NO171017B - ANALOGY PROCEDURE FOR THE PREPARATION OF NEW THERAPEUTIC 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

British patent specification 1 548 844 describes compounds with formula

and their physiologically acceptable acid addition salts which have shown valuable pharmacological properties, such as a mild blood pressure lowering effect, especially a selective heart rate lowering effect. Surprisingly, it has now been found that the new cyclic amine derivatives with the general formula

their N-oxides and their physiologically acceptable acid addition salts with inorganic or organic acids exhibit even more valuable pharmacological properties, in particular a blood pressure-lowering and a long-acting heart rate-lowering effect and a reducing effect on the heart's O2 demand.

The present invention thus relates to a process for the production of the new cyclic amine derivatives of the general formula I, their N-oxides, and their physiologically acceptable acid addition salts with inorganic or organic acids.

In the above general formula I means

A a -CH2-, -CH2-CH2- or -CH=CH group,

B a -CH2-, -CH2-CH2-, -CO- or -CH2CO group,

X

where the carbon atom marked with X is attached to the phenyl nucleus,

E is a straight-chain alkylene group with 1-3 carbon atoms which is optionally substituted with an alkyl group with 1-3 carbon atoms,

G a straight-chain alkylene group with 1-6 carbon atoms, where the methylene group which is connected to an aromatic or heteroaromatic residue R can be replaced by an oxygen atom,

Rx and R2 each a (C^-C^) alkyl or (c1~c3) alkoxy group, or

Rx and R2 together form an alkylenedioxy group with 1 or 2 carbon atoms,

m the number 1, 2, 3, 4, 5 or 6, and

n the number 0, 1, 2 or 3, where however n + m must be the number 3, 4, 5 or 6, and

R an optionally methyl-substituted furyl, thienyl, pyridyl, benzo[b]furyl or benzo[b]thienyl group, a

benzo[b]thienyl group which is substituted with a halogen atom, a methoxy or methanesulfonyloxy group, a naphthyl group which is optionally mono- or disubstituted with methyl or methoxy groups, where the substituents may be the same or different, or when B constitutes a -CH2- or CO group, a phenyl group which is optionally substituted with a methylenedioxy group, a phenyl group which is mono- or

disubstituted with methyl or methoxy groups, where the substituents may be the same or different.

Preferred compounds of the general formula I are those wherein

A, B, G, R, m and n are as initially defined,

E is a straight-chain alkylene group with 1-3 carbon atoms,

Rx is a methyl or methoxy group,

R2 is a methyl or methoxy group or Rx and R2 together constitute a methylenedioxy group and

especially compounds of the general formula

where

R1, R2, R, A, B, E, G, m and n are as defined above, as well as their N-oxides and their physiologically acceptable acid addition salts.

Particularly preferred compounds of the general formula I are those where

A means a -CH2CH2 group,

B is a -CH2-, -CH2-CH2-, -CO- or -CH2CO group,

X

where the carbon atom marked with X is attached to the phenyl nucleus,

E is a methylene or ethylene group,

G is a straight-chain alkylene group with 2-4 carbon atoms, where the methylene group in a straight-chain alkylene group with 3 or 4 carbon atoms which is connected to an aromatic or heteroaromatic residue R, can be replaced with an oxygen atom,

Rx is a methoxy group,

R2 is a methoxy group or Rx and R2 together form a methylenedioxy group,

m is the number 2, 3 or 4,

n is the number 1 and

R means a naphthyl-2-, 6-methoxy-naphthyl-2-, 5-methyl-6-methoxy-naphthyl-2-, thienyl-2-, benzo[b]furyl-2- or benzo[b]thienyl- 3 group or, when B constitutes the -CH2 or -CO group, a 4-methoxyphenyl or 3,4-dimethoxyphenyl group, as well as their physiologically acceptable acid addition salts.

Particularly preferred compounds are the following: 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-methoxyphenoxy)-propyl)-piperidyl-3)-methyl]-6,7-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline, and

3-[(N-(4-(thienyl-2)-butyl)-piperidyl-3)-methyl]-7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3- benzazepine,

and their physiologically acceptable acid addition salts.

According to the invention, the new compounds with the general formula I are obtained by the following methods:

a) Reaction of a compound with the general formula

where

R1r R2, A, B, E, m and n are as previously defined, with a compound of the general formula

where

R and G are as previously defined, and

Zx 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 1X together with the hydrogen atom of the adjacent methylene group constitutes an oxygen atom.

If Z: means a nucleophilic leaving group, the reaction is conveniently carried out in a solvent or a solvent mixture such as acetone, diethyl ether, methylformamide, dimethylformamide, dimethylsulfoxide, benzene, chlorobenzene, tetrahydrofuran, benzene/tetrahydrofuran, dioxane or in an excess of one of the compounds used with the general formula II and/or III and optionally in the presence of an acid binding agent, e.g. an alcoholate such as potassium tert-

in

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 hydride such as sodium hydride, a tertiary organic base such as triethylamine or pyridine, where the latter can also serve as a solvent at the same time, or a catalyst such as potassium iodide, and depending on the reactivity of the nucleophilically replaceable residue, 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 turnover can also be carried out without a solvent. It is particularly advantageous to carry out the reaction in the presence of a tertiary organic base or an excess of the amine used with the general formula II.

If Z1 means a hydroxy group, the reaction is preferably carried out in a suitable solvent such as methanol, ethanol, tetrahydrofuran, dioxane, ethyl acetic acid ester or glacial acetic acid, with hydrogen in the presence of a hydrogenation catalyst such as platinum, palladium/charcoal or Raney nickel at a hydrogen pressure of 2-10 bar, preferably at 5 bar, and at temperatures between 20 and 120°C, preferably at temperatures between 50 and 100°C.

If Z1 together with a hydrogen atom in the adjacent methylene group means an oxygen atom, the reaction is preferably carried out in a suitable solvent such as methanol, ethanol, tetrahydrofuran, dioxane, ethyl acetate or glacial acetic acid, with hydrogen in the presence of a hydrogenation catalyst such as platinum, palladium/coal or Raney- nickel at a hydrogen pressure of 2-10 bar, preferably 5 bar, and at temperatures between 20 and 12 0°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 temperatures between 0 and 50°C, preferably at room temperature.

b) Reaction of a compound with the general formula

where

R 1 , R 2 , A and B are as initially defined, with a compound of the general formula

where

R, E, G, m and n are as initially defined and

22 constitutes a nucleophilic leaving group such as a halogen atom or a sulfonyloxy group, e.g. a chlorine, bromine or iodine atom, or the methanesulfonyloxy, p-toluenesulfonyloxy or ethoxysulfonyloxy group.

The reaction is conveniently carried out in a solvent or a solvent mixture such as methylformamide, dimethylformamide, dimethylsulfoxide, benzene, chlorobenzene, tetrahydrofuran, benzene/tetrahydrofuran or dioxane, in the presence of an acid-binding agent, e.g. 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 or an alkali hydride such as sodium hydride, suitably at temperatures between 0 and 150°C, preferably at temperatures between 0 and 50° C. c) For the preparation of compounds of the general formula I, where B constitutes a -CH2- or -CH2CH2 group:

reduction of a compound with the general formula

where

R, Rx, R2/ E, G, m and n are as initially defined, Ai constitutes a -CH2~, -CH2-CH2~, -CH=CH- or -C0 group,

and

Bx constitutes a -CO- or -CH2CO group,

X

where the carbon atom marked with X is attached to the phenyl nucleus.

The reduction is preferably carried out with a metal hydride such as lithium aluminum hydride or diborane or with a complex of borane and a thioether, e.g. with borane-dimethylsulphide complex, in a suitable solvent such as diethyl ether or tetrahydrofuran, at temperatures between 0 and 80°C, preferably at temperatures < between 10 and 45°C.

d) For the preparation of compounds of the general formula I, where A constitutes a -CH2 group and B a -CO or -CH2C0 group: '

reduction of a compound with the general formula

where

R, R1# R2, E, G, rn and n are as initially defined and

B2 constitutes a -CO- or -CH2CO group,

X

where the carbon atom marked with X is attached to the phenyl nucleus, with nascent 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 nascent hydrogen, e.g. 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) For the preparation of compounds of the general formula I, where G, with the exception of residues containing a sulfur atom, a sulfinyl or sulfonyl group, have the meanings mentioned for G at the beginning and A constitutes the -CH2-CH2 group and B -CH2 ~,

-CO or -CH2CO group:

hydration of a compound of the general formula

where

R, Rlt R2, B, E, m and n are as initially defined,

Gx, with the exception of residues containing a sulfur atom, a sulfinyl or sulfonyl group, have the meanings mentioned for G at the beginning and

B3 constitutes a -CH2-, -CO- or -CH2CO group.

The hydrogenation is carried out in a solvent or a solvent mixture such as methanol, ethanol, ethyl acetate or glacial acetic acid, with catalytically activated hydrogen, e.g. with hydrogen in the presence of platinum or palladium/carbon, at a hydrogen pressure of 1-7 bar, preferably 3-5 bar and at temperatures between 0 and 75°C, preferably at temperatures between 20 and 50°C.

In the reactions described above, possibly occurring reactive groups such as hydroxy, amino, alkylamino or imino groups can be protected during the reaction by means of common protective groups which are split off again after the reaction.

For example, as protective residue for a hydroxy group, the trimethylsilyl, acetyl, benzoyl, benzyl or tetrahydropyranyl group and as protective residue for an amino, alkylamino or imino group, the acetyl, benzoyl, ethoxycarbonyl or benzyl group, come into consideration.

The possibly subsequent cleavage of an applied protective residue preferably takes place hydrolytically in an aqueous solvent, e.g. in 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 at temperatures between 0 and 100°C, preferably at the boiling point of the reaction mixture. However, the removal of a benzyl residue preferably occurs hydrogenolytically, e.g. with hydrogen in the presence of a catalyst such as palladium/charcoal, in a solvent such as methanol, ethanol, 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 1-7 bar, preferably 3-5 bar.

If, according to the invention, a compound with the general formula I is obtained, where R contains a nitro group, then it can be reduced to a corresponding amino compound with the general formula I,

while a compound of the general formula I, where R contains an amino group, can be transferred into a corresponding alkanoylamino compound of the general formula I by means of acylation.

The subsequent reduction of the nitro compound is preferably carried out in a solvent such as water, water/ethanol, methanol, glacial acetic acid, ethyl acetate or dimethylformamide, suitably with hydrogen in the presence of a hydrogenation catalyst such as Raney nickel, platinum or palladium/charcoal, with metals such as iron , tin or zinc in the presence of an acid, with salts such as tin(II) sulfate, tin(II) chloride or sodium dithionite, or with hydrazine in the presence of Raney nickel at temperatures between 0 and 50°C, preferably at room temperature.

The subsequent acylation is conveniently carried out in a solvent such as methylene chloride, chloroform, tetrachloromethane, ether, tetrahydrofuran, dioxane, benzene, toluene, acetonitrile or dimethylformamide, preferably with a reactive derivative of the acid, for example with acetyl chloride, acetic anhydride or propionic anhydride, and optionally in the presence of an inorganic base, such as sodium carbonate, or a tertiary organic base, such as triethylamine or pyridine, which can simultaneously serve as a solvent, at temperatures between -25°C and 100°C, preferably at temperatures between -10°C and the boiling point of the used solvent.

As the obtained compounds of the general formula I have at least one chiral center, they can be resolved by usual methods into their diastereomers, for example by column chromatography, and into their enantiomers, for example by column chromatography on a chiral phase or by crystallization with optical active acids, e.g. with D- or L-monomethyltartaric acid, D- or L-diacetyltartaric acid, D- or L-tartaric acid, D- or L-lactic acid or D- or L-camphoric acid.

The obtained compounds of the general formula I can also be transferred in their acid addition salts, especially for their pharmaceutical use, in their physiologically acceptable acid addition salts with inorganic or organic acids. Acids include, 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 II to VIII which are used as starting materials are partly known from the literature and can partly be obtained by known methods.

Thus, for example, a starting compound with the general formula II is obtained by alkylation of a corresponding imino compound IV, with a cyclic amine protected in the N atom which is substituted in the carbon skeleton with an alkyl residue, which in turn is terminally substituted with a nucleophilic leaving group, and subsequent cleavage of the protective residue used. The necessary cyclic amine is obtained by converting a corresponding hydroxyalk<y>lsubstituer<t> cyclic amine into the suitable halogen or sulfonic acid ester, and the required imino compound with the general formula IV by cyclization of a corresponding compound, e.g. by cyclization of a compound of the general formula

or also with the general formula

optionally with subsequent catalytic hydrogenation and/or reduction of the carbonyl group, for example with

sodium borohydride/glacial acetic acid (see EP-A1 0.007.070, EP-A1 0.065.229 and EP-A1 0.109.639).

A starting compound with the general formula V is obtained by N-alkylation of a corresponding cyclic amine which in the carbon skeleton is substituted with a hydroxyalkyl residue, with a corresponding compound or with a corresponding 1, dihaloalkane and subsequent reaction with a corresponding HO-, SH- or HN compound and, if necessary, by subsequent oxidation, whereby a hydroxyalkyl compound thus obtained is transferred into its reactive halogen or sulfonic acid ester.

Starting compounds of formula VI, VII and VIII are preferably obtained by reacting an equivalent

halogen compound with a corresponding amine, optionally followed by cleavage of protective residues which are used for the protection of amino groups.

As already mentioned, the new compounds of formula I and their physiologically acceptable acid addition salts with inorganic or organic acids exhibit valuable pharmacological properties, in particular a blood pressure-lowering and a particularly long-lasting heart rate-lowering effect as well as a lowering effect on the heart's Oz demand, while central side effects are weak.

The following connections:

A = 3-[(N-(2-(naphthyl-2)-ethyl)-piperidyl-3)-methyl]-7,8- dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzazepine hydrochloride,

B = 3-[ (N-(2-(5-methyl-6-methoxy-naphthyl-2)-ethyl)-piperidyl-3)-

methyl ] -7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzazepine hydrochloride,

C = 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 hydrochloride,

D = 2-[ (N-(2-(6-methoxy-naphthyl-2)-ethyl)-hexahydro-azepinyl-3)-methyl]-6,7-methylenedioxy-1-oxo-1,2,3, 4-tetrahydro-isoquinoline hydrochloride,

E = 2-[(N-(2-(naphthyl-2)-ethyl)-hexahydro-azepinyl-3)-methyl]-6,7-methylenedioxy-1-oxo-1; 2,3,4-tetrahydro-isoquinoline hydrobromide,

F = 2-[(N-(2-(3,4-dimethoxyphenyl)-ethyl)-piperidyl-3)-methyl]-6,7-dimethyl-1,2,3,4-tetrahydro-isoquinoline dihydrochloride,

in

G = 2-[ (N-(2-(3,4-dimethoxyphenyl)-ethyl)-piperidyl-3)-methyl]-6,7-dimethyl-1-oxo-1,2,3,4-rtetrahydro- isoquinoline hydrochloride,

H = 2-[ (N-(3-(4-methoxy-phenoxy)-propyl)-piperidyl-3)-methyl]-6,7-dimethyl-1-oxo-1,2,3,4^tetrahydro-isoquinoline, hydrochloride,

I = 3-[(N-(4-(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-1,3,4,5-tetrahydro- 2H-3-benzazepine hydrochloride and

L = 3-[ (N-(2-(benzo[b]thienyl-3)-ethyl)-piperidyl-3)-methyl]-7,8-dimethoxy-2-oxo-1,3,4,5- tetrahydro-2H-3-benzazepine hydrochloride

M = 2-[(N-(3-(6-methoxy-naphthyl-2-oxy)-propyl)-hexahydro-azepinyl-3)-methyl]-1,3-dihydro-5,6-dimethoxy-isoindole,

N = 2-[(N-(3-(3-methyl-phenoxy)-propyl)-hexahydro-azepinyl-3 )-methyl]-5,6-dimethoxy-1-oxo-1,3-dihydro-isoindole- hydrochloride,

0 = 2-[N-(2-(3,4-dimethoxy-phenyl)-ethyl)-piperidyl-3)-methyl]-5,6-dimethoxy-1-oxo-1,3-dihydro-isoindole hydrochloride ,

P = 2-[(N-(2-(4-methyl-phenyl)-ethyl)-piperidyl-3)-methyl]-5,6-dimethoxy-1-oxo-1,3-dihydro-isoindole,

Q = 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 HC1 x H20 and

R = 3-[(N-(2-(6-methyl-pyridyl-2)-ethyl)-pyrrolidyl-3)-methyl]-7,8-dimethyl-2-oxo-1,3-dihydro-2H- 3-benzazapine dihydrochloride hemihydrate

were examined for their biological properties as follows:

Effect on heart rate in rats:

The effect of the test substance on the heart rate was examined for each dose on two rats with an average weight of 250-300 g. During this, the rats were anesthetized with pentobarbital (50 mg/kg i.p. and 20 mg/kg s.c.). The test substance was injected 1 aqueous solution into the jugular vein (0.1 ml/100 g).

Blood pressure was measured via a cannula in the carotid artery, and heart rate was recorded by ECG derived with needle electrodes (II. or III. lead). The animals' heart rate during the control period was between 350 and 400 beats/minute (S/min.).

The following table contains the obtained values:

The compounds produced according to the invention show no toxic side effects whatsoever in therapeutic doses. With an intravenous supply of the substances A and L, no toxic side effects could be detected, apart from a weak sedative effect, at a high dosage of 20 mg/kg in mice.

Due to their pharmacological properties, the new compounds are suitable for the treatment of sinus tachycardias of various genesis and for the prophylaxis and therapy of ischemic heart disorders.

The necessary dose to achieve an appropriate effect is suitably 1 to 2 times daily administration of 0.01 to 0.2 mg/kg body weight, preferably 0.03-0.15 mg/kg body weight. For this purpose, the compounds of the general formula I, as well as their physiologically acceptable acid addition salts, together with inorganic or organic acids, possibly in combination with other active ingredients, can be incorporated together with one or more inert usual carriers and/or diluents, such as e.g. . corn starch, milk sugar, cane sugar, microcrystalline cellulose, magnesium stearate, polyvinylpyrrolidone, citric acid, tartaric acid, water, water/ethanol, water/glycerol, water/sorbitol, water/polyethylene glycol, propylene glycol, carboxymethyl cellulose, or fatty substances such as hard fat and suitable mixtures thereof, in common galenic preparations such as tablets, dragees, capsules, powders, suspensions, drops, ampoules, syrups or lozenges.

Example A 2-[(piperidyl-3)-methyl]-6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline

a) N-benzyl-3-(hydroxymethyl)-piperidine

A mixture of 40.3 g (0.35 mol) 3-(hydroxymethyl)-piperidine, 97.4 ml (0.70 mol) triethylamine and 40.3 ml

(0.35 mol) of benzyl chloride was heated to 95°C within 30 minutes and held at this temperature for 2 hours. The cooled reaction mixture was dissolved in a mixture of 2 molar caustic soda and acetic acid. The organic phase was washed with water, separated, dried over magnesium sulfate and evaporated in vacuo.

Yield: 57.2 g, (79.6% of the theoretical) ,

Rf value: 0.45 (alumina, neutral, mobile phase: 3% ethanol in methylene chloride).

b) N-Benzyl-3-benzenesulfonyloxymethyl)-piperidine

A mixture of 6.8 g (0.033 mol) N-benzyl-3-(hydroxymethyl)-piperidine, 6.7 ml (0.052 mol)

benzenesulfonic acid chloride, 50 ml of 20% aqueous sodium hydroxide solution, 100 ml of toluene and 1 spatula tip of tetrabutylammonium bromide were stirred for 3 hours at room temperature. The mixture was then diluted with 250 ml of ethyl acetate and the organic phase washed with water. The organic phase was separated, dried over magnesium sulfate and evaporated to dryness in vacuo. The purification of the residue was carried out over 200 g of silica gel (0.063-0.2 mm) with methylene chloride and then with increasing proportions of ethanol (to 5%).

Yield: 9.4 g (92% of theoretical),

Rf value: 0.5 (silica gel, mobile phase: 5% 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) of 6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline were dissolved in 70 ml of dimethyl sulfoxide and, with stirring, added 3.1 g (0.025 mol) of potassium tert .butylate. After 1/2 hour, the obtained potassium salt suspension was added

9.3 g (0.0275 mol) of N-benzyl-3-(benzenesulfonyloxymethyl)-piperidine in 20 ml of dimethylsulfoxide and stirred for 2 hours at 40°C. The mixture was poured onto ice water and extracted 3 times with

120 ml portions of ethyl acetate. The combined organic phases were washed with water, dried over magnesium sulfate and evaporated in vacuo. The obtained residue was purified over 200 g of silica gel (0.063-0.2 mm) with methylene chloride and subsequent increasing proportions of ethanol (to 2%).

Yield: 7.7 g (78.5% of the theoretical),

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

d) 2-[(piperidyl-3)-methyl]-6,7-dimethoxy-1-oxo-1, 2. 3. 4- tetrahydroisoquinoline

9.4 g (0.0238 mol) 2-[(N-benzyl-piperidyl-3)-methyl]-6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline in 200 ml methanol, was hydrogenated in the presence of 2 g of 20% palladium hydroxide/charcoal for 3 hours at room temperature and 5 bar of hydrogen. The catalyst was then sucked off and the filtrate evaporated to dryness in vacuo.

Yield: 7.2 g (99% of theoretical),

Rf value: 0.15 (silica gel, eluent: 10% ethanol in methylene chloride and 1 drop of ammonia).

Example B

3- chloromethyl- N- r 3- f naphthyl- 2- oxy)- propyl]- piperidine

a) 3-hydroxymethyl)-N-\3-(naphthyl-2-oxv)-propyl]-piperidine A mixture of 11.5 g (0.2 mol) 3-hydroxy-methyl-piperidine and 11 g of 2-( 3-Chloropropoxy)-naphthalene was heated for 1 hour at 120°C. The residue was purified over silica gel (0.063-0.2 mm) with ethyl acetate/ethanol/ammonia = 90:10:1.

Yield: 11.5 g (76.6% of the theoretical).

M.p.: 99-101°C.

b) 3-chloromethyl-N-r3-(naphthyl-2-oxy)-propyl-1-piperidine

A solution of 1.5 g (5 mmol) 3-(hydroxymethyl)-N-[3-(naphthyl-2-oxy)-propyl]-piperidine in 25 ml of chloroform was added with 1.5 ml of thionyl chloride and boiled under reflux for 1.5 hours. Evaporation was carried out in vacuo, after which the residue was taken up in methylene chloride, washed with water, 2 molar caustic soda and then again with water. After drying over magnesium sulfate, the methylene chloride phase was evaporated in vacuo. Yield: 1.4 g (87.5% of the theoretical).

Rf value: 0.8 (silica gel, eluent: ethyl acetate/ethanol/-

ammonia = 90:40:2) i

Example C

2-[(hexahydro-azepinyl-3)-methyl]-6,7-methylenedioxy-1-oxo-1. 2. 3. 4- tetrahydro- isoquinoline

a) N-benzylcaprolactam

33.9 g (0.3 mol) caprolactam was dissolved in 250 ml

dimethyl sulfoxide and, with stirring, added 37 g (0.33 mol) of potassium tert.butylate. The reaction temperature thereby rose to 60°C. The mixture was stirred for 1/2 hour at 60°C and then 35 ml (0.3 mol) of benzyl bromide was added dropwise. After a further 2.5 hours at 60°C, the mixture was poured into 1 liter of ice water and decanted 3 times with ethyl acetate. The organic phases were combined, washed with water, dried over magnesium sulfate and evaporated in vacuo.

Yield: 60.3 g (99% of the theoretical),

Rf value: 0.6 (silica gel, eluent: 5% ethanol in

methylene chloride).

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

To 33.9 g = 47.1 ml (0.33 mol) of diisopropylamine in 450 ml

absolute ether, 180 ml of 2.6 molar butyllithium solution in n-hexane at -60°C were added while stirring under nitrogen. It was then added dropwise while continuing to cool

48.8 g (0.24 mol) of N-benzyl-caprolactam dissolved in 150 ml of absolute ether. After 10 minutes of stirring, the cooling bath was removed and carbon dioxide introduced for 15 minutes.

The reaction mixture was poured onto ice, after which the ether phase was separated and decanted twice with 2 molar caustic soda. The aqueous alcohol phases were combined, decanted with ether, acidified with concentrated hydrochloric acid and decanted twice with methylene chloride. The combined methylene chloride phases were dried over magnesium sulfate, and the solvent was distilled off in vacuo.

Yield: 15.7 g (26.5% of the theoretical),

IR spectrum (methylene chloride): 1735 and 1600 cm"<1> (CO).

c. 1-benzoyl-2-hydroxymethyl-hexahydro-azepine

To 6.84 g (0.28 mol) of lithium aluminum hydride in 300 ml of absolute tetrahydrofuran, 14.8 g (0.06 mol) of 1-benzyl-caprolactam-3-carboxylic acid, dissolved in 300 ml of absolute tetrahydrofuran, were added dropwise. The mixture was boiled under reflux for 6 hours and then under cooling with ice water added 6.8 ml of water, 6.8 ml of 2 molar caustic soda and 21 ml of water. The precipitate was suctioned off, washed with tetrahydrofuran and the filtrate evaporated in vacuo. The residue was purified by column chromatography over alumina (activity II, eluent: methylene chloride).

Yield: 8.4 g (63.8% of the theoretical).

IR spectrum (methylene chloride) : 3620 cm"<1> (OH) .

d) l-benzyl-3-(4-toluenesulfonyloxymethyl)-hexahydro-azepine 15 g (0.0684 mol) l-benzyl-3-hydroxymethyl-hexahydro-azepine was dissolved in 150 ml of pyridine and, with stirring, added 14.3 g (0.075 mol) p-toluenesulfonic acid chloride and stirred for 1 hour at room temperature. The mixture was evaporated in vacuo, the residue taken up in methylene chloride and washed with 2 molar sodium hydroxide solution and with water. After drying over magnesium sulfate, the organic phase was evaporated in vacuo.

Yield: 23.3 g (91.3% of the theoretical),

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

e) 2-[(N-benzyl-hexahydro-azepinyl-3)-methyl]-6,7-methylene-dioxv-l-oxo-1.2,3.4-tetrahydro- isoquinoline

7.4 g (0.0387 mol) of 6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline was dissolved in 100 ml of dimethylsulfoxide, to which was added 4.5 g (0.04 mol) of potassium -tert.butylate and stirred for 1/2 hour at room temperature. To the mixture was then added 16.8 g (0.044 mol) of 1-benzyl-3-(4-toluenesulfonyloxymethyl)hexahydro-azepine and stirred for 3 hours at room temperature.

The reaction mixture was dissolved in ethyl acetate and shaken twice with water. The organic phase was dried over magnesium sulfate and evaporated in vacuo. The residue was purified over alumina N (activity II, eluent: methylene chloride, methylene chloride + 2% ethanol).

Yield: 3.0 g (19.6% of the theoretical),

Rf value: 0.6 (silica gel, eluent: 5% 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 in 250 ml methanol was hydrogenated in the presence of 2 g of 20% palladium hydroxide/charcoal for 4 hours at room temperature under 5 bar of hydrogen. The catalyst was then sucked off and the filtrate evaporated in vacuo. The residue was crystallized from acetone. Yield: 4.9 g (95% of theoretical).

M.p.: 267-269°C.

Example D

3- chloromethyl- N-[ 3-( naphthyl- 2- oxy)- propyl]- hexahydro- azepine

a) 3-hydroxymethyl-hexahydro-azepine

16.6 g (0.0757 mol) 1-benzyl-3-hydroxymethyl-hexahydro-azepine in 500 ml of methanol, dissolved in the presence of 16.6 g of 20% palladium hydroxide/charcoal hydrated for 2 hours at room temperature below 5 bar hydrogen. The catalyst was then sucked off and the filtrate evaporated in vacuo.

Yield: 8 g (81.8% of the theoretical).

Rf value: 0.5 (silica gel, eluent: methylene chloride/-

ethanol/ammonia = 5:4:1).

b) 3-hydroxymethyl-N-[3-(naphthyl-2-oxy)-propyl]-hexahydro-azepine-hydrochloride

A mixture of 7.8 g (0.06 mol) of 3-hydroxymethyl-hexahydro-azepine and 6.7 g (0.03 mol) of 2-(3-chloropropoxy)-naphthalene was heated for 1 hour at 120°C. The reaction mixture was purified over silica gel (0.063-0.2 mm) with

ethyl acetate/ethanol/ammonia = 90:10:1.

Yield: 2.3 g (24.3% of the theoretical).

M.p.: 127-129°C.

c) 3-chloromethyl-N-[3-(naphthyl-2-oxy)-propyl]-hexahydroazepine

2.4 g (6.86 mmol) of 3-hydroxymethyl-N-[3-(naphthyl-2-oxy)-propyl]hexahydro-azepine hydrochloride dissolved in 30 ml of chloroform, 5 ml of thionyl chloride was added and boiled under reflux in 1 hour. The mixture was evaporated to dryness in vacuo. The residue was dissolved in methylene chloride, shaken out with water, 2 molar caustic soda and then again with water. The methylene chloride phase was dried over magnesium sulfate and evaporated in vacuo.

Yield: 1.1 g (48.5% of the theoretical),

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

Example E

2~t(pyrrolidyl-3)methyl]-6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydroisoquinoline

a) N-benzyl-2-pyrrolidone

To 25.5 g (0.3 mol) of 2-pyrrolidone in 300 ml of absolute

dimethyl sulfoxide, 14.4 g were added in portions

(0.33 mol) 50% sodium hydride dispersion in oil. The mixture was then stirred for 5 hours at 40-50°C and then at 25-30°C 56.4 g = 39.2 ml (0.33 mol) of benzyl bromide were added dropwise. After stirring for 10 hours at room temperature, the reaction mixture was

dissolved in 500 ml ethyl acetate and shaken several times with water. The organic phase was separated, dried over magnesium sulfate, whereupon the solvent was removed in vacuo. The obtained residue was purified over 900 g of alumina (neutral, activity II) with methylene chloride and 0.1% ethanol.

Yield: 35.6 g (67.7% of the theoretical),

Rf value: 0.77 (alumina, neutral, eluent: 5% ethanol in methylene chloride).

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

To 28.3 g = 39.3 ml (0.28 mol) diisopropylamine in 400 ml

absolute ether, 150 ml of 1.6 molar butyllithium solution in n-hexane was added with stirring and under nitrogen at -60°C. To this, 35.1 g (0.2 mol) of N-benzyl-2-pyrrolidone dissolved in 150 ml of absolute ether were added dropwise at -60°C. The cooling bath was removed, after which dry carbon dioxide was introduced for 15 minutes. After stirring for 10 minutes, the mixture was poured onto ice and the organic phase separated and decanted twice with 2 molar caustic soda. The combined aqueous phases were shaken once with ether and then acidified with concentrated hydrochloric acid while cooling. The aqueous phase was decanted twice with methylene chloride and, after drying the organic phase over magnesium sulphate, evaporated in vacuo. Dividend; 35 g (79.8% of the theoretical),

Rf value: 0.42 (silica gel, eluent: 5% ethanol in

methylene chloride).

c) N-Benzyl-3-hydroxymethyl-pyrrolidine

To 12.2 g (0.32 mol) lithium aluminum hydride in 350 ml

absolute tetrahydrofuran, 35 g (0.16 mol) of N-benzyl-2-pyrrolidone-3-carboxylic acid dissolved in 250 ml of absolute tetrahydrofuran were added dropwise while stirring. After boiling under reflux for 6 hours, 18.2 ml of water, 12.2 ml of 15% aqueous caustic soda and 36.6 ml of water were added while cooling with ice water. The resulting precipitate was suctioned off and washed with tetrahydrofuran. The combined filtrates were evaporated in vacuo, after which the residue obtained was purified over 900 g

aluminum oxide (neutral, activity II) with methylene chloride and then with increasing proportions of ethanol (to 2%).

Yield: 16 g (52.3% of the theoretical),

Rf value: 0.42 (alumina, neutral, eluent: 5%

ethanol in methylene chloride).

d. 3-(benzenesulfonyloxymethyl)-1-benzylpyrrolidine

To a mixture of 3.8 g (20 mmol) N-benzyl-3-hydroxymethyl-pyrrolidine and 3.7 ml (24 mmol)

benzenesulfonic acid chloride, 40 ml of 20% caustic soda was added dropwise over the course of 1 hour. To the mixture was added 150 ml of toluene, the organic phase washed with water, dried over magnesium sulphate and evaporated in vacuo to dryness.

Yield: 5.9 g (89.4% of the theoretical),

Rf value: 0.4 (silica gel, eluent: 5% 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) of 6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline were dissolved in 50 ml of dimethyl sulfoxide and, with stirring at room temperature, added 2 g (17.5 mmol ) potassium tert-butylate. After 1/2 hour, 5.8 g (17.5 mmol) of 3-benzenesulfonyloxymethyl)-1-benzylpyrrolidine in 10 ml of dimethylsulfoxide was added to the resulting potassium salt suspension and stirred for 3 hours at 60°C. The mixture was poured into ice water and extracted with ethyl acetate. The combined organic phases were washed with water and dried over magnesium sulfate. The organic phase was evaporated in vacuo and the residue obtained purified over 350 g of alumina N (activity II) with methylene chloride and then with increasing proportions of ethanol (to 1%).

Yield: 3.3 g (54.4% of the theoretical),

Rf value: 0.74 (alumina N, eluent: 5% ethanol in methylene chloride).

f. 2-[(pyrrolid-3-yl)-methyl]-6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro- isoquinoline

3.2 g (8.4 mmol) of 2-[(N-benzyl-pyrrolid-3-yl)-methyl]-6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline was dissolved in 250 ml of methanol and hydrated in the presence of 1 g of 20% palladium hydroxide/charcoal for 3 hours at room temperature under 5 bar hydrogen. The catalyst was then sucked off and the filtrate evaporated in vacuo to dryness. The residue was purified with 150 g of silica gel (0.063-0.2 mm) with methylene chloride/ethanol/ammonia = 6:1:0.5).

Yield: 0.9 g (37.5% of the theoretical),

Rf value: 0.6 (silica gel, eluent: methylene chloride/-

ethanol/ammonia = 5:4:1).

Example F

3-(p-toluenesulfonyloxymethyl)-N-f[2-(6-methoxy-naphthyl-2)-ethyl]-pyrrolidine

a) 3-hydroxymethyl-pyrrolidine

14 g (0.073 mol) of N-benzyl-3-hydroxymethyl-pyrrolidine were

hydrated for 7 hours at 50°C and 5 bar in 300 ml of methanol in the presence of 1.5 g of 20% palladium hydroxide/activated carbon. The catalyst was then sucked off and the filtrate evaporated in vacuo. Yield: 7.3 g (99% of theoretical).

Mass spectrum: Mole top 101.

in

b. 3-hydroxymethyl-N-r2-(6-methoxynaphthyl-2)ethyl]-pyrrolidine

A mixture of 3.6 g (29.4 mmol) of 3-hydroxymethyl-pyrrolidine and 4.7 g (14.7 mmol) of 2-(2-bromomethyl)-6-methoxy-naphthalene was heated for 2 hours at 120 °C. The reaction mixture was purified over 200 g of silica gel (0.063-0.2 mm) with methylene chloride and then with increasing proportions of ethanol (to 5%). Yield: 3.48 g (82.5% of the theoretical),

M.p.: 121-123°C.

c) 3-(p-toluenesulfonyloxymethyl)-N-[2-(6-methoxy-naphthalene-2)-ethyl1-pyrrolidine

0.8 g (2.8 mmol) of 3-hydroxymethyl-N-[2-(6-methoxy-naphth-2-yl)-ethyl]-pyrrolidine was dissolved in 10 ml of pyridine and, with stirring, added 1.2 g ( 6.3 mmol) p-toluenesulfonic acid chloride. After 2 hours at room temperature, the mixture was evaporated to dryness in vacuo. The residue was dissolved in methylene chloride, washed with 2 molar caustic soda and water. The organic phase was then dried over magnesium sulfate and evaporated in vacuo. The residue was purified over 150 g of silica gel (0.063-0.2 mm) with ethyl acetate and then with increasing proportions of ethanol.

Yield: 0.6 g (48.8% of the theoretical),

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

Example G

2-[(azacyclooctyl-3)-methyl]-6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro- isoquinoline

a) 1-benzyl-2-oxo-azacyclooctane

25 g (0.196 mol) of 2-azacyclooctanone was dissolved in 150 ml

dimethyl sulfoxide and, with stirring, added 24.2 g (0.216 mol) of potassium tert-butylate and stirred for 1/2 hour at 40°C. Then 24 ml (0.2 mol) of benzyl bromide were added dropwise over 1/4 hour, whereby the temperature rose to 80°C. The mixture was stirred for 2 hours, whereby the reaction temperature again dropped to room temperature. The reaction mixture was poured into 1 liter of ice water and shaken four times with 150 ml portions of ethyl acetate. The combined organic phases were washed with water, dried over magnesium sulfate and evaporated in vacuo.

Yield: 42.7 g (100% of the theoretical),

Rf value: 0.55 (silica gel, eluent: 5% ethanol in

methylene chloride).

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

To-26.7 g = 38.4 ml (0.26 mol) diisopropylamine in 250 ml

absolute ether, 147 ml of 1.6 molar butyllithium solution in n-hexane at -60°C were added dropwise while stirring under nitrogen. Then, at -60°C, 42.7 g (0.196 mol) of 1-benzyl-2-oxo-azacyclooctane in 100 ml of absolute ether were added dropwise. After 10 minutes, dry carbon dioxide was introduced for 20 minutes. The reaction mixture was poured onto ice, the ether phase separated and decanted twice with 2 molar caustic soda. The combined aqueous phases were decanted once with ether and then, under cooling, acidified with concentrated hydrochloric acid. They were shaken three times with methylene chloride, after which the methylene chloride phase was dried over magnesium sulfate and evaporated in vacuo.

Yield: 25.9 g (50.6% of the theoretical),

Rf value: 0.15 (alumina, eluent: 5% ethanol in

methylene chloride).

c) 1- benzyl- 3- hydroxymethyl- azacvcloctane

To 22.7 g (0.6 mol) lithium aluminum hydride in 800 ml

absolute ether, 53.6 g (0.205 mol) of 1-benzyl-2-oxo-azacyclooctane-3-carboxylic acid dissolved in 100 ml of absolute tetrahydrofuran were added dropwise while stirring. After 1/2 hour of boiling under reflux cooling, 28.4 ml of water, 19 ml of 15% caustic soda and 57 ml of water were added while cooling with ice water. The resulting precipitate was suctioned off and washed with tetrahydrofuran. The combined filtrates were evaporated in vacuo and the obtained residue purified over 700 g of alumina (neutral, activity II) with 1% ethanol in methylene chloride: Yield: 9.3 g (19.6% of the theoretical),

Rf value: 0.5 (silica gel, eluent: 5% ethanol in

methylene chloride).

d) 1- benzzi- 3- chloromethyl-azacyclooctane

9.3 g (39.8 mmol) of 1-benzyl-3-hydroxymethyl-azacyclooctane

in 30 ml of pyridine was added 10 ml (79.6 mmol)

benzenesulfonic acid chloride and stirred at room temperature for 2.5 hours. The reaction mixture was evaporated in vacuo. The remaining residue was dissolved in 150 ml of methylene chloride, washed with 2N caustic soda and then with water. The organic phase was dried over magnesium sulfate, evaporated to dryness and

purified over 150 g of silica gel (0.063-0.2 mm) with methylene chloride. Yield: 3.5 g (35% of the theoretical),

Rf value: 0.75 (silica gel, eluent: 5% ethanol in

methylene chloride).

e) 2-[(N-benzyl-azacyclooctyl-3)-methyl]-6,7-dimethoxy-1-oxo-1.2,3,4-tetrahydro-isoquinoline

2.3 g (11.1 mmol) of 6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline were dissolved in 40 ml of dimethyl sulfoxide and, with stirring, added 1.33 g (12.2 mmol ) potassium tert-butylate. After 1/2 hour, the obtained potassium salt suspension was added with 3.5 g (9.4 mmol) of 1-benzyl-3-chloromethyl-azacyclooctane in 40 ml of dimethylsulfoxide and stirred for 2.5 hours at 120°C. The mixture was poured into ice water and extracted three times with 50 ml portions of ethyl acetate. The combined organic phases were washed with water, dried over magnesium sulfate and evaporated in vacuo. The obtained residue was purified over 150 g of silica gel (0.063-0.2 mm) with 1% ethanol in methylene chloride.

Yield: 1 g (25.1% of the theoretical),

Rf value: 0.5 (silica gel, eluent: 2% ethanol in

methylene chloride).

f) 2-[(azacyclooctyl-3)-methyl]-6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydroisoquinoline

0.85 g (2 mmol) 2-[(N-benzyl-azacyclooctyl-3)-methyl]-6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline in 50 ml methanol, was hydrated in the presence of 0.85 g of 20%

palladium hydroxide/charcoal for 4.5 hours at room temperature and 5 bar hydrogen. The catalyst was then sucked off and the filtrate evaporated to dryness.

Yield: 0.5 g (74.6% of the theoretical),

Rf value: 0.45 (silica gel, eluent: 25% ethanol in methylene chloride and 1 drop of ammonia).

Example H

1- chloro-3-TN-(4- methoxyphenyl)- methylaminol- propane

10 g (0.073 mol) of N-methyl-4-methoxy-aniline were dissolved in 50 ml of dimethylsulfoxide and 9 g (0.08 mol) of potassium tert-butylate were added while stirring. After 1/2 hour, 10 ml of 1-bromo-3-chloropropane was added and stirring continued for 3 hours at room temperature. The mixture was poured into ice water, decanted with ethyl acetate, after which the organic phase was washed with water, dried over sodium sulfate and evaporated to dryness. The residue was purified over silica gel (0.063-0.2 mm) with methylene chloride. Yield: 9.1 g (58.3% of the theoretical),

Rf value: 0.55 (silica gel, eluent:

methyl ethyl ketone/xylene =1:6).

Calculated: C, 61.82; H, 7.55; N, 6.55; Cl, 16.59 Found: C, 61.71; H, 7.88; N, 6.69; Cl, 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-methylenedioxyphthalimide was dissolved in 100 ml of dimethylsulfoxide and, with stirring, 1.25 g (0.012 mol) of potassium tert-butylate was added. The potassium salt thereby precipitated out. Stirring was continued for 1/2 hour at room temperature, and a solution of 2.5 g (0.01 mol) of 3-chloromethyl-N-(3-(pyridyl-3)-propyl)-piperidine in 20 ml of dimethylsulfoxide was added and the mixture heated to 120°C for 8 hours. The mixture was poured into ice water, shaken three times with 150 ml portions of ethyl acetate and the organic phase, after drying over magnesium sulfate, evaporated in vacuo. The residue was purified over 200 g of silica gel (0.063-0.2 mm) with ethyl acetate/ethanol/ammonia = 80:10:0.5).

Yield: 3 g (74% of the theoretical).

Calcd (2 x HCl): C, 55.42; H, 5.86; N, 8.43; Cl, 14.22 Found: C, 55.28; H, 6.06; N, 8.26; Cl, 14.64

Example K 2-[(N-3-chloropropyl)-3-piperidyl-methyl]-6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline 3 g (0.01 mol) 2 -[(piperidyl-3)-methyl]-6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline was dissolved in 50 ml of dimethylsulfoxide and, with stirring, added 1.3 g (0.011 mol) potassium tert-butylate. After 1/2 hour, 3 ml of 1-bromo-3-chloropropane was added and stirring at room temperature was carried out for 1 hour. The mixture was poured into ice water, extracted with ethyl acetate, after which the organic phase was washed with water, dried over sodium sulfate and evaporated in vacuo to dryness. Yield: 2.7 g (71% of theoretical),

Rf value: 0.65 (silica gel, eluent: ethyl acetate/ethanol/-

ammonia = 50:45:5).

Example 1

2 -[ (N-(3-(2-naphthyl)-propyl)-3-piperidyl)-methyl]-6,7-dimethoxy-1-oxo- l. 2, 3. 4- tetrahydro- isoquinoline- hydrochloride

A mixture of 1 g (3.2 mmol) 2-(piperidyl-3-methyl)-6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline, 5 ml dimethylsulfoxide, 0.5 g (0.36 mmol) of potassium carbonate and 0.75 g (3.66 mmol) of 2-(3-chloropropyl)-naphthalene were heated for 3 hours at 120°C. The reaction mixture was poured into ice water and shaken three times with 50 ml portions of ethyl acetate. The combined organic phases were washed with 2 molar caustic soda and then with water, dried over magnesium sulfate and evaporated in vacuo, after which the residue obtained was purified over silica gel (0.063-0.2 mm) with 1% ethanol in methylene chloride. From an acetone solution, the hydrochloride was precipitated with ethereal hydrochloric acid and crystallized from acetone.

Yield: 0.74 g (44% of theoretical).

M.p.: 179-181°C.

Calculated: C, 70.77; H, 7.37; N, 5.50; Cl, 6.96

Found: C, 70.47; H, 7.40; N, 5.47; Cl, 7.06.

Example 2 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 was dissolved in 30 ml of dimethylsulfoxide and, while stirring, 1.1 g (9.9 mmol) of potassium was added -tert-butylate. After 1 hour, a solution of 2.9 g (9.1 mmol) of 3-chloromethyl-N-[3-(naphthyl-2-oxy)-propyl]-piperidine in 10 ml of dimethyl sulfoxide was added and the reaction mixture was stirred for 16 hours at 80°C. The mixture was then poured into ice water, shaken three times with 50 ml of ethyl acetate and the organic phase washed with water, dried over magnesium sulfate and, after evaporation, purified over silica gel (0.063-0.2 mm) with ethyl acetate/ethanol/ammonia = 95: 5:0.5). From an acetone solution, the hydrochloride was obtained as a hydrate with ethereal hydrochloric acid.

in

Yield: 2 g (45.1% of the theoretical).

M.p.: 152-154°C.

Calculated: C, 70.50; H, 7.69; N, 5.49; Cl, 6.93

Found: C, 70.31; H, 7.52; N, 5.49; Cl, 7.10

Example 3

2-[(N-(3-(naphthyl-2)-propyl)-piperidyl-3)-methyl]-6,7-dimethyl-1. 2. 3, 4- tetrahydro- isoquinoline- dihydrochloride

0.8 g (18 mmol) 2-[(N-(3-(naphthyl-2)-propyl)-piperidyl-3)-methyl]-6,7-dimethyl-1-oxo-1,2,3, 4-tetrahydro-isoquinoline was dissolved in 10 ml absolute tetrahydrofuran and 20 ml absolute ether, added 70 mg (18 mmol) lithium aluminum hydride and refluxed for 1 hour. 5 ml of saturated aqueous sodium sulfate solution was added to the reaction mixture, the precipitated sodium sulfate was filtered off and washed with tetrahydrofuran. The filtrate was dried over magnesium sulfate and, after evaporation, purified over 150 g of silica gel (0.063-0.2 mm) with ethyl acetate/ethanol/ammonia =90:10:0.05). From an acetone solution, the hydrochloride was precipitated with ethereal hydrochloric acid.

Yield: 0.49 g (54.4% of theoretical).

Melting point: 148-150°C.

Calculated: C, 69.61; H, 8.18; N, 5.41; Cl, 13.70

Found: C, 69.46; H, 8.32; N, 5.26; Cl, 14,17

Example 4

2- [(N-(3-(pyridyl-3)-propyl)-piperidyl-3)-methyl]-5,6-methylenedioxy- l- oxo- 1, 3- dihydro-isoindole- dihydrochloride

2.4 g (5.9 mmol) of 2-[(N-(3-(pyridyl-3)-propyl)-piperidyl-3)-methyl]-5,6-methylenedioxyphthalimide was dissolved in 50 ml of glacial acetic acid and boiled under reflux for 5 hours. At 1-hour intervals, 1 g of zinc dust was added. After the end of the reaction time, aspiration and evaporation with ethanol was carried out. The residue was dissolved in methylene chloride, shaken out with concentrated ammonia, dried over magnesium sulfate and, after evaporation in a vacuum, purified over 150 g of silica gel (0.063-

0.2 mm) with ethyl acetate/ethanol/ammonia = 90:10:0.2). From an acetone solution the hydrochloride was precipitated.

Yield: 2.05 g (75% of the theoretical).

M.p.: 165-167°C.

Calculated: C, 59.22; H, 6.27; N, 9.00; Cl, 15,20

Found: C, 59.03; H, 6.45; N, 8.85; Cl, 15.06

Example 5

3- [(N-(3-(pyridyl-3)-propyl)-pyrrolidyl-3)-methyl]-7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3- benzoazepine dihydrochloride

1.1 g (2.6 mmol) 3-[(N-(3-(pyridyl-3)-propyl)-pyrrolidyl-3)-methyl]-7,8-dimethoxy-2-oxo-1,3- dihydro-2H-3-benzoazepine, dissolved in 50 ml of ethanol, was hydrogenated for 2 hours in the presence of 1 g of 10% palladium on activated carbon at 80°C and 5 bar of hydrogen. The catalyst was then sucked off and the filtrate, after evaporation in vacuum, purified over 100 g of silica gel (0.063-0.2 mm) with ethyl acetate/ethanol/ammonia = 80:40:1). From an acetone solution the hydrochloride was precipitated.

Yield: 0.37 g (33% of theoretical).

M.p.: 96-98°C.

Calculated: C, 60.42; H, 7.11; N, 8.46; Cl, 14.28

Found: C, 60.35; H, 7.46; N, 8.43; Cl, 14.58

Example 6

2-[(N-(2-(4-amino-phenyl)-ethyl)-piperidyl-3)-methyl]-5,6-dimethoxy- l - oxo- 1. 3- dihydro- isoindole- dihydrochloride

2.1 g (4.78 mmol) 2-[(N-(2-(4-nitro-phenyl)-ethyl)-piperidyl-3)-methyl]-5,6-dimethoxy-1-oxo-1, 3-dihydro-isoindole was dissolved in 50 ml of glacial acetic acid and, with stirring, added 0.4 ml (8.22 mmol) of hydrazine hydrate and 1 spatula tip of Raney nickel. The addition of 0.2 ml of hydrazine hydrate and a Raney nickel spatula tip was repeated three times at 1 hour intervals. The catalyst was sucked off and washed with methanol, after which the filtrate was dried with magnesium sulfate and evaporated in vacuo and the residue obtained purified over aluminum oxide (neutral, activity II) with methylene chloride and then with increasing proportions of ethanol.

Yield: 1.8 g (91.8% of the theoretical).

1 g was dissolved in acetone and the dihydrochloride was precipitated with ethereal hydrochloric acid.

Yield: 1.02 g (86.4% of theoretical with respect to the base).

M.p.: 232-235°C.

Calcd: C, 59.72; H, 6.89; N, 8.71; Cl, 14.69

Found: C, 59.54; H, 7.08; N, 8.56; Cl, 14.45

Example 7

2-[(N-(2-(4-acetamino-phenyl)-ethyl)-piperidyl-3)-methyl]-5,6-dimethoxy-l-oxo-l. 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 in 10 ml of methylene chloride, after the addition of 0.3 ml (2.2 mmol) of triethylamine, 0.16 ml (2.2 mmol) of acetyl chloride was added dropwise. This raised the reaction temperature to 30°C. The mixture was stirred for 1/2 hour at room temperature, shaken out twice with water and the organic phase dried over magnesium sulfate and

evaporated in vacuum. The residue was crystallized from acetone. Yield: 660 mg (73.2% of the theoretical).

M.p.: 195-196°C.

Calculated: C, 69.16; H, 7.37; N, 9.31

Found: C, 69.33; H, 7.11; N, 9.16

Example 8

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

3.2 g (0.010 mol) 3-[(piperidyl-3)-methyl]-7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzazepine in 100 ml absolute ethanol was hydrated for 2 days in the presence of 1.3 g (0.010 mol) 3-(furyl-2)-propanal and 1 g Raney nickel at 80°C at 5 bar. The catalyst was sucked off, the filtrate evaporated and purified over a silica gel column with methylene chloride/methanol as eluent. The hydrochloride was precipitated with ethereal hydrochloric acid and crystallized from acetone.

Yield: 0.50 g (11% of the theoretical).

M.p.: 204-206°C.

Calcd: C, 64.85; H, 7.62; N, 6.05, Cl, 7.66

Found: C, 64.88; H, 7.76; N, 5.93; Cl, 7.55

Rf value: 0.69 (silica gel; methylene chloride/methanol = 10:1;

ammonia/atmosphere).

Example 9

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

Mainly from 2-[(N-(3-(3-methylphenoxy)-propyl)-piperidyl-3)-methyl]-6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and lithium aluminum hydride in diethyl ether and tetrahydrofuran, analogously to Example 3.

Yield: 92.9% of the theoretical.

M.p.: 100-103°C.

Calculated: C, 61.23; H, 7.99; N, 5.29; Cl, 13.39

Found: C, 61.21; H, 8.13; N, 5.10; Cl, 13,15

Example 10

2 - [ (N- (3 - (na f ty 1 - 2 -oxy) -propyl) -pyrr ol id 1 - 3) -methyl ] - 6,7 - dimethoxy- l - oxo- l , 2, 3, 4 - tetrahydroisoquinoline hydrochloride

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

Yield: 22% of the theoretical.

Melting point: 78-80°C.

Calcd (x H 2 O): C, 65.83; H, 7.04; N, 5.29; Cl, 6.70 Found: C, 65.79; H, 7.00; N, 5.03; Cl, 6.99

Example 11

2-[(N-(3-(naphthyl-2-oxy)-propyl)-pyrrolidyl-3)-methyl]-6,7-methylenedioxy-1-oxo-1,2,3,4-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]-pyrrolidine, analogous to Example 2 .

Yield: 53% of the theoretical.

Melting point: 78-80°C.

Calcd (x H 2 O): C, 65.56; H, 6.48; N, 5.46; Cl, 6.91 Found: C, 65.44; H, 6.32; N, 5.38; Cl, 7.13

Example 12

2- [ (N-(2-(naphthyl-2)-ethyl)-pyrrolidyl-3)-methyl]-6,7-dimethoxy-1, 2. 3. 4- tetrahdro- isoquinoline- hydrochloride

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

Yield: 66.2% of the theoretical.

M.p.: 239-241°C.

Calcd (x H 2 O) : C, 64.48; H, 7.44; N, 5.37; Cl, 13.91 Found: C, 64.30; H, 7.34; N, 5.52; Cl, 13.69

Example 13

2-[(N-((2-methylnaphthyl-1)-methyl)-hexahydro-azepinyl-3)-methyl]-6, 7- dimethoxy-1, 2, 3, 4- tetrahydro- isoquinoline- hydrochloride

Prepared from 2-[(N-((2-methylnaphthyl-1)-methyl)-hexahydro-azepinyl-3)-methyl]-6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro- isoquinoline and lithium aluminum hydride in tetrahydrofuran and ether, analogously to Example 3.

Yield: 73.8% of the theoretical.

M.p.: 182-184°C.

Calcd (x H 2 O): C, 65.56; H, 7.70; N, 5.09; Cl, 12.90 Found: C, 65.52; H, 7.57; N, 5.32; Cl, 12.72

Example 14

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

Prepared from 2-(pyrrolidyl-3-methyl)-6,7-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 2-(4-bromo-butyloxy)-naphthalene, analogously to Example 1 .

Yield: 30% of the theoretical.

M.p.: 133-136°C.

Calculated: C, 67.02; H, 6.92; N, 5.21; Cl, 14.86

Found: C, 67.26; H, 7.03; N, 5.36; Cl, 14.89

Example 15

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

Prepared from 2-(pyrrolidyl-3-methyl)-6,7-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 1-chloromethyl-2-methyl-naphthalene, analogously to Example 1.

Yield: 32.5% of the theoretical.

M.p.: 142-144°C.

Calcd: C, 69.34; H, 7.69; N, 5.77; Cl, 7.37

Found: C, 69.59; H, 7.63; N, 5.72; Cl, 7.89

Example 16

2 - [ (N-(2 - (5-methyl-6-methoxy-naphthyl-2)-ethyl)-pyrrolidyl-3)-methyl]-6,7-dimethyl-1-oxo-1,2,3, 4-tetrahydro-isoquinoline hydrobromide

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

Yield: 19% of the theoretical.

M.p.: 230-232°C.

Calculated: C, 67.02; H, 6.93; N, 5.21; Br, 14.86

Found: C, 67.10; H, 7.12; N, 5.33; Br, 15.01

Example 17

2-[ (N-(2-(naphthyl-2)-ethyl)-pyrrolidyl-3)-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-bromomethyl)-naphthalene, analogously to Example 1.

Yield: 7.8% of the theoretical.

M.p.: 219-221°C.

Calcd (x H 2 O): C, 67.39; H, 7.07; N, 5.61; Cl, 7.10 Found: C, 67.21; H, 7.23; N, 5.57; Cl, 7.63

Example 18

2- [ (N- (2 - (6-Methoxy-naphthyl-2)-ethyl)-pyrrolidyl-3)-methyl]-6,7-dimethoxy- l - 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-bromomethyl)-6-methoxy-naphthalene, analog with Example 1.

Yield: 39.2% of the theoretical.

M.p.: 224-226°C.

Calcd (x H 2 O): C, 65.84; H, 7.05; N, 5.29; Cl, 7.05 Found: C, 66.08; H, 7.13; N, 5.39; Cl, 6.77

Example 19

2- [ (N- (3 - (naphthyl-2)-propyl)-piperidyl-3)-methyl]-6,7-dimethyl-1- oxo- l. 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)-propyl]-piperidine, analogously to Example 2.

Yield: 40.4% of the theoretical.

M.p.: 185-187°C.

Calculated: C, 75.52; H, 7.82; N, 5.87; Cl, 7.43

Found: C, 75.39; H, 7.85; N, 5.82; Cl, 7.52

Example 20

2- [2-(N-(3-(naphthy1-2-oxy)-propyl)-piperidy1-2)-ethyl] -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, analogously to Example 1.

Yield: 21.2% of the theoretical.

M.p.: 85-87°C.

Calcd (x H 2 O): C, 66.59; H, 6.89; N, 5.17; Cl, 6.53 Found: C, 66.77; H, 6.98; N, 4.95; Cl, 6.74

v Example 21

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-tetrahydro- isoquinoline and lithium aluminum hydride in tetrahydrofuran/ether, analogously to Example 3.

Yield: 53% of the theoretical.

M.p.: 133-135°C.

Calcd (x H 2 O): C, 68.30; H, 6.87; N, 5.31; Cl, 13.44 Found: C, 68.05; H, 6.85; N, 5.23; Cl, 13.03

Example 22

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-tetrahydro- isoquinoline and lithium aluminum hydride in tetrahydrofuran/ether, analogously to Example 3.

Yield: 44.7% of the theoretical.

M.p.: 130-132°C.

Calcd (x HzO): C, 63.62; H, 6.62; N, 5.11; Cl, 12.95 Found: C, 63.49; H, 6.86; N, 4.97; Cl, 12.64

Example 23

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

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

Yield: 80.5% of the theoretical.

M.p.: 210-212°C.

Calcd (x H 2 O): C, 65.05; H, 7.53; N, 5.23

Found: C, 65.23; H, 7.78; N, 5.03

Example 24

2-[2-(N-(2-(6-methoxy-naphthyl-2)-ethyl)-piperidyl-2)-ethyl]-6,7-methylenediox- l- oxo- 1. 2, 3, 4- tetrahydroisoquinoline hydrochloride

Prepared from 2-[2-(piperidyl-2)-ethyl]-6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 2-(2-bromomethyl)-6-methoxy- naphthalene, analogously to Example 1. Yield: 27.6% of the theoretical.

M.p.: 112-117°C.

Calcd (x 1/2 H 2 O): C, 67.74; H, 6.82; N, 5.26; Cl, 6.65

Found: '■ C, 67.54; H, 6.73; N, 5.47; Cl, 6.86

Example 25

2- [ (N-(2-(naphthyl-1)-ethyl)-piperidyl-3)-methyl]-6,7-dimethoxy-1-oxo-l, 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, analog with Example 1.

Yield: 26.9% of the theoretical.

Melting point: 220-225°C.

Calcd: C, 67.89; H, 7.27; N, 5.46; Cl, 6.91

Found: C, 67.75; H, 6.92; N, 5.56; Cl, 7.00

Example 2 6

2-[(N-(2-(naphthyl-2)-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-tetrahydro-isoquinoline and benzenesulfonic acid 2-ethyl-(naphthyl-2)-ester, analogous to Example 1.

Yield: 27.9% of the theoretical.

Melting point: 128-130°C.

Calcd (x H 2 O) : C, 67.66; H, 6.69; N, 5.63; Cl, 7.13 Found: C, 67.64; H, 6.70; N, 5.76; Cl, 7.35

Example 27

2 - [ (N-(2 - (5 -methyl 1 -6 -methoxynaphthy 1 -2) -ethyl) -piperidy 1 - 3) - methyl ] -6,7-methylenedioxy-l- 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 2-(2-bromomethyl)-5-methyl-6- methoxy-naphthalene, analogous to Example 1. Yield: 51.2% of the theoretical.

M.p.: 128-131°C.

Calcd: C, 68.88; H, 6.74; N, 5.34; Cl, 6.77

Found: C, 68.90; H, 6.61; N, 5.30; Cl, 7.05

Example 28

2-[(N-((2-methyl-naphthyl-1)-methylj-piperidyl-3)-methyl]-6,7-dimethoxy- l- oxo- 1. 2, 3. 4- tetrahydro- isoquinoline- hydrochloride

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

Yield: 57.9% of the theoretical.

Temp. : 212-214°C.

Calcd (x 2 H 2 O): C, 67.63; H, 7.63; N, 5.44; Cl, 6.88

Found: C, 67.46; H, 7.56; N, 5.54; Cl, 6.67

Example 29

2-[ (N-(4-(naphthyl-2.-oxy)-butyl)-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 2-(4-bromo-butoxy)naphthalene, analogously to Example 1.

Yield: 46.3% of the theoretical.

M.p.: 80-84°C.

Calcd (x H 2 O): C, 66.83; H, 7.41; N, 5.03; Cl, 6.36 Found: C, 66.79; H, 7.22; N, 4.90; Cl, 6.64

Example 30

2-[(N-(2-(6-methoxy-naphthyl-2)-ethyl)-piperidyl-3)-methyl]-6,7-dimethoxy- l - 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 2-(2-bromo-ethyl)-6-methoxy- naphthalene, analogous to Example 1.

Yield: 22.8% of the theoretical.

Melting point: 80-85°C.

Calculated (x H20 x HC1 x CH3COCH3) :

C, 64.01; H, 7.65; N, 4.52; Cl, 5.72

Found: C, 64.26; H, 7.70; N, 4.62; Cl, 5.49

Example 31

2-[3-(N-(2-(6-methoxy-naphthy1-2-ethyl)-piperidyl-3)-propyl]-6, 7- methylenedioxy-l-oxo-l, 2, 3. 4- tetrahydroisoquinoline

Prepared from 2-[3-(piperidyl-3)-propyl]-6,7-methylenedioxy-1-oxo-1, 2, 3, 4-tetrahydro-isoquinoline and 2-(2-bromomethyl)-6-methoxy- naphthalene, analogous to Example 1.

Yield: 36.8% of the theoretical.

M.p.: 118-121°C.

Calculated: C, 74.37; H, 7.25; N, 5.60

Found: C, 74.60; H, 7.43; N, 5.65

Example 32

2-[3-(N-(2-(naphthyl-1)-ethyl)-piperidyl-3)-propyl]-6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline- hydrogen 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, analogous to Example 1.

Yield: 20.8% of the theoretical.

M.p.: 195-197°C.

Calculated: C, 71.07; H, 6.95; N, 5.53; Cl, 6.99

Found: C, 71.30; H, 6.95; N, 5.65; Cl, 6.80

Example 33

2-[2-(N-(2-(5-methyl-6-methoxy-naphthyl-2-ethyl)-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 2-(2-bromomethyl)-5-methyl- 6-methoxy-naphthalene, analogous to Example 1.

Yield: 33.6% of the theoretical.

Melting point: 95-100°C.

Calcd (x 1/2 H 2 O): C, 68.38; H, 7.52; N, 4.98; Cl, 6.30

Found: C, 68.14; H, 7.43; N, 4.92; Cl, 6.77

Example 34

2-[(N-(3-(naphthyl-2-oxy)-propyl)-piperidyl-3)-methyl]-6,7-methylenedioxy-1-oxo-1,2,3,4-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, analogous to Example 2 .

Yield: 27.3% of the theoretical.

M.p.: 104-106°C.

Calcd (x H 2 O): C, 66.09; H, 6.69; N, 5.31; Cl, 6.72 Found: C, 66.19; H, 6.34; N, 5.24; Cl, 7.22

Example 35

2-[(N-(3-(naphthyl-2-oxy)-propyl)-piperidyl-3)-methyl]-6,7-dimethoxy- l - oxo- 1. 2, 3. 4- tetrahydro- isoquinoline- hydrochloride

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

Yield: 28.6% of the theoretical amount.

M.p.: 191-193°C.

Calcd (x H 2 O): C, 66.34; H, 7.23; N, 5.15; Cl, 6.53 Found: C, 66.59; H, 7.19; N, 5.03; Cl, 6.65

Example 3 6

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-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 2-(3-chloro-propoxy)naphthalene, analog with Example 1.

Yield: 16.1% of the theoretical.

M.p.: 86^88°C.

Calcd (x H 2 O) : C, 66.83; H, 7.42; N, 5.03; Cl, 6.36 Found: C, 66.90; H, 7.40; N, 5.26; Cl, 6.87

Example 3 7

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, analogous to Example 2.

Yield: 22.5% of the theoretical.

M.p.: 191-193°C.

Calculated: C, 73.42; H, 7.75; N, 5.52; Cl, 6.99

Found: C, 73.37; H, 7.67; N, 5.52; Cl, 7.12

Example 3 8

2-[(N-(2-(5-methyl-6-methoxy-naphthyl-2)-ethyl)-hexahydro-azepinyl-3 )-methyl]-6,7-dimethoxy-1,2,3,4- tetrahydroisoquinoline 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~tetrahydro-isoquinoline and lithium aluminum hydride in tetrahydrofuran, analogously to Example 3.

Yield: 77.6% of the theoretical.

M.p.: 170-172°C.

Calcd (x H 2 O): C, 64.96; H, 7.49; N, 4.73; Cl, 11.98 Found: C, 65.11: H, 7.62; N, 4.95; Cl, 11.84

Example 39

2-[(N-(2-(5-methyl-6-methoxy-naphthy1-2)-ethyl)-hexahydro-azepinyl-3)-methyl]-6,7-dimethoxy-1-oxo-1,2, 3,4-tetrahydro-isoquinoline

Prepared from 2-[hexahydro-azepinyl-3)methyl]-6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 2-(2-bromomethyl)-5-methyl-6- methoxy-naphthalene, analogous to Example 1. Yield: 43.5% of the theoretical.

M.p.: 125-127°C.

Calculated: C, 74.39; H, 7.80; N, 5.42

Found: C, 74.31; H, 7.82; N, 5.35

Example 40 2-[ (N-(2-methyl-naphthyl-1)-methyl)-hexahydro-azepinyl-3)-methyl]-6. 7-dimethoxy-l-oxo-l. 2, 3. 4- tetrahydro- isoquinoline- hydrochloride

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

Yield: 67.5% of the theoretical.

Melting point: 128-130°C.

Calcd (x 2 H 2 O): C, 66.10; H, 7.58; N, 5.13; Cl, 6.50 Found: C, 66.24; H, 7.44; N, 5.23; Cl, 6.85

Example 41

2- [ (N-(4-(naphthyl-2-oxy)-butyl)-hexahydro-azepinyl-3)-methyl] - 6. 7- dimethoxy-l-oxo-l. 2. 3. 4- tetrahvdro- isoquinoline- hydrochloride

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

Yield: 26% of the theoretical.

M.p.: 192-194°C.

Calculated: C, 69.22; H, 7.80; N, 5.04; Cl, 6.38

Found: C, 70.01; H, 7.70; N, 5.15; Cl, 6.48

Example 42

2- [ (N-(2-(naphthyl-1)-ethyl)-hexahydro-azepinyl-3)-methyl]-6,7-methylenedioxy- l- 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, analogous to Example 1. Yield: 15.4% of the theoretical.

M.p.: 236-238°C.

Calcd (x 1/2 H 2 O) : C, 69.40; H, 6.82; N, 5.58; Cl, 7.06

Found: C, 69.07; H, 6.74; N, 6.13; Cl, 7.29

Example 43 2-[(N-(2-(naphthyl-2)-ethyl)-hexahydro-azepinyl-3)-methyl]-6,7-methylenedioxy-l-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-bromomethyl]-naphthalene, analogous to Example 1.

M.p.: 100-102°C.

Yield: 31.6% of the theoretical.

Calculated: C, 64.80; H, 6.18; N, 5.21; Br, 14.86

Found: C, 65.02; H, 6.07; N, 5.39; Br, 14.78

Example 44

2-[(N-(2-(6-methoxy-naphthyl-2)-ethyl)-hexahydro-azepinyl-3)-methyl]-6,7-methylenedioxy-1-oxo-1,2,3,4- tetrahydroisoquinoline hydrochloride

Prepared from 2-[(hexahydro-azepinyl-3)-methyl]-6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 2-(2-bromomethyl]-6-methoxy- naphthalene, analogous to Example 1. Yield: 34.1% of the theoretical.

M.p.: 147-149°C.

Calcd (x H 2 O): C, 68.62; H, 7.10; N, 5.33; Cl, 6.75 Found: C, 68.88; H, 6.98; N, 5.41; Cl, 6.78

Example 45

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-bromomethyl]-5-methyl- 6-methoxy-naphthalene, analogous to Example 1. Yield: 3 6.1% of the theoretical.

M.p.: 112-114°C.

Calcd (x H 2 O): C, 67.07; H, 7.08; N, 5.04; Cl, 6.38 Found: C, 67.13; H, 7.15; N, 4.97; Cl, 6.56

Example 4 6

2 - [(N-(3-(4-methoxy-phenoxy)-propyl)-piperidyl-3)-methyl]-6,7-dimethoxy- 1, 2, 3. 4- tetrahydro- is6quinoline- dihydrochloride

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

Yield: 88.5% of the theoretical.

M.p.: 189-191°C.

Calcd: C, 59.44; H, 7.76; N, 5.13; Cl, 12.99

Found: C, 59.55; H, 7.99; N, 5.12; Cl, 12.61

Example 47

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

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

Yield: 92.8% of the theoretical.

M.p.: 175-176°C.

Calculated: C, 60.66; H, 7.35; N, 5.33; Cl, 13.49

Found: C, 60.58; H, 7.56; N, 5.32; Cl, 13.22

Example 48

2-[(N-(3-(3-methoxy-phenoxy)-propyl)-piperidyl-3)-methyl]-6. 7- methylenedioxy- l. 2. 3. 4- tetrahydro- isoquinoline- dihydrochloride

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

Yield: 94.5% of the theoretical.

M.p.: 169-171°C.

Calculated: C, 57.03; H, 7.36; N, 5.11; Cl, 13.86

Found: C, 56.91; H, 7.26; N, 5.15; Cl, 13.68

in

Example 49

2-[(N-(2-(3,4-dimethoxyphenyl)-ethyl)-piperidyl-3)-methyl]-6,7-dimethyl- 1. 2, 3, 4- tetrahydro- isoquinoline- dihydrochloride

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

Yield: 91.3% of the theoretical.

M.p.: 140-142°C.

Calculated: C, 62.00; H, 8.34; N, 5.27; Cl, 13.44

Found: C, 61.85; H, 8.27; N, 5.31; Cl, 13.33

Example 50

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, analogously to Example 3.

Yield: 88.3% of the theoretical.

M.p.: 170-172°C.

Calculated: C, 63.14; H, 8.24; N, 5.65; Cl, 14.31

Found: C, 63.09; H, 8.33; N, 5.82; Cl, 14.02

Example 51

2-[(N-(2-(3,4-dimethoxyphenyl)-ethyl)-piperidyl-3)-methyl]-6,7-methylenedioxy- 1. 2. 3. 4- tetrahydro- isoquinoline- dihydrochloride

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

Yield: 93.3% of the theoretical.

M.p.: 150-154°C.

Calculated: C, 60.01; H, 7.34; N, 5.39; Cl, 13.64

Found: C, 59.96; H, 7.41; N, 5.25; Cl, 13.43

Example 52 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 -isoquinoline and lithium aluminum hydride in tetrahydrofuran, analogously to Example 3.

Yield: 95.3% of the theoretical.

M.p.: 182-185°C.

Calculated: C, 61.05; H, 7.09; N, 5.48; Cl, 13.86

Found: C, 61.10; H, 6.95; N, 5.68; Cl, 13.55

Example 53

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

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

Yield: 35.5% of the theoretical.

M.p.: 97-100°C.

Calculated: C, 59.09; H, 7.28; N, 4.62; Cl, 6.65

Found: C, 58.97; H, 7.36; N, 4.66; Cl, 6.52

Example 54

2-[2-(N-(2-(3,4-dimethoxyphenyl)^ethyl)-piperidyl-3)-ethyl]-6,7-dimethoxy-l-oxo- 1. 2, 3, 4 - tetrahydroisoquinoline hydrochloride

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

Yield: 35.9% of the theoretical.

M.p.: 103-105°C.

Calculated: C, 62.60; H, 7.79; N, 5.21; Cl, 6.83

Found: C, 62.41; H, 7.82; N, 5.09; Cl, 7.19

Example 55

2-[3-(N-(2-(3,4-dimethoxyphenyl)-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 l-bromo-2-(3,4-dimethoxyphenyl )-ethane, analogous to Example 1.

Yield: 32.6% of the theoretical.

Temp. : 102-106°C.

Calculated: C, 63.20; H, 7.86; N, 5.08; Cl, 6.43

Found: C, 63.39; H, 7.90; N, 4.86; Cl, 6.13

Example 56

2-[3 - (N-(3-(3,4-methylenedioxy-phenoxy)-propyl)-piperidyl-3)-propyl]-6,7-dimethoxy-1-oxo-1,2,3,4- tetrahydroisoquinoline 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-methylenedioxy -phenoxy)-propane, analogously to Example 1.

Yield: 29.7% of the theoretical.

M.p.: 97-100°C.

Calculated: C, 61.63; H, 7.31; N, 4.96; Cl, 6.47

Found: C, 61.94; H, 7.46; N, 5.16; Cl, 6.48

Example 57

2- [ (N-(3,4-dimethoxybenzyl)-piperidyl-3)-methyl]-6,7-dimethoxy-1- oxo- l. 2, 3, 4- tetrahydro- isoquinoline- hydrochloride

Prepared from 2-(piperidyl-3-methyl)-6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 3,4-dimethoxy-benzyl bromide, analogously to Example 1.

Yield: 53.3% of the theoretical.

M.p.: 127-132°C.

Calculated: C, 63.58; H, 7.18; N, 5.70; Cl, 7.22

Found: C, 63.30; H, 7.22; N, 5.52; Cl, 7.14

Example 58

2-[ (N-(3-(4-Methoxyphenyl)-propyl)-piperidyl-3)-methyl]-6,7-dimethoxy- l - 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 l-bromo-3-(4-methoxyphenyl)-propane, analogous to Example 1.

Yield: 42% of the theoretical.

M.p.: 229-231°C.

Calculated: C, 66.31; H, 7.63; N, 5.73; Cl, 7.25

Found: C, 66.27; H, 7.64; N, 5.65; Cl, 7.33

Example 59

2- [2- (N- (3- (3-methyl-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-methyl-phenoxy) )-propane, analogous to Example 1.

Yield: 52.4% of the theoretical.

M.p.: 142-144°C.

Calcd: C, 66.85; H, 7.81; N, 5.57; Cl, 7.05

Found: C, 66.73; H, 7.68; N, 5.53; Cl, 6.94

Example 60

2-[2-(N-(2-(3,4-dimethoxyphenyl)-ethyl)-piperidyl-2)-ethyl]-6,7-dimethoxy- l - 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 l-bromo-2-(3,4-dimethoxy -phenyl)-ethane, analogously to Example 1.

Yield: 47.3% of the theoretical.

Melting point: 150-155°C.

Calculated: C, 64.72; H, 7.68; N, 5.39; Cl, 6.82

Found: C, 64.40; H, 7.83; N, 5.27; Cl, 6.90

Example 61

2-[2-(N-(3-benzyloxy-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-benzyloxypropane, analogously to Example 1 .

Yield: 56.3% of the theoretical.

M.p.: 116-120°C.

Calcd: C, 66.85; H, 7.81; N, 5.57; Cl, 7.05

Found: C, 66.60; H, 7.75; N, 5.25; Cl, 7.25

Example 62

2-[2-(N-(4-(4-methoxyphenyl)-butyl)-piperidyl-2)-ethyl]-6,7-dimethoxy- l- 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 l-bromo-4-(4-methoxyphenyl)- butane, analogous to Example 1.

Yield: 42.8% of the theoretical.

M.p.: 107-112°C.

Calculated: C, 67.36; H, 7.99; N, 5.42; Cl, 6.86

Found: C, 67.16; H, 8.05; N, 5.35; Cl, 7.34

Example 63

2-[2-(N-(3-(3,5-dimethoxy-phenoxy)-propyl)-piperidyl-2)-ethyl]-6. 7- dimethoxy- l- oxo- l. 2, 3. 4- tetrahdro- 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-dimethoxy -phenoxy)-propane, analogous to Example 1.

Yield: 56.3% of the theoretical.

M.p.: 127-132°C.

Calculated: C, 61.41; H, 7.64; N, 5.10; Cl, 6.46

Found: C, 61.56; H, 7.65; N, 5.28; Cl, 6.89

Example 64

2-[2-(N-(3-(3,4-methylenedioxy-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-(3,4-methylenedioxy -phenoxy)-propane, analogously to Example 1.

Yield: 49% of the theoretical.

M.p.: 118-120°C.

Calculated: C, 63.09; H, 7.00; N, 5.26; Cl, 6.65

Found: C, 62.90; H, 7.04; N, 5.46; Cl, 6.79

Example 65

2-[(N-(3-(3,5-dimethoxy-phenoxy)-propyl)-piperidyl-3)-methyl]-6. 7- dimethoxy-l- oxol- l. 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, analogous to Example 1.

Yield: 37.5% of the theoretical.

M.p.: 98-102°C.

Calcd: C, 62.85; H, 7.35; N, 5.24; Cl, 6.63

Found: C, 62.81; H, 7.41; N, 5.10; Cl, 6.75

Example 66

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

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

Yield: 50% of the theoretical.

M.p.: 236-238°C.

Calcd: C, 64.46; H, 7.01; N, 5.57; Cl, 7.04

Found: C, 64.30; H, 6.97; N, 5.59; Cl, 7.08

Example 67

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

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

Yield: 46.2% of the theoretical.

M.p.: 149-153°C.

Calculated: C, 60.38; H, 6.94; N, 5.21; Cl, 6.60

Found: C, 60.30; H, 6.93; N, 5.29; Cl, 6.37

Example 68

2-[(N-(3-(2,6-dimethyl-phenoxy)-propyl)-piperidyl-3)-methyl]-6. 7- dimethoxy-l-oxo- l. 2, 3, 4- tetrahdro- isoquinoline- hydrochloride

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

Yield: 53.3% of the theoretical.

M.p.: 131-135°C.

Calcd: C, 66.85; H, 7.81; N, 5.57; Cl, 7.05

Found: C, 66.88; H, 7.95; N, 5.59; Cl, 6.85

Example 69

2-[(N-(4-(2,4-dichloro-phenoxy)-butyl)-piperidyl-3)-methyl]-6,7-dimethoxy- l - oxo- l. 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-4-(2,4-dichloro-phenoxy )-butane, analogous to Example 1.

Yield: 54.1% of the theoretical.

M.p.: 125-128°C.

Calculated: C, 58.12; H, 6.32; N, 5.02; Cl, 19.06

Found: C, 58.21; H, 6.38; N, 5.08; Cl, 18.85

Example 70

2-[(N-(2-(3,4-dimethoxyphenyl)ethyl)piperidyl-3)-methyl]-6,7-dimethoxy- l - 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 l-bromo-2-(3,4-dimethoxy-phenyl) -ethane, analogous to Example 1.

Yield: 57.5% of the theoretical.

M.p.: 118-121°C.

Calculated: C, 64.21; H, 7.38; N, 5.55

Found: C, 64.18; H, 7.36; N, 5.19

Example 71

2-[ (N-(3-(3,4-dimethoxy-phenoxy);-propyl)-piperidyl-3)-methyl]-6,7-dimethoxy-1-oxo-1,2,3,4- tetrahydroisoquinoline 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, analogous to Example 1.

Yield: 62.5% of the theoretical.

M.p.: 112-115°C.

Calculated: C, 60.80; H, 7.47; N, 5.24

Found: C, 60.65; H, 7.69; N, 5.27

Example 72

2- [(N-(3-(3,4-dimethoxy-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-(3,4-dimethoxy-phenoxy )-propane, analogous to Example 1. Yield: 60% of the theoretical.

M.p.: 97-100°C.

Calculated: C, 60.38; H, 6.94; N, 5.40; Cl, 6.60

Found: C, 60.20; H, 6.97; N, 5.21; Cl, 6.83

Example 73

2- [ (N-(2-(4-methoxy-phenyl)-ethyl)-piperidyl-3)-methyl]-6,7-methylenedioxy- l- 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-2-(4-methoxyphenyl)-ethane, analogous to Example 1.

Yield: 71.4% of the theoretical.

M.p.: 195-197°C.

Calcd: C, 62.94; H, 6.97; N, 5.87; Cl, 7.73

Found: C, 62.90; H, 6.98; N, 5.68; Cl, 8.04

Example 74

2-[ (N-(2-(3,4-dimethoxyphenyl)-ethyl)-piperidyl-3)-methyl]-6, 7- dimethyl-1-oxo-l. 2. 3, 4- tetrahydro-isoquinoline-hydrochloride

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

Yield: 41.9% of the theoretical.

M.p.: 132-134°C.

Calculated: C, 63.57; H, 8.10; N, 5.49; Cl, 6.95

Found: C, 63.70; H, 8.26; N, 5.45; Cl, 7.13

Example 75

2-[ (N-(3-(4-methoxy-phenoxy)-propyl)-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-1,2,3,4-tetrahydro-isoquinoline and 1-chloro-3-(4-methoxy-phenoxy)- propane, analogous to Example 1.

Yield: 57.8% of the theoretical.

M.p.: 144-146°C.

Calcd: C, 68.55; H, 7.88; N, 5.92; Cl, 7.49

Found: C, 68.45; H, 7.80; N, 6.11; Cl, 7.33

Example 76 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, analogous to Example 1. Yield: 32.5% of the theoretical.

M.p.: 142-145°C.

Calculated: C, 60.58; H, 6.95; N, 5.52; Cl, 6.99

Found: C, 60.42; H, 6.92; N, 5.50; Cl, 7.18

Example 77

2-[(N-(3-(3-methyl-phenoxy)-propyl)-piperidyl-3)-methyl]-6,7-methylenedioxy- l- 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 3-(3-methyl-phenoxy)-1-chloro- propane, analogously to Example 1. Yield: 31.6% of the theoretical.

Melting point: 178-180°C.

Calcd: C, 63.59; H, 6.97; N, 5.70; Cl, 7.22

Found: C, 63.59; H, 6.92; N, 5.86; Cl, 7.50

Example 78

2-[(N-(3-(4-methoxy-N-methyl-phenylamino)-propyl)-piperidyl-3)-methyl]-6,7-dimethoxy-1-oxo-1,2,3,4- tetrahydroisoquinoline dihydrochloride

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

Yield: 52.5% of the theoretical.

M.p.: 180-183°C.

Calculated: C, 60.64; H, 7.45; N, 7.58; Cl, 12.79

Found: C, 60.50; H, 7.35; N, 7.56; Cl, 12.87

Example 79

2 - [ (N-(3 - (4-Methoxy-phenoxy)-propyl)-pyrrolidyl-3)-methyl ] - 6, 7- dimethoxy- l - oxo- l, 2, 3, 4- tetrahydro- isoquinoline - Hydrochloride

Prepared from 6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and N-(3-(4-methoxy-phenoxy)-propyl)-3-benzene-sulfonyloxymethyl-pyrrolidine, analogous to Example 2. Yield: 84.4% of the theoretical.

M.p.: 142-144°C.

Calculated: C, 63.60; H, 7.18; N, 5.71; Cl, 7.22

Found: C, 63.75; H, 7.12; N, 5.64; Cl, 7.32

Example 80

2- [(N-(3-(6-methoxy-naphthyl-2-oxy)-propyl)-pyrrolidyl-3)-methyl]-6,7-dimethoxy-1-oxo-1,2,3,4- tetrahydroisoquinoline

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

Yield: 47% of the theoretical.

M.p.: 142-144°C.

Calculated: C, 71.41; H, 7.19; N, 5.55

Found: C, 71.14; H, 7.16; N, 5.53

Example 81

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)-pyrrolidyl-3)-methyl]-6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro- isoquinoline and lithium aluminum hydride in tetrahydrofuran, analogously to Example 3.

Yield: 90.9% of the theoretical.

Melting point: 248-250°C.

Calculated: C, 60.81; H, 7.46; N, 5.46; Cl, 13.81

Found: C, 60.79; H, 7.61; N, 5.48; Cl, 13.84

Example 82

2-[(N-(3-(4-methoxy-phenoxy)-propyl)-pyrrolidyl-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 N-[3-(4-methoxy-phenoxy)-propyl]-3-benzene-sulfonyloxymethyl-pyrrolidine, analogous to Example 2. Yield: 60.6% of the theoretical.

M.p.: 118-121°C.

Calculated: C, 68.03; H, 7.69; N, 6.10; Cl, 7.72

Found: C, 67.90; H, 7.71; N, 6.04; Cl, 7.90

Example 83

2-[(N-(2-(3,4-dimethoxyphenyl)-ethyl)-pyrrolidyl-3)-methyl]-6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro'-isoquinoline - Hydrochloride

Prepared from 6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and N-[2-(3,4-dimethoxy-phenoxy)-ethyl]-3-benzenesulfonyloxymethyl-pyrrolidine, analogous to Example 2. Yield: 56.7% of the theoretical.

M.p.: 116-118°C.

Calculated: C, 63.60; H, 7.19; N, 5.71; Cl, 7.22

Found: C, 63.82; H, 7.32; N, 5.60; Cl, 7.66

Example 84

2-[(N-(3-(4-methoxy-phenoxy)-propyl)-pyrrolidyl-3)-methyl]-6. 7- dimethyl- l. 2, 3, 4- tetrahydro- isoquinoline- dihydrochloride

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

Yield: 90.9% of the theoretical.

M.p.: 243-246°C.

Calcd: C, 64.85; H, 7.95; N, 5.82; Cl, 14.73

Found: C, 64.88; H, 7.92; N, 5.63; Cl, 14.80

Example 85

2 - [(N-(2-(3,4-dimethoxyphenyl)-ethyl)-pyrrolidyl-3)-methyl]-6,7-dimethoxy- 1. 2, 3, 4- tetrahydro- isoquinoline- dihydrochloride

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

Yield: 92.9% of the theoretical.

M.p.: 240-242°C.

Calculated: C, 60.81; H, 7.46; N, 5.46; Cl, 13.81

Found: C, 60.64; H, 7.61; N, 5.31; Cl, 13.50

Example 86

2 - [ (N-(3-pyridy 1-4)-propyl)-pyrrolidyl-3)-methyl]-5,6-dimethyl- l- oxo- 1. 3- dihydro- isoindole- dihydrochloride- hemihydrate

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

Yield: 65% of the theoretical.

M.p.: 119-122°C.

Calculated: C, 62.02; H, 7.24; N, 9.43; Cl, 15.92

Found: C, 62.25; H, 7.47; N, 9.39; Cl, 15.90

Example 87

2-[3-(N-(3-(pyridyl-3)-propyl)-piperidyl-3)-propyl]-5,6-dimethoxy- l - oxo- 1. 3- dihydro- isoindole- dihydrochloride- monohydrate

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

Yield: 72% of the theoretical.

M.p.: 118-121°C.

Calculated: C, 59.08; H, 7.43; N, 7.95; Cl, 13.41

Found: C, 59.02; H, 7.23; N, 7.12; Cl, 13.27

Example 8 8 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, analogously to Example 4.

Yield: 42% of the theoretical.

M.p.: 91-96°C.

Calculated: C, 59.08; H, 7.43; N, 7.95; Cl, 13.41

Found: C, 59.02; H, 7.23; N, 7.12; Cl, 13.27

Example 89

2-[ (N-(2-(6,7-dimethoxy-isoquinoyl-4)-ethyl)-piperidyl-3)-methyl 1 - 5. 6- dimethoxy- l - oxo- l. 3- dihydro- isoindole

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

Yield: 64% of the theoretical.

M.p.: 85-88°C.

Calculated: C, 65.39; H, 7.19; N, 7.88

Found: C, 65.16; H, 7.27; N, 7.53

Example 90

2-[2-(N-(3-(pyridyl-4)-propyl)-piperidyl-2)-ethyl]-5,6-dimethyl-1- oxo-l. 3- dihydro-isoindole

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

Yield: 73% of the theoretical.

M.p.: 103-104°C.

Calculated: C, 76.68; H, 8.49; N, 10.73

Found: C, 76.57; H, 8.54; N, 10.60

Example 91

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 in tetrahydrofuran/ ether, analogous to Example 3.

Yield: 68% of the theoretical.

Melting range: 118-127°C (amorphous)

Calculated: C, 59.03; H, 7.54; N, 8.98; Cl, 22.73

Found: C, 58.93; H, 7.48; N, 8.84; Cl, 22.92

Example 92

2-[2-(N-(3-(pyridyl-4)-propyl)-piperidyl-2)-ethyl]-5,6-dimethyl- 1.3- 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, analogous to Example 3.

Yield: 70% of the theoretical.

Melting range: 135-148°C (amorphous)

Calculated: C, 54.59; H, 8.24; N, 7.63; Cl, 19.33

Found: C, 54.48; H, 8.26; N, 7.51; Cl, 19.60

Example 93

2-[(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]-5,6-dimethoxy-phthalimide and lithium aluminum hydride in ether, analogously to Example 3.

Yield: 68% of the theoretical.

Melting range: 176-189°C (amorphous)

Calcd: C, 49.76; H, 7.21; N, 7.91; Cl, 20.03

Found: C, 49.93; H, 7.12; N, 8.00; Cl, 20.44

Example 94 2-[(N-(2-(6,7-dimethoxy-isoquinolyl-4)-ethyl)-piperidyl-3)-methyl]-5,6-dimethyl-1,3-dihydro-isoindole-dihydrochloride- semi-horizontal

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

Yield: 22.7% of the theoretical.

Melting range: 222-236°C (amorphous)

Calculated: C, 62.22; H, 7.20; N, 7.50; Cl, 15.83

Found: C, 62.01; H, 7.64; N, 7.08; Cl, 15.79

Example 95

2- [ (N-(1-(pyridyl-4)-methyl)-piperidyl-3)-methyl]-5,6-methylenedioxy- 1, 3- dihydro- isoindole- trihydrochloride- hemihydrate

Prepared from 2-[(N-(1-(pyridyl-4)-methyl)-piperidyl-3)-methyl]-5,6-methylenedioxyphthalimide and lithium aluminum hydride in tetrahydrofuran/ether, analogously to Example 3.

Yield: 55% of the theoretical.

Melting range: 215-225°C (amorphous)

Calculated: C, 53.68; H, 6.22; N, 8.94; Cl, 22.63

Found: C, 53.60; H, 6.45; N, 8.65; Cl, 22.28

Example 96

2-[ (N-(3-(pyridyl-4)-propyl)-pyrrolidyl-3)-methyl]-6,7-dimethyl-1,2,3,4-tetrahydro-isoquinoline-trihydrochloride monohydrate

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, analogously to Example 3.

Yield: 63% of the theoretical.

M.p.: 254-256°C.

Calculated: C, 58.71; H, 7.80; N, 8.56; Cl, 21.66

Found: C, 58.53; H, 7.72; N, 8.25; Cl, 21.53

Example 97

2 - [ (N-(1-(pyridyl-4)-methyl)-piperidyl-3)-methyl]-6,7-dimethoxy-1, 2, 3, 4- tetrahydro- isoquinoline- trihydrochloride- dihydrate

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

Yield: 63% of the theoretical.

Melting range: 158-169°C (amorphous)

Calculated: C, 52.42; H, 7.27; N, 7.97; Cl, 20,18

Found: C, 52.55; H, 7.49; N, 7.57; Cl, 20.25

Example 98

2-[2-(N-(3-(pyridyl-4)-propyl)-piperidyl-2)-ethyl]-6,7-methylenedioxy-1,2,3,4-tetrahydro-isoquinoline-trihydrochloride-trihydrate

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

Yield: 90% of the theoretical.

Melting range: 108-119°C (amorphous)

Calculated: C, 52.58; H, 7.41; N, 7.36; Cl, 18.62

Found: C, 52.56; H, 7.25; N, 7.38; Cl, 19.49

Example 99

2-[(N-(3-(pyridyl-3)-propyl)-piperidyl-3)-methyl]-6,7-methylenedioxy-1,2,3,4-tetrahydro-isoquinoline-dihydrochloride monohydrate

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, analogously to Example 3.

Yield: 72% of the theoretical.

Melting range: 126-138°C (amorphous)

Calculated: C, 59.50; H, 7.28; N, 8.67; Cl, 14.64

Found: C, 59.57; H, 7.29; N, 8.49; Cl, 14.51

Example 100 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, analogously to Example 3.

Yield: 59% of the theoretical.

Melting range: 138-154°C (amorphous)

Calculated: C, 61.66; H, 7.86; N, 8.62; Cl, 21.84

Found: C, 61.53; H, 8.00; N, 8.64; Cl, 21.35

Example 101

2-[(N-(3-(pyridyl-4)-propyl)-pyrrolidyl-3)-methyl]-6,7-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline-dihydrochloride- monohvdrat

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

Yield: 39% of the theoretical.

Melting range: 74-86°C (amorphous)

Calculated: C, 61.53; H, 7.53; N, 8.97; Cl, 15.13

Found: C, 61.42; H, 7.62; N, 8.83; Cl, 15.05

Example 102

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

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

Yield: 45% of the theoretical.

Melting range: 140-148°C (amorphous)

Calculated (x 2 HC1 x H20) :

C, 58.36; H, 7.25; N, 8.16; Cl, 13.78

Found: C, 58.35; H, 7.32; N, 8.04; Cl, 13.65

Example 103

2-[(3-(N-(3-(pyridyl-4)-propyl)-piperidyl-3)-propyl]-6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline -dihydro- ' chloride- dihydrate

Prepared from 2-[3-(piperidyl-3)-propyl]-6,7-dimethoxy-1-oxo-1, 2, 3, 4-tetrahydro-isoquinoline and 4-(3-chloropropyl)pyridine, analogous to Example 1.

Yield: 48% of the theoretical.

Melting range: 85-96°C (amorphous)

Calculated: C, 57.84; H, 7.73; N, 7.49; Cl, 12.65

Found: C, 57.71; H, 7.91; N, 7.35; Cl, 13.04

Example 104

2-[3-(N-(2-(6,7-dimethoxy-isoquinolyl-4)-ethyl)-piperidyl-3)-propyl]-6,7-dimethoxy-1-oxo-1,2,3, 4-tetrahydro-isoquinoline 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, analogous to Example 1.

Yield: 34% of the theoretical.

Melting range: 162-171°C (amorphous)

Calculated: C, 60.17; H, 7.10; N, 6.57; Cl, 11.10

Found: C, 59.85; H, 7.00; N, 6.86; Cl, 11.04

Example 105

2-[(N-(3-(pyridyl-3)-propyl)-piperidyl-3)-methyl]-6,7-methylene-dioxv- l- 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-(pyridyl-3)-propyl]-piperidine, analogously to Example 2.

Yield: 60% of the theoretical.

Melting range: 194-196°C (amorphous)

Calcd: C, 64.92; H, 6.81; N, 9.46; Cl, 7.98

Found: C, 64.91; H, 6.95; N, 9.67; Cl, 7.80

Example 106

2-[(N-(1-(pyridyl-4)-methyl)-piperidyl-3)-methyl]-6,7-dimethoxy-1- oxo- l. 2. 3, 4- tetrahydro- isoquinoline- dihydrochloride- monohydrate

Prepared from 6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline in dimethyl sulfoxide with potassium tert-butylate and 3-chloromethyl-N-[1-(pyridyl-4)-methyl]- piperidine, analogously to Example 2.

Yield: 41% of the theoretical.

Melting range: 142-158°C (amorphous)

Calculated: C, 56.78; H, 6.83; N, 8.63; Cl, 14.58

Found: C, 56.45; H, 6.59; N, 8.66; Cl, 14.62

Example 107

2- [(N-(2-(6,7-dimethoxy-isoquinolyl-4)-ethyl)-piperidyl-3)-methyl]-6,7-dimethyl-1-oxo-1,2,3;4- tetrahydroisoquinoline dihydrochloride

Prepared from 6,7-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline in dimethylsulfoxide with potassium tert-butylate and 3-chloromethyl-N-[2-(6,7-dimethoxy-isoquinolyl- 4)-ethyl]-piperidine, analogously to Example 2.

Yield: 62% of the theoretical.

Melting range: 148-162°C (amorphous)

Calculated: C, 64.27; H, 7.01; N, 7.49; Cl, 12.65

Found: C, 64.11; H, 7.20; N, 7.59; Cl, 12.89

Example 108

2-[2-(N-(3-(pyridyl-4)-propyl)-piperidyl-2)-ethyl]-6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline- dihydrochloride- dihydrochloride

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

Melting range: 115-128°C (amorphous)

Calculated: C, 56.59; H, 7.03; N, 7.92; Cl, 13.37

Found: C, 56.61; H, 6.90; N, 7.84; Cl, 13.41

Example 109

2-[ (N-(3-(pyridyl-3)-propyl)-piperidyl-3)-methyl]-6,7-dimethyl-1-oxo-1. 2. 3. 4- tetrahydro- isoquinoline- dihydrochloride- dihydrochloride

Prepared from 6,7-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline in dimethyl sulfoxide with potassium tert-butylate and 3-chloromethyl-N-[3-(pyridyl-3)-propyl]- piperidine, analogously to Example 2.

Yield: 62% of the theoretical.

Melting range: 118-127°C (amorphous)

Calculated: C, 60.00; H, 7.85; N, 8.39; Cl, 14,16

Found: C, 60.24; H, 8.07; N, 8.36; Cl, 14.62

Example 110

2- [ (N-(3-(pyridyl-3)-propyl)-pyrrolidyl-3)-methyl]-6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline dihydrochloride

Prepared from 6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 3-cl orme ty 1-N-[3-(pyridyl-3)-propyl]-pyrrolidine, analogously to Example 2.

Yield: 26% of the theoretical.

Melting range: 102-113°C (amorphous)

Calculated: C, 59.22; H, 6.27; N, 9.01; Cl, 15,20

Found: C, 59.27; H, 6.49; N, 8.92; Cl, 14.48

Example 111

2- [ (N-(3-(pyridyl-4)-propyl)-pyrrolidyl-3)-methyl]-7,8-methylene-dioxv- 2- oxo- l. 3- dihydro- 2H- 3- benzazepine- dihydrochloride

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

Yield: 58% of the theoretical.

Melting range: 132-141°C (amorphous)

Calculated: C, 60.25; H, 6.11; N, 8.78; Cl, 14.82

Found: C, 60.00; H, 6.40; N, 8.52; Cl, 14.56

Example 112

2-[(N-(3-(pyridyl-3)-propyl)-piperid-3-yl)-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 3-chloromethyl-N-[3-(pyridyl-3)-propyl]-piperidine, analogously to Example 2.

Yield: 67% of the theoretical.

Melting range: 128-134°C (amorphous)

Calculated: C, 57.34; H, 7.21; N, 7.71; Cl, 13.02

Found: C, 57.80; H, 7.37; N, 7.92; Cl, 13.06

Example 113

3- [ (N-(3-(pyridyl-3)-propyl)-piperidyl-3)-methyl]-7,8-dimethyl-2- oxo- l. 3- dihydro- 2H- 3- benzazepine- dihydrochloride- dihydrate

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

Yield: 94% of the theoretical.

Melting range: 77-86°C (amorphous)

Calcd: C, 60.92; H, 7.67; N, 8.19; Cl, 13.83

Found: C, 60.75; H, 7.60; N, 8.37; Cl, 13.72

Example 114

3- [2-(N-(3-(pyridyl-4)-propyl)-piperidyl-2)-ethyl]-7,8-dimethyl- 2- oxo- l. 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, analogous to Example 2.

Yield: 94% of the theoretical.

Melting range: 118-130°C (amorphous)

Calculated: C, 66.11; H, 7.60; N, 8.56; Cl, 14.45

Found: C, 65.92; H, 7.86; N, 8.33; Cl, 14.09

Example 115

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

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, analogous to Example 2.

Yield: 69% of the theoretical.

Melting range: 85-96°C (amorphous)

Calculated: C, 67.73; H, 7.15; N, 7.64

Found: C, 67.96; H, 7.19; N, 7.75

Example 116

3-[3-(N-(3-(pyridyl-3)-propyl)-piperidyl-3)-propyl]-7,8-dimethoxy-2-oxo-1,3-dihydro-2H-3-benzazepine- dihydrochloride monohydrate

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

Yield: 72% of the theoretical.

Melting range: 94-106°C (amorphous)

Calculated: C, 60.64; H, 7.45; N, 7.57; Cl, 12.78

Found: C, 60.80; H, 7.44; N, 7.46; Cl, 12.59

Example 117

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

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

Yield: 67% of the theoretical.

Melting range: 148-161°C (amorphous)

Calculated C, 57.56; H, 6.87; N, 7.74; Cl, 13.07

Found: C, 57.72; H, 7.03; N, 7.61; Cl, 13.62

Example 118 3-[(N-(1-(pyridyl-4)-methyl)-piperidyl-3)-methyl]-7,8-dimethyl-2-oxo-1,3-dihydro-2H-3-benzazepine- dihydrochloride monohydrate

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

Yield: 75% of the theoretical.

Melting range: 113-127°C (amorphous)

Calcd: C, 61.79; H, 7.13; N, 9.01; Cl, 15,20

Found: C, 61.55; H, 7.32; N, 9.04; Cl, 15,11

Example 119

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

Prepared from 3-[(N-(3-(pyridyl-4)-propyl)-pyrrolidyl-3)-methyl]-7,8-methylenedioxy-2-oxo-1,3-dihydro-2H-3-benzazepine and 10% palladium/coal and a hydrogen pressure of 5 bar at room temperature, analogous to Example 5.

Yield: 71% of the theoretical.

Melting range: 95-106°C (amorphous)

Calculated: C, 57.83; H, 6.67; N, 8.43; Cl, 14.22

Found: C, 57.67; H, 6.82; N, 8.27; Cl, 14.05

Example 120

3-[2-(N-(3-(pyridyl-4)-propyl)-piperidyl-2)-ethyl]-7,8-dimethyl-2-oxo-1,3,4,5-tetrahydro-2H- 3-benzazepine dihydrochloride semihydrate

Prepared from 3-[2-(N-(3-(pyridyl-4)-propyl)-piperidyl-2)-ethyl]-7,8-dimethyl-2-oxo-1,3-dihydro-2H-3- benzazepine and 10% palladium/charcoal and a hydrogen pressure of 5 bar at 80°C, analogous to Example 5.

Yield: 73% of the theoretical.

M.p.: 236-238°C

Calculated: C, 64.65; H, 8.04; N, 8.37; Cl, 14,14

Found: C, 64.91; H, 8.02; N, 8.25; Cl, 13.92

Example 121

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

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-methyl -pyridyl-2)-ethyl ester in dimethylsulfoxide with potassium carbonate at 120°C, analogously to Example 1.

Yield: 29% of the theoretical.

Melting range: 105-113°C (amorphous)

Calculated: C, 60.42; H, 7.78; N, 7.55

Found: C, 60.68; H, 7.50; N, 7.42

Example 122

3- [(N-(3-(pyridyl-3)-propyl)-piperidyl-3)-methyl]-7,8-dimethoxy-2-oxo-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-dihydro-2H-3-benzazepine by hydration at 5 bar hydrogen pressure in ethanol with 10% palladium/charcoal at 70°C, analogously to Example 5.

Yield: 52% of the theoretical.

Melting range: 113-122°C (amorphous)

Calculated: C, 61.17; H, 7.30; N, 8.23

Found: C, 61.31; H, 7.50; N, 8.28

Example 123

3-[(N-(2-(6,7-dimethoxy-isoquinolyl-4)-ethyl)-piperidyl-3)-methyl]-7,8-dimethoxy-2-oxo-1,3,4,5- tetrahydro-2H-3-benzazepine x 1/ 2 H?0

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 hydration under 5 bar hydrogen pressure with 10% palladium/charcoal in ethanol at 70°C, analogous to Example 5.

Yield: 50% of the theoretical.

Melting range: 82-86°C (amorphous)

Calculated: C, 66.40; H, 7.55; N, 7.48;

Found: C, 66.26; H, 7.50; N, 7.59;

Example 124

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

Prepared from 3-[3-(N-(3-(pyridyl-3)-propyl)-piperidyl-3)-propyl]-7,8-dimethoxy-2-oxo-1,3-dihydro-2H-3- benzazepine by hydration under 5 bar hydrogen pressure with 10% palladium/charcoal in ethanol at 70°C, analogously to Example 5.

Yield: 64% of the theoretical.

Melting range: 106-115°C (amorphous)

Calculated: C, 58.53; H, 7.89; N, 7.31; Cl, 12.34

Found: C, 58.46; H, 7.61; N, 7.14; Cl, 12.57

Example 125

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

under 5 bar hydrogen pressure with 10% palladium/coal in ethanol at 80°C, analogous to Example 5.

Yield: 81% of the theoretical.

Melting range: 126-138°C (amorphous)

Calculated: C, 58.58; H, 6.88; N, 8.19; Cl, 13.83

Found: C, 58.43; H, 7.00; N, 7.85; Cl, 13.71

Example 126 3-[2-(N-(3-(pyridyl-4)-propyl)-piperidyl-2)-ethyl]-7,8-methylenedioxy-2-oxo-1,3,4,5-tetrahydro- 2H-3-benzazepine-dihydrochloride monohydrate

Prepared from 3-[2-(N-(3-(pyridyl-4)-propyl)-piperidyl-2)-ethyl]-7,8-methylenedioxy-2-oxo-1,3-dihydro-2H-3- benzazepine under 5 bar hydrogen pressure with 10% palladium/charcoal in ethanol at 80°C, analogous to Example 5.

Yield: 74% of the theoretical.

Melting range: 132-146°C (amorphous)

Calculated: C, 59.31; H, 7.08; N, 7.98; Cl, 13.46

Found: C, 59.18; H, 7.41; N, 7.80; Cl, 13.25

Example 127

3-[ (N-(3-(pyridyl-3)-propyl)-piperidyl-3)-methyl]-7,8-dimethyl-2-oxo-1. 3, 4, 5- tetrahydro- 2H- 3- benzazepine dihydrochloride

Prepared from 3-[(N-(3-(pyridyl-3)-propyl)-piperidyl-3)-methyl]-7,8-dimethyl-2-oxo-1,3-dihydro-2H-3-benzazepine and 5 bar hydrogen pressure with 10% palladium/coal in ethanol at 80°C, analogous to Example 5.

Yield: 54% of the theoretical.

Melting range: 92-105°C (amorphous)

Calculated: C, 62.90; H, 7.92; N, 8.46; Cl, 14.28

Found: C, 63.19; H, 7.90; N, 8.45; Cl, 14.30

Example 128

3- [(N-(3-(pyridyl-4)-propyl)-pyrrolidyl-3)-methyl]-7,8-methylenedioxy-1,3,4,5-tetrahydro-2H-3-benzazepine-trihydro- chlorine id monohydrate

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, analogously to Example 3.

Yield: 73% of the theoretical.

Melting range: 96-108°C (amorphous)

Calculated: C, 55.33; H, 6.97; N, 8.06; Cl, 20.42

Found: C, 55.06; H, 7.28; N, 7.77; Cl, 20.07

Example 129

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, analogously to Example 3.

Yield: 71% of the theoretical.

M.p.: 208-210°C

Calcd: C, 62.89; H, 7.91; N, 8.46; Cl, 14.28

Found: C, 62.70; H, 7.53; N, 8.22; Cl, 14.50

Example 130

3-[2-(N-(3-(pyridyl-4)-propyl)-piperidyl-2)-ethyl]-7,8-methylenedioxy-1,3,4,5-tetrahydro-2H-3-benzazepine- trihydrochloride

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, analogously to Example 3.

Yield: 63% of the theoretical.

Melting range: 123-136°C (amorphous)

Calculated: C, 58.81; H, 7.21; N, 7.91; Cl, 20.00

Found: C, 58.51; H, 7.41; N, 7.92; Cl, 19.86

Example 131

3 - [ (N-(3-(pyridyl-3)-propyl)-piperidyl-3)-methyl]-7,8-methylenedioxy-1,3,4,5-tetrahydro-2H-3-benzazepine-trihydrochloride- semi-horizontal

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, analogously to Example 3.

Yield: 75% of the theoretical.

Melting range: 126-138°C (amorphous)

Calculated: C, 57.09; H, 7.10; N, 7.99; Cl, 20,22

Found: C, 57.05; H, 7.32; N, 8.05; Cl, 20.37

Example 132

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, analogously to Example 3.

Yield: 92% of the theoretical.

M.p.: 180-182°C

Calcd: C, 62.96; H, 8.22; N, 8.16; Cl, 20.65

Found: C, 63.00; H, 8.29; N, 8.16; Cl, 20.34

Example 133

3-[(N-(3-(pyridyl-3)-propyl)-piperidyl-3)-methyl]-7,8-dimethyl-1. 3. 4. 5- tetrahydro- 2H- 3- benzazepine trihydrochloride

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

Yield: 81% of the theoretical.

Melting range: 184-196°C (amorphous)

Calculated: C, 60.17; H, 8.16; N, 8.10; Cl, 20.49

Found: C, 60.28; H, 8.25; N, 8.00; Cl, 20.39

Example 134

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 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-naphth tyl-2)-ethyl bromide, analogously to Example 1.

Yield: 20% of the theoretical.

Melting point: 158-160°C

Calcd: C, 69.48; H, 7.47; N, 5.06; Cl, 6.41

Found: C, 69.40; H, 7.56; N, 5.17; Cl, 6.62

Example 135 3-[2-(N-(2-(5-methyl-6-methoxy-naphthyl-2)-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-(5-methyl-6 -methoxy-naphthyl-2)-ethyl bromide, analogous to Example 1. Yield: 28% of the theoretical.

M.p.: 140-143°C

Calcd: C, 69.88; H, 7.64; N, 4.94; Cl, 6.25

Found: C, 69.06; H, 7.57; N, 4.84; Cl, 6.44

Example 136

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, analogous to Example 1.

Yield: 27% of the theoretical.

M.p.: 146-148°C

Calculated: C, 69.06; H, 7.29; N, 5.20; Cl, 6.58

Found: C, 69.00; H, 7.07; N, 5.31; Cl, 6.68

Example 137

3-[2-(N-(2-(naphthyl-1)-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)- ethyl bromide, analogous to Example 1.

Yield: 24% of the theoretical:

Melting point: 148-150°C

Calculated: C, 71.18; H, 7.51; N, 5.36; Cl, 6.78

Found: C, 70.92; H, 7.44; N, 5.57; Cl, 7.06

Example 138

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, analogous to Example 1.

Yield: 39% of the theoretical.

M.p.: 112-114°C

Calcd: C, 69.88; H, 7.64; N, 4.64; Cl, 6.25

Found: C, 69.69; H, 7.58; N, 4.82; Cl, 6.52

Example 139

3-[2-(N-(2-(naphthyl-2-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-2)- ethyl bromide, analogous to Example 1.

Yield: 41% of the theoretical.

M.p.: 120-122°C

Calculated: C, 71.18; H, 7.51; N, 5.36; Cl, 6.78

Found: C, 71.10; H, 7.31; N, 5.40; Cl, 7.05

Example 140

3-[2-(N-((2-methyl-naphthyl-1)-methyl)-piperidyl-2)-ethyl]-7,8-dimethoxy- 2- oxo- l. 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 l-chloromethyl-2-methyl- naphthalene, analogous to Example 1.

Yield: 24% of the theoretical.

M.p.: 144-146°C

Calculated: C, 71.18; H, 7.51; N, 5.36; Cl, 6.78

Found: C, 70.93; H, 7.38; N, 5.48; Cl, 6.89

Example 141 3-[(N-(2-(naphthyl-2)-ethyl)-hexahydroazepin-3-yl)-methyl]-7,8-dimethoxy-2-oxo-1.3.4.5-tetrahydro- 2H- 3- benzazepine 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, analogous to Example 1.

Yield: 58% of the theoretical.

M.p.: 204-205°C

Calculated: C, 71.18; H, 7.52; N, 5.36; Cl, 6.78

Found: C, 71.41; H, 7.51; N, 5.35; Cl, 6.50

Example 142

3-[(N-(2-(naphthyl-2)-ethyl)-piperidyl-3)-methyl]-7,8-dimethoxy-2- oxo- l. 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-(naphthyl-2)-ethyl bromide, analogous to Example 1.

Yield: 35% of the theoretical.

M.p.: 239-240°C

Calculated: C, 70.78; H, 7.33; N, 5.50; Cl, 6.96

Found: C, 70.70; H, 7.10; N, 5.46; Cl, 7.16

Example 143

3- [(N-((naphthyl-2)-methyl)-piperidyl-3)-methyl]-7,8-dimethoxy-2-oxo-l. 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, analogously to Example 1 .

Yield: 27% of the theoretical.

M.p.: 176-177°C.

Calculated: C, 75.95; H, 7.47; N, 6.11

Found: C, 76.11; H, 7.28; N, 6.10

Example 144

3-[ (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, analogous to Example 1.

Yield: 24% of the theoretical.

M.p.: 196-197°C

Calcd: C, 69.48; H, 7.47; N, 5.06; Cl, 6.41

Found: C, 69.30; H, 7.36; N, 4.99; Cl, 6.56

Example 145

3-[(N-(4-(naphthyl-1)-ethyl)-piperidyl-3)-methyl]-7,8-dimethoxy-2- oxo- l. 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-(naphthyl-1)-ethyl bromide, analogous to Example 1.

Yield: 18% of the theoretical.

M.p.: 230-231°C.

Calculated: C, 70.78; H, 7.33; N, 5.50; Cl, 6.96

Found: C, 70.71; H, 7.07; N, 5.67; Cl, 6.99

Example 146

3- [(N-(2-(naphthyl-1-oxy)-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-(naphthyl-1-oxy)- ethyl bromide, analogous to Example 1.

Yield: 40% of the theoretical.

M.p.: 214-215°C.

Calculated: C, 68.62; H, 7.10; N, 5.34; Cl, 6.75

Found: C, 68.40; H, 7.10; N, 5.21; Cl, 6.77

Example 147

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, analogous to Example 1.

Yield: 67% of the theoretical.

M.p.: 242-243°C.

Calculated: C, 70.78; H, 7.33; N, 5.50; Cl, 6.96

Found: C, 70.50; H, 7.22; N, 5.34; Cl, 6.89

Example 148

3-[(N-(2-(6-methoxy-naphthyl-2)-ethyl)-piperidyl-3)-methyl]-7,8-dimethoxy- 2-oxo-l, 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-(6-methoxy-naphthyl- 2) -ethyl bromide, analogously to Example 1.

Yield: 50% of the theoretical.

M.p.: 156-157°C

Calculated: C, 74.07; H, 7.62; N, 5.57

Found: C, 73.90; H, 7.55; N, 5.64

Example 149

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-benzazepine 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, analogously to Example 1. Yield: 53% of the theoretical.

M.p.: 240-241°C

Calcd: C, 69.48; H, 7.47; N, 5.06; Cl, 6.41

Found: C, 69.58; H, 7.48; N, 5.00; Cl, 6.54

Example 150 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, analogously to Example 1.

Yield: 68% of the theoretical.

M.p.: 225-226°C

Calculated: C, 63.60; H, 7.18; N, 5.20; Cl, 7.22

Found: C, 63.61; H, 7.30; N, 5.70; Cl, 7.44

Example 151

2- [ (N-(2-(6-Methoxy-naphthyl-2)-ethyl)-piperidyl-3)-methyl] - 5, 6- dimethoxy- l - oxo- l. 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, analogously to Example 1 .

Yield: 75% of the theoretical.

Temp. : 234-236°C

Calculated: C, 68.16; H, 6.90; N, 5.48; Cl, 6.94

Found: C, 68.10; H, 7.10; N, 5.39; Cl, 7.10

Example 152

2-[(N-(2-(naphthyl-1-oxy)-ethyl)-piperidyl-3)-methyl]-5,6-dimethoxy- l - 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, analogously to Example 1.

Yield: 60% of the theoretical.

M.p.: 150-152°C

Calculated: C, 67.66; H, 6.69; N, 5.63; Cl, 7.13

Found: C, 67.50; H, 6.76; N, 5.74; Cl, 7.54

Example 153 2-[(N-(2-(4-methylphenyl)-ethyl)-piperidyl-3)-methyl]-5,6-dimethoxy-1-oxo-1,3-dihydro-isoindole

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

Yield: 57% of the theoretical.

M.p.: 134-136°C

Calculated: C, 73.50; H, 7.90; N, 6.86

Found: C, 73.40; H, 8.04; N, 7.06

Example 154

2-[(N-(2-(3-methoxyphenyl)-ethyl)-piperidyl-3)-methyl]-5,6-dimethoxy- l - oxo- 1.3- dihydro- isoindole- hydrochloride

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

Yield: 54% of the theoretical.

M.p.: 226-228°C.

Calculated: C, 65.28; H, 7.01; N, 6.09; Cl, 7.71

Found: C, 65.30; H, 7.37; N, 5.91; Cl, 7.61

Example 155

2-[(N-(2-(5-methyl-6-methoxy-naphthyl-2)-ethyl)-piperidyl-3)-methyl- 5, 6- dimethoxy- l- oxo- l. 3- dihydro-isoindole - hydrochloride

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

Yield: 38% of the theoretical.

M.p.: 214-216°C.

Calculated: C, 68.62; H, 7.10; N, 5.33; Cl, 6.75

Found: C, 68.94; H, 7.23; N, 4.98; Cl, 6.61

Example 156

2- [(N-(2-(4-nitrophenyl)-ethyl)-piperidyl-3)-methyl]-5,6-dimethoxy- l - oxo- l, 3- dihydro- isoindole- hydrochloride

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

Yield: 79% of the theoretical.

M.p.: 215-218°C.

Calculated: C, 60.56; H, 6.35; N, 8.83; Cl, 7.45

Found: C, 60.41; H, 6.26; N, 8.84; Cl, 7.62

Example 157

3- [ (N-(2-(thienyl-2)-ethyl)-piperidyl-3)-methyl]-7, 8-dimethoxy-2-oxo-l, 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-bromomethyl)-thiophene, analogous to Example 1.

Yield: 43% of the theoretical.

Temp. : 232-236°C

Calculated: C, 61.99; H, 7.15; N, 6.02; Cl, 7.62; S, 6.89 Found: C, 61.90; H, 7.06; N, 5.78; Cl, 7.96; S, 6.84

Example 158

3- [ (N-(2-(thienyl-3)-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 3-(2-bromomethyl)-thiophene, analogous to Example 1.

Yield: 36% of the theoretical.

Melting point: sinters at 75-80°, melts at 225-23 0°C

Calculated: C, 61.99; H, 7.15; N, 6.02; Cl, 7.62; S, 6.89 Found: C, 62.00; H, 7.08; N, 5.98; Cl, 8.43; S, 6.62

Example 159

3- [ (N-(4-(thienyl-2)-butyl)-piperidyl-3)-methyl]-7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3- benza2epine hydrochloride

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

Yield: 68% of the theoretical.

Melting range: 190-196°C.

Calculated: C, 63.33; H, 7.56; N, 5.68; Cl, 7.19; S, 6.50 Found: C, 63.18; H, 7.72; N, 5.72; Cl, 7.29; S, 6.59

Example 160

3- [ (N-(2-(benzo[b]furyl-2)-ethyl)-piperidyl-3)-methyl]-7,8-dimethoxy- 2- oxo- l. 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-bromomethyl)-benzo[ b]furan, analogous to Example 1.

Yield: 22% of the theoretical.

M.p.: higher than 216°C (decomp.).

Calculated: C, 67.39; H, 7.07; N, 5.61

Found: C, 67.14; H, 7.36; N, 5.53

Example 161

3- [ (N-(2-(benzo[b]thienyl-3)-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 3-(2-bromomethyl)-benzo[ b]thiophene, analogously to Example 1.

Yield: 73% of the theoretical.

Melting range: 70-75°C (decomp.).

Calculated: C, 65.29; H, 6.85; N, 5.44

Found: C, 65.10; H, 6.87; N, 5.73

Example 162 3-[(N-(2-(4-methoxy-benzo[b]thienyl-3)-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 3-(2-chloroethyl)-4- methoxy-benzo[b]thiophene, analogous to Example 1.

Yield: 25% of the theoretical.

Melting range: 85-105°C (decomp.).

Calcd: C, 63.96; H, 6.84; N, 5.14; Cl, 6.50; S, 5.88 Found: C, 63.95; H, 6.85; N, 4.99; Cl, 6.53; S, 5.75

Example 163

3-[(N-(2-(6-methylsulfonyloxy-benzo[b]thienyl-3)-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 3-[2-(methylsulfonyloxy)-ethyl ]-6-methylsulphonyloxy-benzo[b]thiophene, analogously to Example 1.

Yield: 55% of the theoretical.

Melting point: 90°C (decomp.).

Calculated: C, 57.18; H, 6.12; N, 4.60; Cl, 5.82; S, 10.53 Found: C, 57.25; H, 6.14; N, 4.50; Cl, 5.97; S, 10.36

Example 164

3-[(N-(5-(thienyl-2)-pentyl)-piperidyl-3)-methyl]-7,8-dimethoxy-2- oxo- l. 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-(5-methylsulfonyl-oxy-pentyl )-thiophene, analogous to Example 1.

Yield: 39% of the theoretical.

M.p.: 177°C

Calculated: C, 63.95; H, 7.75; N, 5.52; Cl, 6.99; S, 6.32 Found: C, 63.70; H, 7.92; N, 5.40; Cl, 7.24; S, 6.62

Example 165

3- [ (N-(2-(furyl-2)-ethyl)-piperidyl-3)-methyl]-7,8-dimethoxy-2- oxo- 1. 3. 4, 5- tetrahydro- 2H- 3- ben2azepine hydrochloride

Prepared from 3-[(piperidyl-3)-methyl]-7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3-behzazepine and 2-(2-methylsulfonyl-oxy-ethyl )-furan, analogous to Example 1.

Yield: 44% of the theoretical.

Melting range: 205-215°C.

Calculated: C, 64.20; H, 7.41; N, 6.24; Cl, 7.90

Found: C, 64.00; H, 7.45; N, 6.00; Cl, 7.80

Example 166

3- [ (N-(3-(furyl-2)-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-1,3,4,5-tetrahydro-2H-3-benzazepine and 3-(furyl-2)-propionaldehyde, analogous to Example 9.

Yield: 11% of the theoretical.

M.p.: 201-206°C.

Calcd: C, 64.85; H, 7.62; N, 6.05; Cl, 7.66

Found: C, 64.88; H, 7.76; N, 5.93; Cl, 7.55

Example 167

3- [ (N-(6-(thienyl-2)-hexyl)-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-(6-methylsulfonyl-oxy-hexyl )-thiophene, analogous to Example 1.

Yield: 27% of the theoretical.

Melting point: 160°C.

Calculated: C, 64.39; H, 8.10; N, 5.40; Cl, 6.79

Found: C, 64.55; H, 7.90; N, 5.23; Cl, 7.00

Example 168

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-1,3,4,5-tetrahydro-2H-3-benzazepine and 3-(3-methylsulfonyl-1-oxy-propyl )-indole, analogous to Example 1.

Yield: 19% of the theoretical.

Melting point: > 80°C (decomp.).

Calculated: C, 60.42; H, 6.30; N, 6.45

Found: C, 60.32; H, 6.57; N, 6.67

Example 169

3- [ (N-(2-(indolyl-3)-ethyl)-piperidyl-3)-methyl]-7,8-dimethoxy-2- oxo- l. 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 3-(2-methylsulfony 1-oxy- ethyl)-indole, analogous to Example 1.

Yield: 23% of the theoretical.

Melting point: > 80°C (decomp.).

Calculated: C, 65.53; H, 6.42; N, 7.69

Found: C, 65.33; H, 6.55; N, 7.80

Example 170

2-[(N-(3-(naphthyl-2-oxy)-propyl)-hexahydro-azepinyl-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-chloromethyl-[N-(3-naphthyl-2-oxy)-propyl]-hexahydro-azepine, analogous to Example 2.

Yield: 21% of the theoretical.

M.p.: 74-76°C.

Calcd (x 2 H 2 O): C, 64.45; H, 7.02; N, 5.01; Cl, 6.34 Found: C, 64.32; H, 7.20; N, 5.28; Cl, 6.44

Example 171

2-[(N-(3-(naphthyl-2)-propyl)-pyrrolidyl-3)-methyl]-6,7-dimethyl-1- oxo-l. 2. 3, 4- tetrahydro- isoquicholine

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

Yield: 20% of the theoretical.

Temp. : 72-76°C

Calcd (x H 2 O) : C, 72.41; H, 7.75; N, 5.82; Cl, 7.36 Found: C, 72.27; H, 7.85; N, 5.70; Cl, 7.96

Example 172

2-[(N-(3-(5,6-dimethoxy-naphthyl-2-oxy)-propyl)-pyrrolidyl-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, analogously to Example 2.

Yield: 9.5% of the theoretical.

M.p.: 60-63°C

Calcd (x H 2 O): C, 63.20; H, 7.01; N, 4.75; Cl, 6.02 Found: C, 63.40; H, 7.04; N, 4.49; Cl, 6.38

Example 173

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

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

Yield: 63.2% of the theoretical.

M.p.: 199-201°C

Calculated C, 66.15; H, 7.23; N, 4.67; Cl, 5.92

Found: C, 65.99; H, 7.00; N, 4.44; Cl, 6.02

Example 174

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

Yield: 86.3% of the theoretical.

M.p.: 114-116°C

Calculated: C, 61.97; H, 7.56; N, 4.38; Cl, 11.08

Found: C, 62.05; H, 7.65; N, 4.06; Cl, 10.84

Example 175

2-[(N-(2-(4-methoxyphenyl)-ethyl)-pyrrolidy1-3)-methyl]-6,7-methylenedioxy- 1. 2. 3. 4- tetrahydro- isoquinoline- dihydrochloride

Prepared from 2-[(N-(2-(4-methoxyphenyl)-ethyl)-pyrrolidyl-3-methyl]-6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and

lithium aluminum hydride/tetrahydrofuran, analogous to Example 3. Yield: 86.7% of the theoretical.

M.p.: 213-215°C

Calcd: C, 60.49; H, 6.98; N, 5.87; Cl, 14.88

Found: C, 60.59; H, 6.96; N, 5.84; Cl, 14.98

Example 176

2-[(N-(3-(3,4-dimethoxy-phenoxy)-propyl)-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-methylenedioxy-isoquinoline and N-[3-(3,4-dimethoxy-phenoxy)-propyl]-3-benzosulfonyloxymethyl-pyrrolidine, analogous to Example -2.

Yield: 57.4% of the theoretical.

M.p.: 108-110°C.

Calcd: C, 59.76; H, 6.74; N, 5.35; Cl, 7.02

Found: C, 60.07; H, 6.87; N, 5.23; Cl, 7.61

Example 177

2-[(N-(2-(4-methoxyphenyl)-ethyl)-pyrrolidy1-3)-methyl]-6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline hydrochloride

Prepared from 1-oxo-1,2,3,4-tetrahydro-6,7-methylenedioxy-isoquinoline and N-[2-(4-methoxyphenyl)-ethyl]-3-benzenesulfonyloxymethyl-pyrrolidine, analogously to Example 2. Yield : 54.7% of the theoretical.

M.p.: 105-108°C

Calculated: C, 62.26; H, 6.74; N, 6.05; Cl, 7.97

Found: C, 62.34; H, 6.74; N, 5.88; Cl, 8.05

Example 178

3- [(N-(2-(6-methyl-pyridyl-2)-ethyl)-pyrrolidyl-3)-methyl]-7,8-dimethyl- l. 3. 4. 5- tetrahydro- 2H- 3- benzazepine x 2.5 HCl x H?Q

Prepared from 3-[(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, analogously to Example 3.

Yield: 50% of the theoretical.

Mp: 80-91°C amorphous

Calculated: C, 61.68; H, 8.18; N, 8.63; Cl, 18,21

Found: C, 61.55; H, 8.36; N, 8.44; Cl, 18.10

Example 179

3-[(N-(2-(6-methyl-pyridyl-2)-ethyl)-pyrrolidyl-3)-methyl]-7,8-dimethyl-2-oxo-1,3,4,5-tetrahydro- 2H-3-benzazepine dihydrochloride semihydrate

Prepared from 3-[(N-(2-(6-methyl-pyridyl-2)-ethyl)-pyrrolidyl-3)-methyl]-7,8-dimethyl-2-oxo-1,3-dihydro-2H- 3-benzazepine with 10% palladium/charcoal at 5 bar hydrogen and at 80°C in ethanol, analogous to Example 5.

Yield: 92% of the theoretical.

M.p.: 86-94°C amorphous

Calculated: C, 63.41; H, 7.66; N, 8.87; Cl, 14.97

Found: C, 63.52; H, 7.14; N, 8.81; Cl, 14.94

Example 180

2-[(N-(3-(6-Methoxy-naphthy1-2-oxy)-propyl)-pyrrolidyl-3)-methyl-1-6.7-dimethyl-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-[3-(6-methoxy-naphthyl-2-oxy)- propyl]-pyrrolidine, analogously to Example 2. Yield: 44.7% of the theoretical.

M.p.: 102-104°C.

Calculated: C, 76.24; H, 7.68; N, 5.93

Found: C, 75.90; H, 7.62; N, 5.94

Example 181

2- [(N-(3-(6-Methoxy-naphthyl-2-oxy)-propyl)-pyrrolidyl-3)-methyl- 6.7-dimethoxy-1,2,3,4-tetrahydro- isoquinoline

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

Yield: 68% of the theoretical.

M.p.: 106-108°C.

Calculated: C, 73.44; H, 7.82; N, 5.71

Found: C, 73.26; H, 7.72; N, 5.81

Example 182

3- [(N-(3-(indolyl-3)-propyl)-pyrrolidyl-3)-methyl]-7,8-methylene-dioxv- 2- oxo- 1. 3, 4, 5- tetrahydro- 2H- 3- benzazepine monohydrate

Prepared from 3-[(N-(3-(indolyl-3)-propyl)-pyrrolidyl-3)-methyl]-7,8-methylenedioxy-2-oxo-1,3-dihydro-2H-3-benzazepine with 20% palladium/coal at 5 bar hydrogen in ethanol at 80°C, analogous to Example 5.

Yield: 40% of the theoretical.

Melting range: 67-74°C

Calculated: C, 69.95; H, 7.17; N, 9.06

Found: C, 70.00; H, 7.03; N, 8.97

Example 183

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

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

Yield: 81% of the theoretical.

M.p.: 86-98°C amorphous

Calculated: C, 63.68; H, 7.27; N, 8.91; Cl, 15.04

Found: C, 63.39; H, 7.43; N, 8.87; Cl, 14.93

Example 184

2-[(N-(3-(3-methylphenoxy)-propyl)-piperidy1-3)-methyl]-6,7-dimethoxy- l - oxo- 1. 2. 3, 4- tetrahydro- isoquinoline- hydrochloride

Prepared from 6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and N-[3-(3-methylphenoxy)-propyl]-3-benzenesulfonyl-oxymethyl-piperidine, analogously to Example 2 .

Yield: 75.6% of the theoretical.

M.p.: 106-109°C amorphous

Calculated: C, 63.95; H, 7.75; N, 5.52; Cl, 7.25

Found: C, 64.66; H, 7.91; N, 5.48; Cl, 7.28

Example 185

2-[ (N-(2-(5-methyl-6-methoxy-naphth-2-yl)-pyrrolidyl-3)-methyl]-6,7-methylenedioxy-1-oxo-1,2,3,4 -tetrahydro-isoquinoline hydrochloride

Prepared from 6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 3-(p-toluenesulfonyloxymethyl)-N-[2-(5-methyl-6-methoxy-naphth-2- yl)-ethyl]-pyrrolidine, analogously to Example 2.

Yield: 27.1% of the theoretical.

Temp. : 249-251°C

Calcd: C, 68.43; H, 6.53; N, 5.50; Cl, 6.96

Found: C, 68.47; H, 6.66; N, 5.30; Cl, 7.16

Example 186

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

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

Yield: 20.2% of the theoretical.

M.p.: 84-86°C

Calcd: C, 67.88; H, 7.26; N, 5.46; Cl, 6.91

Found: C, 67.86; H, 7.40; N, 5.40; Cl, 7.17

Example 187

2-[(N-(3-(3,4-dimethoxyphenoxy)-propyl)-pyrrolidyl-3)-methyl]-6. 7- dimethoxy- l. 2. 3, 4- tetrahydro- isoquinoline- dihydrochloride

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, analogously to Example 3.

Yield: 92.3% of the theoretical.

Temp. : 220-221°C

Calculated: C, 59.20; H, 6.88; N, 5.31; Cl, 13.44

Found: C, 59.28; H, 6.97; N, 5.20; Cl, 13.44

Example 188

2-[ (N-(2-(3,4-dimethoxyphenyl)-ethyl)-pyrrolidyl-3)-methyl]-6,7-dimethyl-1-oxo-1, 2, 3, 4- tetrahydro- isoquinoline

Prepared from 6,7-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline and N-[2-(3,4-dimethoxyphenyl)-ethyl]-3-benzenesulfonyloxymethyl-pyrrolidine, analogously to Example 2 .Yield: 70% of the theoretical.

M.p.: 168-170°C

Calculated: C, 73.90; H, 8.11; N, 6.63

Found: C, 73.96; H, 8.11; N, 6.55

Example 189

2-[(N-(3-(4-methoxyphenoxy)-propyl)-piperidyl-3)-methyl]-6,7-dimethoxy- l - oxo- 1. 2, 3, 4- tetrahydro- isoquinoliri- hydrochloride

Prepared from 6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and N-[3-(4-methoxyphenoxy)-propyl]-3-benzenesulfonyloxymethyl-piperidine, analogous to Example 2. Yield : 78.7% of the theoretical.

M.p.: 98-102°C

Calculated: C, 63.08; H, 7.51; N, 5.35; Cl, 7.02

Found: C, 62.87; H, 7.69; N, 5.16; Cl, 7.28

Example 19 0

2-[(N-(3-(3-methoxyphenoxy)-propyl)-piperidyl-3)-methyl]-6,7-dimethoxy- l - oxo- 1. 2, 3, 4- tetrahydro- isoquinoline- hydrochloride

Prepared from 6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and N-[3-(3-methoxyphenoxy)-propyl]-3-benzenesulfonyloxymethyl-piperidine, analogous to Example 2. Yield : 87% of the theoretical.

M.p.: 103-105°C

Calculated: C, 64.21; H, 7.38; N, 5.55; Cl, 7.02

Found: C, 64.00; H, 7.55; N, 5.37; Cl, 7.12

Example 191

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-tetrahydro-isoquinoline and lithium aluminum hydride in diethyl ether and tetrahydrofuran, analogously to Example 3.

Yield: 95.4% of the theoretical.

M.p.: 170-173°C

Calculated: C, 60.43; H, 7.70; N, 5.22; Cl, 13.21

Found: C, 60.50; H, 7.71; N, 4.91; Cl, 12.97

Example 192

2-[(N-(2-(3,4-dimethoxyphenyl)-ethyl)-pyrrolidyl-3)-methyl]-6,7-dimethyl- 1, 2, 3. 4- tetrahydro- isoquinoline- 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 hydride in diethyl ether and tetrahydrofuran, analogously to Example 3.

Yield: 94.1% of the theoretical.

M.p.: 260-262°C

Calcd: C, 64.85; H, 7.96; N, 5.82; Cl, 14.73

Found: C, 64.60; H, 8.11; N, 5.91; Cl, 14.67

Example 193

2- [(N-(3-(6-methoxy-naphthy1-2-oxy)-propyl)-azacyclooctyl-3-methyl]-6,7-dimethoxy-1-oxo-1,2,3,4- tetrahydroisoquinoline hydrochloride

Prepared from 2-[(azacyclooctyl-3)-methyl]-6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 2-(3-chloropropoxy)-6-methoxy-naphthalene, analogous to Example 1. Yield: 24.4% of the theoretical.

M.p.: 176-178°C

Calcd: C, 67.96; H, 7.43; N, 4.80; Cl, 6.08

Found: C, 67.74; H, 7.29; N, 4.71; Cl, 6.23

Example 194

3- [(N-(3-(indolyl-3)-propyl)-pyrrolidyl-3)-methyl]-7,8-dimethyl-2- oxo- l. 3. 4. 5- tetrahydro- 2H- 3- benzazepine hydrochloride

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, analogous to Example 1. Yield: 62% of the theoretical.

M.p.: 106-108°C

Calcd: C, 69.47; H, 7.91; N, 8.68; Cl, 7.32

Found: C, 69.57; H, 7.80; N, 8.67; Cl, 8.51

Example 195

3-[ (N-(3 - (6-Methoxy-naphthyl-2-oxy)-propyl)-hexahydro-azepinyl- 3)- methyl 1 - 7, 8- dimethoxy- l, 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- tetrahydro-2-oxo-2H-3-benzazepine and lithium aluminum hydride in tetrahydrofuran/ether, analogously to Example 3.

Yield: 26.8% of the theoretical.

Melting point: 98-100°C

Calcd (x H 2 O): C, 71.97; H, 8.42; N, 5.09

Found: C, 72.07; H, 8.23; N, 5,10

Example 196

3-[ (N-(3-(6-methoxy-naphthyl-2-oxy)-propyl)-hexahydro-azepinyl-3 )-methyl]-1,2,3,4-tetrahydro-2-oxo-2H- 3-benzazepine

Prepared from 3-[(hexahydro-azepinyl-3)-methyl]-1,2,3,4-tetrahydro-2-oxo-2H-3-benzazepine and 2-(3-chloropropoxy)-6-methoxy-naphthalene, analogous to Example 1. Yield: 45% of the theoretical.

M.p.: 109-111°C

Calculated: C, 72.50; H, 7.74; N, 5.12

Found: C, 72.35; H, 7.68; N, 4.93

Example 197

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 in tetrahydrofuran/ether, analogous to Example 3.

Yield: 49.2% of the theoretical.

M.p.: 104-146°C

Calculated: C, 73.78; H, 7.99; N, 5.55

Found: C, 73.63; H, 7.99; N, 5.39

Example 198

3-[(N-(3-(indolyl-3)-propyl)-pyrrolidyl-3)-methyl]-7,8-dimethyl-1, 3, 4, 5- tetrahydro- 2H- 3- benzazepine- dihydrochloride- moriohydrate

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

Yield: 65% of the theoretical.

Temp. : 168-170°C

Calculated: C, 66.39; H, 8.16; N, 8.29; Cl, 13.99

Found: C, 66.29; H, 8.44; N, 8.08; Cl, 14.08

Example 199

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

Prepared from 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 and

lithium aluminum hydride/tetrahydrofuran/ether, analogous to Example 3.

Yield: 25% of the theoretical.

M.p.: 109-111°C

Calculated: C, 74.39; H, 7.80; N, 5.42

Found: C, 74.27; H, 7.94; N, 5.43

Example 2 00

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-

benz a z ep in- hydrochioride

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, analogous to Example 1.

Yield: 68.1% of the theoretical.

Melting range: 104-108°C

Calcd (x 2 H 2 O): C, 65.46; H, 7.38; N, 4.79; Cl, 6.06 Found: C, 65.60; H, 7.25; N, 5.01; Cl, 6.43

Example 201

2-[(N-(3-(6-methoxy-naphthyl-2-oxy)-propyl)-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-(3-chloropropoxy)-6-methoxy- naphthalene, analogous to Example 1. Yield: 18.2% of the theoretical.

M.p.: 65-67°C

Calculated: C, 65.19; H, 6.88; N, 4.90; Cl, 6.20

Found: C, 65.20; H, 6.75; N, 4.82; Cl, 6.54

Example 202

2-[(N-(3-(6-methoxy-naphthyl-2-oxy)-propyl)-piperidyl-3)-methyl]-6,7-methylenedioxy-1-oxo-1,2,3,4- tetrahydroisoquinoline

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, analogously to Example 2.

Yield: 5.3% of the theoretical.

M.p.: 144-146°C

Calcd: C, 71.69; H, 6.82; N, 5.57

Found: C, 71.52; H, 6.62; N, 5.46

Example 203

2-[(N-(3-(6-methoxy-naphthyl-2-oxy)-propyl)-hexahydro-azepinyl-3 )-methyl]-5,6-dimethyl-1,3-dihydro-1-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, analogous to Example 4.

Yield: 18.2% of the theoretical.

M.p.: 232-234°C

Calculated (x acetone): C, 74.97; H, 8.14; N, 5.14 Found: C, 74.96; H, 7.90; N, 5.30

Example 204

2-[(N-(3-(6-methoxy-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-chloro-propoxy)-6- methoxy-naphthalene, analogous to Example 1. Yield: 17.3% of the theoretical.

Melting range: 68-73°C.

Calcd (x 2 H 2 O): C, 67.06; H, 7.93; N, 4.46; Cl, 6.66 Found: C, 67.05; H, 7.73; N, 4.88; Cl, 6.18

Example 205

2-[(N-(3-(6-methoxy-naphthyl-2-oxy)-propyl)-piperidyl-3)-methyl]-6,7-dimethoxy-1-oxo-1,2,3,4- tetrahydroisoquinoline

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, analogous to Example 2. Yield: 12.9% of the theoretical.

M.p.: 124-126°C

Calculated: C, 71.79; H, 7.38; N, 5.40

Found: C, 71.83; H, 7.33; N, 5.21

Example 206

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

Prepared from 3-[(N-(3-(5,6-dimethoxy-naphthyl-2-oxy)-propyl)-hexahydro-azepinyl-3)-methyl]-1,3,4,5-tetrahydro-7, 8-dimethoxy-2-oxo-2H-3-benzazepine and

1lithium aluminum hydride/tetrahydrofuran/ether, analogously to Example 3.

Yield: 29.1% of the theoretical.

M.p.: 94-96°C

Calculated: C, 72.57; H, 8.24; N, 4.98

Found: C, 72.56; H, 8.35; N, 4.94

Example 207

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-(6-methoxy-naphthyl-2-oxy)-propyl)-hexahydro-azepinyl-3)-methyl]-5,6-dimethoxy-phthalimide and zinc/glacial acetic acid, analogous to Example 4.

Yield: 20.5% of the theoretical.

M.p.: 265-267°C

Calcd (x 2 H 2 O): C, 67.13; H, 7.63; N, 5.05

Found: C, 67.11; H, 7.64; N, 5.07

Example 208

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

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

Yield: 52.4% of the theoretical.

M.p.: 129-131°C.

Calculated: C, 70.81; H, 7.69; N, 4.86

Found: C, 70.66; H, 7.84; N, 4.63

Example 209

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

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

Yield: 48.2% of the theoretical.

Melting range: 172-177°C

Calcd (x H 2 O): C, 61.43; H, 7.41; N, 4.47; Cl, 11.33 Found: C, 61.50; H, 7.71; N, 4.59; Cl, 11.45

Example 210

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

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

Yield: 36.4% of the theoretical.

Melting range: 215-223°C

Calcd (x H 2 O): C, 61.87; H, 7.30; N, 4.50; Cl, 5.70 Found: C, 62.08; H, 7.15; N, 4.55; Cl, 5.80

Example 211

2-[(N-(3-(indolyl-3)-propyl)-pyrrolidyl-3)-methyl]-5,6-dimethoxy-1,3-dihydro-isoindole dihydrochloride monohydrate

Prepared from 2-[(N-(3-(indolyl-3)-propyl)-pyrrolidyl-3)-methyl]-5,6-dimethoxy-phthalimide and lithium aluminum hydride in tetrahydrofuran, analogously to Example 3.

Yield: 87% of the theoretical.

M.p.: 262-264°C

Calculated: C, 61.17; H, 7.30; N, 8.23; Cl, 13.89

Found: C, 61.34; H, 7.26; N, 7.92; Cl, 13.90

Example 212

3-[(N-(3-(5,6-dimethoxy-naphthyl-2-oxy)-propyl)-hexahydro-azepinyl-3 )-methyl]-1,3,4,5-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, analogously to Example 3.

Yield: 76.9% of the theoretical.

Melting range: 138-144°C

Calculated: C, 67.64; H, 8.01; N, 4.64; Cl, 11.74

Found: C, 67.73; H, 8.26; N, 4.47; Cl, 11.50

Example 213

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, analogous to Example 1. Yield: 47.5% of the theoretical.

Melting range: 90-96°C

Calculated: C, 68.15; H, 7.90; N, 4.67; Cl, 5.91

Found: C, 67.93; H, 7.94; N, 5.05; Cl, 6.09

Example 214

2-[(N-(3-(5,6-dimethoxy-naphthyl-2-oxy)-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 2-(3-chloropropoxy)-5,6-dimethoxy- naphthalene, analogous to Example 1.

Yield: 22.5% of the theoretical.

Melting range: 93-98°C.

Calcd (x H 2 O): C, 63.42; H, 6.69; N, 4.77; Cl, 6.03 Found: C, 63.59; H, 6.80; N, 4.70; Cl, 6.28

Example 215

2-[(N-(3-(5,6-dimethoxy-naphthyl-2-oxy)-propyl)-pyrrolidyl-3)-methyl]-6,7-methylenedioxy-1-oxo-1,2,3, 4-tetrahydro-isoquinoline hydrochloride

Prepared from 2-[(pyrrolidyl-3)-methyl]-6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 2-(3-chloropropoxy)-5,6-dimethoxy- naphthalene, analogous to Example 1. Yield: 22.5% of the theoretical.

Temp. : 87-90°C.

Calcd (x H 2 O) : C, 62.87; H, 6.50; N, 4.88; Cl, 6.18 Found: C, 62.72; H, 6.38; N, 4.93; Cl, 6.30

Example 216

2-[(N-(3-(5,6-dimethoxy-naphthyl-2-oxy)-propyl)-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-1, 2,3,4-tetrahydro-isoquinoline and 2-(3-chloropropoxy)-5,6-dimethoxy- naphthalene, analogous to Example 1.

Yield: 21.3% of the theoretical.

M.p.: 72-78°C.

Calcd (x H 2 O): C, 67.30; H, 7.59; N, 4.90; Cl, 6.21 Found: C, 67.44; H, 7.74; N, 5.06; Cl, 6.53

Example 217

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-chloro-propoxy)-5, 6-dimethoxy-naphthalene, analogous to Example 1. Yield: 12% of the theoretical.

Melting range: 84-90°C

Calcd (x H 2 O): C, 67.73; H, 7.73; N, 4.78; Cl, 6.06 Found: C, 67.64; H, 7.81; N, 4.94; Cl, 6.20

Example 218

2-[(N-(2-(4-methoxyphenyl)-ethyl)-hexahydro-az epinyl-3)-methyl]-6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline -hydrochloride

Prepared from 6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and N-[2-(4-methoxyphenyl)-ethyl]-3-chloromethyl-hexahydro-azepine, analogously to Example 2 .

Yield: 46.7% of the theoretical.

M.p.: 101-105°C

Calculated: C, 62.44; H, 7.26; N, 5.60; Cl, 7.50

Found: C, 62.62; H, 7.27; N, 5.48; Cl, 7.66

Example 219

2-[(N-(3-(4-methoxy-phenoxy)-propyl)-hexahydro-azepinyl-3)-methyl]-6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro- isoquinoline hydrochloride

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

Yield: 43.8% of the theoretical.

M.p.: 123-126°C.

Calculated: C, 62.23; H, 7.16; N, 5.37; Cl, 7.05

Found: C, 62.42; H, 7.34; N, 5.30; Cl, 6.94

Example 220

2-[(N-(3-(4-methoxy-phenoxy)-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 N-[3-(4-methoxy-phenoxy)-propyl]-3-chloromethyl-hexahydro-azepine, analogous to Example 2.

Yield: 42% of the theoretical.

M.p.: 172-173°C

Calculated: C, 69.04; H, 8.07; N, 5.75; Cl, 7.28

Found: C, 69.06; H, 8.25; N, 5.57; Cl, 7.39

Example 221

2-[(N-(3-(4-methoxy-phenoxy)-propyl)-hexahydro-azepinyl-3)-methyl]-6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro- isoquinoline 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, analogous to Example 2.

Yield: 63.3% of the theoretical.

Melting range: 115-120°C.

Calculated: C, 62.58; H, 7.67; N, 5.21; Cl, 6.83

Found: C, 62.44; H, 7.68; N, 4.91; Cl, 6.81

Example 222

2-[ (N-(2-(4-methoxyphenyl)-ethyl)-hexahydro-azepinyl-3)-methyl]-6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline- hydrochloride

Prepared from 6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and N-[2-(4-methoxyphenyl)-ethyl]-3-chloromethyl-hexahydro-azepine, analogous to Example 2 .

Yield: 51.6% of the theoretical.

M.p.: 110-113°C.

Calcd: C, 61.75; H, 7.87; N, 5.28; Cl, 7.25

Found: C, 61.84; H, 8.02; N, 5.16; Cl, 7.22

Example 223

2-[(N-(2-(3,4-dimethoxyphenyl)-ethyl)-hexahydro-azepinyl-3)-methyl]-6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro- isoquinoline hydrochloride

Prepared from 6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and N-[2-(3,4-dimethoxyphenyl)-ethyl]-3-chloromethyl-hexahydro-azepine, analogous to Example 2.

Yield: 45.5% of the theoretical.

M.p.: 107-111°C.

Calculated: C, 62.61; H, 7.69; N, 5.21; Cl, 6.60

Found: C, 62.78; H, 8.00; N, 5.00; Cl, 6.43

Example 224

2-[(N-(2-(3,4-dimethoxyphenyl)-ethyl)-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 N-[2-(3,4-dimethoxyphenyl)-ethyl]-3-chloromethyl-hexahydro-azepine, analogous to Example 2.

Yield: 44.8% of the theoretical.

M.p.: 162-163°C

Calculated: C, 66.57; H, 8.18; N, 5.54; Cl, 7.02

Found: C, 66.67; H, 8.47; N, 5.35; Cl, 7.11

Example 225

2-[(N-(3-(3-methyl-phenoxy)-propyl)-hexahydro-azepinyl-3)-methyl]-6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro- isoquinoline hydrochloride

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

Yield: 46.8% of the theoretical.

M.p.: 159-161°C.

Calculated: C, 65.37; H, 7.31; N, 5.64; Cl, 7.28

Found: C, 65.44; H, 7.40; N, 5.39; Cl, 7.23

Example 22 6

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

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

Yield: 55.2% of the theoretical.

M.p.: 107-111°C.

Calculated: C, 65.67; H, 7.87; N, 5.47; Cl, 7.05

Found: C, 65.47; H, 8.00; N, 5.50; Cl, 6.97

Example 227

2-[(N-(3-(3,4-methylenedioxy-phenoxy)-propyl)-hexahydro-azepinyl-3 )-methyl]-6,7-dimethyl-1-oxo-1,2,3,4- tetrahydroisoquinoline hydrochloride

Prepared from 6,7-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline and N-[3-(3,4-methylenedioxy-phenoxy)-propyl]-3-chloromethyl-hexahydro-azepine, analogous to Example 2. Yield: 40.6% of the theoretical.

M.p.: 123-126°C.

Calcd: C, 64.78; H, 7.57; N, 5.39; Cl, 6.83

Found: C, 64.88; H, 7.59; N, 5.29; Cl, 7.18

Example 228

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

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

M.p.: 101-105°C.

Calculated: C, 62.61; H, 7.59; N, 5.01; Cl, 6.46

Found: C, 62.56; H, 7.76; N, 4.94; Cl, 6.39

Example 229

2-[(N-(2-(3,4-dimethoxyphenyl)-ethyl)-hexahydro-azepinyl-3)-methyl]- 5, 6- dimethoxy- l- oxo- ol, 3- dihydro- isoindole- hydrochloride

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

Yield: 41.8% of the theoretical.

M.p.: 150-151°C.

Calculated: C, 61.99; H, 7.57; N, 5.35; Cl, 6.57

Found: C, 61.89; H, 7.48; N, 5.17; Cl, 6.52

Example 230

2-[ (N- (3 - (3-methyl-phenoxy)-propyl)-hexahydro-azepinyl-3)-methyl- 5. 6- dimethoxy- l- oxo- l. 3- dihydro-isoindole- hydrochloride

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

Yield: 88.9% of the theoretical.

Melting point: 95-100°C.

Calculated: C, 63.95; H, 7.75; N, 5.52; Cl, 7.25

Found: C, 64.09; H, 7.64; N, 5.35; Cl, 7.37

Example 231

2-[ (N-(3-(4-Methoxy-phenoxy)-propyl)-hexahydro-azepinyl-3)-methyl-1-5.6-dimethoxy-1-oxo-1.3-dihydro-isoindole-hydrochloride

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

Yield: 87.1% of the theoretical.

M.p.: 107-112°C

Calculated: C, 61.99; H, 7.51; N, 5.35; Cl, 7.02

Found: C, 62.07; H, 7.37; N, 5.28; Cl, 7.31

Example 232

2-[(N-(3-(3,4-methylenedioxy-phenoxy)-propyl)-hexahydro-azepinyl-3 )-methyl]-5,6-dimethoxy-1-oxo-1,3-dihydro-isoindole- hydrochloride

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

Yield: 59% of the theoretical.

M.p.: 104-107°C

Calculated: C, 60.38; H, 6.94; N, 5.20; Cl, 7.31

Found: C, 60.40; H, 7.15; N, 4.95; Cl, 7.25

Example 233

2-[(N-(3-(3,4-methylenedioxy-phenoxy)-propyl)-hexahydro-azepinyl-3 )-methyl]-5,6-dimethoxy-1-oxo-1,3-dihydro-isoindole- hydrochloride

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

Yield: 79.4% of the theoretical.

M.p.: 112-116°C

Calculated: C, 62.23; H, 7.15; N, 5.37; Cl, 7.05

Found: C, 62.16; H, 7.25; N, 4.96; Cl, 7.03

Example 234

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

dihvrated

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 with potassium- tert-butylate, analogous to Example 2.

Yield: 86% of the theoretical.

M.p.: 106-108°C

Calculated: C, 58.05; H, 7.40; N, 7.52; Cl, 12.69

Found: C, 57.94; H, 7.55; N, 7.75; Cl, 12.42

Example 235

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

Prepared from 3-[(N-(3-(pyridyl-3)-propyl)-hexahydro-azepinyl-3)-methyl]-7,8-dimethoxy-2-oxo-1,3-dihydro-2H-3- benzazepine and 5 bar hydrogen in the presence of 10% palladium on charcoal in dimethylformamide at 80°C, analogously to Example 5.

Yield: 43% of the theoretical.

M.p.: 119-121°C

Calculated: C, 57.85; H, 7.73; N, 7.49; Cl, 12.65

Found: C, 57.74; H, 7.79; N, 7.23; Cl, 12.50

Example 236

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-tetrahydro- 2H-3-benzazepine and lithium aluminum hydride in tetrahydrofuran and diethyl ether, analogously to Example 3.

Yield: 82% of the theoretical.

M.p.: 139-141°C.

Calculated: C, 57.39; H, 7.85; N, 7.43; Cl, 18.82

Found: C, 57.42; H, 8.15; N, 7.56; Cl, 19.04

Example 237

2- [ (N-(1-(pyridyl-3)-methyl)-pyrrolidyl-3)-methyl]-6,7-methylenedioxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline-dihydrochloride- di<y>drat

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

Yield: 46% of the theoretical.

M.p.: 91-93°C.

Calculated: C, 53.17; H, 6.16; N, 8.85; Cl, 14.95

Found: C, 53.31; H, 5.93; N, 8.71; Cl, 15.01

Example 238

2- [ (N-(1-(pyridyl-3)-methyl)-pyrrolidyl-3)-methyl]-6,7-methylenedioxy-1,2,3,4-tetrahydro-isoquinoline-trihydro-

chloride - 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, analogously to Example 3.

Yield: 67% of the theoretical.

M.p.: 178-181°C.

Calculated: C, 51.70; H, 6.41; N, 8.61; Cl, 21.80

Found: C, 51.63; H, 6.62; N, 8.45; Cl, 21.07

Example 239

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

Prepared from 7,8-dimethoxy-2-oxo-1,3-dihydro-2H-3-benzazepine and N-[2-(6-methyl-pyridy1-2)-ethyl]-3-chloromethyl-hexahydro-azepine in dimethylsulfoxide with potassium tert-butylate, analogously to Example 2.

Yield: 63% of the theoretical.

M.p.: 134-136°C

Calculated: C, 58.05; H, 7.40; N, 7.52; Cl, 12.69

Found: C, 58.15; H, 7.60; N, 7.45; Cl, 12.45

Example 240

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 dimethylsulfoxide with potassium tert-butylate, analogously to Example 2.

Yield: 61% of the theoretical.

Melting point: 78-80°C.

Calculated: C, 57.58; H, 6.96; N, 8.06; Cl, 13.60

Found: C, 57.40; H, 7.18; N, 8.24; Cl, 13.39

Example 241

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 dihydrochloride x 2.5 hydrate

Prepared from 3-[(N-(2-(6-methyl-pyridyl-2)-ethyl)-hexahydro-azepinyl-3)-methyl]-7,8-dimethoxy-2-oxo-1,3-dihydro- 2H-3-benzazepine and 5 bar hydrogen in the presence of palladium/charcoal and dimethylformamide, analogously to Example 5. Yield: 34% of the theoretical.

M.p.: 112-114°C.

Calculated: C, 56.93; H, 7.78; N, 7.38; Cl, 12.45

Found: C, 56.83; H, 8.04; N, -7.43; Cl, 12.26

Example 242

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

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, analogously to Example 3. Yield: 74% of the theoretical.

Melting point: 148-150°C.

Calculated: C, 55.61; H, 7.95; N, 7.20; Cl, 18,24

Found: C, 55.72; H, 8.10; N, 7.03; Cl, 18.00

Example 243

3-[(N-(2-(6-methyl-pyridyl-2)-ethyl)-pyrrolidyl-3)-methyl]-7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro- 2H-3-benzazepine dihydrochloride dihydrate

Prepared from 3-[(N-(2-(6-methyl-pyridyl-2)-ethyl)-pyrrolidyl-3)-methyl]-7,8-dimethoxy-2-oxo-1,3-dihydro-2H- 3-benzazepine and palladium/charcoal in dimethylformamide at 50°C and 6 bar hydrogen, analogously to Example 5.

Yield: 28% of the theoretical.

M.p.: 87-90°C.

Calculated: C, 56.38; H, 7.38; N, 7.89; Cl, 13.31

Found: C, 56.33; H, 7.53; N, 8.09; Cl, 13.43

Example 244

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

Prepared from 7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepine and N-[(2-(6-methyl-pyridyl-2)-ethylj-S-Cbenzenesulfonyloxymethyl)-pyrrolidine in dimethylformamide and triethylamine, analogously to Example 2.

Yield: 42% of the theoretical.

M.p.: 225-227°C

Calculated: C, 54.10; H, 7.62; N, 7.57; Cl, 19,16

Found: C, 54.18; H, 7.55; N, 7.51; Cl, 19.30

Example 245

2-[(N-(3-(indolyl-3)-propyl)-piperidyl-3)-methyl]-5,6-dimethoxy-1-oxo-1,3-dihydro-isoindole x 1.5 benzenesulfonate 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, analogously to Example 1.

Yield: 45% of the theoretical.

M.p.: 87-89°C.

Calculated: C, 58.51; H, 6.54; N, 5.68

Found: C, 58.66; H, 6.43; N, 5.34

Example 246

2-[(N-(3-(indolyl-3)-propyl)-piperidyl-3)-methyl]-6,7-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline-benzenesulfonate- dihydrate

Prepared from 2-[(piperidyl-3)-methyl]-6,7-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 3-(3-benzenesulfonyloxy-propyl)-indole in dimethylformamide and triethylamine, analogously to Example 1.

Yield: 94% of the theoretical.

M.p.: 117-119°C.

Calculated: C, 65.46; H, 7.27; N, 6.73

Found: C, 65.51; H, 6.91; N, 6.72

Example 247

3-[(N-(3-(indolyl-3)-propyl)-pyrrolidyl-3)-methyl]-7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H-3- benzazepine hydrochloride 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 hydrogen in the presence of palladium/charcoal in dimethylformamide at 80°C, analogously to Example 5.

Yield: 58% of the theoretical.

Melting point: 128-130°C.

Calculated: C, 65.16; H, 7.42; N, 8.14; Cl, 6.87

Found: C, 65.12; H, 7.55; N, 8.11; Cl, 7.06

Example 248

3-[(N-(3-(indolyl-3)-propyl)-hexahydro-azepinyl-3)-methyl]-7,8-dimethoxy-2-oxo-1,3,4,5-tetrahydro-2H- 3-benzazepine 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, analogously to Example 1.

Yield: 49% of the theoretical.

Temp. : 56-58°C.

Calcd: C, 70.98; H, 8.14; N, 8.27

Found: C, 71.08; H, 8.10; N, 8.16

Example 249

3-[(N-(3-(indolyl-3)-propyl)-hexahydro-azepinyl-3)-methyl]-7,8-methylenedioxy-1,3,4,5-tetrahydro-2H-3-benzazepine- dihydrochloride monohydrate

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, analogously to Example 3. Yield: 56% of the theoretical.

M.p.: 155-158°C

Calculated: C, 62.26; H, 7.50; N, 7.63; Cl, 12.88 Found: C, 62.31; H, 7.82; N, 7.40; Cl, 12.89

Example 250

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

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

Yield: 60% of the theoretical.

M.p.: 125-128°C

Calculated: C, 62.44; H, 7.67; N, 7.80; Cl, 13,16

Found: C, 62.35; H, 7.87; N, 7.59; Cl, 13.67

Example 251

2-[(N-(3-(indolyl-3)-propyl)-piperidyl-3)-methyl]-6,7-dimethyl-1. 2. 3, 4- tetrahydro- isoquinoline- dihydrochloride- monohydrate

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, analogously to Example 3.

Yield: 90% of the theoretical.

Temp. : 198-201°C

Calculated: C, 66.38; H, 8.16; N, 8.29; Cl, 14.00

Found: C, 66.29; H, 8.21; N, 8.46; Cl, 13.82

Example 252

3-[(N-(3-(indolyl-3)-propyl)-hexahydro-azepinyl-3)-methyl]-7,8-methylenedioxy-2-oxo-1,3,4,5-tetrahydro-2H- 3-benzazepine monohydrate

Prepared from 3-[(hexahydro-azepinyl-3)-methyl]-7,8-methylenedioxy-2-oxo-1,3,4,5-tetrahydro-2H-3-benzazepine and 3-(3-benzenesulfonyloxy-propyl )-indole, analogous to Example 1. Yield: 61.5% of the theoretical.

M.p.: 62-64°C

Calcd: C, 70.84; H, 7.59; N, 8.55

Found: C, 70.73; H, 7.59; N, 8.42

Example 253

2-[ (N-(3-(indolyl-3)-propyl)-pyrrolidyl-3)-methyl]-6,7-dimethyl-1, 2, 3, 4- tetrahydro- isoquinoline- dihydrochloride- hemihydrate

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

Yield: 86% of the theoretical.

M.p.: 143-145°C.

Calculated: C, 67.06; H, 7.92; N, 8.69; Cl, 14.66

Found: C, 66.92; H, 8.07; N, 8.48; Cl, 14.87

Example 254

2-[(N-(3-(indolyl-3)-propyl)-pyrrolidyl-3)-methyl]-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-benzenesulfonyloxy-propyl)-indole, analogous to Example 1.

Yield: 67% of the theoretical.

M.p.: 117-120°C.

Calculated: C, 67.69; H, 7.78; N, 8.77; Cl, 7.40

Found: C, 67.62; H, 7.80; N, 8.72; Cl, 7.93

Example 255

3-[(N-(3-(indolyl-3)-propyl)-pyrrolidyl-3)-methyl]-7,8-methylenedioxy-1,3,4,5-tetrahydro-2H-3-benzazepine dihydrochloride x 1.5 hydrate

Prepared from 7,8-methylenedioxy-1,3,4,5-tetrahydro-2H-3-benzazepine and 3-(benzenesulfonyloxy-methyl)-N-[3-(indolyl-3)-propyl]-pyrrolidine, analogous to Example 2.

Yield: 75% of the theoretical.

M.p.: 191-193°C

Calculated: C, 61.01; H, 7.21; N, 7.90; Cl, 13.34

Found: C, 60.90; H, 7.27; N, 7.85; Cl, 13.70

Example 256

3-[(N-(3-(indolyl-3)-propyl)-hexahydro-azepinyl-3)-methyl]-7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepine- dihydrochloride

monohydrate

Prepared from 3-[(N-(3-(indolyl-3)-propyl)-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, analogously to Example 3.

Yield: 53% of the theoretical.

Melting point: 158-160°C.

Calculated: C, 63.58; H, 8.00; N, 7.41; Cl, 12.51

Found: C, 63.41; H, 8.18; N, 7.36; Cl, 12.23

Example 257

3-[(N-(3-(indolyl-3)-propyl)-pyrrolidyl-3)-methyl]-7,8-dimethyl-1. 3. 4. 5- tetrahydro- 2H- 3- benzazepine- dihydrochloride- monohydrate

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

Yield: 65% of the theoretical.

M.p.: 168-170°C

Calculated: C, 66.39; H, 8.16; N, 8.29; Cl, 13.99

Found: C, 66.29; H, 8.44; N, 8.08; Cl, 14.08

Claims (5)

1. Analogous method for the preparation of therapeutically active cyclic amine derivatives of the general formula where A means a -CH2-, -CH2-CH2- or -CH=CH group, B is a -CH2-, -CH2-CH2-, -CO- or -CH2CO group, X where the carbon atom marked with X is linked to the phenyl atom, E is a straight-chain alkylene group with 1-3 carbon atoms which is optionally substituted with an alkyl group with 1-3 carbon atoms, G is a straight-chain alkylene group with 1-6 carbon atoms, where the methylene group connected to an aromatic or heteroaromatic residue R can be replaced by an oxygen atom, Rj and R2 each mean a (C1-C3)alkyl or (C1-C3)alkyl group, or Rx and R2 together form an alkylenedioxy group with 1 or 2 carbon atoms, m means the number 1, 2, 3, 4, 5 or 6, and n means the number 0, 1, 2 or 3, where however n + m must be the number 3, 4, 5 or 6, and R means an optionally methyl-substituted furyl, thienyl, pyridyl, benzo[b]furyl or benzo[b]thienyl group, a benzo[b]thienyl group which is substituted by a halogen atom, a methoxy or methanesulfonyloxy group, a naphthyl group which optionally is mono- or disubstituted with methyl or methoxy groups, where the substituents may be the same or different, or when B constitutes a -CH2- or C0 group, a phenyl group which is optionally substituted with a methylenedioxy group, a phenyl group which is mono- or disubstituted with methyl or methoxy groups, where the substituents may be the same or different, their N-oxides and their pharmaceutically acceptable acid addition salts, characterized in that a) a compound of the general formula where Ri, R2, A, B, E, m and n are as defined above, reacted with a compound of the general formula Zl-G-R, (III) where R and G are defined as above, and Zx is a nucleophilic leaving group, a hydroxy group, or where Zi together with the hydrogen atom in the adjacent methylene group forms an oxygen atom, or b) a compound with the general formula where Rj., R2, A and B are as defined above, reacted with a compound of the general formula where R, E, G, m and n are as above defined and Z2 constitutes a nucleophilic leaving group, or c) for the preparation of compounds of the general formula I, where B constitutes a -CH2- or -CH2CH2 group, a compound with the general formula where R, Rlf R2, E, G, m and n are as defined above, Ax constitutes a -CH2-, -CH2-CH2-, -CH=CH- or -CO group, and Bx constitutes a -CO- or -CH2CO group, X where the carbon atom marked with X is attached to the phenyl nucleus, is reduced, or d) for the preparation of compounds of the general formula I, where A constitutes a -CH2 group and B a -CO- or -CH2CO group, a compound with the general formula where R, Rlr R2, E, G, m and n are as defined above and B2 constitutes a -CO- or -CH2CO group, X where the carbon atom marked with X is attached to the phenyl nucleus, is reduced by nascent hydrogen, or . e) for the preparation of compounds of the general formula I, where G, with the exception of residues containing a sulfur atom, a sulfinyl or sulfonyl group, have the meanings given for G above, and A constitutes the -CH2-CH2 group and B - The CH2, -C0 or -CH2CO group, a compound of the general formula where R, Rlr R2, B, E, m and n are as defined above, Gj, with the exception of residues containing a sulfur atom, a sulfinyl or sulfonyl group, have the meanings given for G above, and B3 forms a -CH2-, -C0- or -CH2CO group, is hydrogenated, and if necessary, a protective residue used during the reactions a) to e) used to protect reactive groups, such as hydroxy, amino, alkylamino or imino groups are then cleaved off, and/or a thus obtained compound of the general formula I, where R contains a nitro group, optionally transferred by reduction into a corresponding amino compound of the general formula I, and/or a thus obtained compound of the general formula I, where R contains an amino group, optionally transferred by acylation into a corresponding alkanoylamino compound of the general formula I, and/or a thus obtained compound of the general formula I is transferred in its physiologically acceptable acid addition salts with inorganic or organic acids. 2. Process according to claim 1, for the production of 3-[(N-(2-(naphthyl-2)-ethyl)-piperidyl-3)-methyl]-7,8-dimethoxy-2-oxo-1,3, 4,5-tetrahydro-2H-3-benzazepine, and its pharmaceutically acceptable acid addition salts, characterized by the use of corresponding output connections. 3. Method according to claim 1, for the production 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, characterized by using corresponding starting compounds. 4. Process according to claim 1, for the preparation of 2-[(N-(3-(4-methoxyphenoxy)-propyl)-piperidyl-3)-methyl]-6,7-dimethyl-1-oxo-1,2 ,3,4-tetrahydro-isoquinoline, characterized by the use of corresponding starting compounds. 5. 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, characterized using corresponding starting compounds.