FI94343B - Process for the preparation of therapeutically active cyclic amine derivatives - Google Patents

Abstract

Cyclic amine derivatives of the formula <IMAGE> in which A, B, E, G, R, R1, R2, m and n are as defined in Claim 1, their enantiomers, their diastereomers, their N-oxides and their acid addition salts have useful pharmacological properties, in particular a bradycardic action. The novel compounds can be prepared by processes known per se.

Description

c: / * 7 y; U * - * / 0

Method for the preparation of therapeutically active cyclic amine derivatives - Förfarande för framställning av terapeutiskt aktiva cykliska aminderivat

The invention relates to a process for the preparation of therapeutically active cyclic amine derivatives of the general formula (I) R 1 | ^ γΑ \ / ° ¾¾.

R2 ~ | N - E - CH N - O - R, (I) tL n wherein A is -CH 2 -, -CH 2 -CH 2 - or -CH = CH, B is -CH 2 -, -CH 2 -CH 2 -, or - A CO or -CH 2 CO group in which the carbon atom denoted by the letter x is attached to the phenyl ring, E is a straight-chain alkylene group having 1 to 3 carbon atoms optionally substituted by an alkyl group having 1 to 3 carbon atoms.

G is a straight-chain alkylene group having 1 to 6 carbon atoms, wherein the methylene group attached to the aromatic or heteroaromatic group R may be replaced by an oxygen atom, • and R 2 each represents an alkyl or alkoxy group having 1 to 3 carbon atoms, or 2 q '7 λ 7

S '-X-! U

R 1 and 1 * 2 together are 1 or 2 carbon atoms of an alkyloxy group, m is the number 1, 2, 3, 4, 5 or 6 and o is the number 0, 1, 2 or 3, however, the sum of n + m must be a number 3, 4, 5 or 6, and R is an optionally methyl-substituted furyl, thienyl, pyridyl, benzo [b] furyl or benzo [b] thienyl group, a benzo [b] thienyl group substituted by a halogenate a methoxy or methanesulfonyloxy group, a naphthyl group which may be mono- or di-substituted by a methyl or methoxy group, the substituents being identical or different, or also, when B is a -CH2- or -CO group, a phenyl group which is mono- or disubstituted with methyl or methoxy groups, the substituents being identical or different, their N-oxides and their acid addition salts.

British Patent 1,548,844 describes, inter alia, a compound of the formula

. 'TO rC

: CH3 ° O 7h2CH2CH2- N - CH2CH2- <y J- OCH, and its physiologically acceptable acid addition salts. With these. the compounds have valuable pharmacological properties, namely in addition to a mild antihypertensive effect, in particular a selective heart rate lowering effect.

Il g /. z at s “T O * 1- J 3

Surprisingly, it has now been found that the novel cyclic amine derivatives of the general formula I described above, their N-oxides and their acid addition salts, in particular their physiologically acceptable acid addition salts with inorganic or organic acids, have even more valuable pharmacological properties, in particular antihypertensive depressant effect and depressant effect on cardiac C

Particularly preferred are the compounds of general formula (Ia) R1Y ^ VA \ / (CH2 \ .LIr '"\ / - * ·«> r2 B (ch2)' where Ηχ, 1 * 2 'R' A 'B' E 'G' m and n have the same meaning as above, their N-oxides and their acid addition salts, in particular their physiologically acceptable acid addition salts for pharmaceutical use.

Very particularly preferred compounds of the above general formula Ia are those in which A is a -CH 2 -CH 2 group, B is a -CH 2 -, -CH 2 -CH 2 -, -CO- or O 2 CO group, wherein the carbon atom denoted by the letter x is attached to a phenyl ring, E is a methylene or ethylene group, Γ, 'fi -ry -t> j * r 0 4 G is a straight-chain alkylene group having 2 to 4 carbon atoms, wherein R is a methylene group attached to an aromatic or heteroaromatic group of a straight-chain alkylene group having 3 or 4 carbon atoms may be replaced by oxygen,

R 1 is a methoxy group, R 2 is a methoxy group or R 1 and R 2 together are a methylenedioxy group, m is a number 2, 3 or 4, n is a number 1 and R is naphthyl-2-, 6-methoxy-naphthyl-2-, 5- methyl-6-methoxynaphthyl-2-, thienyl-2-, benzo [b] furyl-2- or benzo [b] thienyl-3, or also when B is -CH2- or -CO-, A 4-methoxyphenyl or 3,4-dimethoxyphenyl group, and their physiologically acceptable acid addition salts.

Particularly preferred compounds are: 3 - [(N-2- (naphthyl-2) -ethyl) -piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro -2H-3-benzazepine, 3- [2- (N- (2- (6-methoxy-naphthyl-2 -) - ethyl) -piperidyl-2) -ethyl] -7,8-dimethoxy-2-oxo- 1,3,4,5-Tetrahydro-2H-3-benzazepine, 2 - [(N- (3- (4-methoxy-phenoxy) -propyl) -piperidyl-3-) -methyl] -6.7 -dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline, 3 - [(N- (4-thienyl-2-) butyl) -piperidyl-3 -) - methyl] -7, 8-dimethoxy-2-oxo-l, 3,4,5-tetrahydro-2H-3-benzazepine.

According to the invention, novel compounds of the general formula I are obtained by the following methods: a) a compound of the general formula II * 1 R-j-II H - E - CH N-H, (xi) ä ^ A, / \ / '2 n in which

R 1, R a, A, B, E, m and n are as defined above, are reacted with a compound of general formula III Z, - G - R (III) wherein R and G are as defined above and

Z 1 is a nucleophilic leaving group such as a halogen atom or a sulfonyloxy group, e.g. a chlorine, bromine or iodine atom, a methanesulfonyloxy, p-toluenesulfonyloxy or ethoxysulfonyloxy group, or a hydroxy group or Z 1 together with the hydrogen atom of an adjacent methylene group means an oxygen atom.

If Zi represents a nucleophilic leaving group, the reaction is conveniently carried out in a solvent or solvent mixture such as acetone, diethyl ether, methylformamide, dimethylformamide, dimethylsulfokicide, benzene, chlorobenzene, tetrahydrofuran and the combination of benzene / tetrahydrofuran or di in excess and optionally in the presence of an acid scavenger, for example * an alcoholate such as potassium tert-butylate, an alkali hydroxide such as sodium or potassium hydroxide, an alkali carbonate such as potassium carbonate, an alkali amide such as sodium amide, an alkali metal hydride such as sodium hydride, a tertiary organic base such as the latter • Q · 'Z Λ Ί.

“I JlJ

b can also simultaneously act as solvents, or a reaction-promoting substance such as potassium iodide, depending on the reactivity of the nucleophilic group in each case, suitably at temperatures between 0 and 150 ° C, preferably at temperatures between 50 and 120 ° C, e.g. at the boiling point of the solvent used. However, the reaction can also be carried out without a solvent. Particularly preferably, however, the reaction is carried out in the presence of an excess of a tertiary organic base or the amine used of the general formula II.

If Z 1 represents a hydroxy group, the reaction is best carried out in a suitable solvent such as methanol, ethanol, tetrahydrofuran, dioxane, ethyl acetate or glacial acetic acid using hydrogen in the presence of a hydrogenation catalyst such as platinum, palladium / carbon or Raney nickel at 2 to 10 bar, preferably 5 to 10 bar. and 120 ° C, preferably at temperatures between 50 and 100eC.

If Z 1 together with the hydrogen atom of the adjacent methylene group represents an oxygen atom, then the reaction is best carried out in a suitable solvent such as methanol, ethanol, tetrahydrofuran, dioxane, ethyl acetate or glacial acetic acid using hydrogen in the presence of a hydrogenation catalyst such as platinum, palladium / carbon bar, preferably at a hydrogen pressure of 5 bar and at temperatures between 20 and 120 ° C, preferably at temperatures between 50 and 100 ° C, or in the presence of a suitable complex metal hydride such as sodium cyanoborohydride in a suitable solvent such as methanol, ethanol, tetrahydrofuran, dioxane or acetonitrile at 50 ° C.

b) Compound of general formula IV O A 7 l \ 7> 1v) 1 J 7 R2 __H - h .CIV) in which

R 1, R a, A and B have the same meaning as above, are reacted with a compound of general formula V / (0¾).

Z -E-CH NGR, (V) 2 / X (OH 2>) wherein R, E, G, m and n have the same meaning as above and Zs is a nucleophilic leaving group such as a halogen atom or a sulfonyloxy group, e.g. chlorine, bromine - or an iodine atom, a methanesulfonyloxy, p-toluenesulfonyloxy or ethoxysulfonyloxy group.

The reaction is conveniently carried out in a solvent or solvent mixture such as methylformamide, dimethylformyl; amide, dimethyl sulfoxide, benzene, chlorobenzene, tetrahydrofuran, benzene / tetrahydrofuran or dioxane in the presence of an acid scavenger, e.g. an alcoholate such as potassium tert-butylate, an alkali hydroxide such as sodium or potassium hydroxide , suitably at temperatures between 0 and 10 SOC, most preferably at temperatures between 0 and 50 ° C.

«C) compounds of general formula I in which B is -CH * - or 8 ~ · r ~ r

y H 0 H D

-CH = -CHa group, for the preparation of:

The compound of general formula VI is reduced

VvA / (CHA \ R2 - I. N - E - CH N - G - R, (VI) X <CH2) n7 where R, R1, R5, A, E, G, m and n have the same meaning as above and

B1 is a -CO- or -CH2CO group x wherein the carbon atom denoted by x is attached to the phenyl ring.

The reduction is best performed with a metal hydride such as lithium aluminum hydride or diborane or a complex of borane and thioether, e.g. borane-dimethyl sulfide complex, in a suitable solvent such as diethyl ether or tetrahydrofuran at temperatures between 0 and 80 ° C, but most preferably at temperatures between 10 and 45 ° C.

d) Compounds of general formula I in which A is a -CHa group: and B is a -CO- or -CHaCO group. for the preparation of:

Reduce the compound of general formula VII (CH2 \, 2_pY> - ») - · - * '<ral where R, R *. Ra, E, G, m and n have the same meaning as above and m

II

g Λ 7/17 y * 1 Jt ο

Q

B = is -CO- or -CH = CC> -rvhma.

x wherein the carbon atom denoted by x is attached to the phenyl ring by evolving hydrogen.

The reduction is carried out in a suitable solvent such as glacial acetic acid, glacial acetic acid / water or glacial acetic acid / ethanol with hydrogen, for example in the presence of zinc / glacial acetic acid, tin / hydrochloric acid or tin dichloride / hydrochloric acid at temperatures between 20 and 150 ° C, preferably at the boiling point of the reaction mixture, e.g. at temperatures between 80 and 100 ** C.

e) Compounds of general formula I in which G is the same as G above except for the groups containing a sulfur atom, a sulfinyl or sulfonyl group and A is a -CH 2 -CH * group and B is a methylene or carbonyl group. for the preparation of:

Hydrogenate the compound of general formula VIII "V'T-x p__I N-E-CH N - G1 - R, (VIII) 2 Jk / \ / wherein R, R1, Rz. B, E, m and n have the same meaning as above,

Gi is the same as G above except for groups containing a sulfur atom, a sulfinyl or sulfonyl group, and B »is a -CH * or -CO group.

The hydrogenation is carried out in a solvent or solvent mixture such as methanol, ethanol, ethyl acetate or glacial acetic acid with catalytically activated hydrogen, e.g. hydrogen in the presence of platinum or palladium / carbon, at a hydrogen pressure of 1-7 bar, but preferably 3-5 bar and temperatures between 0 and 75 ° C. , however, best at temperatures between 20 and S0eC.

In the reaction described above, any reactive groups present, such as hydroxy, amino, alkylamino or imino groups, can be protected during the reaction with conventional protecting groups which are again cleaved off after the reaction.

Suitable protecting groups for the hydroxy group are, for example, trimethylsilyl, acetyl, benzoyl, benzyl or tetrahydropyranyl groups and suitable protecting groups for amino, alkylamino or imino groups are acetyl, benzoyl, ethoxycarbonyl or benzyl groups.

Possible subsequent cleavage of the protecting group used is best carried out hydrolytically in an aqueous solvent, e.g. water, isopropanol / water, tetrahydrofuran / water or dioxane / water, in the presence of an acid such as hydrochloric acid or sulfuric acid or in the presence of an alkali base such as sodium hydroxide or potassium hydroxide 100eC, preferably at the boiling point of the reaction mixture. However, the benzyl group is best cleaved hydrogenogenolytically, e.g. with hydrogen in the presence of a catalyst such as palladium / carbon in a solvent such as methanol, ethanol,. . in ethyl acetate or glacial acetic acid, optionally with the addition of an acid such as hydrochloric acid, at temperatures between 0 and 50 ° C, preferably at room temperature, and at a hydrogen pressure of 1 to 7 bar, preferably 3-5 bar.

If according to the invention a compound of general formula I is obtained in which R contains a nitro group, this can be converted by reduction into the corresponding amino compound of general formula 1, or

II

if a compound of general formula I is obtained in which R contains 11,94543 amino groups, this can be converted by acylation into the corresponding alkanoylamino compound of general formula I.

The subsequent reduction of the nitro compound is best carried out in a solvent such as water, water / ethanol, methanol, glacial acetic acid, ethyl acetate or dimethylamide, suitably hydrogen in the presence of a hydrogenation catalyst such as Raney nickel, platinum or palladium / carbon in the presence of , salts such as iron (2) sulphate, stannous chloride or sodium dithionite or hydrazine in the presence of Raney nickel at temperatures between 0 and 50 ° C, but preferably at room temperature.

The subsequent acylation is conveniently carried out in a solvent such as methylene chloride, chloroform, carbon tetrachloride, ether, tetrahydrofuran, dioxane, benzene, toluene, anhydride and sodium hydroxide, optionally with a reactive derivative of an acid such as acetonitrile or dimethylformamide, preferably in the presence of a tertiary organic base such as thiethylamine or pyridine, which can simultaneously act as solvents, at temperatures between -25 and + 100 ° C, but preferably at temperatures between -10 and the boiling point of the solvent used.

The obtained compounds of the general formula I can be further converted into their acid addition salts, in particular their physiologically acceptable acid addition salts for inorganic or organic acids for pharmaceutical use. Suitable acids are, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, acetic acid, lactic acid, citric acid, tartaric acid, succinic acid, maleic acid or fumaric acid.

The compounds of the general formulas II to VIII used as starting materials are known in part from the literature or are obtained by methods known per se.

Thus, e.g. The cyclic amine required for this is obtained by converting the corresponding hydroxyalkyl-substituted cyclic amine into its corresponding halogen or sulfonic acid ester and the necessary imino compound of general formula IV is obtained by cyclizing the corresponding compound, e.g. by cyclizing the compound of general formula IX R1 f * (Ιχ) X ° CH3 or also a compound of general formula X 13

Q Λ 7 /; 7 y -f · „; ‘Τ J

R1 d 'Π NH - COCH.Cl 2 __ / · <»CH2CH2 optionally followed by catalytic hydrogenation and / or reduction of the carbonyl with e.g. sodium borohydride / glacial acetic acid (see EP-A1 0.007.070. EP-A1 0.065.229 and EP-A1 0109639).

The starting compound of general formula V is obtained by N-alkylating the corresponding cyclic amine substituted on the carbon backbone with a hydroxyalkyl group with the corresponding compound or the corresponding 1-Caj dihaloalkane and then reacting with the corresponding HO, SH or HN compound and, if necessary, then oxidizing the hydroxyalkyl compound thus obtained is converted into a reactive halogen or sulfonic acid ester.

* 1 The compound of general formulas VI, VII and VIII used as a starting material is best obtained by reacting the corresponding halogen compound with the corresponding amine and optionally then cleaving off the protecting groups used.

to protect groups.

It has already been mentioned above that the new compounds of the general formula I and their physiologically acceptable acid addition salts with inorganic or organic acids have valuable pharmacological properties, in particular an antihypertensive effect, while the side effects on the central nervous system are minor and particularly long-lasting. need-reducing effect.

• 14

Q! T A ~ Z

y ο ί · 0 The biological properties of the following compounds were examined, for example, as follows: A = 3-1 (N- (2- (naphthyl) -2) -ethyl) -piperidyl-3) -methyl] -7,8-dimethoxy 2-oxo-1,3AS-tetrahydro-2H-3-bentazepine hydrochloride, B = 3 - [(N- (2- (S-methyl-6-naphthyl-2) -ethyl) -piperidyl -3) -methyl] -7,8-dimethoxy-2-oxo-1,3,5,5-tetrahydro-2H-3-benzazepine hydrochloride, C = 3- [2- (N- (2- (6-methoxy-2-naphthyl) ethyl) 2-piperidyl) ethyl] -7,8-dimethoxy-2-oxo-l, 3, A, 5-tetrahydro-2H-3-benz-azepine hydrochloride .

D = 2 - [(N- (2- (6-methoxy-naphthyl-2) -ethyl) -hexahydro-azepinyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2, 3, A-Tetrahydro-isoquinoline hydrochloride, E = 2 - [(N- (2- (naphthyl-2) -ethyl) -hexahydro-azepinyl-3) -raethyl] -6,7-methylenedioxy-1- oxo-1,2,3,A-tetrahydro-isoquinoline hydrobromide, F = 2 - [(N- (2- (3, A-dimethoxy-phenyl) -ethyl) -piperidyl-3) - * methyl 3 -6,7-dimethyl-1,2,3,A-tetrahydro-isoquinoline dihydrochloride, G = 2 - [(N- (2- (3A-dimethoxy-phenyl) -ethyl) -piperidyl-3 ) -methyl] -6,7-dimethyl-1-oxo-1,2,3A-tetrahydro-isoquinoline hydrochloride, H = 2 - [(N- (3- (A-methoxy-phenoxy) -propyl) -piperidyl-3) -methyl] -6,7-dimethyl-1-oxo-1,2,3,A-tetrahydro-isoquinoline hydrochloride, «15 3 4 o 4 3 I = 3 - [(N- (A- ( thienyl (2) -butyl) -piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzazepine hydrochloride, K = 3 - [( N- (2- (benzo [b] furyl-2) -ethyl) -piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,5,5-tetrahydro-2H-3- benzazepine hydrochloride and L = 3 - [(N- (2- (benzotb] thienyl-3) -ethyl) -piperidyl-3) -methyl 1-7,8-dimethoxy-2-oxo-1,3a, 5-tetrahydro-2H -3-benz azepin-hydrochloride.

Effect on heart rate in rats:

The effect of test substances on heart rate was studied per dose in two rats with an average weight of 250-300 g. To this end, rats were anesthetized with pentobarbital (50 mg / kg i.p. and 20 mg / kg s.c.). Test substances were injected in aqueous solution into a vein of Vena jugularis at t-0.1 ml / 100 g).

Blood pressure was measured using a cannula connected to the A. carotis artery, and the heart rate was recorded from an ECG trace obtained with needle electrodes (11th or 3rd derivative). The heart rate of the animals • during the control period was between 350 and A00 beats per minute (S / min).

The values obtained are given in the following table: 16 -Ο Λ - * en -)

Vf / 1 - Λ A.

t 0

Substance Dose Decreased heart rate Blood pressure (mg / kg), S / min. mmHg S min. 20 min. 5 min. 20 min.

after after A 5.0 - 216 - 259 - 46 - 32 B 5.0 - 168 - 218 - 22 - 15 C 5.0 - 236 - 194 - 40 - 31 D 5.0 - 173 - 123 - 21 - 16 E 5 , 0 - 169 - 150 - 30 - 16 F 5.0 - 150 - 120 - 49 - 27 G 5.0 - 207 - 101 - 57 - 8 H 5.0 - 190 - 180 - 57 - 33 I 5.0 - 320 - 253 - 65 - 32 K 2,5 - 138 - 156 - 36 L 2.5 - 110 - 163 - 40 - 24

The compounds of the invention do not have any toxic side effects at therapeutic doses.

For example, when compounds A and L were administered intravenously to mice, even at very high doses of 20 mg / kg, no toxic side effects were observed except for minor sedation.

. Based on their pharmacological properties, the compounds according to the invention are suitable for the treatment of sinus tachycardias of various origins and for the prorylaxis and therapy of ischemic heart diseases.

The dosage required to achieve a similar effect is suitably 1-2 times a day 0.01 to 0.2 mg / kg body weight, most preferably 0.03 to 0.15 mg / kg body weight. For this purpose, the compounds of the general formula I prepared according to the invention and their physiologically acceptable acid addition salts can be processed together with inorganic or organic acids, optionally in combination with other active ingredients.

QA A A 7 7 ^ O * 1- J

or with several inert conventional carriers and / or diluents, e.g. corn starch, milk sugar, cane sugar, microcrystalline cellulose, magnesium stearate, polyvinylpyrrolidone. citric acid, tartaric acid, water, water / ethanol, water / glycerin, water / sorbitol, water / polyethylene glycol, propylene glycol, carboxydimethylcellulose or fatty substances such as hard fat or suitable mixtures thereof, into conventional tablets, powder, suspension, drops, ampoules, juices or sticks.

The following examples are intended to further illustrate the invention:

Example A

2 - [(piperidyl-3H-methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline · N-benzyl-3- (hydroxymethyl) -piperidine

A mixture containing 40.3 g (0.35 moles) of 3- (hydroxymethyl) -,. piperidine, 97.4 ml (0.70 mol) of triethylamine and 40.3 ml of (0.3S mol) benzyl chloride are heated to 95 ° C over 30 minutes and allowed to stand at this temperature for 2 hours. The cooled reaction mixture is dissolved in a mixture of 2 molar sodium hydroxide and acetic acid ester. The organic phase is washed with water, separated, dried over magnesium sulphate and evaporated in vacuo.

Yield: S7. 2 g (79.6% of theory)

Rf value: 0.45 (alumina, neutral, propellant: 37% ethanol in methylene chloride.

18 q A Ί A z y i j ^ t 3 b) N-Benzyl-3- (benzenesulfonyloxymethyl) -piperidine

A mixture containing 6.8 g (0.033 moles) of N-benzyl-3- (hydroxymethyl) -piperidine. 6.7 ml (0.0S2 moles) of benzenesulfonic acid chloride. SO ml of 20% aqueous sodium hydroxide, 100 ml of toluene and one spatula tip of tetrabutylammonium bromide are stirred for 3 hours at room temperature. It is then diluted with 250 ml of acetic acid ester and the organic phase is washed with water. The organic phase is separated, dried over magnesium sulphate and evaporated to dryness in vacuo. The residue is purified on 200 g of silica gel (0.063-0.2 mm) using methylene chloride followed by increasing amounts of ethanol (up to 57).

Yield: 9.4 g (92% of theory)

Rf value: 0.5 (silica gel. Propellant: 5 7. ethanol in methylene chloride.

c) 2 - [(N-Benzyl-piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4, -tetrahydro-isoquinoline ♦ <· 5.2 g (0.025 mol) ) 6,7-Dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline is dissolved in 70 ml of dimethyl sulfoxide and 3.1 g (0.025 mol) of potassium tert-butylate are added with stirring. After half an hour the resulting potassium salt: To a suspension of 9.3 g (0.0275 mole) of N-benzyl-3- (benzene-sulfonyloxymethyl) piperidine in 20 ml of dimethyl sulfoxide and stirred for 2 hours at 40eC for. Pour into ice water and extract three times with 120 ml of acetic acid ester. The combined organic phases are washed with water, dried over magnesium sulphate and evaporated in vacuo. The residue obtained is purified on 200 g of silica gel (0.063-0.2 mm) using methylene chloride and then increasing amounts of ethanol (up to 27).

Yield: 7.7 g (78.5 of 7 theoretical)

Rf value: 0.5 (silica gel, propellant: 5% ethanol in methylene chloride and 1 drop of ammonia).

li 19 94 343 d) 2 - [(piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydroisoquinoline 9.4 g (0.0238 moles) 2 - [(N-benzyl-piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline is hydrogenated in 200 ml of methanol for 3 hours at room temperature and 5 bar of hydrogen pressure, when 2 g of 20% palladium diurahydroxide / carbon is present. The catalyst is then filtered off with suction and the filtrate is evaporated to dryness in vacuo.

Yield: 7.2 g (99 of 7 theoretical)

Rf value: 0.15 (silica gel, propellant: 10 7. ethanol in methylene chloride with 1 drop of ammonia).

Example B

3-Chloromethyl-N- [3- (naphthyl-2-oxy) -propyl] -piperidine a) 3- (Hydroxymethyl) -N- [3- (naphthyl-2-oxy) -propyl] -piperidine

A mixture of 11.5 g (0.2 mol) of 3-hydroxymethylpiperidine and 11 g of 2- (3-chloropropoxy) naphthalene is heated at 120 ° C for 1 hour. The residue is purified on silica gel (0.063-0.2 mm) using a mixture of acetic acid ester / ethanol / ammonia = 90: 10: 1.

Yield: 11.5 g (76.6 of 7 theoretical)

Melting point: 99-101βΟ.

b) 3-Chloromethyl-N- [3- (naphthyl-2-oxy) -propyl] -piperidine

To a solution of 1.5 g (5 mmol) of 3- (hydroxymethyl) -N- [3- (naphthyl-2-oxy) propyl] piperidine in 25 ml of chloroform is added 1.5 ml of thionyl chloride and refluxed for 1.5 hours. . Evaporate to dryness in vacuo. The residue is taken up in methylene chloride, washed with water, 2 molar sodium hydroxide and again with water. The methylene chloride phase is dried over magnesium sulfate and then evaporated in vacuo.

Yield: 1.4 g (87.5 of the 7th theoretical)

Rf value: 0.8 (silica gel: propellant: acetic acid ester / ethanol / ammonia = 90: 40: 2).

Example C

2 - [(hexahydro-azepinyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline a) N-Benzyl-caprolactam 33.9 g (0.3 mol) of caprolactam are dissolved To 250 ml of dimethyl sulfoxide and 37 g (0.33 mol) of potassium tert-butylate are added with stirring. The reaction temperature then rises to 60 ° C. Stir for 1/2 hour at 60 ° C and then add dropwise 35 ml (0.3 mol) of benzyl bromide. Maintain at 60 ° C for a further 2.5 hours, then pour into 1 liter of ice water and shake 3 times with acetic acid ester. The organic phases are combined, washed with water, dried over magnesium sulphate and evaporated in vacuo.

Yield · 60.3 g (99 of 7 theoretical) • Rf value: 0.6 (silica gel, propellant: 57% ethanol in methylene chloride).

b) 1-Benzyl-caprolactan-3-carboxylic acid

To a solution of 33.9 g = 47.1 ml (0.33 mol) of diisopropylamine in 450 ml of absolute ether is added, with stirring and under nitrogen at -60 ° C, 180 ml of 2,6-molar a solution of lithium in N-hexane. 48.8 (0.24 mol) of N-benzyl-caprolactam dissolved in 150 ml of absolute ether are then added dropwise and with further cooling.

* 21

G / 7 Λ 7/1 J1 J

After stirring for 10 minutes, the cold bath is removed and carbon dioxide is introduced into the mixture for 15 minutes. The reaction mixture is poured onto ice, the ether phase is separated off and shaken twice with 2 molar sodium hydroxide. The aqueous-alcoholic phases are combined, shaken with ether, acidified with concentrated hydrochloric acid and shaken twice with methylene chloride. The combined methylene chloride phases are dried over magnesium sulfate and the solvent is distilled off in vacuo.

Yield: 15.7 g (26.5 δ, theoretical) IR spectrum (methylene chloride): 1735 and 1600 cm -1 (CO).

c) 1-Benzyl-3-hydroxymethyl-hexahydro-azepine

To a mixture of 6.84 g (0.28 moles) of lithium aluminum hydride in 30 ml of absolute tetrahydrofuran is added dropwise 14.8 g (0.06 moles) of 1-benzyl-caprolactar-3-carboxylic acid dissolved in 300 ml. absolute tetrahydrofuran. It is then heated at reflux for 6 hours, after which 6.8 ml of water, 6.8 ml of 2-molar sodium hydroxide and 21 ml of water are added under ice-water cooling. The precipitate is filtered off with suction, washed with tetrahydrofuran and the filtrate is evaporated in vacuo. The residue is purified by column chromatography over alumina N (activity II. Eluent: methylene chloride).

Yield: 8.4 g (63.8 7% of theory) IR spectrum (methylene chloride): 3620 cm-1 (OH).

d) 1-Benzyl-3- (4-toluenesulphonyloxymethyl) -hexahydro-azepine 15 g (0.0684 mol) of 1-benzyl-3-hydroxymethyl-hexahydro-azepine are dissolved in 150 ml of pyridine and 14.3 g ( 0.075 moles) of p-toluenesulfonic acid chloride and stirred for 1 hour at room temperature. Evaporate in vacuo, take up in methylene chloride, wash with 2M sodium hydroxide and water. After drying over magnesium sulphate, the organic phase is evaporated in vacuo.

Yield: 23.3 g (91.3% of theory)

Rf value: 0.45 (silica gel, propellant: 5% ethanol in methylene chloride).

e) 2 - [(N-Benzyl-hexahydro-azepinyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline 7.4 g (0.0387 moles) ) Dissolve 6,7-methylenedioxy-1-oxo-1,2,3,4, -tetrahydroisoquinoline in 100 ml of dimethyl sulphoxide, add 4.5 g (0.04 mol) of potassium tert-butylate and mix with 1 / 2 hours at room temperature. 16.8 g (0.044 mol) of 1-benzyl-3- (4-toluenesulfonyloxymethyl) -hexahydro-azepine are then added dropwise and the mixture is stirred for 3 hours at room temperature. The reaction mixture is dissolved in acetic acid ester and shaken twice with water.

The organic phase is dried over magnesium sulfate and evaporated in vacuo. The residue is purified on alumina N (activity 2, eluent: methylene chloride, methylene chloride + 2% ethanol).

Yield: 3.0 g (19.6 of 7 theoretical)

Rf value: 0.6 (silica gel, propellant. · 5 7. ethanol in methylene chloride).

F · 2 - [(hexahydro-azepinyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline 6.7 g (0.017 mol) 2 - [(N-benzyl-hexahydro-azepinyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline is hydrogenated in 250 ml of methanol over 4 hours at room temperature and S bar hydrogen pressure. when 2 grams of 20% palladium hydroxide / carbon is present. The catalyst is then filtered off with suction and the filtrate is evaporated to dryness in vacuo. The residue is crystallized from acetone.

». · 23

G A 7 A 7. y “f ^ -t J

Yield · 4.9 g (95 of 7 theoretical)

Melting point: 267-269eC.

Example D

3-Chloromethyl-N- [3- (naphthyl-2-oxy) -propyl] -hexahydro-azepine a) 3-Hydroxymethyl-hexahydro-azepine 16.6 g (0.0757 moles) of 1-benzyl-3-hydroxymethyl -hexa-hydroazepine is hydrogenated in 500 ml of methanol for two hours at room temperature and 5 bar of hydrogen pressure in the presence of 16.6 g of 20% palladium hydroxy / carbon.

The catalyst is then filtered off with suction and the filtrate is evaporated in vacuo.

Yield: 8 g (81.8 7 »theoretical)

Rf value: 0.5 (silica gel, propellant: methylene chloride / ethanol / ammonia = 5: 4: 1).

»* B) 3-Hydroxymethyl-N- [3- (naphthyl-2-oxy) -propyl] -hexahydroazepine hydrochloride

A mixture of 7.8 g (0.06 mol) of 3-hydroxymethyl-hexahydroazepine and 6.7 g (0.03 molar) of 2- (3-chloropropoxy) -naphthalene is heated at 120 ° C for 1 hour. The reaction mixture is purified on silica gel (0.063-0.2 mm) using acetic acid ester / ethanol / ammonia = 90: 10: 1.

Yield 2.3 g (24.3 of the 7th theoretical)

Melting point · 127-129eC.

c) 3-Chloromethyl-N- [3- (naphthyl-2-oxy) -propyl] -hexahydro-azepine 24

Q Λ 7 Λ 7 ^ J η J

2.4 g (6.86 mmol) of 3-hydroxymethyl-N- [3- (naphthyl-2-oxy) -propyl] -hexahydro-azepine hydrochloride are dissolved in 30 ml of chloroform and 5 ml of thionyl chloride are added to the solution and refluxed. l hour. Evaporate to dryness in vacuo. The residue is dissolved in methylene chloride and washed with water, 2 molar sodium hydroxide and again with water. The methylene chloride phase is dried over magnesium sulfate and evaporated in vacuo.

Yield 1.1 g (48.5% of theory)

Rf value: 0.55 (silica gel, propellant: 5 7. ethanol in methylene chloride).

Example E

2 - [(pyrrolidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydroisoquinoline a) N-Benzyl-2-pyrrolidone in a solution of 25.5 g (0.3 mol) of 2-pyrrolidone in 300 ml of absolute dimethyl sulfoxide, 14.4 g (0.33 mol) of a 50% dispersion of sodium hydride in oil are added portionwise. It is then stirred for 5 hours at 40-50 ° C and 56.4 g * 39.2 ml of * * (0.33 mol) of benzyl bromide are added dropwise at 25-30 ° C. The reaction mixture is stirred for 10 hours at room temperature, then dissolved in 500 ml of acetic acid ester and shaken several times with water. The organic phase is separated, dried over magnesium sulphate and the solvent is removed in vacuo. The residue obtained is purified on 900 g of alumina (neutral, activity 2) using methylene chloride and 0.1% ethanol. Yield: 35.6 g (67.7 7, of theoretical)

Rf value: 0,77 (alumina, neutral, propellant: 5% ethanol in ethylene chloride), »· * # 25

g / 1 7/1 2 / t J Ί O

b) N-benzyl-2-pyrrolidone-3-carboxylic acid

To a solution of 28.3 g = 39.3 ml (0.28 mol) of diisopropylamine in 400 ml of absolute ether is added, with stirring and under nitrogen at -60 ° C, 150 ml of 1.6 molar butyllithium. solution in n-hexane. To this is added dropwise 35.1 g (0.2 mol) of N-benzyl-2-pyrrolidone dissolved at -60 ° C in 150 ml of absolute ether. The cold bath is removed and dry carbon dioxide is bubbled into the mixture for 15 minutes. After stirring for 10 minutes, the mixture is poured onto ice and the organic phase is separated and shaken twice with 2 molar sodium hydroxide. The combined aqueous phases are shaken once with ether and then acidified with concentrated hydrochloric acid while cooling. The aqueous phase is shaken twice with methylene chloride, the organic phase is dried over magnesium sulfate and evaporated in vacuo. Yield: 35 g (79.8 7, of theoretical)

Rf value: 0.42 (silica gel, propellant: 5 7. ethanol in methylene chloride).

c) N-Benzyl-3-hydroxymethyl-pyrrolidine

To a mixture of 12.2 g (0.32 mol) of lithium aluminum hydride in 350 ml of absolute tetrahydrofuran is added dropwise, with stirring, 35 g (0.16 mol) of N-benzyl-2-pyrrolidone-3-carboxylic acid dissolved in 250 ml. ml of absolute tetrahydrofuran. Heat at reflux for 6 hours, then add 18.2 ml of water, 12.2 ml of 15% aqueous sodium hydroxide and 36.6 ml of water while cooling with ice water. The precipitate formed is filtered off with suction and washed with tetrahydrofuran. The combined filtrates are evaporated in vacuo and the residue obtained is purified on 900 g of alumina (neutral, activity 2) using methylene chloride and then increasing amounts of ethanol (up to 2%).

Yield 16 g (52.3 7, theoretical) 9 26 Q / 7/17 y * τ o o

Rf value: 0.42 (alumina, neutral, propellant: 5% ethanol in methylene chloride).

d) 3- (Benzenesulfonyloxymethyl) -1-benzylpyrrolidine 40 ml of 20% sodium hydroxide are added dropwise over 1 hour to a mixture of 3.8 g (20 mmol) of N-benzyl-3-hydroxymethylpyrrolidine and 3.7 ml ( 24 mmol) benzenesulfonic acid chloride. 150 ml of toluene are added, the organic phase is washed with water, dried over magnesium sulphate and evaporated to dryness in vacuo.

Yield 5.9 g (89.4 of the 7th theoretical)

Rf value: 0.4 (silica gel, propellant: 5 7. ethanol in methylene chloride).

e) 2- [N- (Benzyl-pyrrolidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline 3.3 g (15.9 mmol) 6.7 -dimethoxy-1-oxo-1,2,3,4-tetrahydro-f-isoquinoline is dissolved in 50 ml of dimethyl sulfoxide and 2 g (17.5 mmol) of potassium tert-butylate are added with stirring at room temperature. After half an hour the resulting potassium salt is added to a suspension of 5.8 g (17.5 mmol) of 3- (bentsee-nisulf onyylioksimetyyli) -1-benzyl-pyrrolidine ml.-10 C. • dimethyl sulfoxide and stirred for 3 hours at 60 ° C. Pour into ice water and extract with acetic acid ester. The combined organic phases are washed with water and dried over magnesium sulfate. The organic phase is evaporated in vacuo and the residue obtained is purified on 350 g of alumina N (activity II) using methylene chloride and then increasing amounts of ethanol (up to 1%).

Yield: 3.3 g (54.47. Of theory),

Rf value: 0.74 (alumina N, propellant: 57. ethanol in methylene chloride).

I: 27 94 543 f) 2 - ((pyrrolid-3-yl) methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydroisoquinoline 3.2 g (8.4 mmol) 2 - [( N-Benzyl-pyrrolid-3-yl) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline is dissolved in 250 ml of methanol and hydrogenated for 3 hours at room temperature and 5 bar of hydrogen pressure. , in the presence of 1 g of 20% palladium hydroxide / carbon, the catalyst is then filtered off with suction and the filtrate is evaporated to dryness in vacuo. 0.5 mixture.

Yield: 0.9 g (37.5% of theory)

Rf value: 0.6 (silica gel, propellant: methylene chloride / ethanol / ammonia = 5: 4: 1).

Example F

3- (p-Toluenesulfonyloxymethyl) -N- [2- (6-methoxy-naphthyl- * 2) -ethyl] -pyrrolidine a) 3-Hydroxymethyl-pyrrolidine 14 g (0.073 mol) of N-benzyl-3-hydroxymethyl-pyrrolidine • hydrogenated for 7 hours in SO 2 and a hydrogen pressure of 5 bar in 300 ml of methanol in the presence of 1.5 g of 20% palladium hydroxide / activated carbon. The catalyst is then filtered off with suction and the filtrate is evaporated in vacuo.

Yield: 7.3 g (99% of theory)

Mass spectrum: molar peak 101.

b) 3-Hydroxymethyl-N- [2- (6-methoxy-naphthyl-2) -ethyl] -pyrrolidine

A mixture of 3.6 g (29.4 mmol) of 3-hydroxymethylpyrrole 94343 28 lididine and 4.7 (14.7 mmol) of 2- (2-bromomethyl) -6-methoxy-naphthalene is heated for 2 hours at 120 ° C. The reaction mixture is purified on 200 g of silica gel (0.063-0.2 mm) using ethylene chloride followed by increasing amounts of ethanol (up to 5%).

Yield ·: 3.48 g (82.5% of theory)

Melting point: 121-123 ° C.

c) 3- (p-Toluenesulfonyloxymethyl) -N- [2- (6-methoxy-naphthalen-2) -ethyl] -pyrrolidine 0.8 g (2.8 mmol) of 3-hydroxymethyl-N- [2- (6-Methoxy-naphth-2-yl) -ethyl-pyrrolidine is dissolved in 10 ml of pyridine and 1.2 g (6.3 mmol) of p-toluenesulfonic acid chloride are added with stirring. Keep for 2 hours at room temperature, then evaporate to dryness in vacuo. The residue is dissolved in methylene chloride and washed with 2-molar sodium hydroxide and water. The organic phase is then dried over magnesium sulphate and evaporated in vacuo. The residue is purified on 150 g of silica gel (0.063-0.2 mm) using acetic acid ester followed by increasing amounts of ethanol.

Yield: 0.6 g (48.8% of theory)

Rf value: 0.45 (silica gel, propellant: 5% ethanol in methylene chloride).

Example G

2 - [(azacyclooctyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydroisoquinoline a) 1-benzyl-2-oxoazacyclooctane 25 g (0.196 mol) of 2-azacyclooctanone is dissolved in 150 ml of dimethyl sulfoxide and 24.2 g (0.216 mol) of potassium tert-butylate are added with stirring and stirred for half an hour *>

II

29

Q / 7/17 ./ 1 j n O

40eC C. 24 ml (0.2 mol) of benzyl bromide are then added dropwise over 1/4 hour, the temperature rising to 80 ° C. Stir for an additional 2 hours, at which point the reaction temperature drops again to room temperature. The reaction mixture is poured into 1 liter of ice water and shaken 4 times with 150 ml of acetic acid ester. The combined organic phases are washed with water, dried over magnesium sulphate and evaporated in vacuo. Yield: 42.7 g (1007 of theory),

Rf value: 0.55 (silica gel, propellant: 5% ethanol in methylene chloride).

b) 1-Benzyl-azacyclooctane-2-oxo-3-carboxylic acid

To a mixture of 26.7 g = 38.4 ml (0.26 mol) of diisopropylamine in 250 ml of absolute ether is added dropwise, with stirring and under nitrogen, at -6 ° C, 147 ml of 1.6- a molar solution of butyllithium in n-hexane. 42.7 g (0.196 mol) of 1-benzyl-2-oxo-azacyclooctane in 100 ml of absolute ether are then added dropwise at -60 ° C. After 10 minutes, dry carbon dioxide is bubbled in for 20 minutes. The reaction mixture is poured onto ice, the ether phase is separated off and shaken twice with 2 molar sodium hydroxide. The combined aqueous phases are shaken once with ether and then acidified with concentrated hydrochloric acid at the same time? cooling. Shake 3 times with methylene chloride, dry the methylene chloride phase over magnesium sulphate and evaporate.

Yield: 25.9 g (50.6% of theory)

Rf value: 0.15 (alumina, propellant: 5% ethanol in methylene chloride).

c) 1-benzyl-3-hydroxymethyl-azacyclooctane

To a mixture of 22.7 g (0.6 moles) of lithium aluminum hydride in 800 ml of absolute ether is added dropwise, with stirring, 53.6 g (0.205 moles) of 1-benzyl-2-oxoazacyclooctane. 3-carboxylic acid dissolved in 100 ml of absolute tetrahydrofuran. Heat at reflux for 1/2 hour, then add 28 ml of water, 19 ml of 15% sodium hydroxide and 57 ml of water while cooling with ice water. The precipitate formed is filtered off with suction and washed with tetrahydrofuran. The combined filtrates are evaporated in vacuo and the residue obtained is purified on 700 g of alumina (neutral, activity II) using 1% ethanol in methylene chloride.

Yield: 9.3 g (19.6% of theory)

Rf value: 0.5 (silica gel, propellant: 5% ethanol in methylene chloride).

d) 1-Benzyl-3-chloromethyl-azacyclooctane To 9.3 g (39.8 mmol) of 1-benzyl-3-hydroxymethyl-azacyclooctane in 30 ml of pyridine is added 10 ml (79.6 mmol) of mmol) of benzenesulfonic acid chloride and stirred for 2 1/2 hours at room temperature. The reaction mixture is evaporated in vacuo.

The remaining residue is dissolved in 150 ml of methylene chloride and washed with 2N sodium hydroxide and water. The organic phase is dried over sodium sulfate, evaporated to dryness and purified on 150 g of silica gel (0.063-0.2 mm) using methylene chloride.

. Yield: 3.5 g (35% of theory)

Rf value: 0.75% (silica gel, propellant: 5% ethanol in methylene chloride).

e) 2 - [(N-Benzyl-azacyclooctyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,5-tetrahydro-isoquinoline 2.3 g (11.1 mmol) 6 The 7-dimethoxy-1-oxo-1,2,3,4-tetrahydroisoquinoline is dissolved in 10 ml of dimethyl sulfoxide and 1.33 g (12.2 mmol) of potassium tert-butylate are added with stirring. After 1/2 hour, add the resulting potassium salt suspension

II

Q AT AT

3.5 g (9, mmol) of 1-benzyl-3-chloromethyl-aza-cyclooctane in 00 ml of dimethyl sulfoxide and stirred for 2 1/2 hours at 120 ° C. . Pour into ice water and extract 3 times with 50% acetic acid ester. The combined organic phases are washed with water, dried over magnesium sulphate and evaporated in vacuo. The residue obtained is purified on 150 g of silica gel (0.063-0.2 mm) using 1% ethanol in methylene chloride.

Yield: 1 g (25.1% of theory)

Rf value: 0.5 (silica gel, propellant: 2% ethanol in methylene chloride).

f) 2 - [(azacyclooctyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,1-tetrahydroisoquinoline 0.85 g (2 mmol) 2 - [(N -benzyl-azacyclooctyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,5-tetrahydro-isoquinoline is hydrogenated in 50 ml of methanol A for 1/2 hour at room temperature and at a hydrogen pressure of 5 bar in the presence of 0.85 g of 20% palladium hydroxide / carbon. The catalyst is then filtered off with suction and the filtrate is evaporated to dryness in vacuo.

Yield: 0.5 (7A, 6% of theory)

Rf value: 0.05 (silica gel, propellant: 25% ethanol in methylene chloride with 1 drop of ammonia).

> ·

: Example H

1-Chloro-3- [N- (N-methoxyphenyl) methylamino] propane 10 g (0.073 mol) of N-methyl-A-methoxyaniline are dissolved in 50 ml of dimethyl sulfoxide and 9 g (0, 08 moles) of potassium tert-butylate. After 1/2 hour, 10 ml of 1-bromo-3-chloropropane are added and the mixture is stirred for 3 hours at room temperature. Pour into ice water, shake with acetic acid ester, wash the organic phase with water, dry over sodium sulfate and evaporate to dryness. The residue is purified on silica gel (0.063-0.2 mm) using methylene chloride.

Yield: 9.1 g (S6.3% of theory)

Rf value: 0.55 (silica gel, propellant: methyl ethyl ketone / xylene = 1: 6) Calc .: C 61.82 H 7.55 N 6.55 Cl 16.59 Found: 61.71 7.88 6.69 16, 24

Example I

2 - [(N- (3- (pyridyl-3) -propyl) -piperidyl-3) -methyl] -5,6-methylenedioxy-phthalimide 2.1 g (0.011 mol) of 5,6-methylenedioxy-phthalimide are dissolved in 100 ml. dimethyl sulfoxide and 1.25 g (0.012 mol) of potassium tert-butylate are added with stirring. Potassium salt precipitates.

Stir for an additional 1/2 hour at room temperature, add a solution of 2.5 g (0.01 mol) of 3-chloromethyl-N- (3- (pyridyl-3) -propyl) -piperidine in 20 ml of dimethyl sulfoxide, 3 ' a is heated for 8 hours at 120 ° C. Pour into ice water, shake 3 times with 150 ml of acetic acid ester and, after drying over magnesium sulphate, evaporate the organic phase in vacuo. The residue is purified on 200 g of silica gel (0.063-0.2 mm) using a mixture of acetic acid ester / ethanol / ammonia = 80: 10: 0.5.

Yield: 3 g (747th of theoretical) calc. (2 x HCl): C 55.42 H 5.86 N 8.43 Cl 14.22 Found: 55.28 6.06 8.26 14.64

Example K

2 - [(N-3-chloropropyl) -piperidyl-3-methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydroisoquinoline 3 g (0.01 mol) 2 - [ (Piperidyl-3) -methyl] -6,7-dimethoxy-1- {94343 33 oxo-1,2,3,A-tetrahydro-isoquinoline is dissolved in 50 ml of dimethyl sulfoxide and 1.3 g (0.011 mol) are added with stirring. potassium tert.butylaattia. After 1/2 hour, 3 ml of 1-bromo-3-chloropropane are added and the mixture is stirred for 1 hour at room temperature. Pour into ice water, rinse with acetic acid ester, wash the organic phase with water, dry over sodium sulfate and evaporate to dryness under reduced pressure.

Yield: 2.7 g (717th of theoretical)

Rf value: 0.65 (silica gel, propellant. · Acetic acid ester / ethanol / ammonia = 50: AS: 5).

Example 1 2 - [(N- (3- (naphthyl-2) -propyl) -piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,5-tetrahydroisoquinoline hydrochloride

A mixture of 1 g (3.2 mmol) of 2- (piperidyl-3-methyl) -6,7-dimethoxy-1-oxo-1,2,3,5-tetrahydroisoquinoline, 5 ml of dimethyl sulfoxide, 5 g (0.36 mmol) of potassium carbonate and 0.75 g (3.66 mmol) of 2- (3-chloropropyl) naphthalene are heated at 120 ° C for 3 hours. The reaction mixture is poured into ice water and shaken 3 times with 50 ml of acetic acid ester. The combined organic phases are washed with 2M sodium hydroxide and water, dried over magnesium sulphate, evaporated in vacuo and the residue obtained is purified on silica gel (0.063-0.2 mm) using 17th ethanol in methylene chloride. The hydrochloride is mixed with acetic hydrochloric acid from acetone solution and crystallized from acetone.

Yield: 0.74 g (AA% of theory)

Melting point: 179-118 Calc .: C 70.77 H 7.37 N 5.50 Cl 6.96 Found: 70, A7 7, AO 5, A7 7.06.

34

Example 2 QA 7 Λ 7 -7 “2 oij 2 - [(N- {3- (naphthyl-2-oxy) -propyl) -piperidyl-3) -methyl] -6,7-dimethyl-1-oxo- 1,2,3,4-Tetrahydro-isoquinoline hydrochloride Hydrate 1.58 g (9 mmol) of 6,7-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline are dissolved in 30 ml of dimethylsulfoxide and added with stirring. g (9.9 mmol) of potassium tert-butylate. After 1 hour, a solution of 2.9 g (9.1 mmol) of 3-chloromethyl-N- [3- (naphthyl-2-oxy) -propyl] -piperidine and 10 ml of dimethylsulfoxide is added and the reaction mixture is stirred for 16 hours at 80 ° C: in. It is then poured into ice-water, shaken 3 times with 50 ml of acetic acid ester, the organic phase is washed with water, dried over magnesium sulphate and, after evaporation, purified on silica gel (0.63-0.2 mm) using acetic acid ester / ethanol / ammonia = 95: 5: 0.5 mixture. The hydrochloride is obtained as a hydrate from an acetone solution with ethereal hydrochloric acid.

Yield: 2 g (45.1% of theory)

Melting point: 152-154 DEG C. Calculated: C 70.50 H 7.69 N 5.49 Cl 6.93 Found: 70.31 7.52 5.49 7.10.

: Example 3 2 - [(N- (3- (naphthyl-2) -propyl) -piperidyl-3) -methyl] -6,7-dimethyl-1,2,3,4-tetrahydro-isoquinoline dihydrochloride 8.8 g (18 mmol) of 2 - [(N- (3- (naphthyl-2) -propyl) -piperidyl-3) -methyl) -6,7-dimethyl-1-oxo-1,2,3,4 -Tetrahydroisoquinoline is dissolved in a mixture of 10 ml of absolute tetrahydrofuran and 20 ml of absolute ether, 70 mg (18 mmol) of lithium aluminum hydride are added and the mixture is refluxed for 1 hour. The reaction mixture is quenched by the addition of 5 ml of saturated aqueous sodium sulfate solution. the precipitated sodium sulfate is filtered off and washed with tetrahydrofuran. The filtrate is dried over magnesium sulfate and, after evaporation, purified on 150 g of silica gel (0.063-0.2 mm) using acetic acid ester / ethanol / ammonia = 90: 10.0.05. The hydrochloride is mixed with ethereal hydrochloric acid from acetone solution.

Yield: 0.49 g (54.47. Of theory)

Melting point: 148-150 ° C

Calc .: C 69.61 H 8.18 N 5.41 Cl 13.70 Found: 69.46 8.32 5.26 14.17.

Example 4 2 - [(N- (3- (pyridyl-3) -propyl) -piperidyl-3) -methyl] -5,6-methylenedioxy-1-oxo-1,3-dihydro-isoindole dihydrochloride 2,4 g (5.9 mmol) of 2 - [(N- (3- (pyridyl-3) -propyl) -piperidyl-3) -methyl] -s, 6-methylenedioxy-phthalimide are dissolved in 50 ml of glacial acetic acid and boiled 5 hours at reflux. 1 g of zinc dust is added every hour. After the reaction time, it is filtered off with suction and evaporated with ethanol. The residue is dissolved in methylene chloride, extracted with concentrated ammonia, dried over magnesium sulphate and evaporated in vacuo. then purified on 150 g of silica gel (0.063-0.2 mm) with acetic acid ester / ethanol / ammonia = 90: 10: 0.2. The hydrochloride is precipitated from acetone solution.

Yield: 2.05 g (757 of theory)

Melting point: 165-167 * ^ 3 Calc .: C 59.22 H 6.27 N 9.00 Cl 15.20 Found: 59.03 6.45 8.85 15.06.

Example 5 3 - [(N- (3- (pyridyl-3) -propyl) -pyrrolidyl-3) -methyl] -7,8-36

Γ; /, 7. A τ y · η τ O

Dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzoazepine dihydrochloride 1.1 g (2.6 mmol) 3 - [(N- (3- (pyridyl-3) propyl) pyrrolidinyl -3) -methyl] -7,8-dimethoxy-2-oxo-1,3-dihydro-2H-3-benzoazepine dissolved in 50 ml of ethanol is hydrogenated for two hours at 80 ° C and 5 bar of hydrogen. , in the presence of 1 g of 10% palladium on activated carbon. The catalyst is then filtered off with suction and the filtrate is evaporated in vacuo and purified on 100 g of silica gel (0.063-0.2 mm) using a mixture of acetic acid ester / ethanol / ammonia = 80: 40: 1. The hydrochloride is mixed with acetone solution.

Yield: 0.37 g (33% of theory)

Melting point: 96-98eC

Calc .: C 60.42 H 7.11 N 8.46 Cl 14.28 Found: 60.35 7.46 8.43 14.58.

Example 6 2 - [(N- (3- (N-ethyl-3,4-dimethylanilino) propyl) piperidyl-3) methyl] -6,7-dimethoxy-1-oxo-1, 2,3,4-tetrahydro-isoquinoline dihydrochloride

A mixture of 1.3 g (0.0034 mol) of 2 - [(N- (3- (chloropropyl) -piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1, 2,3,4-Tetrahydro-isoquinoline, 15 ml of dimethyl sulphoxide, 1.4 g (0.1 mol) of potassium carbonate and 1 g (0.0066 mol) of N-ethyl-3,4-dimethylaniline, heated for 6 hours at 120 ° C :in.

The reaction mixture is poured into ice water, shaken with ethyl acetate, the organic phase is washed with water, dried over sodium sulfate and evaporated in vacuo. The resulting residue is purified on silica gel (0.032-0.063 mm) using 5% ethanol in methylene chloride. The dihydrochloride is mixed from the acetone solution with ethereal hydrochloric acid.

Yield: 633 g (37.7% of theory) 37 94 343

Melting point · 97-100 ° C

Calc .: C 61.63 H 6.10 N 7.18 Cl 12.12 Found: 61.52 6.15 6.92 11.82.

Example 7 2 - [(N- (2- (4-amino-phenyl) -ethyl) -piperidyl-3) -methyl] -5,6-dimethoxy-1-oxo-1,3-dihydro-isoindole dihydrochloride 2 , 1 g (4.78 mmol) of 2 - [(N- (2- (4-nitro-phenyl) -ethyl) -piperidyl-3) -methyl] -5,6-dimethoxy-1-oxo-1 The 3-dihydro-isoindole is dissolved in 50 ml of glacial acetic acid and 0.4 ml (8.22 mmol) of hydrazine hydrate and 1 spatula tip of Raney nickel are added with stirring. Every three hours, 0.2 ml of hydrazine hydrate and one spatula-tipped Raney nickel are added again. The catalyst is filtered off, washed with methanol, the filtrate is dried over magnesium sulphate, evaporated in vacuo and the residue obtained is purified on alumina (neutral, activity II) using methylene chloride and then increasing amounts of ethanol.

Yield: 1.8 g (91.87. Of theory) of 1 g are dissolved in acetone and the dihydrochloride is precipitated with ethereal hydrochloric acid.

Yield: 1.02 g (86.4% of theory),

• Melting point: 232-235eC

Calc .: C 59.72 H 6.89 N 8.71 Cl 14.69 Found: 59.54 7.08 8.56 14.45.

Example 8 2 - [(N- (2- (4-acetamino-phenyl) -ethyl) -piperidyl-3) -methyl] -5,6-dimethoxy-1-oxo-1,3-dihydro-isoindole 819 mg ( 2 mmol) 2 - [(N- (2- (4-amino-phenyl) -ethyl) -piperidyl-3) -methyl] -5,6-dimethoxy-1-oxo-1,3-dihydro-isoindole 38

Q A ~ Z Λ ~ Z s -r o * t J

dissolved in 10 ml of methylene chloride, 0.3 ml (2.2 mmol) of triethylamine are added, followed by dropwise addition of 0.16 ml (2.2 mmol) of acetyl chloride. The reaction temperature then rises to 30 ° C. Stir for 1/2 hour at room temperature, extract twice with water, dry the organic phase over magnesium sulfate and evaporate in vacuo. The residue is crystallized from acetone.

Yield: 660 mg (73.2% of theory).

Melting point: 195-196®C

Calc .: C 69.16 H 7.37 N 9.31 Found: 69.33 7.11 9.16.

Example 9 3 - [(N- (3- (furyl-2) -propyl) -piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H- 2-Benzazepine hydrochloride 3.2 g (0.010 mol) of 3 - [(piperidyl-3) methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3 -benzazepine is hydrogenated in 100 μl of absolute ethanol for 2 days at 80 ° C at a pressure of 5 bar in the presence of 1.3 g (0.010 mol) of 3- (furyl-2) -propanal and 1 g of Raney nickel. The catalyst is filtered off with suction, evaporated and purified on a silica gel column using methylene chloride / methanol as eluent. Hydrochloride! mixed with ethereal hydrochloric acid and crystallized from acetone.

Yield: 0.50 g (11% of theory).

Melting point: 204-206 ° C

Calc .: C 64.85 H 7.62 N 6.05 Cl 7.66 Found: 64.88 7.76 5.93 7.55.

Rf value: 0.69 (silica gel; methylene chloride / methanol = 10: 1; ammonia / ambient pressure).

m m »39

Example 10 g /, tat

J ~ r u n O

2 - [(N- (3- (3-Methylphenoxy) propyl) -piperidyl-3) -methyl] -6,7-dimethoxy-1,2,3A-tetrahydroisoquinoline dihydrochloride

Prepared from 2 - [(N- (3- (3-methylphenoxy) propyl) piperidyl-3) methyl] -6,7-dimethoxy-1-oxo-1,2,3,5-tetrahydro iso -quinoline and lithium aluminum hydride in diethyl ether and tetrahydrofuran according to Example 3.

Yield: 92.9% of theory,

Melting point: 100-103 * »C

Calc .: C 61.23 H 7.99 N 5.29 Cl 13.39

Found: 61.21 8.13 5.10 13.15.

Example 11 2 - [<N- (3- (Naphthyl-2-oxy) -propyl) -pyrrolidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,5-tetrahydro-isoquinoline- hydro-chloride

Prepared from 6,7-dimethoxy-1-oxo-1,2,3,5-tetrahydro-isoquinoline and 3-chloromethyl-N- [3- (naphthyl-2-oxy) -propyl] -pyrrolidine according to Example 2.

Yield: 22 7. theor., »*> · Melting point: 78-80β0

Lask. (X HaO): C 65.83 H 7.0A N 5.29 Cl 6.70

Found: 65.79 7.00 5.03 6.99.

Example 12 2 - [(N- (3- (Naphthyl-2-oxy) -propyl) -pyrrolidyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3A-tetrahydro-isoquinoline- hydrochloride

Prepared from 6,7-methylenedioxy-1-oxo-1,2,3A-tetrahydro-40 Q Λ 7/12

s ““ i v_ '’f J

isoquinoline and 3-chloromethyl-N- [3- (naphthyl-2-oxy) -propyl] -pyrrolidine according to Example 2.

Yield: 53% of theory,

Melting point: 78-30 ° C

Lask. (X HzO): C 65.56 H 6.48 N 5.46 Cl 6.91

Found: 65.44 6.32 5.38 7.13.

Example 13 2 - [(N- (2- (Naphthyl-2) -ethyl) -pyrrolidyl-3) -methyl] -6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline hydrochloride

Prepared from 2 - [(N- (2- (naphthyl-2) -ethyl) -pyrrolidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and lithium aluminum hydride in tetrahydrofuran and ether according to Example 3.

Yield: 66.2% of theory.

Melting point: 239-24ΐ * Ό

Lask. (X H0): C 64.48 H 7.44 N 5.37 Cl 13.91 Found: 64.30 7.34 5.52 13.69.

Example 14 2-1 (N - ((2-Methyl-naphthyl-1) -methyl) -hexahydro-azepinyl- • (3) -methyl] -6,7-dimethoxy-1,2,3,4-tetrahydro- isoquinoline hydrochloride

Prepared from 2 - [(N - ((2-methyl-naphthyl-1) -methyl) -hexahydro-azepinyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetra -hydroisoquinoline and lithium aluminum hydride in tetrahydrofuran and ether according to Example 3.

Yield: 73.8% of theory,

Melting point: 182-184 ^ 0

Lask. (X HzO): C 6 S 56 H H 7.70 N 5.09 Cl 12.90 Found: 65.52 7.57 5.32 12.72.

li 41

Example 15

g Λ 7 Λ 7 J τ o -r J

2 - [(N- (4- (Naphthyl-2-oxy) -butyl) -pyrrolidyl-3) -methyl] -6,7-dimethyl-1-oxo-1,2,3,5-tetrahydro-isoquinoline hydrochloride

Prepared from 2- (pyrrolidyl-3-methyl) -6,7-dimethyl-1-oxo-1,2,3,A-tetrahydro-isoquinoline and 2- (N-bromo-butyloxy) -naphthalene according to Example 1.

Yield: 30 7. theor.,

Melting point: 133-136 ^ 0

Calc .: C 67.02 H 6.92 N 5.21 Cl IA.86

Found: 67.26 7.03 5.3b IA, 89.

Example 16 2 - [(N- (2-Methyl-naphthyl-1) -methyl) -pyrrolidyl-3) -methyl] -6,7-dimethyl-1-oxo-1,2,3,A-tetrahydro-isoquinoline hydrochloride ψ »

Prepared from 2- (pyrrolidyl-3-methyl) -6,7-dimethyl-1-oxo-1,2,3,A-tetrahydro-isoquinoline and 1-chloromethyl-2-methyl-naphthalene according to Example 1.

Yield: 32.5 Theoretical 7,

Melting point: lA2-lAAeC

Calc .: C 69.3A H 7.69 N 5.77 Cl 7.37

Found: 69.59 7.63 5.72 7.89.

Example 17 2 - [(N- (2- (5-Methyl-6-methoxy-naphthyl-2) -ethyl) -pyrrolidyl-3) -methyl] -6,7-dimethyl-1-oxo-1,2, 3, A-Tetrahydro-isoquinoline hydrobromide

Prepared from 2- [N- (pyrrolidyl-3-methyl)] - 6,7-dimethyl-1 - · · · 42 94343 oxo-1,2,3,4-tetrahydro-isoquinoline and 2- (2-bromoethyl) - 5-methyl-6-methoxy-naphthalene according to Example 1.

Yield: 19 7. theor. .

Melting point: 23ϋ-232 ° Ό

Calc .: C 67.02 H 6.93 N 5.21 Br 14.86 Found: 67.10 7.12 5.33 15.01.

Example 18 2 - [(N- (2- (Naphthyl-2) -ethyl) -pyrrolidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline- hydrochloride

Prepared from 2- (pyrrolidyl-3-methyl) -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 2- (2-bromoethyl) -naphthalene according to Example 1.

Yield: 7.87. theor. ,

Melting point: 219-22 ° C

Lask. (x H 5 O): C 67.39 H 7.07 N 5.61 Cl 7.10 Found: 67.21 7.23 5.57 7.63.

Example 19 2 - [(N- (2- (6-Methoxy-naphthyl-2) -ethyl) -pyrrolidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4- tetrahydro-isoquinoline hydro chloride

Prepared from 2 - ((pyrrolidyl-3) -methyl) -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 2- (2-bromoethyl) -6-methoxy-naphthalene according to Example 1.

Yield: 39.2 Theoretical 7,

Melting point: 224-226eC

Lask. (X HssO): C 65.84 H 7.05 N 5.29 Cl 7.05 Found: 66.08 7.13 5.39 6.77.

2 - [(N- <3- (Naphthyl-2-propyl) -piperidyl-3) -methyl] -6,7-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline hydrochloride 43

Example 20 y η- o 4 3

Prepared from 6,7-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 3-chloromethyl-N- [3- (naphthyl-2) -propyl] -piperidine according to Example 2.

Yield: 40.4 7. theor. .

Melting point: 185-1Ö7 ° C

Calc .: C 75.52 H 7.82 N 5.87 Cl 7.43

Found: 75.39 7.85 5.82 7.52.

Example 21 2- [2- (N- (3- (Naphthyl-2-oxy) -propyl) -piperidyl-2) -ethyl] -7,6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro- isoquinoline hydrochloride

Prepared from 2 - ((piperidyl-2) -ethyl) -6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 2- (3-chloropropoxy) -naphthalene according to Example 1.

Yield: 21.2 7 ..

Melting point: 85-87 ° C

Lask. (X HzO): C 66.59 H 6.89 N 5.17 Cl 6.53

Found: 66.77 6.98 4.95 6.74.

Example 22 2 - [(N- (3- (Naphthyl-2-oxy) -propyl) -piperidyl-3) -methyl] -6,7-dimethyl-1,2,3,4-tetrahydro-isoquinoline dihydrochloride

Prepared from 2 - [(N- (3- (naphthyl-2-oxy) propyl) -piperidyl-3) -methyl] -6,7-dimethyl-1-oxo-1,2,3,4-tetrahydroisoquino and lithium aluminum hydride in tetrahydrofuran / ether according to Example 3.

Yield: 53% of theory.

Melting point: 133-135 ° 0. '

Lask. (x H = G): C t> 8.30 H 6.67 N 5.31 Cl 13.44

Found: 68.05 6.85 S, 23 13.03.

Example 23 2 - {(N- (3- (Naphthyl-2-oxy) -propyl) -piperidyl-3) -methyl] -6,7-methylenedioxy-1,2,3,4-tetrahydro-isoquinoline dihydrochloride

Prepared from 2 - [(N- (3- (naphthyl-2-oxy) propyl) -piperidyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydroisoquinoline and lithium aluminum hydride in tetrahydrofuran / ether according to Example 3.

Yield: 44.7% of theory,

Melting point: 130-132 ° C

Lask. (x HaO): C 63.62 H 6.62 N 5.11 Cl 12.95

Found: 63.49 6.86 4.97 12.64.

Example 24 2 - [(N - ((2-Methyl-naphthyl-1) -methyl) -piperidyl-3) -methyl] -6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline dihydrochloride

Prepared from 2- [tN - ((2-methyl-naphthyl-1) -methyl) -piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-iso- quinoline and lithium aluminum hydride in tetrahydrofuran / ether according to Example 3.

Yield: 80.5 S theor ..

Melting point: 210-212 ^ 0

Lask. (x HaO): C 65.05 H 7.53 N 5.23

Found: 65.23 7.78 5.03.

• 2- [2- {N- (2- (6-Methoxy-naphthyl-2) -ethyl) -piperidyl-2) -ethyl] -6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro -isoquinoline hydrochloride 45

Example 25 94543

Prepared from 2- [2- (piperidyl-2) -ethyl) -6,7-methylenedioxy-oxo-1,2,3,4-tetrahydro-isoquinoline and 2- (2-bromoethyl) -6-methoxy-naphthalene from Example 1 in accordance with.

Yield: 27.6% of theory.

Melting point: 112-117 ° C

Lask. (x 1/2 H 2 O): C 67.74 H 6.82 N 5.26 Cl 6.65

Found: 67.54 6.73 5.47 6.86.

Example 26 2 - [(N- (2- (Naphthyl-1) -ethyl) -piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline- hydrochloride

Prepared from 2 - [(piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and benzenesulfonic acid 2-ethyl- (naphthyl-1) -ester according to Example 1 in accordance with.

Yield: 26.9 7. theor. ,

Melting point: 220-225 ^ 0

Calc .: C 67.89 H 7.27 N 5.46 Cl 6.91

Found: 67.75 6.92 5.56 7.00.

Example 27 2 - [(N- (2- (Naphthyl-2) -ethyl) -piperidyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline- hydro-chloride

Prepared from 2 - [(piperidyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and benzenesulfonyl. ·

Γ \ f- ~ 7 Λ ~ 7 n - / 1 A

s ~ T <w> “τ O 46 from acid 2-ethyl- (naphthyl-2) -ester according to Example 1.

Yield: 27.9 7. theor. .

Melting point: 126-130 ° C

Lask. (x H = O): C 67.66 H 6.69 N 5.63 Cl 7.13

Received:. 67.64 6.70 5.76 7.35.

Example 28 2 - [(N- (2- (5-Methyl-6-methoxy-naphthyl-2) -ethyl) -piperidyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,2 3,4-tetrahydro-iso-quinoline hydrochloride

Prepared from 2 - [(piperidyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 2- (2-bromoethyl) -5-methyl-6-methoxy -naphthalene according to Example 1.

Yield: 51.2 V, theor.,

Melting point: 128-131 ° C

Calcd: C 68.88 H 6.74 N 5.34 Cl 6.77

Found: 68.90 6.61 5.30 7.05.

Example 29 2 - [(N - {(2-Methyl-naphthyl-1) -methyl) -piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro- isoquinoline hydro chloride

Prepared from 2 - [(piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 1-chloromethyl-2-methyl-naphthalene according to Example 1.

Yield: 57.9 7. theor. ,

Melting point: 212-214eC

Lask. (X 2 H = O): C 67.63 H 7.63 N 5.44 Cl 6.88 Found: 67.46 7.56 5.54 6.67.

II

Example 30

OH

2 - [(N- (N- (Naphthyl-2-oxy) -butyl) -piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline-hydro- chloride

Prepared from 2 - [(piperidyl-3) -methyl] -6,7-dimethoxy-i-oxo-1,2,3,4-tetrahydro-isoquinoline and 2- (4-bromo-butoxy) -naphthalene according to Example 1.

Yield: 46.3 7. theor. .

Melting point: 80-84 * »0

Lask. (X HaO): C 66.83 H 7.41 N 5.03 Cl 6.36 Found: 66.79 7.22 4.90 6.64.

Example 31 2 - [(N- (2- (6-Methoxy-naphthyl-2) -ethyl) -piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro- isoquinoline hydrochloride ψ *

Prepared from 2 - [(piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 2- (2-bromo-ethyl) -6-methoxy-naphthalene according to Example 1.

Yield: 22.8 7. theor. .

Melting point: 80-65eC

Calculation: (X HstO X HCl X CHaCOCHa): C 64.01 H 7.65 N 4.52 Cl 5.72 Found: 64.26 7.70 4.62 5.49

Example 32 2- [3- (N- (2- (6-Methoxy-naphthyl-2) -ethyl) -piperidyl-3) -propyl] -6,7-methylenedioxy-1-oxo-1,2, 3,4-tetrahydro-isoquino-aniline

Prepared from 2- [3- (piperidyl-3) -propyl) -6,7-methylene-dioxide · 48

g Λ 7/17 / 1 J J

si-1-oxo-1,2,3A-tetrahydro-isoquinoline and 2- (2-bromoethyl) -6-methoxy-naphthalene according to Example 1.

Yield: 36.8% of theory.

Melting point: 118-121 ° C

Calc .: C 74.37 H 7.25 N 5.60

Found: 74.60 7, A3 5.65.

Example 33 2- (3- (N- (2- (Naphthyl-1) -ethyl) -piperidyl-3) -propyl] -6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro- isoquinoline hydro chloride

Prepared from 2- [3- (piperidyl-3) -propyl] -6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and benzenesulfonic acid 2-ethyl- (naphthyl- 1) ester according to Example 1.

Yield: 20.8 V, theor. ,

Melting point: 195-197 ° C

task: C 71.07 H 6.95 N 5.53 Cl 6.99

Found: 71.30 6.95 5.65 6.80.

Example 34 2- [2- {N- (2- (5-Methyl-6-methoxy-naphthyl-2) -ethyl) -piperidyl-2) -ethyl] -6,7-dimethoxy-1-oxo- l, 2,3,4-tetrahydro-iso-quinoline hydrochloride

Prepared from 2- [2- (piperidyl-2) -ethyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 2- (2-bromo-ethyl) -5-methyl -6-methoxy-naphthalene according to Example 1.

Yield: 33.6% of theory,

Melting point: 95-100 ^ 0

Lask. (X 1/2 H 5 O): C 68.38 H 7.52 N 4.98 Cl 6.30

Found: 68.14 7.43 4.92 6.77.

•. ·

Example 35 49 'wj / i 4 A "7 y * τ o' t 0 2 - [(N- (3- (Naphthyl-2-oxy) -propyl) -piperidyl-3) -methyl] -6,7-methylenedioxy -i-oxo-l, 2,3,4-tetrahydro-isoquinoline hydrochloride

Prepared from 6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 3-chloromethyl-N- [3- (naphthyl-2-oxy} -propyl] -piperidine according to Example 2.

Yield: 27.3 7. theor. ,

Melting point: 104-106 ° C

Lask. (x HaO): C 66.09 H 6.69 N 5.31 Cl 6.72

Found: 66.19 6.34 5.24 7.22.

Example 36 2 - [(N- (3- (Naphthyl-2-oxy) -propyl) -piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline- hydro-chloride

Prepared from 6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 3-chloromethyl-N- [3- (naphthyl-2-oxy) -propyl] -piperidine according to Example 2.

Yield: 28.6 7, theor ..

Melting point: 191-193 ^ 0

Lask. (X HaO): C 66.34 H 7.23 N 5.15 Cl 6.53

Found: 66.59 7.19 5.03 6.6S.

Example 37 2 - [(N- (3- (Naphthyl-2-oxy) -propyl) -hexahydro-azepinyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4- tetrahydro-isoquinoline hydrochloride

Prepared from 2 - [(hexahydro-azepinyl-3) -methyl] -6,7-di-50

O A 7/17> ^ o 't J

methoxy-1-oxo-1,2,3,4-tetrahydroisoquinoline and 2- (3-chloropropoxy) naphthalene according to Example 1.

Yield: 16.1% of theory,

Melting point: 86-88 ° C

Lask. (X Η = ΰ) C 66.83 H 7.42 N S.03 Cl 6.36 Found: 66.90 7, AO S, 26 6.87.

Example 38 2 - [(N- (3- (Naphthyl-2-oxy) -propyl) -hexahydro-azepinyl-3) -methyl] -6,7-dimethyl-1-oxo-1,2,3,4- tetrahydro-isoquinoline hydrochloride

Prepared from 6,7-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 3-chloromethyl-N- [3- (naphthyl-2-oxy) -propyl] -hexahydro-azepine from Example 2 in accordance with.

Yield: 22.5 7. theor.,

Melting point: 19l-193eC

Calc .: C 73.42 H 7.75 N 5.52 Cl 6.99 Found: 73.37 7.67 5.52 7.12.

Example 39 2 - ((N- (2- (5-Methyl-6-methoxy-naphthyl-2) -ethyl) -hexahydro-azepinyl-3) -methyl] -6,7-dimethoxy-1,2,3, 4-tetrahydro-iso-quinoline dihydrochloride

Prepared from 2 - [(N- (2- (5-methyl-6-methoxy-naphthyl-2) -ethyl) -hexahydro-azepinyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2 , 3,4-tetrahydroisoquinoline and lithium aluminum hydride in tetrahydrofuran according to Example 3.

Yield: 77.6 7 · theor. ,

Melting point: 170-172 ° C

Lask. (X HzO): C 64.96 H 7.49 N 4.73 Cl 11.98 Found: 65.11 7.62 4.95 11.84.

•

Example 40 51

0/7/17 s * 7 O J

2 - [(N- (2- (5-Methyl-6-methoxy-2-naphthyl) ethyl) hexahydro-azepinyl-3) -methyl] -6.7-dimethoxy-l-oxo-l, 2,3.4- tetra-hydro-isoquinoline

Prepared from 2-1- (hexahydro-azepinyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 2- (2-bromoethyl) -5-methyl-6 -methoxy-naphthalene according to Example 1.

Yield: A3.5 7. theor. ,

Melting point: 125-1275¾

Calcd: C 74.39 H 7.80 N 5.42

Found: 74.31 7.82 5.35.

Example 41 2 - [(N- (2-Methyl-naphthyl-1) -methyl) -hexahydro-azepinyl-3 ·) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4- tetrahydro-isoquino-aniline hydrochloride

Prepared from 2 - [(hexahydro-azepinyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 1-chloro-1-methyl-2-methyl -naphthalene according to Example 1.

Yield: 67.5 7. theor. ,

Melting point: 128-130¾)

Lask. (X 2 HA): C 66.10 H 7.58 N 5.13 Cl 6.50 Found: 66.24 7.44 5.23 6.85.

Example 42 2 - (N- (4- (Naphthyl-2-oxy) -butyl) -hexahydro-azepinyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4- tetrahydroisoquinoline hydrochloride ·· 52

Q / 4/1 2 s * T o J

Prepared from 2 - [(hexahydro-azepinyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 2- (4-bromo-butyloxy) -naphthalene according to Example 1.

Yield: 26% of theory,

Melting point: 192-194 ^ 0

Calc .: C 69.22 H 7.80 N 5.04 Cl 6.38

Found: 70.01 7.70 5.15 6.48.

Example 43 2 - [(N- (2- (Naphthyl-1) -ethyl) -hexahydro-azepinyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro- isoquinoline hydrochloride

Prepared from 2 - [(hexahydro-azepinyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 2- (2-benzenesulfonyloxy-ethyl) -naphthalene according to Example 1.

Yield: 15.4 7, theor ..

Melting point: 236-238 ^

Lask. (x 1/2 HaO): C 69.40 H 6.82 N 5.58 Cl 7.06

Found: 69.07 6.74 6.13 7.29.

Example 44 2 - [(N- (2- (Naphthyl-2) -ethyl) -hexahydro-azepinyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro- isoquinoline-hydrobromide

Prepared from 2 - [(hexahydro-azepinyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 2- (2-bromo-ethyl] -naphthalene according to Example 1.

Melting point · 100-102 ^

Yield: 31.6% of theory, 53

0 A 7/12 J * t J

Calc .: C 64.80 H 6.18 N 5.21 Br 14.86

Found: 65, U2 6.07 5.39 14.78

Example 45 2 - [(N- (2- (6-Methoxy-naphthyl-2) -ethyl) -hexahydro-azepinyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3, 4-tetrahydro-isoquinoline hydrochloride

Prepared from 2 - [(hexahydro-azepinyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 2- (2-bromo-ethyl] -6-methoxy-naphthalene according to Example 1.

Yield: 34.1% of theory,

Melting point: 147-149 ° C

Lask. (x HssO): C 68.62 H 7.10 N S, 33 Cl 6.75 Found: 68.88 6.98 5.41 6.78.

Example 46 2 - [(N- (2- (5-Methyl-6-methoxy-naphthyl-2) -ethyl) -hexahydro-azepinyl-3) -methyl) -6,7-methylenedioxy-1-oxo-1, 2,3,4-tetrahydro-isoquinoline hydrochloride

Prepared from 2 - [(hexahydro-azepinyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 2- (2-bromo-ethyl] -5-methyl -6-methoxy-naphthalene according to Example "1.

Yield: 36.1 7. theor.,

Melting point: 112-114β0

Lask. (x H * 0): C 67.07 H 7.08 N 5.04 Cl 6.38 Found: 67.13 7.15 4.97 6.56.

*

Example 47 54 g /. 7 / (2 / t-ο 2 - [(N- (3- (4-Methoxy-phenoxy) -propyl) -piperidyl-3) -methyl] -6,7-dimethoxy-1,2,3,4-tetrahydro- isoquinoline dihydrochloride

Prepared from 2- [N- (3- (4-methoxy-phenoxy) -propyl) -piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-iso -quinoline and lithium aluminum hydride in tetrahydrofuran according to Example 3.

Yield: 88.5% of theory,

Melting point: 189-191 ^ 0

Calc .: C 59.44 H 7.76 N 5.13 Cl 12.99

Found: 59.55 7.99 5.12 12.61.

Example 48 2 - [(N- (2- (3,4-Dimethoxy-phenyl) -ethyl) -piperidyl-3) -methyl] -6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline- dihydro-chloride

Prepared from 2 - [(N- (2- (3,4-dimethoxy-phenyl) -ethyl) -piperidyl-3) -methyl) -6,7-dimethoxy-1-oxo-1,2,3,4 -tetrahydro-isoquinoline and lithium aluminum hydride in tetrahydrofuran according to Example 3.

Yield: 92.8% of theory,

Melting point: 175-176 ^

Calc .: C 60.66 H 7.35 N 5.33 Cl 13.49

Found: 60.58 7.56 5.32 13.22

Example 49 2 - [(N- (3- (3-Methoxy-phenoxy) -propyl) -piperidyl-3) -methyl] -6,7-methylenedioxy-1,2,3,4-tetrahydro-isoquinoline dihydrochloride 55,934343

Prepared from 2 - [(N- (3- (3-methoxy-phenoxy) -propyl) -piperidyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4-tetra -hydroisoquinoline and lithium aluminum hydride in tetrahydrofuran according to Example 3.

Yield ': 96.6 7. theor. ,

Melting point: 178-181 ° C

Calc .: C 59.08 H 7.62 N 5.30 Cl 14.31

Found: 58.90 7.50 5.40 14.15.

Example 50 2 - [(N- (3- (3-Methoxy-phenoxy) -propyl) -piperidyl-3) -methyl] -6,7-methylenedioxy-1,2,3,4-tetrahydro-isoquinoline-dihydro- chloride

Prepared from 2 - [(N- (3- (3-methoxy-phenoxy) -propyl) -piperidyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4-tetra -hydroisoquinoline and lithium aluminum hydride in tetrahydrofuran according to Example 3.

Yield: 94.5 7, theor. ,

Melting point: 169-1711Ό

Calc .: 0 57.03 H 7.36 N 5.11 Cl 13.86

Found: 56.91 7.26 5.15 13.68.

• ·

Example 51 2 - [(N- (2- (3,4-Dimethoxy-phenyl) -ethyl) -piperidyl-3) -methyl] -6,7-dimethyl-1,2,3,4-tetrahydro-isoquinoline-dihydro- chloride

Prepared from 2 - [(N- {2- (3,4-dimethoxy-phenyl) -ethyl) -piperidyl-3) -methyl] -6,7-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline and lithium aluminum hydride in tetrahydrofuran according to Example 3.

Yield: 91.3 7, theoretical,> 4 · «56

0 / .7 / 12 7 -t -J't J

Melting point: 140-142 * 0

Calc .: C 62.00 H 8.34 N 5.27 Cl 13.44

Found: 61.85 8.27 5.31 13.33.

Example 52 2 - [(N- (3- (4-Methoxy-phenoxy) -propyl) -piperidyl-3) -methyl] -6,7-dimethyl-1,2,3,4-tetrahydro-isoquinoline dihydrochloride

Prepared from 2 - [(N- (3- (4-Methoxy-phenoxy) -propyl) -piperidyl-3) -methyl] -6,7-dimethyl-1-oxo-1,2,3,4-tetrahydro- -isoquinoline and lithium aluminum hydride in tetrahydrofuran according to Example 3.

Yield: 88.3 7, theor. ,

Melting point: 170-172 * 0

Calc .: C 63.14 H 8.24 N 5.65 Cl 14.31

Found: 63.09 8.33 5.82 14.02.

Example 53 2 - [(N- (2- (3,4-Dimethoxy-phenyl) -ethyl) -piperidyl-3) -methyl] -6,7-methylenedioxy-1,2,3,4-tetrahydro-isoquinoline- di-hydrochloride

Prepared from 2 - [(N- (3- (3,4-Diraethoxy-phenyl) -ethyl) -piperidyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4-tetra -hydroisoquinoline and lithium aluminum hydride in tetrahydrofuran according to Example 3.

Yield: 93.3 7, theor.,

Melting point: 150-154 * 0

Calc .: C 60.01 H 7.34 N 5.39 Cl 13.64 Found: 59.96 7.41 5.25 13.43.

2 - [(N- (3- (4-Methoxy-phenoxy) -propyl) -piperidyl-3) -methyl] -6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline dihydrochloride

Example 54 57 Q /. Λ τ

'“Ί> J n O

Prepared from 2 - [(N- (3- (4-Methoxy-phenoxy) -propyl) -piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-iso -quinoline and lithium aluminum hydride in tetrahydrofuran according to Example 3.

Yield: 95.3 7 »theor. ,

Melting point: 182-185 ° C

Calc .: C 61.05 H 7.09 N 5.48 Cl 13.86 Found: 61.10 6.95 5.68 13.55.

Example 55 2- [2- (N- (3- (3,4-Methylenedioxy-phenoxy) -propyl) -piperidyl-3) -ethyl] -6,7-dimethoxy-1-oxo-1,2,3, 4-tetrahydro-isoquino-aniline hydrochloride

Prepared from 2 - [(piperidyl-3) -ethyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 1-chloro-3- (3,4-methylenedioxy- phenoxy) propane according to Example 1.

Yield: 35.5 7, theor.,

Melting point: 97-100eC

Calc .: C 59.09 H 7.28 N 4.62 Cl 6.65

Found: 58.97 7.36 4.66 6.52.

Example 56 2- [2- (N- (2- (3,4-Diraethoxy-phenyl) -ethyl) -piperidyl-3) -ethyl] -6,7-dimethoxy-1-oxo-1,2,3, 4-tetrahydro-isoquinoline hydro chloride

Prepared from 2 - [(piperidyl-3) -ethyl] -6,7-dimethoxy-1-oxo-58,914,314,2,3,4-tetrahydro-isoquinoline and 1-bromo-2- (3, From 4-dimethoxy-phenyl) -ethane according to Example 1.

Yield: 3S, 9 7 »theor. ,

Melting point: 103-105 * ^

Calc .: C 62.60 H 7.79 N 5.21 Cl 6.83

Found; 62.41 7.82 5.09 7.19.

Example 57 2- [3- (N- (2- (3,4-Dimethoxy-phenyl) -ethyl) -piperidyl-3) -propyl] -6,7-dimethoxy-1-oxo-1,2 , 3,4-tetrahydro-isoquinoline hydrochloride

Prepared from 2- [3- (piperidyl-3) -propyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 1-bromo-2- (3,4-di- methoxyphenyl) ethane according to Example 1.

Yield: 32.6 Theoretical 7,

Melting point: 102-106 ° C

Calculated: C 63.20 H 7.86 N 5.08 Cl 6.43 Found: 63.39 7.90 4.86 6.13.

Example 58 2- [3- (N- (3- (3,4-Methylenedioxy-phenoxy) -propyl) -piperidyl-3) -propyl] -6,7-dimethoxy-1-oxo-1,2,3, 4-tetrahydro-isoquino-aniline hydrochloride

Prepared from 2- [3- (piperidyl-3) -propyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 1-chloro-3- <3,4-methylene- dioxo-phenoxy) -propane according to Example 1. Yield: 29.7 7. theor. ,

Melting point: 97-100eC

Calc .: C 61.63 H 7.31 N 4.96 Cl 6.47

Found: 61.94 7.46 5.16 6.48.

li

Example 59 2 - [(N- (3, A-Dimethoxy-benzyl) -piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,5-tetrahydro-isoquinoline hydrochloride g A 7/7 59

Prepared from 2- (piperidyl-3-methyl) -6,7-dimethoxy-1-oxo-1.2.3, A-tetrahydro-isoquinoline and 3, A-dimethoxy-benzyl bromide according to Example 1.

Yield: 53.3 7 »theor. ,

Melting point: 127-132eC

Calc .: C 63.58 H 7.18 N 5.70 Cl 7.22

Found: 63.30 7.22 5.52 7, IA.

Example 60 2 - [(N- (3- (N-Methoxy-phenyl) -propyl) -piperidyl-3) -methyl 3-6,7-dimethoxy-1-oxo-1,2,3,5-tetrahydro- isoquinoline hydro chloride

Prepared from 2- (piperidyl-3-methyl) -6,7-dimethoxy-1-oxo-1,2,3,A-tetrahydro-isoquinoline and 1-bromo-3- (N-methoxy-phenyl) -propane according to Example 1.

Yield: A2 7, theor. ,

Melting point: 229-231eC

Calc .: C 66.31 H 7.63 N 5.73 Cl 7.25

Found: 66.27 7.6A 5.65 7.33.

Example 61 2- [2- (N- (3- (3-Methyl-phenoxy) -propyl) -piperidyl-2) -ethyl] -6,7-dimethoxy-1-oxo-1,2,3, A- tetrahydro-isoquinoline hydro chloride

Prepared from 2- [2- (piperidyl-2) -ethyl] -6,7-dimethoxy-1-oxo-1,2,3,A-tetrahydro-isoquinoline and 1-chloro-3- (3-methyl- 60 94343 phenoxy) propane according to Example 1.

Yield: 52.4% of theory,

Melting point: 142-144C

Calc .: C 66.85 H 7.81 N 5.57 ci 7.05

Found: 66.73 7.68 5.53 6.94.

Example 62 2- [2- (N- {2- (3,4-Dimethoxy-phenyl) -ethyl) -piperidyl-2) -ethyl] -6,7-dimethoxy-1-oxo-1,2,3, 4-tetrahydro-isoquinoline hydro chloride

Prepared from 2- [2- (piperidyl-2) -ethyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 1-bromo-2- (3,4-dimethoxy-phenyl) -ethane according to Example 1.

Yield: 47.3% of theory,

Melting point: 150-155 ° C

Calc .: C 64.72 H 7.68 N 5.39 Cl 6.82 Found: 64.40 7.83 5.27 6.90.

Example 63 2- [2- (N- (3-Benzyloxy-propyl) -piperidyl-2) -ethyl 3-6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline hydrochloride

Prepared from 2- [2- (piperidyl-2) -ethyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 1-chloro-3-benzyloxy-propane according to Example 1.

Yield: 56.3% of theory,

Melting point: 116-120 ° C

Calc .: C 66.85 H 7.81 N 5.57 Cl 7.05

Found: 66.60 7.75 5.25 7.25.

II

«2- [2- (N- (4- (4-Methoxy-phenyl) -butyl) -piperidyl-2) -ethyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro- -isoquinoline hydrochloride

Example 64 61 Ο A ~ Z A 7. y * i 'o -t sj

Prepared from 2- [2- (piperidyl-2) -ethyl] -6,7-diroethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 1-bromo-4- (4-methoxy-phenyl) -butane according to Example 1.

Yield: 42.8% of theory,

Melting point: 107-112eC

Calculated: C 67.36 H 7.99 N 5.42 Cl 6.86 Found: 67.16 8.05 5.35 7.34.

Example 65 2- [2- (N- (3- (3,5-Dimethoxy-phenoxy) -propyl) -piperidyl-2) -ethyl] -6,7-dimethoxy-1-oxo-1,2,3, 4-tetrahydro-isoquinoline hydrochloride

Prepared from 2- [2- (piperidyl-2) -ethyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 1-chloro-3- {3,5-di- methoxy-phenoxy) -propane according to Example 1.

Yield: 56.3% of theory,

Melting point: 127-132.C

Calc .: C 61.41 H 7.64 N 5.10 Cl 6.46

Found: 61.56 7.65 5.28 6.89.

Example 66 2- [2- (N- (3- (3,4-Methylenedioxy-phenoxy) -propyl) -piperidyl-2) -ethyl] -6,7-dimethoxy-1-oxo-1,2,3, 4-tetrahydro-isoquino-aniline hydrochloride

Prepared from 2- [2- (piperidyl-2) -ethyl] -6,7-dimethoxy-1 - (62 ° C) -N-oxo-1,2,3,4-tetrahydro-isoquinoline and 1 -chloro-3- (3,4-methylenedioxy-phenoxy) -propane according to Example 1.

Yield: 49 7. theor.,

Melting point: 118-120 ^ 0

Calc .: C 63.09 H 7.00 N 5.26 Cl 6.65

Found: 62.90 7.04 5.46 6.79.

Example 67 2 - [(N- (3- (3,5-Dimethoxy-phenoxy) -propyl) -piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4- tetrahydro-isoquinoline hydrochloride

Prepared from 2 - [(piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 1-chloro-3- (3,5-dimethoxy-phenoxy) -propane according to Example 1.

Yield: 37.5 Theoretical 7,

Melting point: 98-102 ^ 0

Calc .: C 62.85 H 7.35 N 5.24 Cl 6.63

Found: 62.81 7.41 5.10 6.75.

Example 68 • 2 - [(N- (3- (3,4-Methylenedioxy-phenoxy) -propyl) -piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4 tetrahydro-isoquino-aniline hydrochloride

Prepared from 2 - [(piperidyl-2) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 1-chloro-3- (3,4-methylene-hydroxyphenyl) -propane according to Example 1.

Yield: 50 7 »theor. ,

Melting point: 236-238 ° C

Calc .: C 64.46 H 7.01 N 5.57 Cl 7.04

Found: 64.30 6.97 5.59 7.08.

«2 - [(N- (3- (3,4-Methylenedioxy-phenoxy) -propyl) -piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro- -isoquinoline hydrochloride

Example 69 63 94343

Prepared from 2 - [(piperidyl-2) -methyl] -6,7-diraethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 1-chloro-3- (3,4-methylenedioxy-phenoxy) -propane according to Example 1. Yield: 46.2 7, theor. ,

Melting point: 149-1SeC

Lask. C 60.38 H 6.94 N 5.21 Cl 6.60 Found: 60.30 6.93 5.29 6.37.

Example 70 2 - [(N- (3- (2,6-Dimethyl-phenoxy) -propyl) -piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4- tetrahydro-isoquinoline-Jiydrokloridi

Prepared from 2-t (piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 1-chloro-3- (2,6-dimethyl-phenoxy) -propane according to Example 1.

Yield: 53.3 7 »theor.,

Melting point: 131-135 ^ 0

Calc .: C 66.85 H 7.81 N 5.57 Cl 7.05 Found: 66.88 7.95 5.59 6.85.

Example 71 2 - [(N- (4- (2,4-Dichloro-phenoxy) -butyl) -piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4- tetrahydro-isoquinoline hydrochloride

Prepared from 2 - [(piperidyl-3) -methyl] -6,7-diraethoxy-1-oxo-♦ 64 9 £ · 7> 4λ ^ · v-iw 1.2.3.4-tetrahydro-isoquinoline and 1-chloro-4 - (2,4-dichloro-phenoxy) -butane according to Example 1.

Yield: 54.1 7, theor. ,

Melting point: 125-128 ^

Calc .: C 58.12 H 6.32 N 5.02 Cl 19.06

Found: 58.21 6.38 5.08 18.85.

Example 72 2 - [(N- (2- (3,4-Dimethoxy-phenyl) -ethyl) -piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4- tetrahydro-isoquinoline hydro chloride

Prepared from 2 - [(piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 1-bromo-2- (3,4-dimethoxy-phenyl) -ethane from Example 1 in accordance with.

Yield: 57.5 7 »theor ..

Melting point: 118-121 ° C

Basque: C 64.21 H 7.38 N 5.55

Found: 64.18 7.36 5.19.

Example 73 • 2 - [(N- (3- (3,4-Dimethoxy-phenoxy) -propyl) -piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4 tetrahydro-isoquinoline hydrochloride

Prepared from 2 - [(piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 1-chloro-3- (3,4-dimethoxy-phenoxy) -propane according to Example 1.

Yield: 62.5% of theory,

Melting point: 112-115eC

Calc .: C 60.80 H 7.47 N 5.24

Found: 60.65 7.69 5.27.

• · 2 - [(N- (3- (3,4-Dimethoxy-phenoxy) -propyl) -piperidyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4- tetrahydroisoquinoline hydrochloride

Example 74 65 94343

Prepared from 2 - [(piperidyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 1-chloro-3- (3,4-dimethoxy- phenoxy) propane according to Example 1.

Yield: 60% of theory,

Melting point: 97-100eC

Calc .: C 60.38 H 6.94 N 5.40 Cl 6.60 Found: 60.20 6.97 5.21 6.83.

Example 75 2 - [(N- (2- (4-Methoxy-phenyl) -ethyl) -piperidyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro- isoquinoline hydrochloride

Prepared from 2 - [(piperidyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydroisoquinoline and 1-chloro-2- (4-methoxyphenyl) -ethane according to Example 1.

Yield: 71.4% of theory.

Melting point: 195-197 ° C

Calc .: C 62.94 H 6.97 N 5.87 Cl 7.73

Found: 62.90 6.98 5.68 8.04.

Example 76 2 - [(N- (2- (3,4-Dimethoxy-phenyl) -ethyl) -piperidyl-3) -methyl] -6,7-dimethyl-1-oxo-1,2,3,4- tetrahydro-isoquinoline hydrochloride. Prepared from 2 - [(piperidyl-3) -methyl] -6,7-dimethyl-1-oxo-· · 66

Q A - A 2 -r. · '' 1 · J

1.2.3.4-tetrahydro-isoquinoline and 1-bromo-2- (3,4-dimethoxy-phenyl) -ethane according to Example 1.

Yield: 41.9 7. theor. ,

Melting point: 132-134 ° C

Calculated: C 63.57 H 8.10 N 5.49 Cl 6.95 Found: 63.70 8.26 5.45 7.13.

Example 77 2 - [(N- (3- (4-Methoxy-phenoxy) -propyl) -piperidyl-3) -methyl] -6,7-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline- hydro-chloride

Prepared from 2 - [(piperidyl-3) -methyl] -6,7-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 1-chloro-3- (4-methoxy-phenoxy) -propane according to Example 1.

Yield: 57.8 Theoretical 7,

Melting point: 144-146 ° C

Calc .: C 68.55 H 7.88 N 5.92 Cl 7.49

Found: 68.45 7.80 6.11 7.33.

Example 78 2 - [(N- (3- (3-Methoxy-phenoxy) -propyl) -piperidyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline- hydrochloride

Prepared from 2 - [(piperidyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 1-chloro-3- (3-methoxy-phenoxy) -propane according to Example 1.

Yield: 32.5 7. theor. ,

Melting point: 142-145 ° C

Calc .: C 60.58 H 6.95 N 5.52 Cl 6.99

Found: 60.42 6.92 5.50 7.18.

«« 2 - [(N- (3- (3-Methyl-phenoxy) -propyl) -piperidyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,5-tetrahydro- isoquinoline hydrochloride

Example 79 67

O · 'T A 7 s Ύ Jt J

Prepared from 2 - [(piperidyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,5-tetrahydro-isoquinoline and 3- (3-methyl-phenoxy) -1-chloro -propane according to Example 1.

Yield: 31.6 7 »theor. ,

Melting point: 178-180 ° C

Calculated: C 63.59 H 6.97 N 5.70 Cl 7.22 Found: 63.59 6.92 5.86 7.50.

Example 80 2 - [(N- (3- (N-Methoxy-N-methyl-phenylamino) -propyl) -piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3, A-tetrahydro-iso- ψ · quinoline dihydrochloride

Prepared from 2 - [(piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,A-tetrahydro-isoquinoline and 1-chloro-3- (A-methoxy-N-methyl- phenylamino) -propane according to Example 1. Yield: 52.5 7, theor.,

Melting point: 180-183 ° C

Calc .: C 60.6A H 7, A 5 N 7.58 Cl 12.79 Found: 60.50 7.35 7.56 12.87.

Example 81 2 - [(N- (3- (N-Methoxy-phenoxy) -propyl) -pyrrolidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,A-tetrahydro- isoquinoline hydrochloride Prepared in 6,7-dimethoxy-1-oxo-1,2,3,5-tetrahydro-isoquino-68 g / 7 / τ

J o *? O

and N- (3- (4-methoxy-phenoxy) -propyl) -3-benzenesulfonyloxymethyl-pyrrolidine according to Example 2. Yield: 84, 47, theor. ,

Melting point: 142-144 ^ 0

Lask. : C 63.60 H 7.18 N 5.71 Cl 7.22 Found: 63.75 7.12 5.64 7.32.

Example 82 2 - [(N- (3- (6-Methoxy-naphthyl-2-oxy) -propyl) -pyrrolidyl-3) -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro- -isoquinoline

Prepared from 6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 3- (p-toluenesulfonyloxymethyl) -N- (6-methoxy-naphthyl-2-oxy) -pyrrolidine from Example 2 in accordance with.

Yield: 47 7, theor.,

Melting point: 142-144 ° C

Calc .: C 71.41 H 7.19 N 5.55

Found: 71.14 7.16 5.53.

Example 83. 2 - [(N- (3- (4-Methoxy-phenoxy) -propyl) -pyrrolidyl-3) -methyl] -6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline dihydrochloride

Prepared from 2 - [(N- (3- (4-Methoxy-phenoxy) -propyl) -pyrrolidin-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro- -isoquinoline and lithium aluminum hydride in tetrahydrofuran according to Example 3.

Yield: 90.9% of theory,

Melting point; 248-250 ° C

Calc .: C 60.81 H 7.46 N 5.46 Cl 13.81

Found: 60.79 7.61 5.48 13.84.

2 - [(N- (3- (4-Methoxy-phenoxy) -propyl) -pyrrolidyl-3) -methyl] -6,7-dimethyl-1-oxo-1,2, 3,4-tetrahydro-isoquinoline hydrochloride

Example 84 69 c: a 7 wi -f u

Prepared from 6,7-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline and N- [3- (4-methoxy-phenoxy) -propyl] -3-benzenesulfonyloxymethyl-pyrrolidine from Example 2 in accordance with. Yield: 60.6 7. theor. ,

Melting point: 118-121 ° C

Calc .: C 68.03 H 7.69 N 6.10 Cl 7.72

Found: 67.90 7.71 6.04 7.90.

Example 85 2 - [(N- (2- (3,4-Dimethoxy-phenyl) -ethyl) -pyrrolidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4- tetrahydro-isoquinoline-tetrahydro-kfloridi

Prepared from 6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and N- [2- (3,4-dimethoxy-phenoxy) -ethyl] -3-benzenesulfonyloxymethyl-pyrrolidine according to Example 2.

Yield: 56.7 7, theor. ,

Melting point: 116-118 ^ 0

Calc .: C 63.60 H 7.19 N 5.71 Cl 7.22

Found: 63.82 7.32 5.60 7.66.

Example 86 2 - [(N- (3- (4-Methoxy-phenoxy) -propyl) -pyrrolidyl-3) -methyl] -6,7-dimethyl-1,2,3,4-tetrahydro-isoquinoline-dihydro- chlorides 70 α /; h / 1 7 y ^ O ‘T o

Prepared from 2- [N- (3- (4-methoxy-phenoxy) -propyl) -pyrrolidin-3) -methyl] -6,7-dimethyl-1-oxo-1,2,3,4-tetrahydro- isoquinoline and lithium aluminum hydride in tetrahydrofuran according to Example 3.

Yield: 90.9 Theoretical 7,

Melting point: 243-246 ° C

Calc .: C 64.85 H 7.95 N 5.82 Cl 14.73

Found: 64.88 7.92 5.63 14.80.

Example 87 2 - [(N- (2- (3,4-Dimethoxy-phenyl) -ethyl) -pyrrolidyl-3) -methyl] -6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline- dihydro-chloride

Prepared from 2 - [(N- (2- (3,4-dimethoxy-phenyl) -ethyl) -pyrro-1-yl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4 -tetrahydroisoquinoline and lithium aluminum hydride in tetrahydrofuran according to Example 3.

Yield: 92.9 Theoretical 7,

Melting point: 240-242 ° C

Calc .: C 60.81 H 7.46 N 5.46 Cl 13.81

Found: 60.64 7.61 5.31 13.50.

* ·

Example 88 2 - [(N- (3-Pyridyl-4) -propyl) -pyrrolidyl-3) -methyl] -5,6-dimethyl-1-oxo-1,3-dihydro-isoindole dihydrochloride semi-hydrate

Prepared from 2-1 (N- (3-Pyridyl-4) -propyl) -pyrrolidyl-3) -methyl] -5,6-dimethyl-phthalimide and zinc / glacial acetic acid according to Example 4.

Yield: 6S 7 »theor. ,

Melting point: 119-122 ° C

• i 71 ^ ^ o 4 3

Calc .: C 62.02 H 7.24 N 9.43 Cl 15.92

Found: 62.25 7.47 9.39 15.90.

Example 89 2- [3- (N- (3- (Pyridyl-3) -propyl) -piperidyl-3) -propyl] -5,6-dimethoxy-1-oxo-1,3-dihydro-isoindole-dihydrochloride- a mono-hydrate

Prepared from 2- [3- (N- (3-pyridyl-3) -propyl) -piperidyl-3) -propyl] -5,6-dimethoxy-phthalimide and zinc / glacial acetic acid according to Example 4.

Yield: 72% of theory,

Melting point: 118-121

Calc .: C 59.08 H 7.43 N 7.95 Cl 13.41

Found: 59.02 7.23 7.12 13.27.

Example 90 ♦ · 2 - [(N- (3- (Pyridyl-3) -propyl) -piperidyl-3) -methyl] -5,6-dimethoxy-1-oxo-1,3-dihydro-isoindole-dihydrochloride- monohydrate * · Prepared from 2 - [(N- (3-pyridyl-3) -propyl) -piperidyl-3) -methyl] -5,6-dimethoxy-phthalimide and zinc / glacial acetic acid according to Example 4.

Yield: 42 7, theor.,

Melting point: 91-96 ^ 0

Calc .: C 59.08 H 7.43 N 7.95 Cl 13.41

Found: 59.02 7.23 7.12 13.27.

Example 91 2 - [(N- (2- {6,7-Diraethoxy-isoquinolyl-4) -ethyl) -piperidyl-3) -. methyl] -5,6-dimethoxy-1-oxo-1,3-dihydro-isoindole 12 ο: ·. Ί Λ 1 -r o ~ t ο

Prepared from 2 - [(Ν- (2- (6,7-dimethoxy-isoquinolyl-4) -ethyl) -piperidyl-3) -methyl] -5,6-dimethoxy-phthalimide and zinc / glacial acetic acid according to Example 4.

Yield: 64 7, theor. ,

Melting point: 85-880C

Calc .: C 65.39 H 7.19 N 7.88

Found: 65.16 7.27 7.53.

Example 92 2- [2- (N- {3- (Pyridyl-4) -propyl) -piperidyl-2) -ethyl] -5,6-dimethyl-1-oxo-1,3-dihydro-isoindole

Prepared from 2- [2- (N- (3- (pyridyl-4) -propyl) -piperidyl-2) -ethyl] -5,6-dimethylphthalimide and zinc / glacial acetic acid according to Example 4.

Yield: 73 7, theor.,

Melting point: 103-104 ° C

Calc .: C 76.68 H 8.49 N 10.73

Found: 76.57 8.54 10.60.

Example 93 • ·. 2 - [(N- (3- (Pyridyl-4) -propyl) -pyrrolidyl-3) -methyl] -5,6-dimethyl-1,3-dihydro-isoindole trihydrochloride semihydrate

Prepared from 2 - [(N- (3- (pyridyl-4) -propyl) -pyrrolidyl-3) -methyl) -5,6-dimethyl-1-oxo-1,3-dihydro-isoindole and lithium aluminum hydride from tetrahydrofuran / in ether according to Example 3.

Yield: 68 7, theor.,

Melting range: 118-127 ° C (amorphous)

Calcd. · C 59.03 H 7.54 N 8.98 Cl 22.73 Found: 58.93 7.48 8.84 22.92.

II

Example 94 73

Q f- ~ T / 7 / “Ty't J

2- [2- (N- (3- (4-Pyridyl) propyl) 2-piperidyl) ethyl] -5,6-dimethyl-l, 3-dihydro-isoindole

Prepared from 2- [2- (N- (3- (pyridyl-4) -propyl) -piperidyl-2) -ethyl] -5,6-dimethyl-1-oxo-1,3-dihydro-isoindole and lithium aluminum hydride in tetrahydrofuran / ether according to Example 3.

Yield: 70 7. theor. ,

Melting range: 135-148 ° C (amorphous)

Calc .: C 54.59 H 8.24 N 7.63 Cl 19.33

Found: 54.48 8.26 7.51 19.60.

Example 95 2-1 (N- (1- (Pyridyl-4) -methyl) -piperidyl-3) -methyl] -5,6-dimethoxy-1,3-dihydro-isoindole trihydrochloride trihydrate

Prepared from 2 - [(N- (1- (pyridyl-4) -methyl) -piperidyl-3) -methyl] -5S, 6-dimethoxy-phthalimide and lithium aluminum hydride in ether according to Example 3.

Yield: 68 7. theor. ,

Melting range: 176-189 ° C (amorphous)

Calc .: C 49.76 H 7.21 N 7.91 Cl 20.03

Found: 49.93 7.12 8.00 20.44.

Example 96 2 - [(N- (2- (6,7-Dimethoxy-isoquinolyl-4) -ethyl) -piperidyl-3) -methyl] -5,6-dimethyl-1,3-dihydro-isoindole-dihydrochloride- semihydraatti

Prepared from 2 - [(N- (2- (6,7-dimethoxy-isoquinolyl-4) -ethyl) -piperidyl-3) -methyl] -5,6-dimethyl-1-oxo-1,3-dihydro-74 94543 from isoindole and lithium aluminum hydride in tetrahydrofuran / ether according to Example 3.

Yield · 22.7 7. theor. ,

Melting range: 222-236 ° C (amorphous)

Calc .: C 62.22 H 7.20 N 7.50 Cl 15.83

Found: 62.01 7.64 7.08 15.79.

Example 97 2 - [(N- {1- (Pyridyl-4) -methyl) -piperidyl-3) -methyl] -5,6-methylenedioxy-1,3-dihydro-isoindole trihydrochloride semi-hydrate

Prepared from 2 - [(N- (1- (pyridyl-4) -methyl) -piperidyl-3) -methyl] -5,6-methylenedioxy-phthalimide and lithium aluminum hydride in tetrahydrofuran / ether according to Example 3. Yield · 55% of theory. ,

Melting range: 215-225eC (amorphous)

Calc .: C 53.68 H 6.22 N 8.94 Cl 22.63

Found: 53.60 6.45 8.65 22.28.

Example 98 1. 2 - [(N- (3- (Pyridyl-4) -propyl) -pyrrolidyl-3) -methyl] -6,7-dimethyl-1,2,3,4-tetrahydro-isoquinoline trihydrochloride- a mono-hydrate

Prepared from 2 - [(N- (3- (pyridyl-4) -propyl) -pyrrolidyl-3) -methyl] -6,7-dimethyl-1-oxo-1,2,3-4-tetrahydro-isoquinoline and lithium aluminum hydride in tetrahydrofuran / ether according to Example 3.

Yield: 63 7. theor.,

Melting point: 254-256 ° C

Calc .: C 58.71 H 7.80 N 8.56 Cl 21.66

Found: 58.53 7.72 8.25 21.53.

i

Example 99 75

2 AT AT y τ o ‘t <J

2 - [(N- (1- (Pyridyl-A) -methyl) -piperidyl-3) -methyl] -6,7-dimethoxy-1,2,3, A-tetrahydro-isoquinoline - trihydrochloride -raatti

Prepared from 2 - [(N- (1- (pyridyl-A) -methyl) -piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3-A-tetrahydro-isoquinoline and lithium aluminum hydride in tetrahydrofuran / ether according to Example 3.

Yield: 63% of theory,

Melting range: 158-169eC (amorphous)

Calc .: C 52, A2 H 7.27 N 7.97 Cl 20.18

Found: 52.55 7.A9 7.57 20.25.

Example 100 2- [2- (N- (3- (Pyridyl-A) -propyl) -piperidyl-2) -ethyl] -6,7-methylenedioxy-1,2,3,5-tetrahydro-isoquinoline-trihydro- kloriditrihydraatti

Prepared from 2- [2- (N- (3- (pyridyl-A) -propyl) -piperidyl-2) -ethyl] -6,7-methylenedioxy-1-oxo-1,2,3-A-tetrahydroisoquino - * * · line and lithium aluminum hydride in tetrahydrofuran / ether according to Example 3.

Yield: 90 7. theor. ,

Melting; 108-119 ° C (amorphous)

Calc .: C 52.58 H 7, Al N 7.36 Cl 18.62

Found: 52.56 7.25 7.38 19, A9.

Example 101 2 - [(N- (3- (Pyridyl-3) -propyl) -piperidyl-3) -methyl] -6,7-methylenedioxy-1,2,3,5-tetrahydro-isoquinoline-dihydro-. chloride monohydrate m 76 94343

Prepared from 2 - [{N- (3- (pyridyl-3) -propyl) -piperidyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3-4-tetrahydro-isoquinoline and lithium aluminum hydride in tetrahydrofuran / ether according to Example 3.

Yield: 72 7. theor. ,

Melting range: 126-138 ° C (amorphous)

Calc .: C 59.50 H 7.28 N 8.67 Cl 14.64

Found: 59.57 7.29 8.49 14.51.

Example 102 2 - [(N- (3- (Pyridyl-3) -propyl) -piperidyl-3) -methyl] -6,7-dimethyl-1,2,3,4-tetrahydro-isoquinoline trihydrochloride

Prepared from 2 - [(N- (3- (pyridyl-3) -propyl) -piperidyl-3) -methyl] -6,7-dimethyl-1-oxo-1,2,3-4-tetrahydro-isoquinoline and lithium aluminum hydride in tetrahydrofuran / ether according to Example 3.

Yield: 59 7 »theor.,

Melting range: 138-154eC (amorphous)

Calc .: C 61.66 H 7.86 N 8.62 Cl 21.84

Found: 61.53 8.00 8.64 21.35.

Example 103 2 - [(N- (3- (Pyridyl-4) -propyl) -pyrrolidyl-3) -methyl] -6,7-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline- dihydroklo-hydrochloride monohydrate

Prepared from 6,7-dimethyl-1-oxo-1,2,3-4-tetrahydro-isoquinoline and 3-chloromethyl-N- [3- (pyridyl-4) -propyl] -pyrrolidine according to Example 2.

Yield: 39% of theory,

Melting range: 74-86eC (amorphous) Ο Λ 7 A 7 y '-i'y.J' T J 77

Calc .: C 61.53 H 7.53 N 8.97 Cl 15.13

Found: 61.42 7.62 8.83 15.05.

Example 104 2 - [(N- (3- (Pyridyl-3) -propyl) -piperidyl-3) 'methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline- dihydrochloride monohydrate

Prepared from dimethylsulfoxy-6,7-dimethoxy-1-oxo-1,2,3-4-tetrahydro-isoquinoline and 3-benzenesulfonic acid N- [3- (pyridyl-3) -propyl) -piperidyl-3] -methyl ester using potassium tert-butylate according to Example 2.

Yield: 45 7. theor. ,

Melting range: 140-148 ° C (amorphous)

Lask. (x 2 HCl x HaO): C 58.36 H 7.25 N 8.16 Cl 13.78 Found: 58.35 7.32 8.04 13.65.

Example 105 2- [3- (N- (3- (Pyridyl-4) -propyl) -piperidyl-3) -propyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro- isoquinoline dihydrochloride dihydrate

Prepared from 2- [3- (piperidyl-3) -propyl] -6,7-dimethoxy-1-oxo-1,2,3-4-tetrahydro-isoquinoline and 4- (3-chloro-propyl) -pyridine from Example 1 in accordance with.

Yield: 48 X theor.,

Melting range: 85-96 ° C (amorphous)

Calc .: C 57.84 H 7.73 N 7.49 Cl 12.65

Found: 57.71 7.91 7.35 13.04.

Example 106 78 k Q 17/12 s · <-J * -r 0 2- [3- (N- (2- (6,7-Dimethoxy-isoquinolyl-4) -ethyl) -piperidyl-3) -propyl] -6,7-dimethoxy-l-oxo-l, 2,3,4-tetrahydro-isoquino-aniline dihydrochloride monohydrate

Prepared from 2- [3- (pyridyl-3) -propyl] -6,7-dimethoxy-1-oxo-1,2,3-4-tetrahydro-isoquinoline and 4- (2-chloroethyl) -6,7-dimethoxy -isoquinoline according to Example 1.

Yield: 34% of theory,

Melting range: 162-171 ° C (amorphous)

Calc .: C 60.17 H 7.10 N 6.57 Cl 11.10

Found: 59.85 7.00 6.86 11.04.

Example 107 2 - [(N- (3- (Pyridyl-3) -propyl) -piperidyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydroisoquinoline- hydro-chloride

Prepared from 6,7-raethylenedioxy-1-oxo-1,2,3-4-tetrahydro-isoquinoline and 3-chloromethyl-N- [3- (pyridyl-3) -propyl] -piperidine according to Example 2.

. Yield: 60 7. theor.,

Melting range: 194-196 ^ 0 (amorphous)

Calc .: C 64.92 H 6.81 N 9.46 Cl 7.98

Found: 64.91 6.95 9.67 7.80.

Example 108 2 - [(N- (1- (Pyridyl-4) -methyl) -piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline- dihydroklo-hydrochloride monohydrate

6,7-Dimethoxy-1-oxo-1,2,3-4-tetrahydro-iso-797 is prepared.

y * τ o -t ο quinoline in dimethyl sulfoxide using potassium tert. -butylate and 3-chloromethyl-N- [1- (pyridyl-4) -methyl] -piperidine according to Example 2.

Yield: 41 7. theor.,

Melting range: 142-158eC (amorphous)

Calc .: C 56.78 H 6.83 N 8.63 Cl 14.58 Found: 56.45 6.59 8.66 14.62.

Example 109 2 - [(N- (2- (6,7-Dimethoxy-isoquinolyl-4) -ethyl) -piperidyl-3) -methyl] -6,7-dimethyl-1-oxo-1,2,3, 4-tetrahydro-isoquinoline dihydrochloride

Prepared from 6,7-dimethyl-1-oxo-1,2,3-4-tetrahydro-isoquinoline in dimethyl sulfoxide using potassium tert-butylate and 3-chloromethyl-N- [2- (6,7-dimethoxy-isoquino) -lyl-4-ethyl] -piperidine according to Example 2.

Yield: 62 7 »theor.,

Melting range: 148-162 ^ 0 (amorphous)

Calc .: C 64.27 H 7.01 N 7.49 Cl 12.65 Found: 64.11 7.20 7.59 12.89.

Example 110 2- [2- (N- (3- (Pyridyl-4) -propyl) -piperidyl-2) -ethyl] -6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro- dihydro-isoquinoline-hydrochloride-dihydrate

Prepared from 6,7-methylenedioxy-1-oxo-1,2,3-4-tetrahydro-isoquinoline and 2- (2-chloroethyl) -N- [3- (pyridyl-4) -propyl] -piperidine from Example 2 in accordance with.

Melting range: H5-128 ° C (amorphous)

Calc .: C 56.59 H 7.03 N 7.92 Cl 13.37

Found: 56.61 6.90 7.84 13.41.

Example ill 80

Q /: a Λ 7 ^ * v O t J

2 - [(N- (3- (3-Pyridyl) propyl) 3-piperidyl) methyl] -6,7-dimethyl-l-oxo-l, 2,3 A-tetrahydro-isoquinoline-dihydrochloride di-dihydrate

Prepared from 6,7-dimethyl-1-oxo-1,2,3-A-tetrahydro-isoquinoline in dimethyl sulfoxide using potassium tert. -butylate and 3-chloromethyl) -N- [3- (pyridyl-3) -propyl] -piperidine according to Example 2.

Yield: 62% of theory,

Melting range: 118-127 ° C (amorphous)

Calc .: C 60.00 H 7.85 N 8.39 Cl IA, 16

Found: 60.2A 8.07 8.36 IA, 62.

Example 112 2 - [(N- (3- (Pyridyl-3) -propyl) -pyrrolidyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,5-tetrahydroisoquinoline- dihydro-chloride

Prepared from 6,7-methylenedioxy-1-oxo-1,2,3-A-tetrahydro-isoquinoline and 3-chloromethyl-N- [3- (pyridyl-3) -propyl] -pyrrolidine according to Example 2.

Yield: 26% of theory,

Melting range: 102-113 ° C (amorphous)

Calc .: C 59.22 H 6.27 N 9.01 Cl 15.20 Found: 59.27 6, A9 8.92 1A, A8.

Example 113 2 - [(N- (3- (Pyridyl-A) -propyl) -pyrrolidyl-3) -methyl] -7,8-methylenedioxy-2-oxo-1,3-dihydro-2H-3-benzazepine- dihydrochloride 81 g A Ί Α ζ / “r J * t Ο

Prepared from 7,8-methylenedioxy-2-oxo-1,3-dihydro-2H-3-benzazepine and 3-chloromethyl-N- [3- (pyridyl-4) -propyl] -pyrrolidine according to Example 2.

Yield: 58 7 »theor. ,

Melting range: 132-14ΐβΰ (amorphous)

Calc .: C 60.25 H 6.11 N 8.78 Cl IA, 82

Found: 60.00 6.40 8.52 14.56.

Example 114 2 - [(N- (3- (Pyridyl-3) -propyl) -piperid-3-yl) -methyl] -7,8-dimethoxy-2-oxo-1,3-dihydro-2H-3- dihydroklo-benzazepine hydrochloride dihydrate

Prepared from 7,8-dimethoxy-2-oxo-1,3-dihydro-2H-3-benzazepine and 3-chloromethyl-N- [3- (pyridyl-3) -propyl] -piperidine according to Example 2.

Yield: 67 7, theor.,

Melting range: 128-134 ° C (amorphous)

Calc .: C 57.34 H 7.21 N 7.71 Cl 13.02

Found: 57.80 7.37 7.92 13.06.

Example 115 3 - [(N- (3- (Pyridyl-3) -propyl) -piperidyl-3) -methyl] -7,8-dimethyl-2-oxo-1,3-dihydro-2H-3-benzazepine- di-dihydrochloride dihydrate

Prepared from 7,8-dimethyl-2-oxo-1,3-dihydro-2H-3-benzazepine and 3-chloromethyl-N- [3- (pyridyl-3) -propyl] -piperidine according to Example 2.

Yield: 94 7. theor. ,

Melting range: 77-86eC (amorphous)

Calc .: C 60.92 H 7.67 N 8.19 Cl 13.83

Found: 60.75 7.60 8.37 13.72.

Example 116 82

Q Λ 1 A Z y * 1 'J 1 J

3- [2- (N- (3- (Pyridyl-4) -propyl) -piperidyl-2) -ethyl] -7,8-dimethyl-2-oxo-1,3-dihydro-2H-3-benzazepine- dihydrochloride

Prepared from 7,8-dimethyl-2-oxo-1,3-dihydro-2H-3-benzazepine and 2- (2-chloroethyl) -N- [3- (pyridyl-4) -propyl] -piperidine from Example 2 in accordance with.

Yield: 94% of theory,

Melting range: 118-130 ^ 0 (amorphous)

Calc .: C 66.11 H 7.60 N 8.56 Cl 14.45

Found: 65.92 7.86 8.33 14.09.

Example 117 3 - [(N- (2- (6,7-Dimethoxy-isoquinolyl-4) -ethyl) -piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3-dihydro- 2H-3-benzazepine-oonohydraatti

Prepared from 7,8-dimethoxy-2-oxo-1,3-dihydro-2H-3-benzazepine and 3-chloromethyl-N- [2- (6,7-dimethoxy-isoquinolyl-4) -ethyl] -piperidine according to Example 2.

Yield: 69 Theoretical 7, * Melting range: 85-96 ** C (amorphous)

Calc .: C 67.73 H 7.15 N 7.64

Found: 67.96 7.19 7.75.

Example 118 3- [3- (N- (3- (Pyridyl-3) -propyl) -piperidyl-3) -propyl] -7,8-dimethoxy-2-oxo-1,3-dihydro-2H-3- benzazepine-dihydro-chloride monohydrate

Prepared from 7,8-diraethoxy-2-oxo-1,3-dihydro-2H-3-benzazepine and 3- (3-chloropropyl) -N- [3- (pyridyl-3) -propyl) -83 Q / z / 17 yt s.) of piperidine according to Example 2.

Yield: 72% of theory. ,

Melting range: 94-106 ^ (amorphous)

Calc .: C 60.64 H 7.45 N 7.57 Cl 12.78

Found ·: 60.80 7.44 7.46 12.59.

Example 119 3- [2- (N- (3- (Pyridyl-4) -propyl) -piperidyl-2) -ethyl] -7,8-methylenedioxy-2-oxo-1,3-dihydro-2H-3- benzazepine-dihydro-chloride dihydrate

Prepared from 7,8-methylenedioxy-2-oxo-1,3-dihydro-2H-3-benzazepine and 2- (2-chloroethyl) -N- [3- (pyridyl-4) -propyl] -piperidine in dimethyl sulfoxide and potassium tert-butylate according to Example 2.

Yield: 67% of theory,

Melting range: 148-161eC (amorphous)

Calcd: C 57.56 H 6.87 N 7.74 Cl 13.07 Found: 57.72 7.03 7.61 13.62.

Example 120 3 - [(N- (1- (Pyridyl-4) -methyl) -piperidyl-3) -methyl] -7,8-dimethyl-2-oxo-1,3-dihydro-2H-3-benzazepine- dihydroklo-ridimonohydraatti

Prepared from 7,8-dimethoxy-2-oxo-1,3-dihydro-2H-3-benzazepine and 3-chloromethyl-N- [1- (pyridyl-4) -methyl] -piperidine in diraethylsulfoxide and potassium tert-butylate according to Example 2.

Yield: 75% of theory,

Melting range: H3-i27eC (amorphous)

Calc .: C 61.79 H 7.13 N 9.01 Cl 15.20. Found: 61.55 7.32 9.04 15.11.

3 - [(N- (3- (Pyridyl-4) -propyl] -pyrrolidyl-3) -methyl] -7,8-methylenedioxy-2-oxo-1,3,4,5-tetrahydro-2H-3- benzazepine dihydrochloride monohydrate

Example 121 84 94343

Prepared from 3 - [(N- (3- (pyridyl-4) -propyl) -pyrrolidyl-3) -methyl] -7,8-methylenedioxy-2-oxo-1,3-dihydro-2H-3H-benzazepine and 107. palladium / carbon at 5 bar hydrogen pressure and room temperature according to Example 5.

Yield: 71 ¾ theor.,

Melting range: 95-106 ° C (amorphous)

Calc .: C 57.83 H 6.67 N 8.43 Cl 14.22

Found: 57.67 6.82 8.27 14.05.

Example 122 3- [2- (N- (3- (Pyridyl-4) -propyl) -piperidyl-2) -ethyl] -7,8-diethyl-2-oxo-1,3,4,5- tetrahydro-2H-3-benzazepine-di-hydrochloride semihydraatti

Prepared from 3- [2- (N- (3- (pyridyl-4) -propyl) -piperidyl-2) -ethyl] -7,8-dimethyl-2-oxo-1,3-dihydro-2H-3-benzazepine · 10¾ palladium / carbon at 5 bar hydrogen pressure at 80eC according to Example 5.

Yield: 73 7. theor.,

Melting point: 236-238 ° C

Calc .: C 64.65 H 8.04 N 8.37 Cl 14.14

Found: 64.91 8.02 8.25 13.92.

Example 123 3- [3- (N- (2- (2-Methyl-pyridyl-6) -ethyl) -piperidyl-3) -propyl] -7,8-dimethoxy-2-oxo-1,3,4, 5-Tetrahydro-2H-3-benzazepine dihydrochloride monohydrate «» · 85

0 A 7/17 “* f J

Prepared from 3- [3- (piperidyl-3) -propyl) -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzazepine and 2-benzenesulfonic acid {6- from methyl pyridyl-2) -ethyl ester in dimethyl sulfoxide using potassium carbonate at 120 ° C according to Example 1.

Yield: 29 7. theor.,

Melting range: 105-113 ° C (amorphous)

Calc .: C 60.42 H 7.78 N 7.55

Found: 60.68 7.50 7.42.

Example 124 3 - [(N- (3- (Pyridyl-3) -propyl) -piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H- 3-benzazepine-di-hydrochloride

Prepared from 3 - [(N- (3-pyridyl-3) -propyl) -piperidyl-3) -methyl 3-7,8-dimethoxy-2-oxo-1,3-dihydro-2H-3-benzazepine by hydrogenation At 5 bar hydrogen pressure in ethanol using 10¾ palladium / carbon at 70eC according to Example 5.

Yield: 52 7. theor.,

Melting range: 113-122 ° C (amorphous)

Calcd: C 61.17 H 7.30 N 8.23: · Found: 61.31 7.50 8.28.

Example 125

3 - [(N- (2- (6,7-Dimethoxy-4-isoquinolyl) ethyl) 3-piperidyl) methyl] -7,8-dimethoxy-2-oxo-l, 3,4,5- tetrahydro-2H-3-benzazepine x 1/2 H 2 O.

Prepared from 3 - [(N- (2- (6,7-Dimethoxy-isoquinolyl-4) -ethyl) -piperidyl-3) -methyl) -7,8-dimethoxy-2-oxo-1,3-dihydro-2H -3-benzazepine by hydrogenation at 5 bar under 10% hydrogen with 10% palladium on carbon in ethanol at 70 ° C according to Example 5.

«86 9 Λ -. Λ 7

Yield: 50 7. theor. ,

Melting range: 82-86 ° C (amorphous)

Calcd: C 66.40 H 7.55 N 7.48 Found: 66.26 7.50 7.59.

Example 126 3- [3- (N- (3- (Pyridyl-3) -propyl) -piperidyl-3) -propyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro- 2H-3-benzazepine dihydrochloride dihydrate

Prepare 3- [3- (N- (3- (pyridyl-3) -propyl) -piperidyl-3) -propyl] -7,8-dimethoxy-2-oxo-1,3-dihydro-2H-3-benzazepine by hydrogenation at 5 bar under a hydrogen pressure of 107, with palladium / carbon in ethanol at 70 ° C according to Example 5.

Yield: 64 7. theor.,

Melting range: 106-115 ° C (amorphous)

Calc .: C 58.53 H 7.89 N 7.31 Cl 12.34

Found: 58.46 7.61 7.14 12.57.

Example 127 3 - [(N- (3- (Pyridyl-3) -propyl) -piperidyl-3) -methyl] -7,8-methylenedioxy-2-oxo-1,3,4,5-tetrahydro-2H- 3-benzazepine dihydrochloride monohydrate

Prepared from 3 - [(N- (3- (pyridyl-3) -propyl) -piperidyl-3) -methyl] -7,8-methylenedioxy-2-oxo-1,3-dihydro-2H-3-benzazepine At 5 bar hydrogen pressure 107 on palladium / carbon at 80 ° C according to Example 5.

Yield: 81 7, theor. ,

Melting range: 126-138 ° C (amorphous)

Calc .: C 58.58 H 6.88 N 8.19 Cl 13.83

Found: 58.43 7.00 7.8S 13.71.

II

3- [2- (Ν- (3- (Pyridyl-4) -propyl) -piperidyl-2) -ethyl] -7,8-methylenedioxy-2-oxo-1,3,4,5-tetrahydro-2H- 3-Benzazepine dihydrochloride monohydrate

Example 128 87 g a z λ ζ / t J τ Ο

Prepare 3- [2- (N- (3- (pyridyl-4) -propyl) -piperidyl-2) -ethyl] -7,8-methylenedioxy-2-oxo-1,3-dihydro-2H-3-benzazate of silicon at 5 bar under a hydrogen pressure of 10¾ palladium / carbon in ethanol at 80 ° C according to Example 5.

Yield: 74 ¾ theor. ,

Melting range: 132-146 ° C (amorphous)

Calc .: C 59.31 H 7.08 N 7.98 Cl 13.46

Found: 59.18 7.41 7.80 13.25.

Example 129 3 - [{N- (3- (Pyridyl-3) -propyl) -piperidyl-3) -methyl] -7,8-dimethyl-2-oxo-1,3,4,5-tetrahydro-2H- 3-benzazepine-di-hydrochloride

Prepare 3 - [(N- (3- (pyridyl-3) -propyl) -piperidyl-3) -methyl] -7,8-dimethyl-2-oxo-1,3-dihydro-2H-3-benzazepine- · Lithium aluminum hydride at 5 bar under a hydrogen pressure of 10¾ palladium / carbon in ethanol at 80 ° C according to Example 5. Yield: 54 ¾ theor.,

Melting range: 92-105 ° C (amorphous)

Calc .: C 62.90 H 7.92 N 8.46 Cl 14.28

Found: 63.19 7.90 8.45 14.30.

Example 130 3 - [(N- (3- (Pyridyl-4) -propyl) -pyrrolidyl-3) -methyl] -7,8-methylenedioxy-1,3,4,5-tetrahydro-2H-3-benzazepine- trihydrochloride monohydrate 88 O · '7/17 y "vo τ o

Prepared from 3 - [(N- (3- (pyridyl-4) -propyl) -pyrrolidyl-3) -methyl] -7,8-methylenedioxy-2-oxo-1,3,4,5-tetrahydro-2H-3 -benzazepine and lithium aluminum hydride in tetrahydrofuran / ether according to Example 3.

Yield: 73 7% of theory. ,

Melting range: 96-108 ° C (amorphous)

Calc .: C 55.33 H 6.97 N 8.06 Cl 20.42

Found: 55.06 7.28 7.77 20.07.

Example 131 3 - [(N- (3- (Pyridyl-3) -propyl) -piperidyl-3) -methyl] -7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepine- dihydrochloride

Prepared from 3 - [(N- (3- (pyridyl-3) -propyl) -piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3 -benzazepine and lithium aluminum hydride in tetrahydrofuran / ether according to Example 3.

Yield: 71 7, theor.,

Melting point: 208-210 ** C

Calc .: C 62.89 H 7.91 N 8.46 Cl 14.28

Found: 62.70 7.53 8.22 14.50.

Example 132 3- [2- (N- (3- (Pyridyl-4) -propyl) -piperidyl-2) -ethyl] -7,8-methylenedioxy-1,3,4,5-tetrahydro-2H-3- benzazepine-tri-hydrochloride

Prepared from 3- [2- (N- (3- (pyridyl-4) -propyl) -piperidyl-2) -ethyl] -7,8-methylenedioxy-2-oxo-1,3,4,5-tetrahydro-2H -3-benzazepine and lithium aluminum hydride in tetrahydrofuran / ether according to Example 3.

Yield: 63 7 · theor. ,

Melting range: 123-136 * ^ (amorphous) Q 7/12 7 n O t ϋ 89

Calc .: C 58.81 H 7.21 N 7.91 Cl 20.00

Found: 58.51 7.41 7.92 19.86.

Example 133 3 - [(N- {3- (Pyridyl-3) -propyl) -piperidyl-3) -methyl] -7,8-methylenedioxy-1,3,4,5-tetrahydro-2H-3-benzazepine- tri-hydrochloride semihydraatti

Prepared from 3 - [(N- (3- (pyridyl-3) -propyl) -piperidyl-3) -methyl] -7,8-methylenedioxy-2-oxo-1,3,4,5-tetrahydro-2H-3 -benzazepine and lithium aluminum hydride in tetrahydrofuran / ether according to Example 3.

Yield: 75 7, theor. ,

Melting range: 126-138 ° C (amorphous)

Calc .: C 57.09 H 7.10 N 7.99 Cl 20.22

Found: 57.05 7.32 8.05 20.37.

Example 134 3- [2- (N- (3- (Pyridyl-4) -propyl) -piperidyl-2) -ethyl] -7,8-dimethyl-1,3,4,5-tetrahydro-2H-3- benzazepine trihydrochloride «

Prepared from 3- [2- (N- (3- (pyridyl-4) -propyl) -piperidyl-2) -ethyl] -7,8-dimethyl-2-oxo-1,3,4,5-tetrahydro-2H -3-benzazepine and lithium aluminum hydride in tetrahydrofuran / ether according to Example 3.

Yield: 92 7 »theor. ,

Melting point: 180-182 ° C

Calc .: C 62.96 H 8.22 N 8.16 Cl 20.65

Found: 63.00 8.29 8.16 20.34.

3 - [(N- {3- (Pyridyl-3) -propyl) -piperidyl-3) -methyl) -7,8-dimethyl-1,3,4,5-tetrahydro-2H-3-benzazepine trihydro- chloride·

Example 135 90 q /. - / 1 7

Prepared from 3 - [(N- (3- (pyridyl-3) -propyl) -piperidyl-3) -methyl] -7,8-dimethyl-2-oxo-1,3,5,5-tetrahydro-2H-3 -benzazepine and lithium aluminum hydride in tetrahydrofuran / ether according to Example 3.

Yield: 81 7. theor. ,

Melting range: 184-196 ° C (amorphous)

Calc .: C 60.17 H 8.16 N 8.10 Cl 20.49

Found: 60.28 8.25 8.00 20.39.

Example 136 3-2- (N- (2- (6-Methoxy-naphthyl-2) -ethyl) -piperidyl-2) -ethyl] -7,8-dimethoxy-2-oxo-1,3,5, 5 tetrahydro-2H-3-benzathine-benzodiazepine hydrochloride

Prepared from 3- [2- (piperidyl-2) -ethyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzazepine and 2- {6-methoxy-naphthyl -2) -ethyl bromide according to Example 1.

Yield: 20 7. theor. ,

Melting point: 158-160 ^ 0

Lask. C 69.48 H 7.47 N 5.06 Cl 6.41 Found: 69.40 7.56 5.17 6.62.

Example 137 3- [2- (N- (2- (5-Methyl-6-methoxy-naphthyl-2) -ethyl) -piperidyl-2) -ethyl) -7,8-dimethoxy-2-oxo- 1,4,5,5-tetrahydro-2H-3-benzazepine hydrochloride 1 · • i 91 q A? /! 7

J 7? u 1-t U

Prepared from 3- [2- (piperidyl-2) -ethyl] -7,8-dimethoxy-2-oxo-1,3,5,5-tetrahydro-2H-3-benzazepine and 2- (S-methyl-6- methoxy-naphthyl-2) -ethyl bromide according to Example 1.

Yield: 28 7. theor. ,

Melting point: 140-143 ° C

Lask. : C 69.88 H 7.64 N 4.94 Cl 6.25

Found: 69.06 7.57 4.84 6.44.

Example 138 3- [2- (N- (2- (Naphthyl-1-oxy) -ethyl) -piperidyl-2) -ethyl] -7,8-dimethoxy-2-oxo-1,3,4,5- tetrahydro-2H-3-benzazepine hydrochloride

Prepared from 3- [2- (piperidyl-2) -ethyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzazepine and 2- (naphthyl-1-oxy) -ethyl bromide from Example 1 in accordance with.

Yield · 27 7. theor. ,

Melting point: 146-148®C

Lask. C 69.06 H 7.29 N 5.20 Cl 6.58 Found: 69.00 7.07 5.31 6.68.

‘·

Example 139 3- [2- (N- (2- (Naphthyl-1) -ethyl) -piperidyl-2) -ethyl] -7,8-dimethoxy-2-oxo-1,3,4,5- tetrahydro-2H-3-benzazepine-hydro-chloride

Prepared from 3- [2- (piperidyl-2) -ethyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzazepine and 2- (naphthyl-1) -ethyl bromide according to Example 1.

Yield: 24 7. theor ..

Melting point: 148-150 ° C

«<» ·? 2 0/17/17

^ -s ο * ΐ sJ

Lask. : C 71.18 H 7.51 N 5.36 Cl 6.78

Found: 70.92 7.44 5.57 7.06.

Example 140 3- [2- (N- (4- (Naphthyl-2-oxy) -butyl) -piperidyl-2) -ethyl] -7,8-dimethoxy-2-oxo-1,3,4,5- tetrahydro-2H-benzazepine hydrochloride

Prepared from 3- [2- (piperidyl-2) -ethyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzazepine and 4- (naphthyl-2-oxy) -butyl bromide according to Example 1.

Yield: 39 7 »theor. ,

Melting point: 112-114eC

Lask. C 69.88 H 7.64 N 4.64 Cl 6.25 Found: 69.69 7.58 4.82 6.52.

Example 141 3- [2- (N- (2- (Naphthyl-2) -ethyl) -piperidyl-2) -ethyl] -7,8-diethoxy-2-oxo-1,3,4,5- tetrahydro-2H-3-benzazepine hydrochloride. · * Prepared from 3- [2- (piperidyl-2) -ethyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzazepine and 2- (naphthyl-2) - ethyl bromide according to Example 1.

Yield: 41 7 »theor.,

Melting point: 120-122 ^ 0

Lask. C 71.18 H 7.51 N 5.36 Cl 6.78

Found: 71.10 7.31 5.40 7.05.

Example 142 3- [2- (N - ({2-Methyl-naphthyl-1) -methyl) -piperidyl-2) -ethyl] -7,8-dimethoxy-2-oxo-1,3,4,5- tetrahydro-2H-3-benzacetic • · • «

II

93 g of A 7/1 7 ^ n o n silicon hydrochloride

Prepared from 3- [2- (piperidyl-2) -ethyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzazepine and 1-chloromethyl-2-methyl-naphthalene according to Example 1.

Yield: 24 7. theor. ,

Melting point: i44-146eC

Lask. C 71.18 H 7.51 N 5.36 Cl 6.78 Found: 70.93 7.38 5.48 6.89.

Example 143 3 - [(N- (2- (Naphthyl-2) -ethyl) -hexahydro-azepin-3-yl) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro- 2H-3-bentBatse-benzodiazepine hydrochloride

Prepared from 3 - [(hexahydro-azepin-3-yl) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzazepine and 2- (naphthyl- 2) -ethyl bromide according to Example 1.

Yield: 58 7 »theor. ,

Melting point: 204-205 ** C

Calc .: C 71.18 H 7.52 N 5.36 Cl 6.78

Found: 71.41 7.51 S, 35 6.50.

«« ·

Example 144 3 - [(N- (2- (Naphthyl-2) -ethyl) -piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro 2H-3-benzazepine-hydro-chloride

Prepared from 3 - [(piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzazepine and 2- (naphthyl-2) -ethyl bromide according to Example 1.

Yield: 35 7. theor.,

Melting point: 239-240eC

. · · A 94

Q Λ 2 ΛΎ s * τ o ‘f J

Calc .: C 70.78 H 7.33 N 5.50 Cl 6.96

Found: 70.70 7.10 5.46 7.16.

Example 145 3 - [(N - ((Naphthyl-2H-methyl) -piperidyl-3) -methyl} -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H- 3-benzazepine

Prepared from 3 - ((piperidyl-3) -methyl) -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzazepine and 2-bromomethyl-naphthalene according to Example 1.

Yield: 27 7. theor.,

Melting point: 176-177 ° C

Calc .: C 75.95 H 7.47 N 6.11

Found 76.11 7.28 6.10.

Example 146

• I

3-C (N- (4- (Naphthyl-2-oxy) -butyl) -piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H- 3-benzazepine hydrochloride

Prepared from 3 - [(piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzazepine and 4- (naphthyl-2-oxy) -butyl bromide according to Example 1.

Yield: 24 7, theor. ,

Melting point: 196-197eC

Lask. : C 69.48 H 7.47 N 5.06 Cl 6.41

Found: 69.30 7.36 4.99 6.56.

Example 147 3 - [(N- (4- (Naphthyl-1) -ethyl) -piperidyl-3) -methyl) -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro- 2H-3-Benzazepine hydrochloride 95 0/7/17 3 -r vj o

Prepared from 3 - [(piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,5,5-tetrahydro-2H-3-benzazepine and 2- (naphthyl-1) -ethyl bromide from Example 1 in accordance with.

Yield: 18 7. theor.,

Melting point: 230-23 ° C

Calc .: C 70.78 H 7.33 N 5.50 Cl 6.96

Found: 70.71 7.07 5.67 6.99.

Example 148 3 - [(N- (2- (Naphthyl-1-oxy) -ethyl) -piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro- 2H-3-benzazepine-hydro-chloride

Prepared from 3 - [(piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,5,5-tetrahydro-2H-3-benzazepine and 2- (naphthyl-1-oxy) ethyl bromide according to Example 1. Yield: AO% theor.,

Melting point: 214-215 ° C

Lask. : C 68.62 H 7.10 N 5.34 Cl 6.7S

Found: 68.40 7.10 5.21 6.77

Example 149 3 - [(N - ((2-Methyl-naphthyl-1) -methyl) -piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro- 2H-3-benzazepine hydrochloride

Prepared from 3 - [(piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzazepine and 1-chloromethyl-2-methyl-naphthalene from Example 1 in accordance with.

Yield: 67 7, theor. ,

Melting point: 242-243 ° ΰ

Lask. : C 70.78 H 7.33 N 5.50 Cl 6.96

Found: 70.50 7.22 5.34 6.89.

• ·

Example ISO

96 3 - [(N- (2- (6-Methoxy-naphthyl-2) -ethyl) -piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo- 1,3,4,5-tetrahydro-2H-3-benzacepine hydrochloride

Prepared from 3 - [(piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzazepine and 2- (6-methoxy-naphthyl-2) -ethyl bromide from Example 1 in accordance with.

Yield: 50 7, theor. ,

Melting point: 156-157eC

Calc .: C 74.07 H 7.62 N 5.57

Found: 73.90 7.55 5.64.

Example 151 3 - [(N- (2- (5-Methyl-6-methoxy-naphth-2-yl) -ethyl) -piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1, 3,4,5-tetrahydro-2H-3-benz-azepine hydrochloride

Prepared from 3 - [(piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzazepine and 2- (5-methyl-6-methoxy-naphth-2- yl) -ethyl bromide according to Example 1.

. Yield: 53% of theory,

Melting point: 240-24 ° C

Calc .: C 69.48 H 7.47 N 5.06 Cl 6.41

Found: 69.58 7.48 5.00 6.54.

Example 152 2- [N- (2- (3,4-Dimethoxy-phenyl) -ethyl) -piperidyl-3) -methyl] -5,6-dimethoxy-1-oxo-1,3-dihydro-isoindole hydrochloride

Prepared from 2 - [(piperidyl-3) -methyl] -5,6-dimethoxy-1,3-dihydro-isoindole and 2- (3,4-dimethoxy-phenyl) -ethyl bromide - · g A 7 A 7

J 1 to J

97 according to Example 1.

Yield: 68 f. Theor. ,

Melting point: 225-226 ° ¾

Calculated: C 63.60 H 7.18 N 5.20 Cl 7.22

Found: - 63.61 7.30 5.70 7.44.

Example 153 2 - [(N- (2- (6-Methoxy-naphthyl-2) -ethyl) -piperidyl-3) -methyl] -5,6-dimethoxy-1-oxo-1,3-dihydro-isoindole- hydrochloride

Prepared from 2 - [(piperidyl-3) -methyl] -5,6-dimethoxy-1-oxo-1,3-dihydro-isoindole and 2- (6-methoxy-naphthyl-2) -ethyl bromide according to Example 1.

Yield: 75 V. theor.,

Melting point: 234-236eC

Calc .: C 68.16 H 6.90 N 5.48 Cl 6.94

Found: 68.10 7.10 5.39 7.10.

m ·

Example 154 2 - [(N- (2- (Naphthyl-1-oxy) -ethyl) -piperidyl-3) -methyl] -5,6-dimethoxy-1-oxo-1,3-dihydro-isoindole hydrochloride

Prepared from 2 - [(piperidyl-3) -methyl] -5,6-dimethoxy-1-oxo-1,3-dihydro-isoindole and 2- (naphthyl-1-oxy) -ethyl bromide according to Example 1.

Yield: 60 7. theor.,

Melting point: 150-152eC

Lask. C 67.66 H 6.69 N 5.63 Cl 7.13 Found: 67.50 6.76 5.74 7.54.

Example 155 2 - [(N- (2- (4-Methyl-phenyl) -ethyl) -piperidyl-3) -methyl] -98

Q AT AT

y τ -j t vj 5,6-dimethoxy-1-oxo-1,3-dihydro-isoindole

Prepared from 2- [1- (piperidyl-3) -methyl] -5,6-dimethoxy-1-oxo-isoindole and 2- (4-methyl-phenyl) -ethyl bromide according to Example 1.

Yield: 57 7 * theor. ,

Melting point: l34-136eC

Calc .: C 73.50 H 7.90 N 6.86

Found: 73.40 8.04 7.06.

Example 156 2 - [(N- (2- (3-Methoxy-phenyl) -ethyl) -piperidyl-3) -methyl] -5,6-dimethoxy-1-oxo-1,3-dihydro-isoindole hydrochloride

Prepared from 2 - [(piperidyl-3) -methyl] -5,6-dimethoxy-1-oxo-isoindole and 2- (3-methoxy-phenyl) -ethyl bromide according to Example 1.

Yield: 54 7, theor.,

Melting point: 226-228eC

Calc .: C 65.28 H 7.01 N 6.09 Cl 7.71

Found: 65.30 7.37 5.91 7.61.

. Example 157 2 - [(N- (2- (5-Methyl-6-methoxy-naphthyl-2) -ethyl) -piperidyl-3) -methyl] -5,6-dimethoxy-1-oxo-1,3- dihydro-isoindole-hydro-chloride

Prepared from 2 - [(piperidyl-3) -methyl] -5,6-dimethoxy-1-oxo-1,3-dihydro-isoindole and 2- (S-methyl-6-methoxy-naphthyl-2) -ethyl bromide from Example 1 in accordance with.

Yield: 38 7. theor. ,

Melting point: 214-216 ° C

»·« Li 99 /. 7/17

S vJ '"f yJ

Lask. : C 68.62 H 7.10 N 5.33 Cl 6.75

Found: 68.9 * 4 7.23 4.98 6.61.

Example 158 2 - [(N- (2- (4-Nitro-phenyl) -ethyl) -piperidyl-3) -methyl] -5,6-dimethoxy-1-oxo-1,3-dihydro-isoindole hydrochloride

Prepared from 2 - [(piperidyl-3) -methyl] -5,6-dimethoxy-1-oxo-1,3-dihydro-isoindole and 2- (4-nitro-phenyl) -ethyl bromide according to Example 1.

Yield: 79% of theory,

Melting point · 215-2180C

Lask. C 60.56 H 6.35 N 8.83 Cl 7.45

Found: 60.41 6.26 8.84 7.62.

Example 159 3 - [(N- (2- (Thienyl-2) -ethyl) -piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H- 3-benzazepine-hydro-chloride

Prepared from 3 - [(piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzazepine and 2- (2-bromoethyl) -thiophene according to Example 1.

Yield: 43 7 * theor.,

Melting point: 232-236eC

Calc .: C 61.99 H 7.15 N 6.02 Cl 7.62 S 6.89

Found: 61.90 7.06 5.78 7.96 6.84.

Example 160 3 - [(N- (2- (Thienyl-3) -ethyl) -piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H- 3-Benzazepine hydrochloride 100 ° J 1 A 7

> r -> ‘i · O

Prepared from 3 - [(piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzazepine and 3- (2-bromoethyl) -thiophene according to Example 1.

Yield: 36 7. theor. ,

Melting point: sintered at 75-80 ° C, melts at 225-230 ° C Calculation: C 61.99 H 7.15 N 6.02 Cl 7.62 S 6.89 Found: 62.00 7.08 5, 98 8.43 6.62.

Example 161 3 - [(N- (4- (Thienyl-2) -butyl) -piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro- 2H-3-benzazepine-hydro-chloride

Prepared from 3 - [(piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzazepine and 2- (4-bromobutyl) thiophene according to Example 1.

Yield: 68 7. theor.,

Melting range: 190-196eC

Calc .: C 63.33 H 7.56 N 5.68 Cl 7.19 S 6.50

Found: 63.18 7.72 5.72 7.29 6.59.

Example 162 3 - [(N- (2- (Benzo [b] furyl-2) -ethyl) -piperidyl-3) -methyl] - 7,8-dimethoxy-2-oxo-1,3,4,5- tetrahydro-2H-3-benzazepine hydrochloride

Prepared from 3 - [(piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzazepine and 2- (2-bromoethyl) -benzo [b ] furan according to Example 1.

Yield: 22 7, theor.,

Melting point: above 2160C (dec.)

Calc .: C 67.39 H 7.07 N 5.61

Found: 67.14 7.36 5.53.

li • G A 7 A 2 s * 7 O “1 3

Example 163 101 3 - [(N- (2- (Benzo [b] thienyl-3) -ethyl) -piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,5, 5 tetrahydro-2H-3-benzazepine hydrochloride

Prepared from 3 - {(piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzazepine and 3- (2-bromoethyl) -benzo [ b] thiophene according to Example 1. Yield: 73% of theory,

Melting range: 70-75oC (dec.)

Calcd: C 65.29 H 6.85 N 5.44

Found: 65.10 6.87 5.73.

Example 164 3 - [(N- {2- (4-Methoxy-benzo [b] thienyl-3) -ethyl) -piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3, 4, S-tetrahydro-2H-3-benz-azepine hydrochloride

Prepared from 3 - [(piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzazepine and 3- (2-chloroethyl) -4 -methoxy-benzo [b] thiophene according to Example 1.

.1 Yield: 25% of theory Melting range: 85-105βϋ (dec.)

Calc .: C 63.96 H 6.84 N 5.14 Cl 6.50 S 5.88

Found: 63.95 6.85 4.99 6.53 5.75.

Example 165 3 - [(N- (2- (6-Methylsulfonyloxy-benzo [b] thienyl-3) -ethyl) -piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3, 4,5-tetra-hydro-2 H-3-benzazepine hydrochloride

3 - [(Piperidyl-3) -methyl) -7,8-dimethoxy-2-oxo-. ·,, · / T J u 1C2 1.3, A, 5-tetrahydro-2H-3-benzazepine and 3- [2- (methylsulfonyloxy) ethyl] -6-methylsulfonyloxybenzothib] thiophene according to Example 1.

Yield: 55 7. theor. ,

Melting point: 90 ° C (dec.)

Calc .: C 57.18 H 6.12 N A, 60 Cl 5.82 S 10.53

Found: 57.25 6.1A A, 50 5.97 10.36.

Example 166 3 - [(N- (5- (Thienyl-2) -pentyl) -piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,5,5-tetrahydro-2H- 3-benzazepine-hydro-chloride

Prepared from 3 - [(piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,5,5-tetrahydro-2H-3-benzazepine and 2- (5-methylsulfonyloxy-pentyl) -thiophene according to Example 1. Yield: 39 7 · theor. ,

Melting point: 177 ^ 0

Calc .: C 63 95 H 7.75 N 5.52 Cl 6.99 S 6.32

Found: 63.70 7.92 5, A0 7.2A 6.62.

Example 167 • · 3 - [(N- (2- (Furyl-2) -ethyl) -piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,5,5- tetrahydro-2H-3-benzazepine-hydro-chloride

Prepared from 3 - [(piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,5,5-tetrahydro-2H-3-benzazepine and 2- (2-methylsulfonyloxyethyl) -furan according to Example 1. Yield: aa 7, theor. ,

Melting range: 205-215eC

Calc .: C 6A.20 H 7, Al N 6.2A Cl 7.90

Found: 6A.00 7, A5 6.00 7.80.

<· 1 ii ·

Example 168 103 QA 7H-7 '- 3' - (N- (3- (Furyl-2) -propyl) -piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo -1,3,5,5-tetrahydro-2H-3-benzazepine hydrochloride

Prepared from 3 - [(piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzazepine and 3- (furyl-2) -propionaldehyde according to Example 9.

Yield: 11 7. theor. ,

Melting point: 20l-206 ° C

Lask. : C 64, 85 H 7.62 N 6.05 Cl 7.66

Found: 64.88 7.76 5.93 7.55.

Example 169 3 - [(N- (6- (Thienyl-2) -hexyl) -piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro- 2H-3-benzazepine-hydro-chloride

Prepared from 3 - [(piperidyl-3) -methyl) -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzazepine and 2- (6-methylsulfonyloxy-hexyl) -thiophene according to Example 1.

Yield: 27 7, theor.,

Melting point: 160 ° C

Calc .: C 64.39 H 8.10 N 5.40 Cl 6.79

Found: 64.55 7.90 5.23 7.00.

Example 170 3 - [(N- (3- (Indolyl-3) -propyl) -piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H- 3-Benzazepine hydrochloride. Prepared from 3 - [(piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-04

/ · / ‘I’ Z

^ ‘T -.J’ 1 ~ J

1.3.4,5-Tetrahydro-2H-3-benzazepine and 3- (3-methylsulfonyloxy-propyl) -indole according to Example 1.

Yield: 19 7. theor.,

Melting point:> 80 ° C (dec.)

Calc .: C 60.42 H 6.30 N 6.45

Found: 60.32 6.57 6.67.

Example 171 3 - [(N- (2- (Indolyl-3) -ethyl) -piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3 benzazepine-hydro-chloride

Prepared from 3 - [(piperidyl-3) -methyl] -7,8-diraethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzazepine and 3- (2-methylsulfonyloxy-ethyl) -indole from Example 1 in accordance with.

Yield: 23 7. theor.,

Melting point:> 80 ° C (dec.) Ir .: C 65.53 H 6.42 N 7.69

Found: 65.33 6.55 7.80.

Example 172 2 - [(N- (3- (Naphthyl-2-oxy) -propyl) -hexahydro-azepinyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4- tetrahydro-isoquino-aniline

Prepared from 6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 3-chloromethyl- [N- (3-naphthyl-2-oxy) -propyl] -hexahydro-azepine according to Example 2.

Yield · 21 7. theor. ,

Melting point: 74-76 ^ 0

Lask. (x 2 HaO): C 64.45 H 7.02 N 5.01 Cl 6.34

Found: 64.32 7.20 5.28 6.44.

«•

Example 173 105 GA-Z / 1 Z 7 ^ 013 2 - [(N- (3- (Naphthyl-2) -propyl) -pyrrolidyl-3) -methyl] -6,7-dimethyl-i-oxo-1 , 2,3,4-tetrahydro-isoquinoline

Prepared from 6,7-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 3- (p-toluenesulfonyloxymethyl) -N- [3- (naphthyl-2) -propyl] -pyrrolidine from Example 2 in accordance with. Yield · 20 7. theor. ,

Melting point: 72-76 ** C

Lask. (X HzO): C 72.41 H 7.75 N 5.82 Cl 7.36 Found: 72.27 7.85 5.70 7.96.

Example 174 2 - [(N- (3- (5,6-Dimethoxy-naphthyl-2-oxy) -propyl) -pyrrolidin-3) -methyl] -6,7-dimethoxy-1-oxo-1, 2,3,4-tetrahydro-isoquinoline hydrochloride

Prepared from 6,7-dimethoxy-1-oxo-1,3,4,5-tetrahydro-isoquinoline and 3- (p-toluenesulfonyloxymethyl) -N- [3- (5,6-dimethoxy-naphthyl-2-oxy) ) -propyl] -pyrrolidine according to Example 2.

- Yield: 9,5% of theory,

·· Melting point: 60-63 * »C

Lask. (x H * O>: C 63.20 H 7.01 N 4.75 Cl 6.02 Found: 63.40 7.04 4.49 6.38.

Example 175 2 - [(N- (3- (5,6-Diraethoxy-naphthyl-2-oxy) -propyl) -hexahydro-azepinyl-3) -methyl] -6,7-dimethoxy-1-oxo-1, 2,3,4-tetrahydro-isoquinoline-hydrochloride

6,7-Dimethoxy-1-oxo-1,2,3,4-tetrahydro-iso- [·> <> · 106,94543 quinoline and 3- (p-toluenesulfonyloxymethyl) -N- [3- (5,6) -di-methoxy-naphthyl-2-oxy) -propyl] -hexahydroazepine according to Example 2.

Yield: 63.2% of theory,

Melting point: 199-201 ° C

Calcd: C 66.15 H 7.23 N 4.67 Cl 5.92

Found: 65.99 7.00 4.44 6.02.

Example 176 2 - (N- (3- (S, 6-Dimethoxy-naphthyl-2-oxy) -propyl) -hexahydro-azepinyl-3) -methyl] -6,7-dimethoxy-1,2,3, 4-tetrahydro-iso-quinoline dihydrochloride

Prepared from 2 - [(N- (3- (5,6-dimethoxy-naphthyl-2-oxy) -propyl) -hexahydro-azepinyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2 , 3,4-tetrahydroisoquinoline and lithium aluminum hydride in tetrahydrofuran / ether according to Example 3.

Yield: 86.3% of theory,

Melting point: 114-116eC

Calc .: C 61.97 H 7.56 N 4.38 Cl 11.08

Found: 62.05 7.65 4.06 10.84.

Example 177 2 - [(N- (2- (4-Methoxy-phenyl) -ethyl) -pyrrolidyl-3) -methyl] -6,7-methylenedioxy-1,2,3,4-tetrahydro-isoquinoline-dihydro- chloride

Prepared from 2 - [(N- (2- (4-methoxy-phenyl) -ethyl) -pyrrolidyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and lithium aluminum hydride / tetrahydrofuran according to Example 3.

Yield: 86.7% of theory,

Melting point: 213-215 * ^ «· 107 Q / 7 Λ τ 7 τ ο τ ο

Calc .: C 60.49 Η 6.98 Ν 5.87 Cl 14.88

Found: 60.59 6.96 5.84 14.98.

Example 178 2 - [(N- (3- (3,4-Dimethoxy-phenoxy) -propyl) -pyrrolidyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4- tetrahydro-iso-quinoline hydrochloride

Prepared from 1-oxo-1,2,3,4-tetrahydro-6,7-methylenedioxyisoquinoline and N- [3- (3,4-dimethoxy-phenoxy) -propyl] -3-benzosulfonyloxymethyl-pyrrolidine according to Example 2.

Yield: 57.4 Theoretical 7,

Melting point: 108-110 ° C

Calc .: C 59.76 H 6.74 N 5.35 Cl 7.02

Found: 60.07 6.87 5.23 7.61.

Example 179 2 - [(N- (2- (4-Methoxy-phenyl) -ethyl) -pyrrolidyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro- isoquinoline hydrochloride • ·

Prepared from 1-oxo-1,2,3,4-tetrahydro-6,7-methylenedioxyisoquinoline and N- [2- (4-methoxyphenyl) ethyl] -3-benzenesulfonyloxymethyl-pyrrolidine according to Example 2. Yield · 54.7 7 »theor.,

Melting point: 105-108 ° C

Calcd. · C 62.26 H 6.74 N 6.05 Cl 7.97

Found: 62.34 6.74 5.88 8.05.

Example 180. 3 - [(N- (3- (4-Methoxy-N-methyl-phenylamino) -propyl] -108,94545 piperid-3-yl) -methyl] -7,8-methylenedioxy-2-oxo-1,3, 4,5-tetrahydro-2H-3-benzazepine dihydrochloride

Prepared from 3- (piperidyl-3-methyl) -7,8-methylenedioxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzazepine and 1-chloro-3- (4-methoxy-N- methylphenylamino) propanine according to Example 1.

Yield: 24.2 7% of theory. ,

Melting point: 219-221 ° C

Calc .: C 58.94 H 7.25 N 7.61

Found: 59.08 7.45 7.75.

Example 181 3 - [(N- (2- (6-Methyl-pyridyl-2) -ethyl) -pyrrolidyl-3) -methyl] -7,8-dimethyl-1,3,4,5-tetrahydro- 2H-3-benzazepine x 2.5 HCl x H * 0

Prepared from 3-C (N- (2- (6-methyl-pyridyl-2) -ethyl) -pyrrolidyl-3) -methyl] -7,8-dimethyl-2-oxo-1,3,4,5-tetrahydro -2H-3-benzazepine and lithium aluminum hydride in diethyl ether and tetrahydrofuran according to Example 3.

Yield: 50% of theory,

Melting point: 80-9 ° C amorphous.

Calc .: C 61.68 H 8.18 N 8.63 Cl 18.21

Found: 61.55 8.36 8.44 18.10.

Example 182 3 - [(N- (2- (6-Methyl-pyridyl-2) -ethyl) -pyrrolidyl-3) -methyl] -7,8-dimethyl-2-oxo-1,3,4,5- tetrahydro-2H-3-benzathine-benzodiazepine-dihydro-chloride semihydraatti

Prepared from 3 - [(N- (2- (6-methyl-pyridyl-2) -ethyl) -pyrrolididyl-3) -methyl) -7,8-dimethyl-2-oxo-1,3-dihydro- 2H-3-109

Q,: TAT

s ** r s-J * t from benzazepine 107. palladium on carbon / carbon at 5 bar hydrogen pressure and 80 ° C in ethanol according to Example 5.

Yield.- 92 7. theor. ,

Melting point: 86-9AeC amorphous.

Calc .: C 63, Al H 7.66 N 8.87 Cl IA, 97

Found: 63.52 7, IA 8.81 1A.9A.

Example 183 2 - (N- (3- (6-Methoxy-naphthyl-2-oxy) -propyl) -pyrrolidyl-3) -methyl] -6,7-dimethyl-1-oxo-1,2,3, A tetrahydro-isoquinoline

Prepared from 6,7-dimethoxy-1-oxo-1,2,3,5-tetrahydro-isoquinoline and 3- (p-toluenesulfonyloxy-ethyl) -N- [3- (6-methoxy-naphthyl-2-oxy) - propyl] -pyrrolidine according to Example 2.

Yield: AA, 7% of theory.

Melting point: 102-10AeC

Bas .: C 76.2A H 7.68 N 5.93

Found: 75.90 7.62 5.9A.

Example 18A

2 - (N- (3- (6-Methoxy-naphthyl-2-oxy) -propyl) -pyrrolidyl-3) -methyl] -6,7-dimethoxy-1,2,3,5-tetrahydro -isoquinoline

Prepared from 2- [N- (3- (6-methoxy-naphthyl-2-oxy) -propyl) -pyrrolidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,5-A- tetrahydroisoquinoline and lithium aluminum hydride in tetrahydrofuran and ether according to Example 3.

Yield: 68 7, theor.,

Melting point: 106-1084¾

Calc .: C 73, AA H 7.82 N 5.71

Found: 73.26 7.72 5.81.

«• · 110

Example 185 0/7/12 X * N- * 1 '[3 - [(N- (3- (Indolyl-3) -propyl) -pyrrolidyl-3) -methyl] -7,8-methylenedioxy-2- oxo-l, 3,4,5-tetrahydro-2H-3-benzazepine-raonohydraatti

Prepared from 3- [N- (3- (indolyl-3) -propyl) -pyrrolidyl-3) -methyl] -7,8-methylenedioxy-2-oxo-1,3-dihydro-2H-3-benzazepine 207 palladium / carbon at 5 bar hydrogen pressure in ethanol at 80 ** C according to Example 5.

Yield · AO 7, theor. ,

Melting range: 67-74 * »C

Calculated: C 69.95 H 7.17 N 9.06

Found: 70.00 7.03 8.97.

Example 186 3 - [(N- (2- (6-Methyl-pyridyl-2) -ethyl) -pyrrolid-3-yl) -methyl] -7,8-dimethyl-2-oxo-1,3 dihydro-2H-3-benzazepine dihydrochloride semihydraatti

Prepared from 7,8-dimethyl-2-oxo-1,3-dihydro-2H-3-benzazepine and 3-chloromethyl-N- [2- (6-methyl-pyridyl-2) -ethyl] -pyrrolidine according to Example 2 .

Yield: 81% of theory,

Melting point: 86-98 ° C amorphous.

Calc .: C 63.68 H 7.27 N 8.91 Cl 15.04

Found: 63.39 7.43 8.87 14.93.

Example 187 2 - [(N- {3- (3-Methylphenoxy) propyl) -piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydroisoquinoline hydro -chlorides · «li 111 94343

Prepared from 6,7-dimethoxy-1-oxo-1,2,3,5-tetrahydro-isoquinoline and N- [3- (3-Methyl-phenoxy) -propyl] -3-benzenesulfonyl-oxymethyl-piperidine from Example 2 in accordance with. Yield: 75.6% of theory,

Melting point: 106-109 ° C amorphous.

Calculation: C 63.95 H 7.75 N 5.52 Cl 7.25

Found: 6A, 66 7.91 5.48 7.28.

Example 188 2 - [(N- (2- (5-Methyl-6-methoxy-naphth-2-yl) -pyrrolidyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3 A-tetrahydro-isoquino-aniline hydrochloride

Prepared from 6,7-methylenedioxy-1-oxo-1,2,3,5-tetrahydro-isoquinoline and 3- (p-toluenesulfonyloxymethyl) -N- [2- (5-methyl-6-methoxy-naphth-2-yl) ) -ethyl] -pyrrolidine according to Example 2.

Sa & nto: 27.1 7. theor. ,

Melting point: 2A9-51 ° C

Calc .: C 68, A 3 H 6.53 N 5.50 Cl 6.96

Found: 68, A7 6.66 5.30 7.16.

Example 189 2 - [(N- (3- (Naphthyl-2) -propyl) -pyrrolidyl-3) -methyl] -6,7-dimethoxy-1-oxo-isoquinoline hydrochloride

Prepared from 6,7-dimethoxy-1-oxo-1,2,3,5-tetrahydro-isoquinoline and 3- (p-toluenesulfonyloxymethyl) -N- [3- (naphthyl-2) -propyl] -pyrrolidine from Example 2 in accordance with.

Yield: 20.2% of theory,

Melting point: 8A-86eC

Calc .: C 67.88 H 7.26 N 5, A6 Cl 6.91

Found: 67.86 7, AO 5, AO 7.17. · 112

Example 190 Q Λ 1 Λ 7 7 * -! υ 2 - [(Ν- (3- (3,4-dimethoxyphenoxy) -propyl) -pyrrolidyl-3) -methyl] -6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline dihydro- chloride

Prepared from 2 - [(N- [3- (3,4-dimethoxyphenoxy) propyl) pyrrolidyl-3) methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro -isoquinoline and lithium aluminum hydride in diethyl ether and tetrahydrofuran according to Example 3.

Yield: 92.3 7. theor. ,

Melting point: 220-221 ° C

Calc .: C 59.20 H 6.88 N 5.31 Cl 13.44

Found: 59.28 6.97 5.20 13.44.

Example 191 2 - [(N- (2- (3,4-Dimethoxyphenyl) ethyl) pyrrolidyl-3) methyl] -N, 7-dimethyl-1-oxo-1,2,3,4-tetrahydroisoquinoline

Prepared from 6,7-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline and N- [2- (3,4-dimethoxy-phenyl) -ethyl] -3-benzosulfonyloxymethyl-pyrrolidine from Example 2 in accordance with.

Yield: 70 7. theor.,

Melting point: 168-170 ° C

Calc .: C 73.90 H 8.11 N 6.63

Found: 73.96 8.11 6.55.

Example 192 2 - [(N- (3- (4-Methoxyphenoxy) -propyl) -piperidyl-3) -methyl] -1,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline hydro -chloride

Prepared from 6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-iso-·· 113 q 7 A 7-ol-quinoline and N- [3- (4-methoxyphenoxy} -propyl ] -3-benzosulfonyloxymethyl-piperidine according to Example 2. Yield · 78.7 7, theoretical,

Melting point: 98-102 ° C

Lask. C 63.08 H 7.51 N 5.35 Cl 7.02

Found: 62.87 7.69 5.16 7.28.

Example 193 2 - [(N- (3- (3-Methoxyphenoxy) -propyl) -piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline hydro- chloride

Prepared from 6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and N- [3- (3-methoxyphenoxy) -propyl] -3-benzosulfonyloxymethyl-piperidine according to Example 2. Yield: 87 7. theor.,

Melting point: 103-105eC

Lask. C 64.21 H 7.38 N 5.55 Cl 7.02

Found: 64.00 7.55 5.37 7.12.

Example 194 2 - [(N- (3- (3-Methoxyphenoxy) -propyl) -piperidyl-3) -methyl] -6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline dihydrochloride

Prepared from 2 - [(N- (3- (3-methoxyphenoxy) propyl) -piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydroisoquinoline and lithium aluminum hydride in diethyl ether and tetrahydrofuran according to Example 2.

Yield · 95.4% of theory,

Melting point: 170-173 ^ 0

Calc .: C 60.43 H 7.70 N 5.22 Cl 13.21

Found: 60.50 7.71 4.91 12.97.

• 114

Example 195

0 / .7 / 17 τ J't J

2 - [(N- (2- (3,4-Dimethoxyphenyl) ethyl) pyrrolidyl-3) methyl] -6,7-dimethyl-1,2,3,4-tetrahydroisoquinoline dihydrochloride

Prepared from 2 - [(N- (2- (3,4-dimethoxyphenyl) ethyl) pyrrolidyl-3) methyl] -6,7-dimethyl-1-oxo-1,2,3,4-tetrahydro- isoquinoline and lithium aluminum urahydride in diethyl ether and tetrahydrofuran according to Example 3.

Yield: 94.1% of theory,

Melting point: 260-262 ° C

Calc .: C 64.85 H 7.96 N 5.82 Cl 14.73

Found: 64.60 8.11 5.91 14.67.

Example 196 2 - [(N- (3- (6-Methoxy-naphthyl-2-oxy) -propyl) -azacyclooctyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2 , 3,4-tetrahydro-isoquinoline hydrochloride

Prepared from 2 - [(azacyclooctyl-3) -methyl) -6,7-dimethoxy] -oxo-1,2,3,4-tetrahydro-isoquinoline and 2- (3-chloropropoxy) -6-methoxy- naphthalene according to Example 1.

Yield: 24.4 V, theor ..

Melting point: 176-178 ° C

Calc .: C 67.96 H 7.43 N 4.80 Cl 6.08

Found: 67.74 7.29 4.71 6.23.

Example 197 3 - [(N- (3- (Indolyl-3) -propyl) -pyrrolidyl-3) -methyl] -7,8-dimethyl-2-oxo-1,3,4,5-tetrahydro-2H- 3-Benzazepine Hydrochloride 115 OA-ZA 7

V "f vJ‘ t J

Prepared from 3 - [(pyrrolidyl-3) -methyl] -7,8-dimethyl-2-oxo-1,2,3,4-tetrahydro-2H-3-benzazepine and 3- (3-benzenesulfonyloxy-propyl) -indole according to Example 1.

Yield: 62 7, theor. ,

Melting point: 106-108 ° C

Calc .: C 69.47 H 7.91 N 8.68 Cl 7.32

Found: 69.57 7.80 8.67 8.51.

Example 198 3- (N- (3- (6-Methoxy-naphthyl-2-oxy) -propyl) -hexahydro-azepinyl-3) -methyl] -7,8-dimethoxy-1,2,3, 4-tetrahydro-2H-3-benzazepine

Prepared from 3 - [(N- (3- (6-methoxy-naphthyl-2-oxy) -propyl) -hexahydro-azepinyl-3) -methyl] -7,8-dimethoxy-1,2,3,4-tetra -hydro-2-oxo-2H-3-benzazepine and lithium aluminum hydride in tetrahydrofuran / ether according to Example 3.

Yield: 26.8 7 · theor.,

Melting point: 98-100 ° C

Lask. (X H0): C 71.97 H 8.42 N 5.09

Found: 72.07 8.23 5.10.

Example 199 3 - [(N- (3- (6-Methoxy-naphthyl-2-oxy) -propyl) -hexahydro-azepinyl-3) -methyl] -1,2,3,4-tetrahydro-2-oxo- 2H-3-benzathine-benzodiazepine

Prepared from 3 - [(hexahydro-azepinyl-3) -methyl] -1,2,3,4-tetrahydro-2-oxo-2H-3-benzazepine and 2- (3-chloropropoxy) -6-methoxy-naphthalene according to Example 1. Yield: 45 7, theor. ,

Melting point: 109 ° C

116 g, · 7 a τ y t ν '.

Calc .: C 72.50 H 7.74 N 5.12

Found: 72.35 7.68 4.93

Example 200 2- (N- (3- (6-Methoxy-naphthyl-2-oxy) -propyl) -hexahydro-azepinyl-3) -methyl] -1,3-dihydro-5,6-dimethoxy-isoindole

Prepared from 2 - [(N- (3- (6-methoxy-naphthyl-2-oxy-propyl) -hexahydro-azepinyl-3) -methyl] -5,6-dimethoxy-phthalimide and lithium aluminum hydride from tetrahydrofuran / ether according to Example 3.

Yield: 49.2 7, theor.,

Melting point: 104-146 ^ 0

Calculated: C 73.78 H 7.99 N 5.55

Found: 73.63 7.99 5.39

Example 201 • 3 - [(N- (3- (Indolyl-3) -propyl) -pyrrolidyl-3) -methyl] -7,8-dimethyl-1,3,4,5-tetrahydro-2H-3- Benzazepine dihydrochloride monohydrate, Prepared 3 - [(N- (3- (indolyl-3) -propyl) -pyrrolidyl-3) -methyl) -7,8-dimethyl-2-oxo-1,3,4,5,5 -tetrahydro-2H-3-benzazepine and lithium aluminum hydride in tetrahydrofuran / ether according to Example 3.

Yield: 65 7, theor.,

Melting point: 168-170 ^

Calculated: C 66.39 H 8.16 N 8.29 Cl 13.99 Found: 66.29 8.44 8.08 14.08.

Example 202 3 - [(N- (3- (6-Methoxy-naphthyl-2-oxy) -propyl) -hexahydro-acetic acid 117 qa τ λ 2 7 τ o -phenyl-3) -methyl] -i ) 314.5-tetrahydro-7,8-methylenedioxy-2H-3-benzazepine

Prepared from 3 - [(N- {3- (b-methoxy-naphthyl-2-oxy) -propyl) -hexahydro-azepinyl-3) -methyl] -1,3,4,5-tetrahydro-7,8-methyl- lenedioxy-2-oxo-2H-3-benzazepine and lithiural urine hydride in tetrahydrofuran / ether according to Example 3. Yield: 25 7 »theor. ,

Melting point: 109-111 ° C

Calc .: C 74.39 H 7.80 N 5.42

Found: 74.27 7.94 5.43.

Example 203 3 - [(N- (3- (6-Methoxy-naphthyl-2-oxy) -propyl) -hexahydro-azepinyl-3) -methyl] -1,3,4,5-tetrahydro-7, 8-methylenedioxy-2-oxo-2H-3-benzazepine hydrochloride

Prepared from 3 - [(hexahydro-azepinyl-3) -methyl] -1,3,4,5-tetrahydro-7,8-methylenedioxy-2-oxo-2H-3-benzazepine and 2- (3-chloropropoxy) -6 -methoxy-naphthalene according to Example 1.

Yield: 68.1 7, theor.,

Melting range: 104-I08ec

Lask. (X 2 HaO): C 65.46 H 7.38 N 4.79 Cl 6.06 Found: 65.60 7.25 5.01 6.43.

Example 204 2 - [(N- (3- (6-Methoxy-naphthyl-2-oxy) -propyl) -hexahydro-azepinyl-3) -methyl 1-6,7-methylenedioxy-1-oxo-1,2, 3,4-tetra-hydro-isoquinoline-hydrochloride

Prepared from 2-C (hexahydro-azepinyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 118 G A 7/17.

From 2- (3-chloropropoxy) -6-methoxy-naphthalene according to Example 1.

Yield: 18.2% of theory.

Melting point: 65-67 ° C

Lask. · (X H * O): C 65.19 H 6.88 N 4.90 Cl 6.20 Found: 65.20 6.75 4.82 6.54.

Example 205 2 - [(N- (3- (6-Methoxy-naphthyl-2-oxy) -propyl) -piperidyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3, 4-tetrahydro-isoquinoline

Prepared from 6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 3- (benzenesulfonyloxymethyl) -N- [3- (6-methoxy-naphthyl-2-oxy) -propyl] -piperidine according to Example 2.

Yield: 5.3% of theory,

Melting point: 144-146 ^ 0

Calc .: C 71.69 H 6.82 N 5.57

Found: 71.52 6.62 5.46.

Example 206 2 - [(N- (3- (6-Methoxy-naphthyl-2-oxy) -propyl) -hexahydro-azepinyl-3) -methyl] -5,6-dimethyl-1,3-dihydro- -l-oxo-isoindole

Prepared from 2 - [(N- (3- (6-methoxy-naphthyl-2-oxy) -propyl) -hexahydro-azepinyl-3) -methyl] -5,6-dimethyl-phthalimide and zinc / glacial acetic acid according to Example 4.

Yield: 18.2% of theory,

Melting point: 232-234βΟ

Lask. (x acetone): C 74.97 H 8.14 N 5.14 found: 74.96 7.90 5.30 • • ·

Example 207 119 Q / .7 A 7

/ i j n J

2 - [(N- {3- (6-methoxy-naftyy1i-2-oxy) propyl) hexahydro-ATSE-pinyyli-3) -methyl] -6,7-dimethyl-l-oxo-l, 2, 3,4-tetrahydro-isoquinoline hydrochloride

Prepared from 2 - [(hexahydro-azepinyl-3) -methyl] -6,7-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 2- (3-chloro-propoxy) -6 -methoxy-naphthalene according to Example 1. Yield: 17.3 7, theor. ,

Melting range: 68-73 * ^

Lask. (x 2 HaO): C 67.06 H 7.93 N A, 46 Cl 6.66

Found: 67.05 7.73 4.88 6.18.

Example 208 2 - [(N- (3- (6-Methoxy-naphthyl-2-oxy) -propyl) -piperidyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3, 4-tetrahydro-isoquinoline 0 ·

Prepared from 6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 3- (benzenesulfonyloxymethyl) -N- [3- (6-methoxy-naphthyl-2-oxy) -propyl] -piperidine according to Example 2.

Yield: 12.9 7, theor ..

Melting point: 124-126 ** C

Calc .: C 71.79 H 7.38 N 5.40

Found: 71.83 7.33 5.21.

Example 209 3 - [(N- (3- (5,6-Dimethoxy-naphthyl-2-oxy) -propyl) -hexahydro-azepinyl-3) -methyl] -1,3,4,5-tetrahydro-7, 8-dimethoxy-2H-3-benzazepine

Prepare 3 - [(N- (3- (5,6-dimethoxy-naphthyl-2-oxy) -pro-120q · · λ λζ S * t si kt 0 pyl) -hexahydro-azepinyl-3) -methyl] -1,3,5,5-tetrahydro-7,8-dimethoxy-2-oxo-2H-3-benzazepine and lithium aluminum hydride / tetrahydrofuran / ether according to Example 3.

Yield: 29.1 7 »theor.,

Melting point: 9A-96eC

Calc .: C 72.57 H 8.2A N A, 98

Found: 72.56 8.35 A.9A.

Example 210 2 - [(N- (3- (6-Methoxy-naphthyl-2-oxy) -propyl) -hexahydro-azepinyl-3) -methyl] -1,3-dihydro-5,6-dimethoxy-1- oxo-isoindole

Prepared from 2 - [(N- (3- (b-methoxy-naphthyl-2-oxy) -propyl) -hexahydro-azepinyl-3) -methyl] -5,6-dimethoxy-phthalimide and zinc / glacial acetic acid according to Example A.

Yield: 20.5 7, theor.,

Melting point: 265-267 ^ 0

Lask. (x 2 H * O): C 67.13 H 7.63 N 5.05

Found: 67.11 7.6A 5.07.

Example 211 • · 3 - [(N- (3- (5,6-Dimethoxy-naphthyl-2-oxy) -propyl) -hexahydro-azepinyl-3) -methyl] -1,3,5,5-tetrahydro- 7,8-dimethoxy-2-oxo-2H-3-benzazepine

Prepared from 3 - [(hexahydro-azepinyl-3) -methyl] -1,3,5,5-tetrahydro-7,8-dimethoxy-2-oxo-2H-3-benzazepine and 2- (3-chloropropoxy) -5 , 6-dimethoxy-naphthalene according to Example 1.

Yield: 52, A 7, theor ..

Melting point: 129-131 ^

Calc .: C 70.81 H 7.69 N A, 86

Received: 70.66 7.8A A, 63 • · ·

Example 212 121 q /. 7/7 2 - [(N- (3- (5,6-Dimethoxy-naphthyl-2-oxy) -propyl) -hexahydro-azepinyl-3) -methyl] -5,6-dimethoxy-1,3-dihydro- isoindole-di-hydrochloride

Prepared from 2 - [(N- (3- (5,6-dimethoxy-naphthyl-2-oxy) -propyl) -hexahydro-azepinyl-3) -methyl) -5,6-dimethoxy-phthalimide and lithium aluminum hydride from tetrahydrofuran / in ether according to Example 3 Yield: 48.2 7, theor. ,

Melting range: 172-177 ° C

Lask. (x H * O): C 61.43 H 7.41 N 4.47 Cl 11.33

Found: 61.50 7.71 4.59 11.45.

Example 213 2 - [(N- (3- (5,6-Dimethoxy-naphthyl-2-oxy) -propyl) -hexahydro-azepinyl-3) -methyl] -5,6-dimethoxy-1,3-dihydro- 1-oxo-iso- ψ · indole hydrochloride

Prepare 2 - [(N- (3- (5,6-dimethoxy-naphthyl-2-oxy) -propyl) -hexahydro-azepinyl-3) -methyl] -5,6-dimethoxy-phthalic acid. track and zinc / glacial acetic acid according to Example 4.

• ·

Yield: 36.4 7, theor.,

Melting range: 215-223eC

Lask. (X H 2 O): C 61.87 H 7.30 N 4.50 Cl 5.70

Found: 62.08 7.15 4.55 5.80.

Example 214 2 - [(N- (3- (Indolyl-3) -propyl) -pyrrolidyl-3) -methyl) -5,6-dimethoxy-1,3-dihydro-isoindole dihydrochloride monohydrate

Prepared from 2-1 (N- (3- (indolyl-3) -propyl) -pyrrolidyl-3) - * «122 C A 7/17

✓ 'TJt J

methyl] -5,6-dimethoxy-phthalimide and lithium aluminum hydride in tetrahydrofuran according to Example 3.

Yield: 87 7, theor. .

Melting point: 262-264eC

Calc .: C 61.17 H 7.30 N 8.23 Cl 13.89

Found: 61.34 7.26 7.92 13.90.

Example 215 3 - [(N- (3- (5,6-Diraethoxy-naphthyl-2-oxy) -propyl) -hexahydro-azepinyl-3) -methyl] -1,3,5,5,5-tetrahydro-7 8-dimethyl-2H-3-benzazepine dihydrochloride

Prepared from 3 - [(N- (3- (5,6-dimethoxy-naphthyl-2-oxy) -propyl) -hexahydro-azepinyl-3) -methyl] -1,3,4,5-tetrahydro-7,8 -dimethyl-2-oxo-2H-3-benzazepine and lithium aluminum hydride / tetrahydrofuran / ether according to Example 3.

Yield: 76.9 7 »theor.,

Melting range: 138-144 ° C

Calc .: C 67.64 H 8.01 N 4.64 Cl 11.74 Found: 67.73 8.26 4.47 11.50.

Example 216 • * • 3 - [(N- (3- (5,6-Dimethoxy-naphthyl-2-oxy) -propyl) -hexahydro-azepinyl-3) -methyl] -1,3,4,5-tetrahydro -7,8-dimethyl-2-oxo-2H-3-benzazepine hydrochloride

Prepared from 3 - [(hexahydro-azepinyl-3) -methyl] -1,3,4,5-tetrahydro-7,8-dimethyl-2-oxo-2H-3-benzazepine and 2- (3-chloropropoxy) -5,6-dimethoxy-naphthalene according to Example 1.

Yield: 47.5 7 · theor.,

Melting range: 90-96eC

II

• · 123 O f: 7/1 7

J “i J

Lask. (X HzO): C 68.15 H 7.90 N 4.67 Cl 5.91 Found: 67.93 7.94 5.05 6.09.

Example 217 2 - [(N- (3- (5,6-dimethoxy-naphthyl-2-oxy) -propyl) -piperidyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2, 3,4-tetrahydro-iso-quinoline hydrochloride

Prepared from 2 - [(piperidyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 2- (3-chloropropoxy) -5,6-dimethoxy -naphthalene according to Example 1.

Yield: 22.5 7. Theoretical Melting range: 93-98 * C

Lask. (x H0): C 63.42 H 6.69 N 4.77 Cl 6.03 Found: 63.59 6.80 4.70 6.28.

Example 218 * · 2 - [(N- (3- (5,6-Dimethoxy-naphthyl-2-oxy) -propyl) -pyrrolidin-3) -methyl] -6,7-methylenedioxy-1-oxo -1,2,3,4-Tetrahydro-isoquinoline hydrochloride ··· Prepares 2 - [(pyrrolidyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4 -tetrahydro-isoquinoline and 2- (3-chloropropoxy) -5,6-dimethoxy-naphthalene according to Example 1. Yield: 22.5% of theory

Melting point: 87-90 * 0

Lask. (X HaO): C 62.87 H 6.50 N 4.88 Cl 6.18 Found: 62.72 6.38 4.93 6.30.

Example 219 2 - [(N- (3- (5,6-Dimethoxy-naphthyl-2-oxy) -propyl) -piperidyl-3) -methyl] -6,7-dimethyl-1-oxo-1,2,2 3,4-Tetrahydro-isoquino- • · 174 O / 7 / I 7 ^ * τ oj line hydrochloride

Prepared from 2 - [(piperidyl-3) -methyl] -6,7-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 2- (3-chloropropoxy) -5,6-dimethoxy-naphthalene according to Example 1.

Yield: 21.3 7 »theor. ,

Melting range: 72-78 ° C

Lask. (x HaO): C 67.30 H 7.59 N 4.90 Cl 6.21

Found: 67.44 7.74 5.06 6.53.

Example 220 2 - [(N- (3- (5,6-Dimethoxy-naphthyl-2-oxy) -propyl) -hexahydro-azepinyl-3) -methyl] -6,7-dimethyl-1-oxo-1 , 2,3,4-tetrahydro-isoquinoline-hydrochloride

Prepared from 2 - [(hexahydro-azepinyl-3) -methyl] -6,7-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 2- (3-chloropropoxy) -5,6-dimethoxy -naphthalene according to Example 1.

Yield: 12 7. theor.,

Melting range: 84-90ec. Lask. (x H * 0): C 67.73 H 7.73 N 4.78 Cl 6.06 • * ·

Found: 67.64 7.81 4.94 6.20.

Example 221 2 - [(N- (2- (4-Methoxy-phenyl) -ethyl) -hexahydro-azepinyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4- tetrahydro-isoquino-aniline hydrochloride

Prepared from 6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and N- [2- (4-methoxy-phenyl) -ethyl] -3-chloro-methyl-hexahydro-azepine according to Example 2.

.. Yield: 46.7% of theory. , 125

α '7/17 ^ -r * 1 · J

Melting point: 101-105 ^ 0

Calc .: C 62, 44 H 7.26 N S, 60 Cl 7.50 Found: 62.62 7.27 5.48 7.66.

Example 222 2 - [(N- (3- (4-Methoxy-phenoxy) -propyl) -hexahydro-azepinyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4- tetrahydro-iso-quinoline hydrochloride

Prepared from 6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and N- [3- (4-methoxy-phenoxy) -propyl] -3-chloro-ethyl-hexahydro-azepine from Example 2 in accordance with.

Yield: 43.8 7, theoretical Melting point: 123-126 ° C

Calculated: C 62.23 H 7.16 N 5.37 Cl 7.05 Found: 62.42 7.34 5.30 6.94.

Example 223 2 - [(N- (3- (4-Methoxy-phenoxy) -propyl) -hexahydro-azepinyl-3) -methyl] -6,7-dimethyl-1-oxo-1,2,3,4- tetrahydro-isoquino-. line hydrochloride ··

Prepared from 6,7-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline and N- [3- (4-methoxy-phenoxy) -propyl] -3-chloromethyl-hexahydro-azepine according to Example 2.

Yield: 42 7, theor. ,

Melting point: 172-173 ° C

Calculated: C 69.04 H 8.07 N 5.75 Cl 7.28 Found: 69.06 8.25 5.57 7.39.

Example 224 2 - [(N- (3- (4-Methoxy-phenoxy) -propyl) -hexahydro-azepinyl-12β-β (3'-d) -methyl] -6,7-dimethoxy-1-oxo- 1,2,3, Q-tetrahydro-isoquino-aniline hydrochloride

Prepared from 6,7-dimethyl-1-oxo-1,2,3,5-tetrahydro-isoquinoline and N- [3- (N-methoxy-phenoxy) -propyl] -3-chloromethyl-hexahydro-azepine according to Example 2.

Yield: 63.3 7. theor. ,

Melting range: 115-120®C

Calc .: C 62.58 H 7.67 N 5.21 Cl 6.83

Found: 62, AA 7.68 A, 91 6.81

Example 225 2 - [(N- (2- (N-Methoxy-phenyl) -ethyl) -hexahydro-azepinyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3, A- tetrahydro-isoquinoline hydrochloride

Prepared from 6,7-dimethoxy-1-oxo-1,2,3,5-tetrahydro-isoquinoline and N- [2- (N-methoxy-phenyl) -ethyl] -3-chloro-ethyl-hexahydro-azepine according to Example 2.

Yield: 51.6% of theory,

Melting point: 110-113 ° C

Calc .: C 61.75 H 7.87 N 5.28 Cl 7.25 Found: 61.8A 8.02 5.16 7.22.

Example 226 2 - [(N- (2- (3, A-Diraethoxy-phenyl) -ethyl) -hexahydro-azepinyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3, A tetrahydro-iso-quinoline hydrochloride

Prepared from 6,7-dimethoxy-1-oxo-1,2,3,5-tetrahydro-isoquinoline and N- [2- (3,5-dimethoxy-phenyl) -ethyl) -3-chloromethyl -hexahydro-azepine according to Example 2.

: Yield: A5.5 7, from theoretical ·· 127 94343

Melting point: l07-1lieC

Calc .: C 62.61 H 7.69 N 5.21 Cl 6.60

Found: 62.78 8.00 5.00 6, A3.

Example 227 2 - [(N- (2- (3, A-Dimethoxy-phenyl) -ethyl) -hexahydro-azepinyl-3) -methyl] -6,7-dimethyl-1-oxo-1,2, 3, A-tetrahydro-iso-quinoline hydrochloride

Prepared from 6,7-dimethyl-1-oxo-1,2,3,5-tetrahydro-isoquinoline and N- [2- (3,3-dimethoxy-phenyl) -ethyl] -3-chloromethyl-hexahydro -azepine according to Example 2.

Yield: AA, 8 7. theor.

Melting point: 162-163eC

Calc .: C 66.57 H 8.18 N 5.5A Cl 7.02

Found: 66.67 8.A7 S, 35 7.11.

Example 228 3 - [(N- (2- (3, A-Dimethoxy-phenyl) -ethyl) -hexahydro-azepinyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3, A, 5-tetrahydro-2H3-benzazepine hydrochloride • ♦

Prepared from 7,8-dimethoxy-2-oxo-1,3,5,5-tetrahydro-2H-3-benzazepine and N- [2- (3,3-dimethoxyphenyl) ethyl] -3-chloromethyl -hexahydro-azepine according to Example 2. Yield: AI, 7 7, from theoretical.

Melting point: 102-105 * ^ 3

Calc .: C 63.19 H 7.36 N 5.08 Cl 6.65 Found: 63.09 7.52 A, 9A 6.72.

Example 229 3 - [(N- (2, (3, A-Dimethoxy-phenyl) -ethyl) -hexahydro-azepino-4 H 128 94343-yl) -methyl] -7,8-methylenedioxy-2 -oxo-1,3,5,5-tetrahydro-2H-3-benzazepine hydrochloride

Prepared from 7,8-methylenedioxy-2-oxo-1,3,5,5-tetrahydro-2H-3-benzazepine and N- [2- (3,5-dimethoxyphenyl) ethyl] -3-chloromethylhexahydro -azepine according to Example 2. Yield: 38.7 7, theor.

Melting point: 98-10 ° C

Calc .: C 61.01 H 7.69 N 5.08 Cl 6, A 3 Found: 60.86 7, A 3 A, 87 6.25.

Example 230 3 - [(N- (2- (N-Methoxy-phenyl) -ethyl) -hexahydro-azepinyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,5,5- tetrahydro-2H-3-benz-azepine hydrochloride

Prepared from 7,8-dimethoxy-2-oxo-1,3,5,5-tetrahydro-2H-3-benzazepine and N- [2- (N-methoxyphenyl) ethyl] -3-chloroethyl hexahydroxy azepine according to Example 2.

Yield: 51.2% of theory,

Melting point: 110-113 ° C

Calc .: C 63, A 3 H 7.98 N 5.28 Cl 7.02 · Found: 63.31 7.99 A, 93 7.05.

Example 231 3 - [(N- (3- (3, A-Methylenedioxy-phenoxy) -propyl) -hexahydro-azepinyl-3) -methyl] -7,8-methylenedioxy-2-oxo-1,3,4, 5-tetrahydro-2H-3-benzazepine hydrochloride

Prepared from 7,8-methylenedioxy-2-oxo-1,3,5,5-tetrahydro-2H-3-benzazepine and N- [3- (3,3-methylenedoxy-phenoxy) -propyl] -3-chloromethyl-hexahydro -azepine according to Example 2.

«129

O A 7 4 7 y ‘t u 4 J

Yield: 0.6% of theory,

Melting point: 106-109 ° C

Calc .: C 62.27 H 6.71 N 5.18 Cl 6.68

Found: 62.36 6.70 5.00 6.46.

Example 232 3 - [(N- (3- (3-Methyl-phenoxy) -propyl) -hexahydro-azepinyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5- tetrahydro-2H-3-benz-azepine hydrochloride

Prepared from 7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzazepine and N- [3- (3-methyl-phenoxy) -propyl] -3-chloromethyl-hexahydro-azepine according to Example 2. Yield: 44.4 Theoretical 7,

Melting point: 112-115 ° C

Calc .: C 66.20 H 8.04 N 5.32 Cl 6.86

Found: 65.98 7.96 5.36 6.90.

Example 233 3 - [(N- (3- (4-Methoxy-phenoxy) -propyl) -hexahydro-azepinyl-3) -methyl] -6,7-methylenedioxy-2-oxo-1,3,4,5- tetrahydro-2H3-> ·· benzazepine hydrochloride

Prepared from 6,7-methylenedioxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzazepine and N- [3- (4-methoxy-phenoxy) -propyl] -3-chloromethyl-hexahydro -azepine according to Example 2. Yield: 38.7% of theory.

Melting point: 121-126 ^ 0

Calc .: C 62.84 H 7.34 N 5.23 Cl 6.86 Found: 63.05 7.33 5.28 7.04.

it ·· • * 2 - [(N- (3- (3-Methyl-phenoxy) -propyl) -hexahydro-azepinyl-3) -methyl] -6,7-methylenedioxy-i-oxo-1,2,3 , A-tetrahydro-isoquinoline hydrochloride

Example 234 130 q /; 7 A 7 ^ ~ su -t u

Prepared from 6,7-methylenedioxy-1-oxo-1,2,3,5-tetrahydro-isoquinoline and N- [3- (3-methyl-phenoxy) -propyl] -3-chloro-methyl-hexahydro-azepine from Example 2 in accordance with.

Yield: A6.8 7. theor.

Melting point: 159-161 ° C

Calc .: C 65.37 H 7.31 N 5.6A Cl 7.28

Found: 65, AA 7.AO 5.39 7.23.

Example 235 2 - [(N- (3- (3-Methyl-phenoxy) -propyl) -hexahydro-azepinyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2,3, A- tetrahydro-isoquino-lxini hydrochloride

Prepared from 6,7-dimethoxy-1-oxo-1,2,3,5-tetrahydro-isoquinoline and N- [3- (3-methoxy-phenoxy) -propyl] -3-chloromethyl-hexahydro-azepine according to Example 2.

·· Yield: 55.2 7, theor.,

Melting point: 107-111 ° 0

Calc .: C 65.67 H 7.87 N 5, A7 Cl 7.05

Found: 65, A7 8.00 5.50 6.97.

Example 236 2 - [(N- (3- (3, A-Methylenedioxy-phenoxy) -propyl) -hexahydro-azepinyl-3) -methyl] -6,7-dimethyl-1-oxo-1,2,3, A-tetrahydroisoquinoline hydrochloride. Prepared from 6,7-dimethyl-1-oxo-1,2,3,A-tetrahydro-isoquino-131Q-7/17-J line and N- [3- (3, A-methylenedioxy-phenoxy) - propyl] -3-chloromethyl-hexahydro-azepine according to Example 2. Yield: 40.6% of theory,

Melting point: 123-126 ^ 0

Calculated: C 64.78 H 7.57 N 5.39 Cl 6.83 Found: 64.88 7.59 5.29 7.18.

Example 237 2 - [(N- (3- (3,4-Dimethoxy-phenoxy) -propyl) -hexahydro-azepinyl-3) -methyl] -6,7-dimethoxy-1-oxo-1,2, 3,4-tetrahydro-iso-quinoline hydrochloride

Prepared from 6,7-diraethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and N- [3- (3,4-dimethoxy-phenoxy) -propyl] -3-chloromethyl-hexahydro -azepine according to Example 2. Yield: 30.6 7. theoretical,

Melting point: 101-105 ° C

Calc .: C 62.61 H 7.59 N 5.01 Cl 6.46

Found: 62.56 7.76 4.94 6.39.

Example 238 * 2 - (N- (2- (3,4-Dimethoxy-phenyl) -ethyl) -hexahydro-azepinyl-3) -methyl] -5,6-dimethoxy-1-oxo-1,3 dihydro-isoindole-hydrochloride

Prepared from 2 - [(N- (2- (3,4-dimethoxy-phenyl) -ethyl) -hexahydro-azepinyl-3) -methyl] -5,6-dimethoxy-phthalimide and zinc / glacial acetic acid according to Example 4.

Yield: 41.8 Theoretical 7,

Melting point: 150-151eC

Calc .: C 61.99 H 7.57 N 5.35 Cl 6.57

Found: 61.89 7.48 5.17 6.52 «2 - [(N- (3- (3-Methyl-phenoxy) -propyl) -hexahydro-azepinyl-3) -methyl 3-5,6-dimethoxy -1-oxo-1,3-dihydro-isoindole hydrochloride

Example 239 132

<J / 1 i / 1 7 ^ "f J * t J

Prepared from 2 - [(N- (3- (3-methyl-phenoxy) -propyl) -hexahydro-azepinyl-3) -methyl 3-5,6-dimethoxy-phthalimide and zinc / glacial acetic acid according to Example 4.

Yield: 88.9 7. theor. ,

Melting point: 95-100 ° C

Calc .: C 63.95 H 7.75 N 5.52 Cl 7.25

Found: 64.09 7.64 5.35 7.37.

Example 240 2 - [(N- (3- (4-Methoxy-phenoxy) -propyl) -hexahydro-azepinyl-3) -methyl] -5,6-dimethoxy-1-oxo-1,3-dihydro-isoindole- hydro-chloride

Prepared from 2 - [(N- (3- (4-methoxy-phenoxy) -propyl) -hexahydro-azepinyl-3) -methyl] -5,6-dimethoxy-phthalimide and zinc / glacial acetic acid according to Example 4.

• Yield: 87.1 Theoretical 7,

Melting point · 107-112 ° 0

Calc .: C 61.99 H 7.51 N 5.35 Cl 7.02

Found: 62.07 7.37 7.28 7.31.

Example 241 2 - [(N- (3- (3,4-Methylenedioxy-phenoxy) -propyl) -hexahydro-azepinyl-3) -methyl] -5,6-dimethoxy-1-oxo-1,3-dihydro- big-indole hydrochloride

Prepare 2 - (N- (3- (3,4-methylenedioxyphenoxy) propyl) -1,133

0/7/12 τ sj -r J

hexahydro-azepinyl-3-methyl] -5,6-dimethoxy-phthalimide and zinc / glacial acetic acid according to Example 4.

Yield: 59% of theory,

Melting point: 104-107 ^ 0

Calculated: C 60.38 H 6.94 N 5.20 Cl 7.31

Found: 60.40 7.15 4.95 7.25.

Example 242 2 - [(N- (3- (3,4-Methylenedioxy-phenoxy) -propyl) -hexahydro-azepinyl-3) -methyl] -5,6-dimethoxy-1-oxo-1,3-dihydro- big-indole hydrochloride

Prepared from 2 - [(N- (3- (3,4-methylenedioxy-phenoxy) -propyl) -hexahydro-azepinyl-3) -methyl] -5,6-dimethoxy-phthalimide and zinc / glacial acetic acid according to Example 4.

Yield: 79.4% of theory,

Melting point: 112-116 ° C

Found: C 62.23 H 7.15 N 5.37 Cl 7.05 Found: 62.16 7.25 4.96 7.03.

Example 243 3 - [(N- (3- (Pyridyl-3) -propyl) -hexahydro-azepinyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3-dihydro-2H-3- benzazepine dihydrochloride dihydrate

Prepared from 7,8-dimethoxy-2-oxo-1,3-dihydro-2H-3-benzazepine and N- [3- (pyridyl-3) -propyl] -3-chloromethyl-hexahydro-azepine in dimethylsulfoxide in potassium with tert-butylate according to Example 2.

Yield: 86 7, theor ..

Melting point: 106-108 ° C

Calc .: C 58.05 H 7.40 N 7.52 Cl 12.69 Found: 57.94 7.55 7.75 12.42.

3 - [(N- (3- (Pyridyl-3) -propyl) -hexahydro-azepinyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H- 3-Benzazepine dihydrochloride dihydrate

Example 244 134 Γ ** / '7 fl "7 y h o 4 ό

Prepared from 3 - [(N- (3- (pyridyl-3) -propyl) -hexahydro-azepinyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3-dihydro-2H-3-benzazepine At 5 bar hydrogen pressure in the presence of 10¾ palladium / carbon in dimethylformamide at 0 ° C according to Example 5.

Yield: 43 7. theor. ,

Melting point: 119-121 ° 0

Calculated: C S7.85 H 7.73 N 7.49 Cl 12.65 Found: 57.74 7.79 7.23 12.50.

Example 245 3 - [(N- (3- (Pyridyl-3) -propyl) -hexahydro-azepinyl-3) -methyl] -7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3- benzazepine trihydrochloride-monohydrate

Prepared from 3 - [(N- (3- (pyridyl-3) -propyl) -hexahydro-azepinyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetra- hydro-2H-3-benzazepine and lithium aluminum hydride in tetrahydrofuran and diethyl ether according to Example 3.

Yield: 82 7 · theor.

Melting point: 139-144 ° C

Calc .: C 57.39 H 7.85 N 7.43 Cl 18.82

Found: 57.42 8.15 7.56 19.04.

Example 246 2 - [(N- (1- (Pyridyl-3) -methyl) -pyrrolidyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydroisoquinoline dihydrochloride dihydrate 135 Ο / 17/17

* 1 -w · '' 7 J

Prepared from 6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 3-chloromethyl-N-t (pyridyl-3) -methyl] -pyrrolidine in dimethylsulfoxide with potassium tert-butylate according to Example 2.

Yield: 46 7% of theory. ,

Melting point: 91-93 ° C

Calculated: C 53.17 H 6.16 N 8.85 Cl 14.95 Found: 53.31 5.93 8.71 15.01.

Example 247 2 - [(N- (1- (Pyridyl-3) -methyl) -pyrrolidyl-3) -methyl] -6,7-methylenedioxy-1,2,3,4-tetrahydro-isoquinoline trihydrochloride-1, 5 x hydrate

Prepared from 2 - [(N- (1- (Pyridyl-3) -methyl) -pyrrolidyl-3) -methyl] -6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and lithium aluminum hydride in tetrahydrofuran and diethyl ether according to Example 3.

Yield: 67% of theory,

Melting point: 178-181®C

Calculated: C 51.70 H 6.41 N 8.61 Cl 21.80 Found: 51.63 6.62 8.45 21.07.

Example 248 3 - [(N- (2- (6-Methyl-pyridyl-2) -ethyl) -hexahydro-azepinyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3- dihydro-2H-3-benzazepine dihydrochloride dihydrate

Prepared from 7,8-dimethoxy-2-oxo-1,3-dihydro-2H-3-benzazepine and N- [2- (6-methyl-pyridyl-2) -ethyl] -3-chloromethyl-hexahydro-azepine in dimethyl sulfoxide potassium 136 Q AT. A 7 '· ν' 'T o with tert-butylate according to Example 2.

Yield · 63% of theory. ,

Melting point: 13A-136 ° C

Calc .: C 58.05 H 7, AO N 7.52 Cl 12.69 Found: 58.15 7.60 7, A5 12, A5.

Example 2A9 3 - [(N- (2- (6-Methyl-pyridyl-2) -ethyl) -pyrrolidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3-dihydro-2H- 3-Benzazepine dihydrochloride x 1.5 hydrate

Prepared from 7,8-dimethoxy-2-oxo-1,3-dihydro-2H-3-benzazepine and 3-chloromethyl-N- [2- (6-methyl-pyridyl-2) -ethyl] -pyrrolidine in dimethyl sulfoxide using potassium tert-butylate according to Example 2.

Yield: 61% of theory,

Melting point: 78-80eC

Calculated: C 57.58 H 6.96 N 8.06 Cl 13.60 Found: 57, AO 7.18 8.2A 13.39.

Example 250 3 - [(N- (2- (6-Methyl-pyridyl-2) -ethyl) -hexahydro-azepinyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3, A, 5-Tetrahydro-2H-3-benzazepine dihydrochloride x 2.5 hydrate

Prepared from 3 - [(N- (2- (6-methyl-pyridyl-2) -ethyl) -hexahydroazepinyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3-dihydro-2H -3-benzazepine at 5 bar hydrogen pressure in the presence of palladium / carbon and diraethylformamide according to Example 5.

Yield: 3A% of theory,

Melting point: 112-11A ° C

Calc .: C 56.93 H 7.78 N 7.38 Cl 12, A5 Found: 56.83 8.0A 7, A3 12.26.

3 - [(N- (2- (6-Methyl-pyridyl-2) -ethyl) -hexahydro-azepinyl-3) -methyl] -7,8-dimethoxy-1,3,4,5-tetrahydro- 2H-3-Benzazepine trihydrochloride dihydrate

Example 251 137 94 - Λ 2

s -r o t J

Prepared from 3 - [(N- (2- (6-methyl-pyridyl-2) -ethyl) -hexahydro-azepinyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4 , 5-tetrahydro-2H-3-benzazepine and lithium aluminum hydride in tetrahydrofuran and diethyl ether according to Example 3.

Yield: 74 7. Theoretical,

Melting point: 148-150 ^ 0

Calc .: C 55.61 H 7.95 N 7.20 Cl 18.24 Found: 55.72 8.10 7.03 18.00.

Example 252 3-1 (N- (2- (6-Methyl-pyridyl-2) -ethyl) -pyrrolidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5- tetrahydro-2H-3-benzazepin-ne-dihydrochloride dihydrate

Prepared from 3 - [(N- (2- (6-methyl-pyridyl-2) -ethyl) -pyrrolidin-3) -methyl] -7,8-dimethoxy-2-oxo-1,3-dihydro-2H From 3-benzazepine and palladium / carbon in dimethylformamide at 50 ° C: 883 at 6 bar hydrogen pressure according to Example 5.

Yield: 28 7% of theory. ,

Melting point: 87-90eC

Calculated: C 56.38 H 7.38 N 7.89 Cl 13.31 Found: 56.33 7.53 8.09 13.43.

Example 253 3 - [(N- (2- (6-Methyl-pyridyl-2) -ethyl) -pyrrolidyl-3) -methyl] -7,8-dimethoxy-1,3,4,5-tetrahydro-2H- 3-Benzazepine trihydrochloride dihydrate 138

O A 2 A 7 '* r J * t J

Prepared from 7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepine and N- (2- (6-methyl-pyridyl-2) -ethyl] -3- (benzenesulfonyloxymethyl) -pyrrolidine in dimethylformamide and triethylamine according to Example 2.

Yield: 42 7, theor. ,

Melting point: 225-227 ** C

Calc .: C 54.10 H 7.62 N 7.57 Cl 19.16

Found: 54.18 7.55 7.51 19.30.

Example 254 2 - ((N- (3- (Indolyl-3) -propyl) -piperidyl-3) -methyl] -5,6-dimethoxy-1-oxo-1,3-dihydro-isoindole x 1.5 benzene sulfone carbonate trihydrate

Prepared from 2 - [(piperidyl-3) -methyl] -5,6-dimethoxy-1-oxo-1,3-dihydro-isoindole and 3- (3-benzenesulfonyloxy-propyl) -indole in dimethylformamide and triethylamine according to Example 1 .

Yield: 45 7, theor.,

Melting point: 87-89 ** C

Calc .: C 58.51 H 6.54 N 5.68

Found: 58.66 6.43 5.34.

Example 255 2 - [(N- (3- (Indolyl-3) -propyl) -piperidyl-3) -methyl] -6,7-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline- benzene-sulfonate-dihydrate

Prepared from 2 - [(piperidyl-3) -methyl] -6,7-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 3- (3-benzenesulfonyl-oxy-propyl) -indole in dimethylformamide and triethyl - 139 9 4543 in the amine according to Example 1.

Yield: 94 7. theor. ,

Melting point: 117-119 ** C

Calc .: C 65.46 H 7.27 N 6.73

Found: '65.51 6.91 6.72.

Example 256 3 - [(N- (3- (Indolyl-3) -propyl) -pyrrolidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H- 3-benzazepine-tetrahydro-chloride monohydrate

Prepared from 3 - [(N- (3- (indolyl-3) -propyl) -pyrrolidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3-dihydro-2H-3-benzazepine and 5 bar of hydrogen in the presence of palladium / carbon in dimethylformamide at 80 ° C according to Example 5.

Yield: 58 7 »theor ..

Melting point: 12-30 ° C

m.p .: C 65.16 H 7.42 N 8.14 Cl 6.87 Found: 65.12 7.55 8.11 7.06.

Example 257 3 - [(N- (3- (Indolyl-3) -propyl) -hexahydro-azepinyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro- 2H-3-benz-azepine-monohydrate

Prepared from 3 - [(hexahydro-azepinyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzazepine and 3- (3-benzenesulfonyloxy- propyl) indole in dimethylformamide and triethylamine according to Example 1.

Yield: 49 7, theor. ,

Melting point: 56-58 ** C

Calc .: C 70.98 H 8.14 N 8.27

Found: 71.08 8.10 8.16.

Example 258 3 - [(N- (3- (Indolyl-3) -propyl) -hexahydro-azepinyl-3) -methyl] -7,8-methylenedioxy-1,3,4,5-tetrahydro-2H-3- benzazepine dihydrochloride monohydrate 94343 140

Prepared from 3 - [(N- (3- (indolyl-3) -propyl) -hexahydro-azepinyl-3) -methyl] -7,8-methylenedioxy-2-oxo-1,3,4,5-tetrahydro -2H-3-benzazepine and lithium aluminum hydride in diethyl ether and tetrahydrofuran according to Example 3.

Yield: 56 7. theor. ,

Melting point: 155-158 ** C

Calc .: C 62.26 H 7.50 N 7.63 Cl 12.88 Found: 62.31 7.82 7.40 12.89.

Example 259 3 - {(N- (3- (Indolyl-3) -propyl) -pyrrolidyl-3) -methyl] -7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepine- di-dihydrochloride monohydrate

Prepared from 3 - [(N- (3- (indolyl-3) -propyl) -pyrrolidyl-3) -6 * methyl] -7,8-dimethoxy-2-oxo-1,3,4,5- tetrahydro-2H-3-benzazepine and lithium aluminum hydride in diethyl ether and tetrahydrofuran according to Example 3.

Yield: 60% of theory,

Melting point: 125-128 ° C

Calc .: C 62.44 H 7.67 N 7.80 Cl 13.16 Found: 62.35 7.87 7.59 13.67.

Example 260 2 - [(N- (3- (Indolyl-3) -propyl) -piperidyl-3) -methyl] -6,7-dimethyl-1,2,3,4-tetrahydro-isoquinoline dihydrochloride mono- hydrate 94343 141

Prepared from 2 - [(N- (3- (indolyl-3) -propyl) -piperidyl-3) -methyl] -6,7-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline and lithium aluminum hydride in diethyl ether and tetrahydrofuran according to Example 3.

Yield: 90 7. theor.,

Melting point: 198-201 ** C

Calc .: C 66.38 H 8.16 N 8.29 Cl 14.00 Found: 66.29 8.21 8.46 13.82.

Example 261 3 - [(N- (3- (Indolyl-3) -propyl) -hexahydro-azepinyl-3) -methyl] -7,8-methylenedioxy-2-oxo-1,3,4,5-tetrahydro- 2H-3-benzazepine hydrochloride monohydrate

Prepared from 3 - [(hexahydro-azepinyl-3) -methyl] -7,8-methylene-hydroxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzazepine and 3- (3- benzenesulfonyloxypropyl) indole according to Example 1.

Yield: 61.5% of theory,

Melting point: 62-64eC

Calc .: C 70.84 H 7.59 N 8.55

Found: 70.73 7.59 8.42.

Example 262 2 - [{N- (3- (Indolyl-3) -propyl) -pyrrolidyl-3) -methyl 3-6,7-dimethyl-1,2,3,4-tetrahydro-isoquinoline dihydrochloride semi- hydrate

2 - [(N- (3- (indolyl-3) -propyl) -pyrrolidyl-3) -methyl] -6,7-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline is prepared. and lithium aluminum hydride in ether according to Example 3 94343 142.

Yield: 86 7, theor. ,

Melting point: 143-145 ° C

Calculated: C 67.06 H 7.92 N 8.69 Cl 14.66 Found: 66.92 8.07 8.48 14.87.

Example 263 2 - (N- (3- (Indolyl-3) -propyl) -pyrrolidyl-3) -methyl 1-6,7-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline- hydrochloride x 1.5 hydrate

Prepared from 2 - [(pyrrolidyl-3) -methyl] -6,7-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 3- (3-benzenesulfonyl-oxy-propyl) -indole from Example 1 in accordance with.

Yield: 67 7, theor. ,

Melting point: H7-120eC

Calc .: C 67.69 H 7.78 N 8.77 Cl 7.40

Found: 67.62 7.80 8.72 7.93.

Example 264 3 - [(N- (3- (Indolyl-3) -propyl) -pyrrolidyl-3) -methyl] -7,8- ·· methylenedioxy-1,3,4,5-tetrahydro-2H-3- benzazepine dihydrochloride - 1.5 x hydrate

Prepared from 7,8-methylenedioxy-1,3,4,5-tetrahydro-2H-3-benzazepine and 3- (benzenesulfonyloxymethyl) -N- [3- (indolyl-3) -propyl] -pyrrolidine according to Example 2.

Yield: 75 7, theor.,

Melting point: 191-193 ** C

Calc .: C 61.01 H 7.21 N 7.90 Cl 13.34

Found: 60.90 7.27 7.85 13.70.

• ·

Example 26S

3 - [(N- (3- (Indolyl-3) -propyl) -hexahydro-azepinyl-3) -methyl] -7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepine- dihydrochloride monohydrate 143

Q A 1 Λ 7 / tot J

Prepare 3 - [(N- (3- (indolyl-3) -propyl) -hexahydro-azepinyl-3) -methyl] -7,8-diraethoxy-2-oxo-1,3,4,5-tetrahydro -2H-3-benzazepine and lithium aluminum hydride in tetrahydrofuran and diethyl ether according to Example 3.

Yield: 53 7. theor. ,

Melting point: 158-160eC

Calculated: C 63.58 H 8.00 N 7.41 Cl 12.51 Found: 63.41 8.18 7.36 12.23.

Example 266 3 - [(N- (3- (Indolyl-3) -propyl) -pyrrolidyl-3) -methyl] -7,8-dimethyl-1,3,4,5-tetrahydro-2H-3-butylenazazepine dihydro chloride monohydrate

Prepared from 3 - [(N- (3- (indolyl-3) -propyl) -pyrrolidyl-3) -methyl] -7,8-dimethyl-2-oxo-1,3,4,5-tetrahydro-2H-3 -ben-, • azepine and lithium aluminum hydride in tetrahydrofuran / ether according to Example 3.

Yield: 65 7, theor.,

Melting point: 168-170®C

Calculated: C 66.39 H 8.16 N 8.29 Cl 13.99 Found: 66.29 8.44 8.08 14.08.

Claims (5)

144 Ο Λ 1 Λ 7 S ^ «J‘ t J A process for the preparation of therapeutically active cyclic amine derivatives of the general formula (I) R 1 / CH 2> m R 2 -r N 1 - E - CH N - G - R, (I) (ch 2) / wherein A is -CH 2 - , -CH 2 -CH 2 - or -CH = CH group, B is -CH 2 - / -CH 2 -CH 2 · / or -CO- or -CH 2 CO group, wherein the carbon atom denoted by x is attached to the phenyl nucleus, E is 1 - a straight-chain alkylene group having 1 to 3 carbon atoms optionally substituted by an alkyl group of 3 carbon atoms, G is a straight-chain alkylene group having 1 to 6 carbon atoms, wherein the methylene group attached to the aromatic or heteroaromatic group R may be replaced by an oxygen atom, R 1 and R 2 each , having 1 to 3 carbon atoms, or R 1 and R 2 together are an alkylenedioxy group having 1 or 2 carbon atoms, m is 1, 2, 3, 4, 5 or 6 and n is 0, 1, 2 or 3, however the sum n + m must be 3, 4, 5 or 6 and R is optionally methyl-substituted furyl, road a yl, pyridyl, benzo [b] furyl or benzo [b] thienyl group, a benzo [b] thienyl group substituted by a halogen atom, a methoxy or methanesulfonyloxy group, a naphthyl group which may be mono- or disubstituted by a methyl or a methoxy group, the substituents may be the same or different, or also, when B is a -CH 2 - or -CO group, a phenyl group optionally substituted by a methylenedioxy group, a phenyl group which is mono- or disubstituted with methyl or methoxy groups, the substituents being identical or different, their N-oxides and their acid addition salts, characterized in that a) the compound of the general formula II is (VA) / (C '2K FU-r- I NE-); CH NH, (II) 1 / Z n wherein R 1, R 2 / A, B, E, m and n are as defined above are reacted with a compound of general formula III Zx - G - R (III) wherein R and G are same as above and Z 1 is a nucleophilic exit a group, a hydroxy group or together with the hydrogen atom of an adjacent methylene group represents an acid atom, or b) a compound of general formula IV R 1 r 2 - | J - H, (IV) 94343 146 wherein R 1, 1 * 2 »A and B have the same meaning as above, are reacted with a compound of general formula V / (CHaV Z„ - E - CH N - G - R. ) 2 / X (CH 2) / wherein R, E, G, m and n are as defined above and Z 2 is a nucleolyl leaving group, or c) compounds of general formula I wherein B is -CH 2 - or -CH 2 CH 2 - group, is prepared by reducing a compound of general formula VI "W /% \ R, - '. N - E - CH N - G - R, (VI) ^ X. / \ / (CH2> n where R, R R 2, A, E, G, m and n have the same meaning as above and B 1 is a -CO- or -CH 2 CO group in which the carbon atom denoted by x is attached to the phenyl ring, or d) compounds of the general formula I in which A is - CH2w group and B is a -CO- or -CH2CO group, to be prepared by reduction with a evolving hydrogen of a compound of general formula VII 94343 147 1 / cil2) \ R Γ I ne-ch n - g - r, (VII) / \ / (CH2 ^ n wherein R,, R2, E, G, m and n have the same meaning as ede and B2 is a -CO- or -C ^ CO group wherein the carbon atom denoted by the letter x is attached to the phenyl ring, or e) compounds of general formula I in which G is the same as G above except for groups containing a sulfur atom, a sulfinyl or sulfonyl group, and A is a -CH 2 -CH 2 - group and B is a -CH 2 -, -CO- or -Cl 2 CO group, to prepare a compound of general formula VIII R 1, v / CH 2> m is hydrogenated; n__ NE-CH N - G- - R (VIII) JJL / \ / where R, R1, R2, B, E, m and n have the same meaning as above, G1 means the same as G above except for the sulfur atom, sulfinyl- or sulfonyl-containing groups and B3 is a -CH2-, -CO- or -CH2_CO- group, and 94343148, if necessary, are then cleaved off during the reaction a) to e) by reactive groups such as hydroxy, amino, alkylamino or imino groups. the protecting group used for protection and / or, if desired, the resulting compound of general formula I in which R contains a nitro group is subsequently converted to the corresponding amino compound of general formula I and / or the compound of general formula I thus obtained in which R contains an amino group is converted by acylation to the corresponding alkanoylamino and / or the compound of the general formula I thus obtained is converted into its acid addition salts, in particular into its physiologically acceptable acid addition salts. or organic acids. A process according to claim 1 for the preparation of 3 - [(N- (2- (naphthyl-2) -ethyl) -piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4,5 -tetrahydro-2H-3-benzazepine, and a pharmaceutically acceptable acid addition salt thereof, characterized in that the corresponding starting materials are used. A process according to claim 1 for the preparation of 3- [2- (N- (2- (6-methoxy-naphthyl-2) -ethyl) -piperidyl-2) -ethyl] -7,8-; dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzazepine, and a pharmaceutically acceptable acid addition salt thereof, characterized in that the corresponding starting materials are used. A process according to claim 1 for the preparation of 2 - [(N- (3- (6-methoxy-phenoxy-2) -propyl) -piperidyl-3) -methyl] -6,7-dimethyl-1-oxo-1,2 , 3,4-tetrahydroisoquinoline, and a pharmaceutically acceptable acid addition salt thereof, characterized in that the corresponding starting materials are used. 149 J H Zi * T 3 A process according to claim 1 for the preparation of 3 - [(N- (4- (thienyl-2) -butyl) -piperidyl-3) -methyl] -7,8-dimethoxy-2-oxo-1,3,4 , 5-tetrahydro-2H-3-benzazepine, and a pharmaceutically acceptable acid addition salt thereof, characterized in that the corresponding starting materials are used. 94343 150