromethyl-3H-azepi, 5-b-quinoline and 2,3,4, 5-tetrahydro-11-methyl-9-trifluoromethyl-1 H-azepino-4,3-b-quinoline. From 2-amino-5-trifluoromethylacetophenone and hexahydroazepinone- (4) hydrochloride (similarly to Example 49), a 4.5-1 e-isomer dihydrochloride is obtained, yield 24%, mp. 283 ° C, and 4,3-b dihydrochloride isomer, yield 23%, mp. 274 ° C. Example 59. 11-Amino-3-benzyl-1, 2,4,5-tetrahydro-ZN-azepino-4,5-β-quinoline and 11-amino-2-benzyl-2,3,4,5-tetrahydro -1H-azepino-4,3-L-quinoline. 118 g (1OO mmol) o-aminobenzonitrile, 24.0 g (100 mmol) of 1-benzylhexahydroazepinone-hydrochloride (4) and 250 g of polyphosphoric acid are stirred for 1 hour at 140 ° C, decomposed with ice-cold water, chloroform and sodium hydroxide are added, concentrated, the residue is chromatographed on a column of silica gel in the system chloroformmethanol (3: 1) and the 4,5-b-isomer is isolated, yield 13%, m.p. , and 4.3-1) -isomer, yield 13%, so pl. 1490C. Example 6 O. Dihydrochlorides 1,2, 3,5-tetrahydro-a 1-methyl-3-propyl-3 H-azepino-4, 5-1) -quinoline and 2,3,4,5-tetrahydro-11- methyl 2-propyl-1 H-azepino-4.3-13-quinoline. 1.35 g (7.1 mmol) of p-toluenesulfonic acid in 20 ml of toluene is heated to boiling with a water separator for 15 hours, 0.96 g (7.1 mmol) of 2-amino-acetoPhenone and 1.3 g (7 D mmol) are added 4-ethoxy-2,3 6,7-tetrahydro-1-propylazepine, heated to boiling for 4 hours with a water separator, toluene is distilled off, the residue is dissolved in 2n. sodium hydroxide solution and extracted with chloroform, chromatographed on a column of silica gel, eluted with methanol, an isopropanol solution of hydrochloric acid was added, and a 4,5-bz-isomer dihydrochloride was obtained, yield 5%, mp. 2460C, and dihydrochloride 4, 3-1) -isomer, yield 21%, so pl. . Example 61. 1,2, 4,5-tetrahydro-11-methyl-3-propyl-3 Pi-azepino-4,5-b-quinoline dihydrochlorides and 2,3,4,5-tetrahydro-11-methyl-2 -propyl-1 H-azepino 4,3-L-quinoline. From the 4-ethoxy-1,2,6,7-tetrahydro-1-propyl-5H-azepine and 2-amino-acetophenone analogously to example 60, the 4,5-b-isomer dihydrochloride is obtained, yield 15%, mp. 245-246 ° C, and 4,3-tl dihydrochloride isomer, 10% yield, m.p. . Example 62. 1,2, 4,5-tetrahydro-11-methyl-3-propyl-3N-azepino-C4, 5-1} quinoline and 2,3,4,5-tetrahydro-11-methyl-2 dihydrochlorides -propyl-1H-azepino 4, 3-b -quinoline 2 g (8.9 mmol) of 1-propylhexahydroazepinone- (4) diethyl ketal and 1.18 g (8.7 mmol) of 2-aminoacetophenone are heated for 2 hours to 1400С The mixture is cooled, suspended in 2N sodium hydroxide, extracted with chloroform, and the isomers are separated as in Example 36. The pure isomers are treated with isopropanol solution of hydrochloric acid to obtain the 4,5-b-isomer dihydrochloride. yield 16%, so pl. 246 ° C, and dihydrochloride 4,3-b-isomer, yield 14%, mp.282 ° C Example 63, 1,2,4,5-tetrahydro-11-methyl-3-azepino ethyl ester hydrochlorides {4, 5-1) -quinolinecarboxylic acid and 2,3,4,5-tetrahydro-ll-methyl-H-2-azepin6-4,3-1) -quinolinecarboxylic acid. From an isomeric mixture of 1-ethoxycarbonyl-4-ETOXI-2, 3,6,7-tetrahydroazepine and 1-ethoxycarbonyl-4-ethoxy-5H-1,2,6,7-tetrahydroazepine (1: 1) and 2-aminoacetophenone similarly Example 60 is prepared dihydrochloride G4,5-1 -isomer, yield 52%, so pl. 247 ° C, and dihydrochloride G4,3-b-isomer, yield 43%, mp. 210 ° C. Example 64. Hydrochlorides ethyl-t oy esters of 1,2,4,5-tetrahydro-11-methyl-3-azepino-f 4, S-lj-quinolinecarboxylic acid and 2,3,4,5-tetrahydro-ll-methyl -lH-2-azepino-, 3-13 -quinolinecarboxylic acid. From 1-ethoxy arbonylhex agidroazepinone - {4) -ethyl ketal and 2-aminoacetophenone, as in Example 6O, 4,5-b-isomer dihydrochloride is obtained, yield 18%, mp.247 ° C and 4,3-b dihydrochloride - isomer, yield 17%, so pl. 2190C Example 65, Tetrahydro-11-methi-7-trifluoromethyl-ZN-azepino-4,5-1)} -quinoline and 2,3,4,5-tetrahydro-ll-methyl-7-trifteropromytil-1H-azepino-4 , 3-Y-quinoline. From 2-amino-3-trifluoromethylacetophenone and hexahydroazepinone hydrochloride, the sec-butyl ester (T) b is the corresponding DL target product. five

Table 3 - (4), similarly to Example 49, 4, 5-bl-isomer is obtained, yield 28%, mp. 78 ° C, and 4.3-1) 3-isomer, yield 27%, mp. 94 ° C. Example 66. 1,2,4,5-tetrahydro-11-methyl-3-azepino-4,5-131 -quinolinecarboxylic acid ethyl ester hydrochloride. 11 g (51.7 mmol) of 1,2,4,5-tetrahydro-11-methyl-ZN-azepino-4,5-b-quinoline is dissolved by heating in 275 ml of benzene and 9.8 are added dropwise at the same time. ml (103.4 mmol) ethyl chloroformate in 70 ml of benzene and 14.3 ml (103.4 mmol) of triethylamine in 70 ml of benzene, heated for 2 hours to reflux temperature, cool, add 15 O ml of ice water and alkalinize 2n. caustic soda. The benzene phase is separated by perspiration, the aqueous phase is extracted with chloroform, the combined organic phases are dried over sodium sulfate, evaporated, the oily residue is mixed with ether and 11 g (75%) of base are obtained, m.p. 126 ° C, which is dissolved in 60 ml of isopropanol while heating, is filtered, 10 ml of isopropanol solution of hydrochloric acid is added and 12 g (72%) of hydrochloride are separated, m.p. 247 ° C (decomp.). Examples 6 7-75. Similarly to Example 66, hydrochlorides of various 1,2,4,5-tetrahydro-11-methyl-3-azepino-4, 5-1) -quinolinecarboxylic acid esters are prepared using the corresponding chloroformate esters. The properties of the compounds obtained are given in Table 3. - chloroformic acid and obtained Examples 76-91. 1,2,4,5-tetrahydro-P-3-azepino-4, 5-β-quinoline-carboxylic acid ethyl ester hydrochlorides are obtained from 1,2,4,5-tetrahydro-B-3-azepino-4, 5-b1 -quinoline and ethyl Bc 5-OXY-1, 2,4,5-tetrahydro-11-methyl-ZN Example 92. Ethyl hydrochloride of 2,3,4,5-tetrahydro-ll-methyl-lH-2-azepine- f4, 3-ll J - quinolinecarboxylic kis, lots. From 2,3,4,5-tetrahydro-11-methyl-1H-azepino-f4, 3-bl-quinoline and ethyl chloroformic acid, the target product is synthesized analogously to Example 66, 58% yield, mp. 219 ° C (decomp.) Example 93. 2,3,4,5-tetrahydro-1H-2-azepino-4, 3-β-quinolinecarboxylic acid ethyl ester hydrochloride. From 2, 3,4,5-tetparido-1H-azepino 4, 3-Tz I -quinoline and ethyl chloroformic acid, as in Example 66, the desired compound is obtained, yield 81%, mp. 214 ° C (decomp.). Example 94. Ethyl ester of 5- (this is xycarbonyloxy) -2,3,4,5-tetrahydro-1H53 4 chloroformate as in Example 66. The properties of the compounds obtained are given in table. 4. Table 4 azepino-4,5-b2-quinoline. -2-azepino-4,3-b-quinoline carboxylic acid. From 5-axi-2,3,4,5-tetrahydro-1 H-azepino-4, 3-t) -quinoline and chloroformic acid ethyl ester, as in Example 66, the desired product is obtained, yield 80%, mp . 4EP Example 95. 9-chloro-2,3,4,5-tetrahydro-ll-phenyl-1H-2-azepino-f4,3-b-quinopicarboxylic acid ethyl ester hydrochloride. From 9-chloro-2,3,4,3-tetrahydro-11-phenyl-1H-azepino-4, 3-13 -quinoline and chloroformic acid ethyl ester as in Example 66, the target product is obtained, yield 89%, mp. 186 ° C. Example 96 11-chloro-1, 2,4,5-tetrahydro-3H-aaepino 4, 5-131 hydrochloric ester, quinolinecarboxylic acid. 2 g (7.7 mmol) 3-ethyl-11-hpor-1,2 4,5-tetrahydroxy-AH-azepinone-14,5-b1 -quinoline B 15 MP methylene chloride at 5 ° C are added dropwise to a solution of 1.2 g (7, .7 mmol) of phenyl chloroformate in 2 O ml of megylene chloride, incubated overnight, diluted with ether twice, the precipitate is filtered off with suction and recrystallized from acetone. Yield 35.7%. m.p. 157 ° C. The target compound can be synthesized from 3-benzyl-11-chloro-1,2,4,5-tetrahydro-ZN-azepino-4, 5-L1 -quinoline and the phenyl ester of chloroformic acid. Yield 72%, TP. 157 ° C. Example 97. 11-chloro-1, 2,4,5-tetrahydro-3-azepino-4,5-bl-quinolinecarboxylic acid ethyl ester. From H-benzyl-11-chloro-1,2,4,5-tetrahydro-ZN azepino-14,5-b} quinopene and ethyl chloroformic acid, similarly to example 96, the desired product is obtained, yield 97%, t. square 1 ° 40 °. G p and m 8 p 98. 11-hlcp-2 phenyl ester, 3,4,5-tetrohydro-1H-2-azepino-4, 3-b -quinolinecarboxylic acid. Analogously to example 96 from 2-ethyl-11-chloro-2, 3,4,5 - tetrahydro - 1H-azepino - 4, 3-bl-quinoline and phenyl ester chlorine ether are obtained in a yield of 18.5% of the target product, t .pl. 137 ° C. Example 99. 11-oxch-1 phenyl ester, 2,4,5-tetrahydro-3-azepino-4,5-N-quinolinecarboxylic acid. To 13.6 g (44.7 mmol) of 3-benzyl-11-hydroxy-1, 2.4, 5 - tetrahydro-3H-azepino {4, 5-b1-hinoin. in 250 ml of methylene chloride at 5 ° C, 14 g (89.4 mmol) of phenyl chloroformate ester are added dropwise, left overnight, then 5.8 g (44.7 mmol) of diisopropylethylamine are added, stirred for 6 hours at room temperature, washed with water, dried over magnesium sulphate, evaporated, the 11-phenoxycarbonyloxy-1,2,4, 5-tetraido-ZN-azepino-4,5-b-quinoline carboxylic acid phenyl ester was separated, heated in 250 ml of 1N hydrochloric acid for 1 hour to lOO-C, alkalinize, extract with chloroform, evaporate, add acetone to boil and suction yvyat. Yield 44%, mp. 232 ° C. Example 1OO. Ethyl ester 1 1-hydroxy-1, 2,4,5-tetrahydro-3-azepino-4,5-N-quinolinecarboxylic acid. From Z-benzyl-11-hydroxy-1,2,4,5-tetrahydro-ZN-azepipo-4,5-1}} - quinoline and chloroformate ethyl ester get the target product, yield 20%, mp, 252 ° C. Example 1O1. 11-hydroxy-2, 3,4,5-tetrahydro-H-2-azepipo-4, 3-1} phenyl ester; xct1-lincarboxylic acid. From 2-benzyl-11-OXY-2,3,4,5-tetrahydro-1H-azepino-4, 3- |) 1-quinoline and phenyl ester of chloroformic acid get the target product, yield 51%, mp.299 ° C Example 102 3-acetyl-1, 2,4,5-tetrahydro-11-methyl-3N-azePINO-G4, 5-b 3-quinoline hydrochloride. From 1,2,4,5-tetrahydro-11-methyl-3H-azepino-4, 5-b -quinoline and acetyl chloride, as in Example 66, the final product is obtained, yield 60%, mp. 210 ° C (decomp.) Example 103. 3-acetyl-1, 2,4,5-tetrahydro-11-phenyl-3H-azepino-4, 5-b1 -quinoline hydrochloride. From 1,2,4,5-tetrahydro-11-phenyl-3N-azepino-4, 5-b-quinoline and acetyl chloride, as in Example 66, the desired hydrochloride is obtained, yield 90%, mp 210 ° C (decomp.) . Example 10-4. 3- (4-X. orbenzoyl) -l, 2,4, 5-tetrahydro-11-methyl-3H-azepino-4, 1 -quinoline. From 1,2,4,5-tetrahydro-11-methyl-3 H-azepino-4, 5-L-quinoline and 4-chlorobenzoyl chloride in pyridine with a yield of 65% get the target compound, so pl. 163 ° C. Example 105. 2-acetyl-2, 3,4,5 hydrochloride of tetrahydro-11-methyl-1H-azepino-4,5-bl-quinoline. From 2,3,4,5-tetrahydro-1 l-methyl-lH-azepino-4, 3-N-quinopine and acetyl chloride, as in Example 66, the desired product is obtained, yield 75%, mp. 275 ° C (decomp.). Example 1O6. 2-acetyl-2, 3,4, 5-tetrahydro-11-phenyl-1H-azepino-4,5-t) 1 -quinoline hydrochloride. From 2,3,4,5-tetrahydro-11-phenyl-1H-azepino-4, 3-bz-quinoline and acetic anhydride, the target product is obtained with a yield of 92%, mp. 275-C (decomp.). Example 107. 2-aaetyl-11-chloro-2, 3,4,5-tetrahydro-1H-azepino-4, 3- t) -quinoline hydrochloride. To 11.8 g (50 mmol) of 11-chloro-2.3,4, 5-tetrahydro-1H-azepino-4,3-х -quinoline and 5.5 (55 mmol) of triethylamine in AOO ml of chloroform are added dropwise m 4.3 g (55 mmol) of acetyl chloride, after 1OO hour, washed with water, evaporated, the crystalline residue is chromatographed on a column with silica gel in the benzene-acetone system (2: 1). Hydrochloride is precipitated in isopropanol with isopropanol solution of hydrochloric acid. Yield 27%, mp. (razp.).

27 Example 108 2-Acep-2,3,4,5-tetrahydro-11-metip-1H-azepino-4,3-L-quinopin-6-oxide. 6 g (23.8 mmop) of 2-acetyl-2,3,4,5-tetrahydro-11-metip-1 H-azepino-4,3-b-quinopine are dissolved in 7 ml of glacial acetic acid, added 4 ml of 30% hydrogen peroxide are heated for 2 hours to 6 ° -80 ° C, the solvent is distilled off, the residue is diluted in 2N sodium hydroxide, extracted with chloroform, the solvent is distilled off and the residue is recrystallized from ethyl acetate. 83% yield, m.p. 168 ° C. Example 109. 1,2 4,5-tetrahydro-11-methyl-3H-azepino 4, 5-1 1-quinolinecarboxylic acid-6-oxyl ethyl ester From 1,2,4,5-tetrahydro-11-methyl ethyl ester ZN-azepino-4, 5-13 -quinoline carboxylic acid and hydrogen peroxide as in example 108 receive the target product, yield 66%, so pl. 164 ° C. Example 110. 3-Acetyl-1,2,4,5-tetrahydro-11-methyl-3H-azepino-4, 5-1) -CHINOLIN-6-OXID. From H-acetyl-1,2,4,5-tetrahydro-ll-methyl-3H-azepino-4, 5-b1-quinoline and hydrogen peroxide, similarly to Example 1O8, the desired product is obtained, yield 83.5%, mp. 128 ° C. Example 111 2,3 4,5-tetrahydro-11-methyl-1H-2-azepino-4, 3-b1 -quinolinecarboxylic acid ethyl ester, 6-oxide. As in example 108, from ethyl ester 2, 3,4,5-tetrahydro-11-methyl-1H-2-azepino-4, 3-1z1 -quinolinecarboxylic acid and hydrogen peroxide receive the target product, yield 60%, so pl . 129 ° C. Example 112. 3-hydroxyethyl-1, 2,4,5-tetrahydro-11-methyl-3H-azepino-4, 5-131 -quinoline hydrochloride. To 4.24g {20 mmol) 1,2,4,5-tetrahydro-11-methyl-3 N azepino-4,5-b1 -hi noline in 30 ml of ethyl methyl ketone was added 3.68 g (8O mmol) of oxide ethylene and heated for 6 hours in an autoclave to IO-C, the solvent is distilled off, the residue is dissolved in dilute hydrochloric acid, extracted with chloroform, alkalinized with sodium hydroxide, extracted with chloroform, dried, chased with chloroform, dried and added to the residue ethanol isopropanol solution of hydrochloric acid. Yield 33%, so pl. 252 C (decomp.). Example 113. 1,2, 4,5-tetrahydro-3- (2-hydroxypropyl) -11-methyl-3H-azepino-4, 5-b-quinoline dihydrochloride. Analogously to example 112, from 1,2,4,5-tetrahydro-11-methyl-3N-azepino-4, 528 1z -quinoline and propylene oxide, the desired product is obtained, yield 58%, t, pl. 273 ° C. Example 114. 2- -oxyethyl-2, 3,4,5-tetrahydro-11-methyl-1H-azepino-4,3-Yquinoline dihydrochloride. Similarly to example 112, from 2,3,4,5-tetrahydro-ll-methyl-1H-azepine-4,3-b-quinoline and ethylene oxide, the expected product is obtained, yield 24%, mp. 268 ° C (decomp.). Example 115 2,3, 4,5-tetrahydro-2- (2-hydroxypropyl) -11-methyl-1H-azepino-4,3-β-quinoline dihydrochloride. Analogously to example 112, from 2,3,4,5-tetrahydro-11-methyl-1H-azepino-4,3-N-quinoline and propylene oxide, the final product is obtained. Example 116. 1,2,4,4-5-tetrahydro-21-methyl-3-azepino-4, 5-tll-quinoline-carboxylic acid hydrochloride hydrochloride. A targeted product is obtained in the same manner as in Example 66 using t-butyl chloroformate. Yield 61%, mp. 212 ° C (decomp.). Example 117. 1,2, 4,5-tetrahydro-3- (2-methoxyethylethyl) -11-methyl-3H-azepino-4,5-b1-quinoline dihydrochloride. To 1.9 g (5O mmol) lithium aluminum hydride suspended in 1O ml of absolute THF, is added dropwise a warm solution of 1,2,4,5-tetrahydro-3- (2-methoxyacetyl) -11-methyl-3H- azepino-4,5-L-quinoline in 60 ml of THF, stirred for 30 minutes, an excess of lithium aluminum hydride was destroyed with 6 ml of ethyl acetate, 6 ml of water was added, and aluminum hydroxide was suction filtered and washed. chloroform, the organic layer is dried over sodium sulfate, concentrated, the residue is dissolved in isopropanol with heating and an isopropanol solution of hydrochloric acid is added. The yield of 4.9 g (87%), so pl. 2500s Example 118. 3-Hexyl-1, 2,4,5-tetrahydro-11-methyl-3N-azepino-4,5-L 1 -quinoline dihydrochloride. From 3-caproyl-1,2,4,5-tetrahydro-11-methyl-3N-azepino-4, 5-L quinoline and lithium aluminum hydride, as in Example 117, the desired dihydrochloride was obtained, yield 83%, mp. . 24 ° C. Example 119. 3- -butyl-1,2,4,5-tetrahydro-11-methyl-3Nazepino-4,5-1) -quinoline dihydrochloride. From H-butyl-1,2,4,5-tetrahydro-11-methyl-3H-azepino-4,5-L-quinoline and lithium aluminum hydride as in Example 117, the target compound was isolated, yield 85%, mp. 2780C. Example 120, 9,11-dimethyl-1,2,4,5-tetrahydro-3-azepino-4, 5-b-quinolinecarboxylic acid ethyl ester hydrochloride, 1.1 g (5 mmol) 9,11-dimethyl 1,2,4, 5-tetrahydro-ZN-azepino-4,5-13 quinoline is dissolved in 30 ml of benzene, 1 g (10 mmop) of triethylamine in 10 m of benzene and 1.08 g (10 mmol) of ethyl ether are added chloroformic acid, heated to boiling for 2 hours, cooled, mixed with 50 ml of ice water and alkalinized with 2N caustic soda. The benzene phase is separated, the aqueous phase is re-extracted with chloroform, the combined organic phases are dried over sodium sulfate, evaporated, the residue is dissolved in acetone during heating and acidified with an isopropanol hydrochloric acid. Yield 85%, mp 212 ° C (decomp.). Example 121. 8-Chloro-1,2,4,5-tetrahydro-11 ethyl ester hydrochloride methyl 3-azepino-4,5-b-quinolinecarboxylic acid. From 8-chloro-3,2,4,5-tetrahydro-11-meOTIGX1 with; -1,1 Tyl-oH-azepino-4,5-oJ-quinoline and chloroformic acid ethyl ester, analogously to Example 120, receive the desired product, yield 7O%, mp. 23 ° C. Example 122. 8, 11-dimethyl-2,3,4,5-tetrahydro-1H-2-azepino-4,3-b-quinolinecarboxylic acid ethyl ester. From 8, ll-dimethyl-2,3,4,5-tetrahydro-lH-azepino- 4, 3-b-quinoline and ethyl-j. 11-dociinjiu-, - J a-L1G1p-Lip and cJinvi cw- GO chloroformate ester analogue to example 1, the target compound is obtained, yield 42%, so pl. 132 ° C. Example 123. 1,2 4,5-tetrahydro-11-hydroxymethyl-3-azepino-4, 5-b-quinolinecarboxylic acid ethyl ester. Using 1,2, 4,5-tetrahydro-3-azepino-4,5-b-quinoline-carboxylic acid-11-carboxylic acid ethyl ester and lithium aluminum hydride, the desired product is obtained in THF at room temperature, yield 12%, mp . 158 ° C. Example 124. 1,2, 4,5-tetrahydro-3-azepino-4,5-1-quinolinecarboxylic acid-11-carboxylic acid-6-oxide ethyl ester. 7 g (22 mmol) of 1,2, 4,5-tetrahydro-3-azepino-4,5-b1 -quinolinecarboxylic acid-11-carboxylic acid ethyl ester are suspended in 7 ml of glacial acetic acid, 7 ml of 3% is added Hydrogen peroxide was heated to 16 ° C for 7OOC and the solvent was distilled off, the residue was dissolved in water, extracted with chloroform, dried over sodium sulfate, evaporated and the residue crystallized from ethyl acetate. Yield 2.7 g (37%), mp 202 ° C (decomp.). Example 125. 5-ethoxy-1, 2,4,5-tetrahydro-11-methyl-3-azepino-4, 5-b-quinolinecarboxylic acid ethyl ester 6-oxide. From 5-acetoxy-1,2,4, 5-tetrahydro-11-methyl-3-azepino-4,5-N-quinolinecarboxylic acid ethyl ester as in Example 124, the expected product is obtained, yield 23%, mp. 1300s Example 126. 5-hydroxy-1, 2,4,5-tetrahydro-11-methyl-3-azepino-4, 5-L3 -quinolinecarboxylic acid-6-oxide ethyl ester. Starting from 5-hydroxy-1,2, 4,5-tetrahydro-11-methyl-3-azepino-4,5-blquinolinecarboxylic acid ethyl ester and hydrogen peroxide, as in Example 124, the desired compound is obtained, yield 17%, t. square 199 ° C. Example 127. 5-hydroxy-1, 2,4,5-tetrahydro-3-azepino-4,5-t) -quinolinecarboxylic acid ethyl ester-11-carboxylic acid. From the ethyl 1,2,4,5-tetrahydro-3-azech1Ho 4,5-b-quinolinecarboxylic acid-11-carboxylic acid-6-oxide and acetic anhydride in benzene, followed by saponification of the 2-acetoxy compound, the expected product is obtained, yield 1 % m.p. (different). Example 128. 5-hydroxy-1, 2,4,5-tetrahydro-11-oxymetip-3-azepino-4, 5-b-quinolinecarboxylic acid ethyl ester. 1.5 g (4.75 mmol) of ethyl 5-hydroxy-1,2,4,5-tetrahydro-11-methyl-3-azepino-4, 5-b -quinolinecarboxylic acid-6-N-oxide in 50 ml of acetic anhydride is heated for 2 hours to 110 ° C, acetic anhydride and acetic acid are distilled off, 2N is added. hydrochloric acid, heated for 30 minutes under reflux, inflate 2n. it is caustic soda, extracted with chloroform, evaporated and the residue is chromatographed on a column of silica gel, eluting with ethyl acetate. Output 0.4 g (35%), so pl. 1710s Example 129. 5-methoxy-1, 2,4,5-tetrahydro-11-methyl-3-azepino-4,5-b-quinolinecarboxylic acid ethyl ester. From 2 g (b, 65 mmol) of ethyl 5-hydroxy-1,2,4,5-tetrahydro-11-methyl-3-azepino-4, -quinolinecarboxylic acid in 50 ml of absolute THF and 0.32 g (7 mmol) 50% sodium hydride get sodium salt, which is methylated

0.43 ml (7 mmol) of methyl iodide. Output 1.3 g (62%), so pl. 2 ° C.

Example 130, 1, 2-dihydro-ll-methyl-3-azepino-4, 5-b1-quinopicarboxylic acid ethyl ester hydrochloride.

From 1,2-dihydro-11-methyl-ZN-azepino-4, 5-1) 3-quinoline and ethyl chloroformate as in the example

Acylating agent

Chloride Butyric Acid Chloride Propionic Acid

Isobutyryl chloride

Caproyl chloride

Lauroyl chloride

2-methoxyacetic acid

Trifluoroacetic acid

Metipsulfonyl chloride

p-Toluensulfonyl chloride

Chloride 4 - Chlorobenzene Sulfate

The reaction is carried out in benzene.

“„

Hydrochloride is obtained.

EXAMPLE 141. 2-f 1,2,4,5-tetrahydro-11-methyl-3H-azepino-4,5-b1 -quinolin-3-yl-acetic acid ethyl ester dihydrochloride.

To a solution of 30 g (141 mmol) of 1,2,4, 5-tetrahydro-11-methyl-3K-azepino-4,5-tjJ quinoline in 200 ml of benzene and 20 ml of triethylamine is added dropwise at a boiling point of 15 ml (141 mmol) of ethyl acetate with chloroacetic acid, the triethylamine hydrochloride is filtered off, the solvent is distilled off and the residue in ethanol is treated with an ethanolic hydrochloric acid solution. Yield 61%, mp. 2250s,

Example 142. 3--11,2,4,5-tetrahydro-11-methyl-3K-azepino-4,5-S-quinolin-3 or g-propanoic acid ethyl ester dihydrochloride,

To a solution of 5 g (23.6 mmol) 1,2,4,5-tetrapro-11-meth. Tl

 -CHIKOLG.T1

100 MP

In addition, 2.6 ml (24.0 mmol) of ethyl ester of acrylic acid in 2 O ml of gaccpp are added in drops of temperature, heated for 2 hours to temperature: i-ieHii / -i,

120 get the target product, yield 42%, so pl, 218 ° C

Examples 131-14O, 2, 4,5-tetrahydro-11-methyl-ZN-azepino T4, 5-b-quinolines are obtained by acylated 1,2,4,5-tetrahydro-11-methyl-ZN-azepino-4, 5-1) -quinoline with various acylating agents in pyridine. The data obtained are given in table. 5.

T a

faces

3-r

Mp, ° C

Output, %

67

130

72

128-13О

50 107

82 109

86 10О

79,116

66,147

73,265

silt 50

236 (different

fonil73 189

almost all of the ethanol is added and the ethanolic hydrochloric acid solution is added. Exit 72 5% mp, 19 OES.

Example 143. 2-) l, 2,4,5-tetrahydro-11-ethyl-3H-azepino-4, 5-b3-quinolin-3-yl} -acetonitrile dihydrochloride,

From 1,2,4,5-tetrahydro-11-methyl-ZN-azepino-4, 5-13 -quinoline and chloroacetonitrile, analogously to example 142, the desired product is obtained, yield 25%, t, mp, 2500s,

Example 144, 3- | l Dihydrochloride, 2,4,5-tetrahydro-11-methyl-3H-azepino-4,5-N-quinoline-3-yl} -propionitrile.

From 1,2,4,5-tetrahydro-11-methyl-3H-azepino-4, 5-1) -quinoline and acrylonitrile, analogous to example 141, the desired product is obtained, yield 86%, mp.

Example 145. 2-Jl, 2, -1, 5-tbtrahydro-11-methyl-3H-avepino 4, 5-1) -quinolin-3-yl | -HUSOHI ACID dihydrochloride-dimethyl-amide

Claims (3)

 1 .. 2.4. 5-ReggL-idro-11-methyl-3H-azepins-1 .5-C J-chi ;; ylkka to chloroacetyldimetrykmkdk tax hfs}; pi: .- sru 141 receive the final product, yield 68%, so pl. 261 ° С (razp.) .. Example 146. Morphopid-dihydrochloride 2- | 1,2,4,5-tetrahydro-3 1-metip-3H-azepino-4.5-13-quinoline-3-un-acetic acid. Starting from 1,2,4,5-tetrahydro-11-meth-3H-azepino-4,5-111-quinoline and tipmorpholide chloraceta, analogously to Example 141, the target compound is obtained, yield 59%, mp. 253 ° C (razp.). Example 147. 1,2 4,5-tetrahydro-11-oxymethyl-3-azepino-4,5-b carboxylic acid 6-oxide ethyl ester. 1,2,4,5-tetrahydro-11-hydroxymethyl-3-azepino-4,5-b-quinoline-carboxylic acid ethyl ester and hydrogen peroxide, as in Example 124, give the desired product, yield 21%, t. square 207 ° C. Example 148. 1 (2, 4,5-tetrahydro-11-methyl-8-trifluoromethyl-3-azepino-4,5-N-chicolinecarboxylic acid ethyl ester. Starting from 1,2,4,5-tetrahydro-11- methi-8-trifluoromethyl-3H-azepino-4,5-bl-quinoline and ethyl chloroformate, like the example 120, give the desired compound, yield 98%, mp 142 ° C. Example 149. Ethyl ether 1, 2, 4,5-tetrahydro-11-methyl-9-trifluorometi-3-azepino-4,5-131 -quinolinecarboxylic acid. From 1,2,4,5-tetrahydro-11-methyl-9 trifluoromethyl-3H-azepino-4, 5-t} l-quinoline and ethyl chloroformate as in Example 12O, the desired product is isolated, yield 90%, mp 152 ° C. Example 150. 11-methoxy-1, 2,4,5-tetrahydro-3-azepino-4, 5-1) 1-quinoline-carboxylic acid ethyl ester. 3.7 g (11.6 mmol) 3-benzyl-11-meto si-1,2,4,5-tetrahydro-3H-azepino-4,5-b1-quinoline and 1.1 ml (11.6 mmol ) These chloroformate ester are stirred for 24 hours at 5 ° C in 35 ml of chloroform, concentrated and chromatographed on a column of silica gel in the toluene-acetone system (8: 1). Yield 62%, mp. 122 ° C. Example 151. Ethyl ether 11. -methoxy-1,2,4,5-tetrahydro-3-azepino-4, -quinolinecarboxylic acid-6-oxide. The 11-methoxy-1,2,4, 5-tetrahydro-3-azepino-4,5-L1 -quinolinecarboxylic acid ethyl ester and hydrogen peroxide analogously to example 124 were isolated the target compound, yield 15%, mp. 135 ° C. Example 152. 3-Benzyl-11- (2-phenylethyl) -oxy-1,2,4,5-tetrahydro-3H-azepino-4, quinoline. 4.5 g (15 mm OL) 3-benzyl-11-hydroxy-1, 2,4,5-tetrahydro-3I-azepino-4,5-L-quinoline, 4.2 g (30 mmol) of 2-phenylethyl chloride , 4.15 g (30 mmol) of potassium carbonate and 5 g of sodium iodide in 100 ml of butanone (2) are boiled for 207 hours, filtered off with suction and chromatographed on a column of silica gel, eluting with ethyl acetate. Yield 73%, mp. 2 ° C. Example 153. 11- (2-Phenylethyl) -oxy-1,2,4,5-tetrahydro-3-azepino-4.5-131 -quinolinecarboxylic acid ethyl ester hydrochloride. From 3-benzyl-11- (2-phenylethyl) -oxy-1, 2,4,5-tetoagidro-ZN-azepino-G4,5-b1 -quinoline and ethyl chloroformate as in Example 150, the expected product is obtained, yield 51 % m.p. 153 ° C. Example 154. DL-11-G1-carboethoxyethyl- (1) -oxy-1, 2,4,5-tetrahydro-ZH-azepino-4,5-b-quinoline. 8 g (25.4 mmol) of 3-ethyl-11-hydroxy-1, 2,4,5-tetrahydro-3H-azepino-4, 5-β-quinoline dihydrochloride, 8.3 g (6 O mmol) of potassium carbonate, 5.3 g (30 mmol) of 21-ii-bromopropionic acid ethyl ester and 5 g of sodium iodide in 100 ml of butanone- (2) are boiled for 10-15 hours, concentrated, mixed with sodium bicarbonate solution, extracted with ethyl acetate, concentrated and the residue is chromatographed on a column of silica gel in the system chloroform-methanol (5: 1) Yield 22.4%, so pl. : 2EP Example 155. Ethyl hydrochloride ester TK L -1 - - -carbethoxyethyl- (1) 1-hydroxy-1,2,4,5-tetrahydro-3-azepino-4, 5-1) 1-quinoline carboxylic acid. From H-ethyl-11-1-carbethoxyethyl- (1) -oxy-1, 2,4,5-tetrahydro-3H-azepino-4,5-b-quinoline and ethyl chloroformate as in Example 15O, the expected product is obtained, yield 39.5%, so pl. 133 ° C. Example 156. 11-chloro-1, 2,4,5-tetrahydro-3-azepino-4, -quinolinecarboxylic acid-6-oxide ethyl ester. From 11-chloro-1,2,4,5-tetrahydro-3-azepino-4,5-BI-quinoline-carboxylic acid ethyl ester and 30% water peroxide, as in Example 124, a target product is obtained, yield 29%, mp. 170 ° C. Example 157. 11 oxy-2, 3,4,5-tetrahydro-1H-2-azepino 4, 3-b1 -quinolinecarboxylic acid ethyl ester. From 2-benzyl-11-hydroxy-2,3,4,5-tetraidro-1H-azepino-4,3-L1 -quinoline and ethyl chloroformate, like Example 150, the end product was isolated, yield 9%, t. square 285 ° C. Example 158. 1,2 4,5-tetrahydro-11-methyl-7-trifluoromethyl-3-azepino-4,5-T -quinolinecarboxylic acid ethyl ester. From 1,2,4,5-tetrahydro-11-methyl-7-trifluoromethyl-3H-azepino-4,5-1-quinoline and chloroformic acid ethyl ester, as in Example 120, a target substance is obtained, yield 92%, t. square 136 ° C. Example 159. Z-Amidino-1,2,4,5-tetrahydro-11-methi-3 H-azepino-4,5-β-quinoline. 5 g (23.6 mmol) of 1,2,4,5-tetrahydro-11-methyl-ZN-azepino-4, 5-1) -quinoline is dissolved in 2.7 ml of glacial acetic acid and 2 O ml of ethanol 72 hours, stirred at room temperature with 1.12 g (26.6 MMOLB) of cyanamide, dissolve the separated product in water and precipitate with caustic soda. O yield, 6 g (10%), mp. 140 ° C. Example 160. 3-Carbamoyl-1,2,4, 5 tetrahydro-11-methyl-3H-azepino-4,5-L-quinoline. 3.3 g (11.6 mmol) of 1,2,4,5-tetrahydro-11-methyl-3N-azepino-4,5-til-quinoline in 5 O of water is treated with 0, O4 g (11.6 mmol) potassium cyanate at room temperature. After 4-6 hours, the reaction product crystallizes out. Yield 1 g (34% m.p. 215 ° C (decomp.). Claim 1. Investigation of quinoline derivatives of the general formula: where A is a group of the general formula-CH Nff-j R, is hydrogen, is alkyl; 11 ci is hydrogen or halogen, hydroxy- or carboxy-group, unbranched or branched C-C-alkyl, C „-C„ - cycloalkyl, -alcoxy O. o forces, which can be replaced by phenyl or.-carbalkoxy, Cr-C -carbalkoxy, oxymethyl , phenyl, phenoxy, amino group, pyrrolidine residue or morpholine; identical or different, hydrogen or halogen, methyl, hydroxy, methoxy, cyano, amino, nitro, trifluoro ethyl, carbox group, acetyl, C-C -carbalkoxy or two radicals of, R or R instead of: They form a methylenedioxy group, hydrogen, unbranched or branched -alkyl, which 1 fo can be replaced by oxy, mtTOXI, carboxy, cyano, dimethylaminocarbonyl, morpholinocarbonyl or C2-C6-carbalkoxy, unsubstituted or methoxy-substituted straight-chain or branched aliphatic which is unsubstituted or substituted by halogen, benzoyl, C -C -karbalkoksil C .- C -karbtsikloalkoksil, unsubstituted or substituted by methyl, benzyl, substituted phenylsulfonyl, C-C alkenyl, phenyl, trifluoroacetyl, amidine residue, amido, thioamido, phenoxycarbonyl, benzyloxycarbonyl or methylsulfonyl; hydrogen or together form a double bond, their salts or their isomers, a result of which, by the compound of the formula Y.BI —in 1, the above-mentioned D lower C —C-alkoxy or DioV oxygen and Y and Y — hydrogen, lower Alkoxyl, D are mixed; the bond and Y Li B together with Y form a carbon dioxide and Y hydrogen, the interaction with the compound is where 37 where Rn - have the aforementioned anachenes; 2, the cyano group is a residue of the general formula, where K has the same meaning as R, and a mono- or disubstituted amino group, under water-splitting conditions, followed by isolation of yroyukta in free form, fei saline or partition of isomer mixtures. 2. A method according to ni, exposing 53503 4 38 so that sodium hydroxide solution, hydrochloric acid, sulfuric acid, phosphoric acid, phosphorus oxychloride, polyphosphoric acid or l-toluene acid glycol ™ “water formed permanently” is used as a water separator. the reaction mixture in the form of azeot ropa, 3. The method according to claims 1 and 2, is also distinguished by the fact that the reaction is carried out at Q 20OOC.