GB2088873A

GB2088873A - Chemical Compounds

Info

Publication number: GB2088873A
Application number: GB8137051A
Authority: GB
Original assignee: Dr Karl Thomae GmbH
Current assignee: Boehringer Ingelheim Pharma GmbH and Co KG
Priority date: 1980-12-10
Filing date: 1981-12-09
Publication date: 1982-06-16
Also published as: FR2498596B1; PT74112A; CS229924B2; CA1202636A; YU290381A; ZA818529B; PT74112B; IL64498A0; HU185676B; ES512914A0; AR227802A1; AU547655B2; ES8304538A1; IE52007B1; AU7841481A; NO152649B; NO152649C; ES512913A0; DE3146623A1; BE891416A

Abstract

Compounds of general formula I <IMAGE> wherein R1 represents a hydroxy group or an optionally substituted amino group; R2 and R3 each represents a halogen atom, a trifluoromethyl, cyano or nitro group or one of the radicals R2 or R3 represents a hydrogen atom; R4 represents a hydrogen atom or an alkyl group; R5 represents a hydrogen atom, an alkyl, cycloalkyl, alkenyl or aralkyl group; A represents a methylene, ethylene or hydroxymethylene group; and B represents an optionally substituted aralkyl group, in which the methylene group adjacent to the phenyl nucleus may be replaced by an oxygen or sulfur atom, or a sulfinyl or sulfonyl group; all optical isomers thereof, and mixtures of the aforesaid optical isomers; and acid addition salts thereof. Processes for the preparation of the new compounds as well as pharmaceutical compositions containing them are also objects of this invention. The new compounds show valuable pharmacological properties, especially effects on the heat and circulation.

Description

SPECIFICATION Chemical Compounds This invention relates to new phenylalkylamines, to processes for their preparation and to pharmaceutical compositions containing them, and to their use in the treatment of disorders of the heart and circulation.

According to one feature of the present invention there are provided compounds of general formula I

[wherein R, represents a hydroxy group, an amino group (optionally substituted by an alkanoyl group containing 1 to 3 carbon atoms or an alkoxycarbonyl group containing 2 to 4 carbon atoms) or an alkylamino or dialkylamino group in which each alkyl part may contain from 1 to 3 carbon atoms and may each optionally be substituted by a phenyl group; R2 and R3, which may be the same or different, each represents a halogen atom or a trifluoromethyl, cyano or nitro group, or one of the radicals R2 or R3 represents a hydrogen atom; R4 represents a hydrogen atom or an alkyl group containing 1 to 3 carbon atoms;; P5 represents a hydrogen atom, a straight-chained or branched alkyl group containing 1 to 4 carbon atoms, a cycloalkyl group containing 3 to 6 carbon atoms, an alkenyl group containing 2 to 5 carbon atoms or an aralkyl group containing 7 to 10 carbon atoms; A represents a methylene, ethylene or hydroxymethylene group; and B represents a group of formula

wherein Rb represents a hydrogen or halogen atom, a hydroxy group, an alkoxy group containing 1 to 3 carbon atoms optionally substituted by a phenyl group, or an alkylsulfenyl or alkylsulfinyl group containing 1 to 3 carbon atoms and R, represents a hydrogen atom, a hydroxy group or an alkoxy group containing 1 to 3 carbon atoms; or R6 and R7 together represent a methylenedioxy group; R8 represents a hydrogen atom or an alkyl group containing 1 to 3 carbon atoms; D represents an oxygen or sulfur atom, or a sulfinyl or sulfonyl group; n is 1 or 2; and E represents a straight-chained alkylene group containing 3 to 5 carbon atoms optionally substituted by one or two alkyl groups containing 1 to 3 carbon atoms each, or (when A represents a methylene or ethylene group, and/or P1 represents an amino group substituted by an alkanoyl group containing 1 to 3 carbon atoms or by an alkoxycarbonyl group containing 2 to 4 carbon atoms, a hydroxy group or an alkylamino or dialkylamino group in which each alkyl part may contain from 1 to 3 carbon atoms and each may optionally be substituted by a phenyl group, and/or R2 represents a trifluoromethyl, cyano or nitro group, and/or R3 represents a fluorine atom, and/or R4 represents an alkyl group containing 1 to 3 carbon atoms, and/or R5 represents an alkyl group containing 1 to 4 carbon atoms, a cycloalkyl group containing 3 to 6 carbon atoms, an alkenyl group containing 2 to 5 carbon atoms, or an aralkyl group containing 7 to 10 carbon atoms, and/or R6 represents a fluorine or chlorine atom, or an alkylsulfenyl or alkylsulfenyl or alkylsulfinyl group containing 1 to 3 carbon atoms each) E may further represent an ethylene group or (when A represents a methylene group) E may further represent a group of formula

wherein P9 represents an alkyl group containing 1 to 3 carbon atoms] and acid addition salts thereof.

For pharmaceutical use, the acid addition salts referred to above will of course be physiologically compatible acid addition salts but other acid addition salts may find use in the preparation of the compounds of formula I and their physiologically compatible acid addition salts. The term "acid addition salts" includes salts with organic and inorganic acids.

It is to be understood that, although in the above general formula I, no particular configuration at chiral centres is specified, various optical isomers are possible, and the present invention includes within its scope all possible racemic, enantiomeric and diastereoisomeric forms of the compounds of formula I.

R, may represent, for example, a hydroxy, amino, methylamino, ethylamino, propylamino, isopropylamino, benzylamino, 1-phenylethylamino, 2-phenylethylamino, 3-phenylpropylamino, dimethylamino, diethylamino, dipropylamino, diisopropylamino, dibenzylamino, di-(2-phenylethyl)amino, di(3-phenylpropyl)-amino, methyl-ethyl amino, methyl-propylamino, methyl-isopropylamino, ethyl-isopropylamino, methyl-benzylamino, ethyl-benzylamino, propyl-benzylamino, pyrrolidino, piperidino, hexamethyleneimino, formylamino, acetylamino, propionylamino, methoxycarbonylamino, ethoxycarbonylamino, propoxycarbonylamino or isopropoxycarbonylamino group;; R2 and R3, which may be the same or different, may each represent, for example, a fluorine, chlorine, bromine or iodine atom or a trifluoromethyl, cyano or nitro group, or one of R2 and R3 may represent a hydrogen atom; R4 and R8, which may be the same or different, may each represent, for example, a hydrogen atom, or a methyl, ethyl, propyl or isopropyl group; P5 may represent, for example, a hydrogen atom or a methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert.-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, allyl, crotyl, pententyl, benzyl, 1phenylethyl, 2-phenylethyl, 3-phenylpropyl-or 4-phenylbutyl group;; R6 may represent, for example, a hydrogen, fluorine chlorine or bromine atom, or a hydroxy, methoxy, ethoxy, propoxy, isopropoxy, methylsulfenyl, ethylsulfenyl, methylsulfinyl, propylsulfinyl, benzyloxy, 2-phenylethoxy or 3-phenylpropoxy group; R7 may represent, for example, a hydrogen atom or a hydroxy, methoxy, ethoxy, propoxy, or isopropoxy group or R6 and R7 together may represent a methylenedioxy group; P9 may represent, for example a methyl, ethyl, propyl or isopropyl group; and E may represent, for example, an ethylene, n-propylene, n-butylene, n-pentylene, 1-methyl-n- propylene, 1-ethyl-n-propylene, 1-propyl-n-propylene, 1 1 -dimethyl-n-propylene, 1,1 -diethyl-n- propylene, 1,1 -dipropyl-n-propylene, 1 -methyl-1 -ethyl-n-propylene, 1 -methyl-1 -propyl-n-propylene, 1 -ethyl-1 -propyl-n-propylene, 1 -methyl-n-butylene, or 1 -methyl-n-pentylene group.

Preferred compounds of general formula I are those wherein P1 represents an amino group optionally substituted by a benzyl group or an alkoxycarbonyl group containing 2 to 4 carbon atoms or an alkylamino or dialkylamino group, in which each alkyl part may contain from 1 to 3 carbon atoms; R2 represents a hydrogen, chlorine, bromine or iodine atom or a trifluoromethyl, cyano or nitro group; R3 represents a fluorine, chlorine, or bromine atom or a cyano group; R4 represents a hydrogen atom or a methyl group; R5 represents a hydrogen atom, an alkyl group containing 1 to 3 carbon atoms optionally substituted by a phenyl group, or an allyl or cyclopropyl group; A represents a methylene, ethylene or hydroxymethylene group; and B represents a group of formula

wherein R8, D and n are as hereinbefore defined;R6 represents a hydrogen, fluorine or chlorine atom or a hydroxy, methoxy, ethoxy, benzyloxy, methylsulfenyl or methylsulfinyl group and R7 represents a hydrogen atom or a methoxy group: or R6 and R7 together represent a methylenedioxy group; and E represents an n-propylene, 1-methyl-n-propylene, 1.1 -dimethyl-n-propylene or n-butylene group or (when A represents a methylene or ethylene group; and/or P1 represents an amino group optionally substituted by a benzyl group or by an alkoxycarbonyl group containing 2 to 4 carbon atoms, or an alkylamino or dialkylamino group in which each alkyl part may contain from 1 to 3 carbon atoms; and/or R2 represents a trifluoromethyl, cyano or nitro group; and/or R3 represents a fluorine atom; and/or P5 represents an alkyi group containing 1 to 3 carbon atoms optionally substituted by a phenyl group, or an allyl or cyclopropyl group) E may further represent an ethylene group.

Especially preferred compounds of general formula I are those wherein P1 represents an amino group optionally substituted by an ethoxycarbonyl group, or an alkylamino or dialkylamino group in which each alkyl part may contain from 1 to 3 carbon atoms; R2 represents a hydrogen, chlorine or bromine atom or a cyano group; R3 represents a fluorine or chlorine atom or a cyano group; R4 represents a hydrogen atom or a methyl group; P5 represents a hydrogen atom, an alkyl group containing 1 to 3 carbon atoms (optionally substituted by a phenyl group) or an allyl or cyclopropyl group;A represents a methylene or hydroxymethylene group; and B represents a group of formula

wherein E represents an n-propylene, 1-methyl-n-propylene, 1,1 -dimethyl-n-propylene or n-butylene group, or (when Rl represents an ethoxycarbonylamino group and/or R2 represents a cyano group and/or R3 represents a fluorine atom and/or P5 represents an alkyl group containing 1 to 3 carbon atoms optionally substituted by a phenyl group, or an allyl or cyclopropyl group) E may further represent an ethylene group; R6 represents a hydrogen atom or a hydroxy or methoxy group; and R7 represents a hydrogen atom or a methoxy group.

The compounds of general formula I may, for example, be prepared by the following processes, which processes constitute further features of the present invention: a) Reduction of a compound of general formula II

(wherein P1, R2, R3, P5 and B are as hereinbefore defined) and X represents a group of formula

(wherein R4 is as hereinbefore defined, acyl represents an organic acyl group such as an acetyl, propionyl or benzoyl group; and Z represents a reductively cleavable group, for example a bromine or iodine atom or a carbonic ester radical, e.g. a methoxycarbonyloxy or ethoxycarbonyloxy group).

Depending on the meaning of the radical X the reduction may, for example, be carried out in a solvent such as methanol, methanol/water, ethanol, ethanol/water, isopropanol, trifluoroacetic acid, butanol, diethyl ether, tetrahydrofuran, tetrahydrofuran/water, dioxan or hexamethyl-phosphoric acid triamide, and conveniently at temperatures between -200C and the boiling point of the reaction mixture, e.g. at temperatures between -200C and 1000C.

Suitable reducing agents include, for example, hydrides, aluminium isopropylate in the presence of a primary or secondary alcohol, catalytically activated hydrogen or nascent hydrogen.

For the preparation of compounds of general formula I, wherein A represents a hydroxymethylene group, the reduction is appropriately carried out, for example, with a complex metal hydride such as sodium borohydride or lithium aluminium hydroxide in a solvent such as, for example, methanol, methanol/water, diethyl ether or tetrahydrofuran at -200C to 500 C; with aluminium isopropylate in isopropanol conveniently at the boiling temperature, the acetone thus formed being distilled off; with catalytically activated hydrogen conveniently with hydrogen in the presence of a catalyst such as for example platinum, palladium, raney-nickel or raney-cobalt at room temperature and at a hydrogen pressure of 1 to 5 bar; or with nascent hydrogen, e.g. from activated metallic aluminium and water or zinc and hydrochloric acid, at temperatures up to the boiling temperature of the solvent used.

If in the compound of general formula II used in the above reduction, X represents a -CO CHP4grnup, the reaction is conveniently carried out at temperatures between 0 and 500 C, preferably at room temperature, e.g. with sodium borohydride in methanol/water, ethanol/water or isopropanol or with lithium aluminium hydride in diethyl ether or tetrahydrofuran; if X represents the

group, the reaction is preferably carried out with a hydride in a solvent such as, for example, ether, tetrahydrofuran or dioxan, e.g. with diborane or lithium aluminium hydride in tetrahydrofuran at lovver to slightly elevated temperatures, e.g. at temperatures between 0 and 1 00 C, and conveniently, at the boiling point of the reaction mixture.

For the preparation of compounds of general formula I, wherein A represents the methylene or ethylene group, the reduction is appropriately carried out with, for example, a hydride such as sodium borohydride, lithium aluminium hydride, sodium cyanoborohydride or pyridineborane in a solvent such as, for example, ethanol, isopropanol, tetrahydrofuran, dioxan, trifluoroacetic acid or hexamethylphosphoric acid triamide and conveniently at temperatures between 0 and 1 000C.

If in the compound of general formula Il used in the above reduction, X represents the -CH2- CO- group, the reaction is preferably carried out at elevated temperatures, e.g. with lithium aluminium hydride in tetrahydrofuran at the boiling temperature of the reaction mixture; if X represents the hydroxy-ethylene group, the reaction is preferably carried out with pyridine-borane in trifluoroacetic acid at temperatures between 25 and 1 OO"C, the reaction components having been mixed at lower temperatures, e.g. at -1 OOC; if X represents a

group, the reaction is preferably carried out with sodium borohydride, sodium cyanoborohydride or lithium aluminium hydride in a solvent such as, for example, isopropanol, hexamethyl-phosphoric acid triamide, tetrahydrofuran or dioxan at temperatures between 20 and 1 00 C.

b) Reaction of a carbonyl compound (optionally formed in the reaction mixture) of general formula III K-L (III) [wherein K together with a neighbouring hydrogen atom in the alkyl part of the radical L represents an oxygen atom; and L has one of the meanings hereinbefore recited for B or (with the exception of a hydrogen atom) R5 or represents a group of formula

in which Ra, R2, R3 and R4 are as hereinbefore defined; and A' represents a carbonyl, methylene or ethylene group] or an aldehyde hydrate thereof with an amine of general formula IV

(wherein M and Q, which are different, represent B and P5 as hereinbefore defined, or one of the radicals M or Q represents a group of formula

in which R, R2, R3, R4 and A are as hereinbefore defined) and a reducing agent.

The reaction is preferably carried out in a solvent such as, for example, methanol, methanol/water, ethanol, ethanol/water, butanol, diethyl ether, tetrahydrofuran or dioxan in the presence of a reducing agent at temperatures between --200C and 500 C, preferably, however, at temperatures between 0 and 250C. Suitable reducing agents include, for example, a complex metal hydride or catalytically activated hydrogen.

Where the reaction is carried out with a secondary amine of general formula IV it is preferably carried out in tetrahydrofuran as a solvent and with sodium cyanoborohydride at pH < 7, e.g. at pH 66.5, and subsequently with sodium borohydride at room temperature.

Where the reaction is carried out with a primary amine of general formula IV, the Schiff's base formed in the reaction mixture is preferably reduced with a complex metal hydride such as sodium borohydride or lithium aluminium hydride in a solvent such as, for example, methanol, methanol/water, diethyl ether or tetrahydrofuran at temperatures between -200C and the boiling point of the used solvent, e.g. at temperatures between 0 and 800 C, or with catalytically activated hydrogen, e.g. with hydrogen in the presence of a catalyst such as, for example, platinum, palladium, raney nickel, or raney cobalt, at temperatures between 0 and 1 000C, preferably, however, at room temperature, and at a hydrogen pressure of 1 to 5 bar.

Methylation of an amine centre may also be carried out using formaldehyde and formic acid as the reducing agent at elevated temperatures, e.g at the boiling point of the reaction mixture.

If the reaction is carried out with a compound of general formula IV in which R, represents an amino or alkylamino group containing 1 to 3 carbon atoms, and with a carbonyl compound of general formula Ill, wherein L is as defined for R5, the aforesaid R, group can also be alkylated at the nitrogen centre, especially when using an excess of the carbonyl compound of general formula Ill.

c) Removal of one or more protective radicals from a compound of general formula V

wherein R2, R3 and R4 are as hereinbefore defined; P1, represents R, as hereinbefore defined or represents a hydroxy or amino group protected by a protective radical; A" represents A as hereinbefore defined or represents a hydroxymethylene group protected by a protective radical; P5, represents R5 as hereinbefore defined or represents a protective radical for an amino group; and B' represents B as hereinbefore defined or represents a group of formula

wherein R8, D, E and n are as hereinbefore defined; and R6' and P7,, which may be the same or different, are as hereinbefore defined for R6 and R7 respectively or represent hydroxy groups protected by protective radicals, wherein at least one of the radicals R,', A", P5, and B' represent or must contain one of the above-mentioned protective radicals.

Suitable protective radicals include, for example, acyl or alkoxycarbonyl radicals such as an ethoxycarbonyl, acetyl, propionyl or benzoyl group or a benzyl group and for A" an acetic, methoxycarbonyl or ethoxycarbonyl group.

The cleavage of one or more of the above-mentioned acyl and/or alkoxy carbonyl radicals is preferably carried out hydrolytically in an aqueous solvent, e.g. in water, isopropanol/water, tetrahydrofuran/water or dioxan/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 1 00 C, preferably at the boiling point of the reaction mixture.

The cleavage of a benzyl radical is preferably carried out hydrogenolytically, e.g. with hydrogen in the presence of a catalyst such as, for example palladium/charcoal, conveniently in a solvent such as methanol, ethanol, ethyl acetate or glacial acetic acid and optionally under addition of an acid such as hydrochtoric acid at temperatures between 0 and 500 C, preferably, however, at room temperature and at a hydrogen pressure of 1 to 7 bar, preferably 3 to 5 bar.

d) For the preparation of compounds of general formula I, wherein one of the radicals R2 or R3 represents a hydrogen atom: Dehalogenation of a compound of general formula VI

wherein P1, R3, R4, R5, A and B are as hereinbefore defined and Hal represents a chlorine, bromine or iodine atom.

The dehalogenation is preferably be carried out in a solvent, e.g. with triphenyl phosphine in benzene or toluene, with hydrogen in methanol, ethanol, ethyl acetate or tetrahydrofuran and in the presence of a hydrogenation catalyst or with a complex metal hydride such as lithium aluminium hydride or sodium diethoxy-aluminium hydride in tetrahydrofuran, dioxan or toluene. Depending on the method used, the reaction may be carried out at room temperature or at an elevated temperature, for example at temperatures between 600C and 1 500 C, and at a normal pressure or a moderately elevated pressure. When using raney-nickel or palladium/charcoal the dehalogenation may, for example, be carried out at room temperature and at normal pressure.

e) Alkylation of a compound of general formula VII

wherein P1, R2, R3, R4 and A are as hereinbefore defined; R5" is as hereinbefore defined for R5; and B" represents B as hereinbefore defined provided that if R5" does not represent a hydrogen atom, at least one of the radicals R6 or R7 must represent a hydroxy group or R, must represent an amino group optionally substituted by an alkyl group containing 1 to 3 carbon atoms, which alkyl group may additionally be substituted by a phenyl radical.

The reaction is preferably carried out in a solvent e.g. in water/methanol, ethanol/water, tetrahydrofuran, dioxan, acetone or dimethylsulfoxide, with an alkylating agent such as, for example, methyl iodide, dimethyl sulfate, ethyl bromide, diethyl sulfate, benzyl bromide, 2-phenylethyl bromide or methyl-p-toluene sulfate, optionally in the presence of a base such as sodium hydroxide or potassium carbonate. Preferred temperatures are those between --100 and 500 C, preferably between 0 and 300C. The reaction can, however, be carried out without a solvent.

The alkylation of a nitrogen atom can also be carried out using formaldehyde/formic acid at elevated temperatures, e.g. at the boiling point of the reaction mixture, or with a corresponding carbonyl compound and a complex metallic hydride, preferably with sodium cyanoborohydride at pH < 7, e.g. at pH 6 to 6.5, in a solvent such as, for example, water/methanol, ethanol, ethanol/water or tetrahydrofuran at temperatures between 0 and 500 C, preferably, however, at room temperature.

Moreover, the alkylation of a phenolic hydroxy group can be carried out with, for example, a corresponding diazo alkane in a solvent such as diethyl ether or tetrahydrofuran. Preferred temperatures are those between 0 and 500 C, and preferably room temperature.

f) For the preparation of compounds of general formula I as hereinbefore defined wherein R, represents an amino group substituted by an alkanoyl group containing 1 to 3 carbon atoms or by an alkoxycarbonyl group containing 2 to 4 carbon atoms, and R5 does not represent a hydrogen atom:: Acyiation of a compound of general formula VIII

(wherein R2, R,, R4, R,, A and B are as hereinbefore defined) with a compound of general formula iX Y-CO-R10, (IX) (wherein Rro represents a hydrogen atom, a methyl or ethyl group or an alkoxy group containing 1 to 3 carbon atoms, and Y represents a nucelophilically exchangeable group such as for example a halogen atom, a nitrophenyl radical, an imidazolyl group or a radical of formula -0-COP10).

The reaction may, for example, be carried out with acetyl chloride, acetic anhydride, propionic acid anhydride or a corresponding chloroformate, e.g. ethyl chloroformate, which simultaneously may serve as a solvent. The reaction is optionally effected in the presence of a solvent such as water/tetrahydrofuran, diethyl ether, tetrahydrofuran or methylene chloride, optionally in the presence of a base such as triethylamine or pyridine (in which case the tertiary organic base may optionally serve as a solvent), at temperatures between 0 and 1000 C, preferably, however, at room temperature. The reaction can also be carried out without a solvent.

g) For the preparation of compounds of general formula I, wherein D represents a sulfinyl or sulfonyl group: Oxidation of a compound of general formula X

wherein Ra, R2, R3, R4, R5, R6, R7, R8, A and n are as before defined and m is O or 1.

The oxidation is preferably carried out in a solvent, e.g. in water, water/pyridine, ethanol, methanol, acetone, glacial acetic acid, formic acid, dilute sulfuric acid or trifluoroacetic acid, depending on the oxidising agent used and conveniently at temperatures between -80 and 1 O00C.

For the preparation of sulfinyl compounds of general formula I the oxidation is conveniently carried out with an equimolar amount of the oxidising agent used. Suitable oxidising agents include, for example, hydrogen peroxide in glacial acetic acid, trifluoroacetic acid or formic acid at O to 200C or in acetone at O to 600C; a peracid such as performic acid in glacial acetic acid or trifluoroacetic acid at 0 to 500C; m-chloroperbenzoic acid in methylene chloride or chloroform at -20 to 600 C; and sodium metaperiodate in aqueous methanol or ethanol at 1 5 to 250C.

For the preparation of sulfonyl compounds of general formula I the oxidation is conveniently carried out with one or with two or more moles of oxidising agent per mole of compound of formula X.

Suitable oxidising agents include e.g. hydrogen peroxide in glacial acetic acid, trifluoroacetic acid or formic acid at 20 to 1 000C or in acetone at 0 to 60"C; a peracid such as performic acid or mchloroperbenzoic acid in glacial acetic acid, trifluoroacetic acid, methylene chloride or chloroform at temperatures between 0 and 600 C; and potassium permanganate in glacial acetic acid, water/sulfuric acid or in acetone at 0 to 200C.

h) For the preparation of compounds of general formula I, as hereinbefore defined, wherein D represents an oxygen or sulfur atom and R5 does not represent a hydrogen atom: Reaction of a compound of general formula Xl

(wherein R1, R2, R3, R4, R,, R8 and n are as hereinbefore defined; V represents a nucleophilically exchangeable group such as a halogen atom or a sulfonic acid ester radical, e.g. a chlorine, bromine or iodine atom or a p-toluene sulfonyloxy or methane sulfonyloxy group; and A"' represents a methylene or ethylene group) with a compound of general formula XII

(wherein R6 and R7 are as hereinbefore defined and D' represents an oxygen or sulfur atom) or an alkali metal salt or alkaline earth metal salt thereof.

The reaction may, for example, be carried out in a solvent such as chioroform, tetrahydrofuran, dioxan or toluene, and preferably, in an anhydrous aprotic solvent such as acetone, dimethyl formamide or dimethyl sulfoxide, optionally in the presence of an alkali base such as sodium carbonate, potassium carbonate, sodium hydroxide, sodium hydride or potassium tert.-butoxide. Preferred temperatures are those between -1 O0C and the boiling point of the solvent, e.g. at temperatures between -1 OOC and 1 000C, and preferably, at temperatures between 0 and 500 C. The reaction can, however, also be carried out without a solvent.

The compounds of general formula I, which contain one or more chiral centres, may subsequently be resolved into their optical isomers, and diastereoisomeric racemates and their optical isomers using known techniques.

Resolution of the racemates of a compound of general formula I may conveniently be carried out by fractional crystallisation of the diastereoisomeric salts formed by the said compound and an optically active acid such as, for example, D(--)-tartaric acid, L(+)-tartaric acid, dibenzoyl-D-tartaric acid, dibenzoyl-L-tartaric acid, (+)-camphor-1 O-sulfonic acid, L(-)-malic acid, L(+)-mandelic acid, d-a- bromo-camphor-n-sulfonic acid or l-quinic acid and subsequent isolation of the respective optically active base. Resolution of the racemates may also be effected by column chromatography over an optically active carrier, e.g. over acetyl cellulose.

Purification of the diastereoisomeric racemates is effected for example by fractional crystallization and/or column chromatography over an inert carrier.

Further, the compounds of formula I prepared as hereinbefore disclosed may optionally be converted with inorganic or organic acids into their physiologically compatible acid addition salts, for example by conventional methods such as reacting the compounds as bases with a solution of the corresponding acids in a suitable solvent.

Particularly preferred acids include, for example hydrochloric, hydrobromic, sulfuric, phosphoric, fumaric, succinic, lactic, citric, tartaric and maleic acids.

The compounds of general formulae II to XII used as starting materials are known from the literature or may be obtained according to known processes.

Thus, compounds of general formula II, wherein X represents a -COHP4 group, can be obtained, for example, by reaction of an a-halo-ketone with the corresponding amine; compounds of general formula II, wherein X represents the -CH2-COgroup, can be obtained by reaction of a phenylacetic acid derivative with the corresponding amine.

Compounds of general formula Ill, wherein A' represents a carbonyl group and R4 represents a hydrogen atom, can be obtained, for example, by selenium dioxide oxidation of the corresponding acetophenone; compounds of general formula III, wherein A' represents a methylene or ethylene group, can be obtained by converting a hydroxy compound into the corresponding halogen compound, or by acylating a hydroxy compound with the corresponding chloroformate, and subsequent reduction.

Compounds of general formula V can be obtained, for example, by reaction of an ev-phenylalkyi halide with the corresponding amine.

Compounds of general formulae VI, VII and VIII can be obtained, for example, by reduction of a carboxylic acid amide or amino-acetophenone.

Compounds of general formula X can be obtained, for example, by alkylation of the corresponding mercapto compound and optional subsequent oxidation.

Compounds of general formula XI can be obtained, for example, by alkylation of the corresponding phenylalkylamine.

The compounds of general formula I possess valuable pharmacological properties, and show beneficial effects on heart and circulation, and especially an activity on the blood pressure, an antiarrhythmic and/or cardiotonic activity; further, they show only a low toxicity and slight side-effects.

For example the following compounds have been tested with regard to their biological properties: A=1 -(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-methoxy-phenyl)-prnpyl]amino]ethanol, B=1 -(4-Amino-3-cyano-5-fíuoro-phenyl)-2-[N-[3-(4-methoxy-phenyl)-propyl]methyl- amino]ethanol, C=1 -(4-Amino-3,5-dichloro-phenyl)-2-[N-(3-phenyl-propyl)-2-prdpylamino]ethanol hydrochloride, D=1 -(4-Amino-3,5-dichloro-pbenyl)-2-[N-[3-(4-hydroxy-phenyl)- 1 -methyl-propyl]methyl amino]ethanol, E=N-[ 1 -Methyl-2-(4-amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4-methoxy-phenyl)- propyl]amine hydrochloride, F=N-[2-(4-Amino-3,5-dichioro-phenyl)-ethyl]-N-[3-(4-chlorophenyl)-propyl]isopropylamine, G=N-[3-(4-Chloro-phenyl)-propylj-N-[2-(3,5-dichloro-4-isopropylamino-phenyl)- ethyl]iso propylamine, and H=N-[2-(4-Amino-3-bromo-5-cyano-phenyl)-ethyl]-N-[4-(4-methoxy-phenyl)-butyl]methyl amine.

1. Determination of the Contractility Parameter dp/dtmaX or Heart Frequency in Narcotized Cats Male and female cats having a body weight of approx. 2 to 4 kg were narcotized with pentobarbital sodium (40 mg/kg intraperitoneal) and anaesthesia was maintained by continuously infusing pentobarbital sodium (8 mg/kg/h).

The animals breathed spontaneously.

The body temperature was kept at 380C by means of a heating pad and a thermostat.

The pressure in the left ventricle was measured by means of a pressure transducer (Millar PC 350), which was introduced into the left ventricle via the right arteria carotis. From the pressure signal the rate of pressure rise (dp/dt) within the left ventricle was determined by means of a differentiator.

The heart frequency was measured by means of a Grass tachograph (model 7P4). As trigger signal either a ECG or the left ventricular pressure curve was used. All parameters were registered by a Grass polygraph.

All substances were injected into the V. saphena as solution (water or polyethylene glycol 200).

Each dose was 0.3 mg/kg i.v. The maximum activity and the time after application at which the activity was reduced to half of the maximum were measured.

The following tables show the results: Table I Test Increase of Half life time compound dpidtmax % in minutes A + 93 38 B +124 > 140 C + 83 112 D +105 > 100 Table II Test Decrease of heart Half life time compound frequency % in minutes E -27 39 F -17 150 G -13 > 90 H -14 > 52 2. Acute Toxicity: The acute toxicity was determined in male and female mice having a body weight of approx. 20 g after intravenous administration (V. saphenaJ of each test compound (0.1 or 0.2 mí/10 g of body weight) or by administration into the stomach.After an observation time of 14 days the LDso was determined according to the methods described by Litchfield and Wilcoxon: Test LD50 mg/kg compound Lav. P.O.

A 19 > 100 C 32 250 The compounds of general formula I are suitable for the treatment of cardiovascular diseases such as e.g. cardiac insufficiency (due to their positive inotropic activity), and cardiac arrhythmias and coronary heart diseases (due to their activity in lowering the heart frequency).

According to a yet further feature of the present invention there are provided pharmaceutical compositions comprising, as active ingredient, at least one compound of general formula I as hereinbefore defined or a physiologically compatible salt thereof, in association with one or more pharmaceutical carriers or excipients.

For pharmaceutical administration the compounds of general formula I or their physiologically compatible salts may be incorporated into conventional preparations in either solid or liquid form, optionally in combination with other active ingredients. The compositions may, for example, be presented in a form suitable for oral, rectal or parenteral administration. Preferred forms include, for example, plain tablets, coated tablets, powders, suppositories, suspensions, drops or ampoules, e.g. for injection.

The active ingredient may be incorporated in excipients customarily employed in pharmaceutical compositions such as, for example, corn starch, lactose, gelatine, magnesium stearate, citric acid, aqueous or non-aqueous vehicles, fatty substances of animal or vegetable origin, paraffin derivatives, glycols, various wetting, dispersing or emulsifying agents and/or preservatives.

Advantageously the compositions may be formulated as dosage units, each dosage unit being adapted to supply a fixed dose of active ingredient. Suitable single dosage units for adults contain from 5 to 75 mg, preferably 10 to 50 mg, of active ingredient according to the invention. Such dosage units may, for example, be administered 1 to 4 times daily. The total daily dosage may, however, be varied according to the compound used, the subject treated and the complaint concerned.

According to a still further feature of the present invention there is provided a method of treating a patient suffering from or susceptible to cardiovascular diseases which comprises administering to the said patient an effective amount of a compound of formula I, as hereinbefore defined, or a physiologically compatible acid addition salt thereof.

The following non-limiting examples serve to illustrate the present invention.

Example 1 1 -(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-methoxy-phenyl)propyl] methyla mino]ethanol 0.5 g (13.5 m mol) of sodium borohydride were added in portions to a solution of 3.45 g (9 m mol) of 4'-amino-3',5'-dichloro-2-[N-[3-(4-methoxy-phenyl)-propyl]methylamino]acetophenone in 40 ml of methanol and 15 ml of water, whereby the pH value was kept between 3 and 6 by means of 2 N hydrochloric acid. After addition the reaction mixture was stirred for 30 minutes and the solution was evaporated in a rotation evaporator. The residue obtained was distributed between 100 ml of ether and 100 ml of 2 N ammonia solution. The ethereal phase was washed with water, dried with sodium sulfate, and evaporated.The remaining oil was chromatographed over silica gel with methylene chloride:methanol=1 9.1 as eluent (Macherey and Nagel 70-230 mesh ASTM). The fractions containing the desired compound were combined, evaporated and in vacuo the remaining solvent was removed from the oil at 400 C.

IR spectrum (methylene chloride): OH 3610 cm~l NH2 3400+3490 cm~' CH2 2850+2940 cm~' OCH3 2830 cam~' N-alkyl 2800 cam~' C=C 1610cam~' UV spectrum (ethanol): A max. 243 nm (0.23) 280 nm (0.08) 300 nm (0.08) Example 2 1 -(4Amino-3,5-dichloro-phenyl)-2-[N-(3-phenyl-prnpyl)-methylamino]ethanol Hydrochloride 10 g (0.035 mol) of 4'-amino-2-bromo-3',5'-dichloro-acetophenone, 6.7 g (0.036 mol) of N-(3phenyl-propyl)-ethylamine hydrochloride and 10.5 mol (0.075 mol) of triethylamine were added to 250 ml of methylene chloride. This mixture was refluxed for 6 hours and subsequently allowed to stand overnight at room temperature. The mixture was then washed with water, dried over sodium sulfate, and evaporated in a rotation evaporator. The oily residue, which consisted of 4'-amino-3',5'-dichloro-2 [N-(3-phenyl-propyl)-methylamino]acetophenone, was dissolved in 100 ml of 90% ethanol. Under stirring and external cooling with water 5 g of sodium borohydride were added in portions. After standing for 1 hour at room temperature the excess sodium borohydride was destroyed by means of acetone. The reaction mixture was diluted with water and extracted with methylene chloride. The methylene chloride phase was separated, washed with water, dried over sodium sulfate, and evaporated in vacuo in a rotation evaporator.The yellowish oily residue was chromatographed over silica gel (eluent:methylene chloride: ethyl acetate=4:1 ). The fractions containing the desired compound were evaporated. The remaining oily residue was dissolved in isopropanol, acidified with ethereal hydrochloric acid, and mixed with ether until crystallization commenced. A colourless, crystalline product was obtained.

M.p.: from 850C (under sintering).

Example 3 1 -(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-hydroxy-phenyl)-1 -methyl-propyl] methylamino]ethanol 0.2 mol of sodium borohydride were added in portions to a solution of 0.1 mol of 4'-amino-3',5' dichloro-2-Iru-[3-(4-hydroxy-phenyl)- 1 -meth.yl-propyl]methylamino]acetophenone in 300 ml of tetrahydrofuran and 50 ml of water, which was cooled with ice-water. The reaction solution was stirred for 60 minutes at room temperature, and after acidifying with 2 N hydrochloric acid, the tetrahydrofuran was distilled off in a rotation evaporator. The aqueous acidic residue obtained was extracted twice with each 250 ml of ether after addition of 8.5 N ammonia until basic.

Subsequently, the ether extracts were washed twice with each 75 ml of water and dried with magnesium sulfate. The filtrate was evaporated in a rotation evaporator and the obtained evaporation residue was purified over silica gel 60 (Macherey and Nagel, 70-230 mesh-ASTM). As eluent a mixture of methylene chloride:methanol=30:1 was used. The residue, which was obtained after fractionation and evaporation in a rotation evaporator, crystallized after addition of a small amount of previously prepared compound. The obtained diastereoisomeric crystals in a 1:1 mixture were recrystallized from methyllene chloride.

M.p.: 112-1150C.

Example 4 1 -(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-methoxy-phenyl)-1 -methyl-propyl] methyl aminojethanol 0.02 mol of 1 -(4-amino-3,5-dichloro-phenyl)-2-[N-[3-(4-hydroxyphenyl)- 1-methyl- propyl]methylamino]ethanol were dissolved in 22 ml of 1 N sodium hydroxide solution and 10 ml of water. To this solution were dropped under stirring and cooling with ice-water 0.022 mol of dimethyl sulfate and the reaction solution was stirred after addition of 50 ml of tetrahydrofuran for 20 hours at room temperature.Subsequently, 100 ml of ether were added, the organic phase was separated, washed with 50 ml of 0.5 N sodium hydroxide solution and thrice with 75 ml portions of water, and dried over magnesium sulfate. the organic phase was evaporated in a rotation evaporator and the residue was purified over silica gel 60 (Macherey and Nagel, 70-230 mesh, ASTM) (eluent:methylene chloride:methanol=30:1). The obtained oily evaporation residue was liberated from the solvent residues in vacuo over sulfuric acid. The oil obtained was a 1:1 mixture of the diastereoisometric racemates.

IR spectrum (methylene chloride): OH 3200-3500 cm-' broad (below NH2) NH2 3480+3390 cm~' CH2 2930, 2850 cam~' OCH3 2830 cm- N-alkyl 2800 cam~' C=C 1580, 1510, 1485 cm-l C=C+NH2 deformation 1620 cam~' UV spectrum (ethanol):: A max. 244 nm (0.27) 280 nm (0.08) 300 nm (0.08) Example 5 1 -(4-Ethoxycarbonyla mino-3-cyano-5-fluoro-phenyl}-2-[N-[3-(4-methoxyphenyl)-propyl]- amino]ethanol 0.5 g of celite and afterwards 2.5 g (0.01 mol) of 4'-ethoxycarbonylamino-3'-cyano-5'-fluoro- acetophenone were added in portions to a solution of 1.16 g (0.01 mol) of selenium dioxide in 12 ml of dioxan and 0.7 ml of water at 600C under stirring. Subsequently, the reaction mixture was refluxed for 4 hours and the undissolved solids were filtered off. Into this solution were dropped after cooling and external cooling with ice, 2.01 g (0.01 mol) of 3-(4-methoxy-phenyl)-propylamine hydrochloride and 1.01 g (0.01 mol) of triethylamine, dissolved in 12 ml of ethanol.The solution containing the crude 4' ethoxycarbonylamino-3'-cyano-5"-f I uoro-phenyl-glyoxylidene-3-(4-methoxy-phenyl)-propylamine, was reacted in portions under stirring and cooling with ice with 1.5 g of sodium borohydride and allowed to stand overnight at room temperature. Subsequently, the excess sodium borohydride was destroyed with acetone, the reaction mixture was evaporated in vacuo to a small volume, mixed with water, and extracted with methylene chloride. The methylene chloride solution was washed with water, dried with sodium sulfate, and evaporated in vacuo to dryness. The remaining oily residue was chromatographed over 200 g of silica gel (eluent:methylene chloride:methanol=20:1 ). The fractions containing the desired compound were evaporated and a colourless crystalline product was obtained.

M.p.: 111112 C.

Example 6 1 -(4-Ethoxycarbonylamino-3-cyano-5-fluoro-phenyl)-2-[N-[3-(4-methoxy-phenyi)-propyl]- methylamino]ethanol 1 5 g (0.06 mol) of 4'-ethoxywarbonylamino-3'-cyano-5'-fluoroacetophenone were added in portions at 600C to a solution of 6.6 g (0.06 mol) of selenium dioxide in 60 ml of dioxan and 2 ml of water whilst stirring. Subsequently, the reaction mixture was refluxed for 4 hours, then diluted with 100 ml of tetrahydrofuran and filtered off from the undissolved solids. 10.7 g (0.06 mol) of N-[3-(4 methoxy-phenyl)-propyl]methylamine, dissolved in 100 ml of tetrahydrofuran, were added to this solution of 4'-ethoxywarbonylamino-3'-cyano-5'-fluoro-phenylglyoxal after cooling at room temperature.The solution obtained was mixed in portions with 8 g (0.13 mol) of sodium cyanoborohydride, the solution being kept at pH 6 by dropwise addition of 2 N hydrochloric acid. The reaction mixture was allowed to stand overnight at room temperature, mixed with 5 g of sodium borohydride and again allowed to stand at room temperature for 5 hours. After destroying the excess sodium borohydride with acetone, the reaction mixture was diluted with water and extracted with methylene chloride. The methylene chloride solution was washed with water, dried over sodium sulfate, and evaporated in vacuo to dryness. The remaining oily residue was chromatographed over 70G g of silica gel with ethyl acetate as eluent. The fractions containing the desired compound were combined, evaporated and in vacuo at 400C the remaining solvent was removed from the oil obtained.

IR spectrum (methylene chloride): OH 3600cm-' NH 3400 cm-' CH2 2930 cm-1 OCH3 2830 cm-' N-alkyl 2800 cm-t CN 2220cm-1 NHCOOC2Hs 1735 cm-t UV spectrum (ethanol): A max. 228 nm (shoulder; 0.19) 240 nm (shoulder; 0.12) 285 nm (0.06) UV spectrum (ethanol+KOH): A max. 223 nm (shoulder; 0.39) 253-265 nm (shoulder; 0.1) 318 nm (0.06) Example 7 N-{2-(4-Amino-3-bromo-phenyl)-ethyl]-N-[3-(4-methoxy-phenyl)-propyl] methyla mine Di hydrochloride 2.9 g (0.077 mol) of lithium aluminium hydride were suspended in a nitrogen atmosphere in 100 ml of absolute tetrahydrofuran.A solution of 14.4 g (0.031 mol) of 4-amino-3,5-dibromo-N-[3-(4methoxy-phenyl)-propyl]-N-methyl-phenylacetamide in 100 ml of absolute tetrahydrofuran was dropped thereto whilst stirring at room temperature. Subsequently, the reaction mixture was refluxed for 1 hour, the excess lithium aluminium hydride was decomposed with ethyl acetate and water, 10 N sodium hydroxide solution was added dropwise until the inorganic material precipitated as a granulate.

The supernatant tetrahydrofuran phase was decanted, dried over sodium sulfate, and evaporated in a rotation evaporaton The evaporation produce was chromatographed over silica gel (eluent:methylene chloride:methanol=1 9:1) (Macherey and Nagel, 70-230 mesh, ASTM). The fractions containing the desired product were combined and evaporated. The oil obtained was dissolved in littie absolute ethanol and by means of ethanolic hydrochloric acid and addition of ether, the crystalline dihydrochloride was prepared.

M.p.: 168-171 0C (decomp.).

Example 8 N-[2-(4-Amino-3,5-dibromo-phenyl)-ethyl]-N-[4-(4-methoxy-phenyl)-butyl] methylamine 2.9 g (0.077 mol) of lithium aluminium hydride were suspended, in a nitrogen atmosphere, in 100 ml of absolute teftahydrofuran. A solution of 15.0 g (0.031 mol) of 4-amino-3,5-dibromo-N-[4-(4 methoxy-phenyl)-butyl]-N-methyl-phenylacetamide in 100 ml of absolute tetrahydrofuran was added thereto whilst stirring at room temperature. Subsequently, the reaction mixture was refluxed for 1 hour, the excess lithium aluminium hydride was decomposed with ethyl acetate and water, and 10N sodium hydroxide solution was added until the inorganic material precipitated as a granulate.The supernatant tetrahydrofuran phase was decanted, dried over sodium sulfate, and evaporated in a rotation evaporator. The evaporation product was chromatographed over silica gel (Macherey and Nagel, 70- 230 mesh, ASTM) with methylene chloride:methanol=1 9:1 as eluent. The fractions containing the desired product were combined and evaporated. The oil obtained was liberated in vacuo at 400C from the solvent residues.

IR spectrum (methylene chloride): NH2 3380+3470 cm~ N-alkyl 2790 cm-l OCH3 2830 cam~' aliphat. CH2 2850+2930 cm-' C=C 1610 cam~' UV spectrum (ethanol): A max. 246 nm (0.24) 281 nm (0.08) 305 nm (0.09).

Example 9 N-[2-(4-Amino-3-chloro-5-cyano-phenyl )-ethyl]-N-[3-(4-methoxyphenyl)-propyl] methyla mine 6.6 g (0.014 mol) of 1 -(ethoxycarbonyloxy)-1 -(4-amino-3-chloro-5-cyano-phenyl)-2-[N-[3-(4- methoxy-phenyl)-propyl]methylamino]ethane were dissolved in 70 ml of isopropanol and stirred overnight with 5.5 g (0.14 mol) of sodium borohydride at room temperature. The solution obtained was evaporated to dryness and taken up in 100 ml of water. The excess sodium borohydride was destroyed with 50 ml of 2 N hydrochloric acid. Subsequently, the reaction mixture was basified with 100 ml of 2 N ammonia, and extracted twice with 1 50 ml of ethyl acetate. The organic phase was dried with magnesium sulfate, and evaporated.The oil obtained was chromatographed over silica gel (Macherey and Nagel, 70-230 mesh, ASTM) with methylene chloride/methanol=1 9:1 as eluent. The fractions which contained the desired compound were combined, and evaporated. The oil obtained was liberated in vacuo at 400C from the solvent residues.

IR spectrum (methylene chloride): NH2 3400+3500 cm~' N-alkyl 2800 cam~' aliphat. CH2 2860+2940 cam~' aromat. C=C 1600 cm-' NH2 deformation 1625 cm-' UV spectrum (ethanol): A max. 244 nm (0.23) 278 nm (0.06) 330 nm (0.13).

Example 10 N-[2-(4-Amino-3-chloro-5-cyano-phenyl)-ethyl]-N-[3-(4-methoxyphenyl)-propyl]methylamine 1.3 g (0.0027 mol) of 1 -(4-amino-3-chloro-5-cyano-phenyl)-2-[N-[3-(4-methoxy-phenyl)- propyl]methylamino]ethyl iodide were dissolved in 30 ml of hexamethyl phosphoric acid triamide. 0.25 g (0.004 mol) of sodium cyanoborohydride were added thereto, and the reaction solution was subsequently heated for 3 hours up to 700 C. After cooling, the reaction mixture was diluted with 100 ml of water, and extracted with ether. The ethereal solution was washed with water, dried over sodium sulfate, and evaporated to dryness in vacuo. The remaining oily residue was chromatographed over silica gel (eluent:methylene chloride:methanol=20:1).The oily evaporation residue obtained was liberated in vacuo from the solvent residues.

Mass spectrum: found M+ 357/59 Molecular weight: 357.8.

Example 11 1-(4-Amino-3-fluoro-phenyl)-2-[N-[3-[(4-methoxy-phenyl)-propyl]-methylamino]ethanol A solution of 3.9 g (0.0095 mol) of 1 -(4-amino-3-bromo-5-fluorophenyl)-2-[N-[3-(4-methoxy- phenyl)-propyl]methylamino]ethanol in 50 ml of methanol was reacted with 2 g of 1 0% Palladium/charcoal and hydrogenated in an autoclave at room temperature and a pressure of 3.5 bar.

When the theoretically calculated amount of hydrogen had been taken up, the catalyst was filtered off and the filtrate was evaporated in a rotation evaporator. The 4 g of oil thus obtained was chromatographed (Macherey and Nagel, 70-230 mesh, ASTM) with chloroform:methanol=1 9:1 as eluent. The fractions containing the desired compound were combined and evaporated. The oil obtained was dissolved in isopropanol and the hydrochloride was precipitated with isopropanolic hydrochloric acid and ethyl acetate. The crystals were filtered off with suction, washed with little cold isopropanol and dried in vacuo.

M.p.: 1 100C (decomp.).

Example 12 1-(4-Ethoxycarbonylamino-3-bromo-phenyl)-2-[N-[4-(4-methoxyphenyl)-butyl]methyl amino]ethanol 1.5 ml (0.015 mol) of ethyl chloroformate were added under ice-cooling at 0 C to a solution of 5.1 g (0.0125 mol) of 1-(4-amino-3-bromo-phenyl)-2-[N-[4-(4-methoxy-phenyl)-butyl]methylamino]- ethanol in 40 ml of absolute pyridine. The solution obtained was kept over night at +40C in the refrigerator. Subsequently, the pyridine was distilled off in a rotation evaporator at 500 C. The oil obtained was dissolved in 100 ml of methylene chloride, and washed twice with 100 ml of water. The organic phase was dried over sodium sulfate, filtered, and evaporated in a rotation evaporator.The oil obtained was chromatographed over silica gel (Macherey and Nagel, 70-230 mesh, ASTM) with methylene chloride:methanol=9:1 as eluent. The fractions containing the desired compound were combined and evaporated. The oil obtained was liberated in vacuo at 40 C from the solvent residues.

IR spectrum (methylene chloride): OH 3610 cm-' NH 3400 cm- OCH3 2830 cm- N-alkyl 2800 cm-' aliphat. CH2 2860+2940 cm-' C=O 1735 cm- aromat. C=C 1610 cm- UV spectrum (ethanol): # max. 224 nm (0.42) 240 nm (0.29) 280 nm (0.04) Example 13 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4-hydroxyphenyl)-1-methyl-propyl]methylamine 0.012 mol of N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4-hydroxy-phenyl)-1 -methylpropyl]amine were dissolved in 13 ml of 1 N sodium hydroxide solution. Whilst cooling with ice-water 0.014 mol of dimethyl sulfate were added dropwise to this solution. After a short time an oily reaction product precipitated, which was dissolved by addition of 1 50 ml of tetrahydrofuran.The reaction solution was stirred for 24 hours at room temperature and subsequently extracted twice with 1 50 ml portions of ether. The organic extracts were washed with water, dried over magnesium sulfate and evaporated in vacuo. The evaporation residue obtained was purified over silica gel (Poiygosil 601525; Macherey and Nagel) with methylene chloride:methanol:conc. ammonia=19:1:0.1 as eluent.

The oily evaporation residue was removed from the solvent residues in vacuo over potassium hydroxide.

IR spectrum (methylene chloride): OH 3580 cm- NH2 3480+3380 cm~ CH2 2930,2960, 2850 cm- N-alkyl 2790 cm- C=C 1580,1510, 1480cm1 C=CtNH2 deformation 1610 cm- UV spectrum (ethanol): A max. 240 nm (0.26; shoulder) 288 nm (0.08) 301 nm (0.08) UV spectrum (ethanol+KOH): A max. 241 nm (0.56) 299 nm (0.17).

Example 14 1 -(4-Amino-3,5-dichloro-phenyl)-2-[N-[2-(4-methoxy-phenylsulfinyl)-ethyl]methyl- amino]ethanol 7.0 g of 1 -(4-amino-3,5-dichloro-phenyl)-2-[N-[2-(4-methoxyphenylsulfenyl)-ethyl]methyl- aminolethanol were dissolved in 100 ml of glacial acetic acid and mixed with 2.0 g of 30% hydrogen peroxide whilst stirring at room temperature. Stirring was continued overnight at the same temperature, and then the solvent was evaporated in vacuo. The residue was taken up in water and mixed with potassium carbonate until basic. The reaction mixture was extracted with dichloromethane, the organic phase was washed with water, dried with magnesium sulfate, and evaporated in vacuo.

The residue was purified chromatographically (column: 40x200 mm; silica gel 60, of Messrs. E. Merck, grain size: 0.064.2 mm, methylene chloride:methanol=50:1). After evaporating the desired fractions in vacuo, the title compound was obtained as an oil.

IR spectrum (methylene chloride): NH2 3390+3480 cm-' CH2 2940 cm-1 OCH3 2840 cm-' N-alkyl 2800 cm- C=C 1590,1510+ 1480 cm- S=O 1040 cm- (shoulder) UV spectrum (ethanol): # max. 244 nm (0.54) 300 nm (0.07; shoulder) Example 15 1 -(4-Amino-3,5-dichloro-phenyl)-2-[N-[2-(4-methoxy-phenylsulfonyl)-ethyl] methyl amino]ethanol 7.0 g of 1 -(4-amino-3,5-dichloro-phenyl)-2-[N-[2-(4-methoxyphenylsulfenyl)-ethyl]methyl- amino]ethanol were converted to the sulfinyl derivative as described in Example 14.The residue (4.7 g) obtained after evaporating the dichloromethane extract was dissolved in 100 ml of dioxan and 30 ml of water and mixed with 4.0 g of magnesium sulfate 2.5 g of powdered potassium permanganate were added in corresponding portions under stirring. After the addition was finished, stirring was continued for 2 hours and the insoluble solids were filtered off over celite. After removing the dioxan in vacuo the residue was distributed between dichloromethane and water. The evaporation residue of the dried organic phase was purified twice by chromatography (1. column: 60x300 mm, Al203 II neutral, methylene chloride:tetrahydrofuran=5:1 ; 2. column: 35x300 mm, silica gel 60, Messrs. E. Merck, grain size: 0.015-0.025 mm, dichloromethane, 8.5 bar).After evaporating the desired fractions in vacuo the title compound was obtained as an oil.

IR spectrum (methylene chloride): NH2 3395+3480 cm- CH2 2940 cm- OCH3 2840 cm- N-alkyl 2800 cm- C=C 1595, 1520+1495 cm- SO2 1150+1315 cm- UV spectrum (ethanol): A max. 241 nm (0.59) 300 nm (0.09).

Example 16 1 -(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-hydroxy-phenyl-propyl] methylamino]ethanol 9.2 g of 1 -(4-amino-3,5-dichloro-phenyl)-2-[N-[3-(4-benzyloxyphenyl)-propyl]- methylamino]ethanol were dissolved in 150 ml of methanol. The solution was mixed with 1 g of 5% palladium/charcoal and hydrogenated at room temperature under a hydrogen pressure of 5 bar. After taking up the calculated amount of hydrogen, the catalyst was filtered off, the solution was evaporated to dryness in a rotation evaporator, and the oily residue was chromatographed over silica gel with methylene chloride: methanol=20:1 as eluent. The fractions containing the desired compound were combined, evaporated and the remaining oil was liberated from the solvent residues in vacuo at 400 C.

IR spectrum (methylene chloride): OH 3580 cm- NH2 3395+3495 cm- N-alkyl 2800 cm-1.

Example 17 1-(4-Amino-3-bromo-phenyl)-2-[N-[4-(4-methoxy-phenyl)-butyl]-methylamino]ethanol 3 g of 1 -(4-acetami no-3-bro mo-phenyl )-2-[N-[4-(4-methoxy-phenyl)-butyl]methyl- amino]ethanol were refluxed in 100 ml of semi-concentrated hydrochloric acid for 1 hour. After cooling, the reaction mixture was basified with 10 N sodium hydroxide solution, extracted with methylene chloride, the methylene chloride solution was washed with water, dried over sodium sulfate, and evaporated in a rotation evaporator to dryness. The remaining oil was chromatographed over silica gel with methylene chloride:methanol=20:1 as eluent. From the fractions containing the desired compound, the title compound was obtained by evaporation in vacuo at 400 C. Oil.

IR spectrum (methylene chloride): OH 3590 cm-1 NH2 3380+3470 cm-t N-alkyl 2800 cm- OCH3 2830 cm- aliph. CH2 2850+2930 cm- aromat. C=C 1620 cm- UV spectrum (ethanol): A max. 224 nm (0.20) 243 nm (0.14) 280 nm (0.04) 300 nm (0.04) Example 18 1-(4-Amino-3-cyano-5-fluoro-phenyl)-2-[N-[3-(4-methoxy-phenyl)-propyl]methylamino]ethanol Prepared analogously to Example 1 from 4'-amino-3'-cyano-5'-fluoro-2-[N-[3-(4-methoxy- phenyl)propyl]methylamino]acetophenone and sodium borohydride in 90% methanol.

IR spectrum (methylene chloride): OH 3590 cm-' NH2 3400+3490 cm- CH2 2850+2940 cm- OCH3 2830 cm- N-alkyl 2800 cm- C#N 2210 cm- NH2 deformation 1635 cm-t aromat. C=C 1610 cm- UV spectrum (ethanol): A max. 242 nm (0.3) 325 nm (0.14).

Example 19 1 -(4-Amino-3-bromo-5-cyano-phenyl)-2-[N-[3-(4-methoxy-phenyl)-propyl] methyl amino]ethanol Prepared analogously to Example 1 from 4'-amino-3'-bromo-5'-cyano-2-[N-[3-(4-methoxy- phenyl)propyl]methylamino]acetophenone and sodium borohydride in 80% methanol.

IR spectrum (methylene chloride): OH 3590 cm- weak NH2 3400+3480 cm- CH2 2850+2930 cm- C#N 2200 cm- C=C 1640 cm- UV spectrum (ethanol): A max. 243 nm (0.20) 280 nm (0.04) 334 nm (0.12).

Example 20 1 -(4-Amino-3,5-dibromo-phenyl)-2-[N-[3-(4-methoxy-phenyl)-propyl] methyla mino]ethanol Prepared analogously to Example 1 from 4'-amino-3',5'-dibromo-2-[N-[3-(4-methoxy-phenyl)- propyl]methylamino]acetophenone and sodium borohydride in 80% methanol.

IR spectrum (methylene chloride): OH 3590 cm- NH2 3380+3460 cm- N-alkyl 2800 cm- OCH3 2830 cm- aliphat. CH2 2850+2940 cm- C=C 1610 cm- UV spectrum (ethanol): # max. 244 nm (0.16) 303 nm (0.06).

Example 21 1-(4-Amino-3,5-dichloro-phenyl-2-[N-[1,1-dimethyl-3-(4-methoxyphenyl)-propyl]amino]ethanol Prepared analogously to Example 13 from 1 -(4-amino-3,5-dichlorophenyl)-2-[N-[1,1-dimethyl- 3-(4-hydroxy-phenyl)-propyl]amino]ethanol, tetrahydrofuran, sodium hydroxide solution and dimethylsulfate. Oil.

IR spectrum (methylene chloride): OH 3600 cm-' NH2 3390+3490 cm-' CH2 2860+2960 cm- OCH3 2830 cm- C=C 1580+1620 cm- UV spectrum (ethanol): A max. 243 nm (0.23) 280 nm (0.08) 300 nm (0.08) Example 22 1 -(4-Amino-3,5-dichloro-phenyl)-2-[N-[(1,1 -dimethyl-3-(4-methoxyphenyl)-propyl] methylamino] ethanol Prepared analogously to Example 13 from 1 -(4-amino-3,5-dichlorophenyl)-2-[N-[1,1-dimethyl- 3-(4-hydroxyphenyl)-propyl]aminoethanol], tetrahydrofuran, sodium hydroxide solution, and dimethylsulfate. Oil.

Calc.: C 61.31 H 6.86 Cl 17.24 N 6.81 Found: 61.13 6.99 17.25 6.75 Example 23 1 -(4-Amino-3-chloro-5-trifluoromethyl-phenyl )-2-[N-[3-(4-methoxyphenyl)-propyl] methylamino]ethanol Prepared analogously to Example 1 from 4'-amino-3'-chloro-5'-trifluoromethyl-2-[N-[3-(4- methoxy-phenyl)-propyl]methylamino]acetophenone and sodium borohydride in 80% methanol.

IR spectrum (methylene chloride): OH 3590 cm- NH2 3410+3510 cm- N-alkyl 2800 cm- OCH3 2830 cm-' aliphat. CH2 2850+2940 cm-' C=C 1630 cm- UV spectrum (ethanol): A max. 225 nm (0.36) 245 nm (0.31) 280 nm (0.05) 310 nm (0.1).

Example 24 1-(3,5-Dichloro-4-hydroxy-phenyl)-2-[N-[3-(4-methoxy-phenyl)propyl]methylamino]ethanol Prepared analogously to Example 1 from 3',5'-dichloro-4'-hydroxy-2-[N-[3-(4-methoxy-phenyl)- propyl]methylamino]acetophenone and sodium borohydride in 80% methanol.

M.p.: 156-1570C.

Example 25 1-(3,5-Dibromo-4-hydroxy-phenyl)-2-[N-[3-(4-methoxy-phenyl)-propyl]methylamino]ethanol Prepared analogously to Example 1 from 3',5'-dibromo-4'-hydroxy-2-[N-[3-(4-methoxy-phenyl)- propyl]methylamino]acetophenone and sodium borohydride in 80% methanol.

M.p. of the hydrochloride: 1 59-1 620C.

Example 26 1-(4-Amino-3-bromo-5-fluoro-phenyl)-2-[N-[3-(4-methoxy-phenyl)propyl]methylamino]ethanol Prepared analogously to Example 1 from 4'-amino-3'-bromo-5'-fluoro-2-[N-[3-(4-methoxy- phenyl)-propyl]methylamino]acetophenone and sodium borohydride in 80% methanol.

M.p. of the hydrochloride (amorphous): from 600C.

Example 27 1-(4-Amino-3-chloro-5-fluoro-phenyl)-2-[N-[3-(4-methoxy-phenyl)propyl]methylamino]ethanol Prepared analogously to Example 1 from 4'-amino-3'-chloro-5'-fluoro-2-[N-[3-(4-methoxy- phenyl)-propyl]methylamino]acetophenone and sodium borohydride in 80% methanol.

M.p. of the hydrochloride: 103-1 080C (decomp.).

Example 28 1 -(4-Amino-3-chloro-5-cyano-phenyl)-2-[N-[3-(4-methoxy-phenyl)-propyl] methylamino]ethanol Prepared analogously to Example 1 from 4'-amino-3'-chloro-5'-cyano-2-[N-[3-(4-methoxy- phenyl)-propyl]methylamino]acetophenone and sodium borohydride in 80% of methanol.

IR spectrum (methylene chloride): OH 3590 cm- NH2 3400+3500 cm- N-alkyl 2800 cm- OCH3 2830 cm- aliphat. CH2 2850+2940 cm- C#N 2210 cm- C=C 1625 cm- UV spectrum (ethanol: A max. 245 nm (0.26) 278 nm (0.06) 332 nm (0.16).

Example 29 1-(4-Amino-3-chloro-5-nitro-phenyl)-2-[N-[3-(4-methoxy-phenyl)-propyl]methylamino]ethanol Prepared analogously to Example 1 from 4'-amino-3'-chloro-5'-nitro-2-[N-[3-(4-methoxy- phenyl)-propyl]methylamino]acetophenone and sodium borohydride in 80% methanol.

IR spectrum (methylene chloride): OH 3590 cm- NH2 3390+3500 cm- N-alkyl 2800 cm- OCH3 2830 cm- aliphat. CH2 2850+2940 cm -1 C=C 1630 cm- NO2 1330+1515 cm- UV spectrum (ethanol): A max. 227 nm (0.64) 280 nm (0.16) 400 nm (0.12) Example 30 1-(4-Amino-3-chloro-phenyl)-2-[N-[3-(4-methoxy-phenyl)-propyl]-methylamino]ethanol Prepared analogously to Example 1 from 4'-amino-3'-chloro-2-[N-[3-(4-methoxy-phenyl)- propyl]methylaminoacetophenone and sodium borohydride in 80% methanol.

IR spectrum (methylene chloride): OH 3600 cm- NH2 3380+3470 cm- N-alkyl 2800 cm- OCH3 2830 cm- aliphat. CH2 2850+2940 cm- C=C 1620 cm- UV spectrum (ethanol): A max. 225 nm (0.44) 243 nm (0.36) 280 nm (0.09) 295 nm (0.08) Example 31 1-(4-Amino-3-bromo-phenyl)-2-[N-[3-(4-methoxy-phenyl)propyl]-methylamino]ethanol Prepared analogously to Example 1 from 4'-amino-3'-bromo-2-[N-[3-(4-methoxy-phenyl)propyl]methylamino]acetophenone and sodium borohydride in 80% methanol.

M.p. of the dihydrochloride: 1370C (decomp.).

Example 32 1-(4-Amino-3,5-dicyano-phenyl)-2-[N-[3-(4-methoxy-phenyl)-propyl]-methylamino]ethanol Prepared analogously to Example 1 from 4'-amino-3',5'-dicyano-2-[N-[3-(4-methoxy-phenyl)- propyl]methylamino]acetophenone and sodium borohydride in 80% methanol.

M.p. of the hydrochloride: 167-1 700C.

Example 33 1 -(4-Amino-3-bromo-phenyl)-2-[N-[4-(4-methoxy-phenyl)-butyl]-methylamino]ethanol Prepared analogously to Example 1 from 4'-amino-3'-bromo-2-[N-[4-(4-methoxy-phenyl)butyl]methylamino]acetophenone and sodium borohydride in 80% methanol.

IR spectrum (methylene chloride): OH 3590 cm- NH2 3380+3470 cm- N-alkyl 2800 cm- OCH3 2830 cm- aliphat. CH2 2850+2930 cm- C=C 1620 cm- UV spectrum (ethanol): A max. 224 nm (0.44) 243 nm (0.28) 280 nm (0.08) 300 nm (0.06).

Example 34 1-(4-Amino-3-bromo-phenyl)-2-[N-[2-(4-methoxy-phenyl)-ethyl]methylamino]ethanol Prepared analogously to Example 1 from 4'-amino-3'-bromo-2-[N-[2-(4-methoxy-phenyl)ethyl]methylamino]acetophenone and sodium borohydride in 80% methanol.

IR spectrum (methylene chloride): OH 3590 cm- NH2 3380+3470 cm- N-alkyl 2800 cm- OCH3 2830 cm- aliphat. CH2 2840+2940 cm- C=C 1620 cm- UV spectrum (ethanol): A max. 225 nm (0.43) 243 nm (0.36) 280 nm (0.08) 296 nm (0.08).

Example 35 1 -(4-Amino-3,5-dichloro-phenyl)-2-[N-[4-(4-methoxy-phenyl)butyl] methylemino]ethanol Prepared analogously to Example 1 from 4'-amino-3',5'-dichloro-2-[N-[4-methoxy-phenyl)- butyl]methylamino]acetophenone and sodium borohydride in 80% methanol.

IR spectrum (methylene chloride): OH 3590 cm- NH2 3390+3490 cm- N-alkyl 2800 cm- OCH3 2830 cm- aliphat. CH2 2850+2930 cm- C=C 1610 cm- UV spectrum (ethanol): A max. 245 nm (0.25) 320 nm (0.48).

Example 36 1 -(4-Amino-3-bromo-5-cyano-phenyl )-2-[N-[4-(4-methoxy-phenyl)butyl] methylamino]ethanol Prepared analogously to Example 1 from 4'-amino-3'-bromo-5'-cyano-2-[N-[4-(4-methoxy- phenyl)-butyl]methylamino]acetophenone and sodium borohydride in 80% methanol.

IR spectrum (methylene chloride): OH 3590 cm- NH2 3390+3490 cm- N-alkyl 2800 cm- OCH3 2830 cm- aliphat. CH2 2850+2930 cm- C#N 2210 cm- C=C 1620 cm- UV spectrum (ethanol: A max. 245 nm (0.27) 278 nm (0.08) 330 nm (0.15).

Example 37 1 -(4-Amino-3-bromo-5-cyano-phenyl)-2-[N-[2-(4-methoxy-phenyl)-ethyl] methylamino]ethanol Prepared analogously to Example 1 from 4'-amino-3'-bromo-5'-cyano-2-[N-[2-(4-methoxy- phenyl)-ethyl]methylamino]acetophenone and sodium borohydride in 80% methanol.

IR spectrum (methylene chloride): OH 3590 cm- NH2 3390+3490 cm- N-alkyl 2800 cm- OCH3 2830 cm- aliphat. CH2 2850+2950 cm- C#N 2210 cm- C=C 1620 cm- UV spectrum (ethanol): A max. 245 nm (0.25) 277 nm (0.09) 331 nm (0.10).

Example 38 1 -(4-Amino-3,5-dichloro-phenyl)-2-[N-[2-(4-methoxy-phenyl)-ethyl] methylamino]ethanol Prepared analogously to Example 1 from 4'-amino-3',5'-dichloro-2-[N-[2-(4-methoxy-phenyl)- ethyl]methylamino]acetophenone and sodium borohydride in 80% methanol.

IR spectrum (methylene chloride): OH 3590 cm- NH2 3390+3490 cm- N-alkyl 2800 cm- OCH3 2830 cm- aliphat. CH2 2850+2930 cm- C=C 1610 cm- Example 39 1 -(4-Amino-3-chloro-5-cyano-phenyl)-2-[N-[4-(4-methoxy-phenyl)butyl] methylamino]ethanol Prepared analogously to Example 1 from 4'-amino-3'-chloro-5'-cyano-2-[N-[4-(4-methoxy- phenyl)-butyl]methylamino]acetophenone and sodium borohydride in 80% methanol.

IR spectrum (methylene chloride): OH 3590 cm- NH2 3400+3500 cm- N-alkyl 2800 cm- OCH3 2830 cm- aliphat. CH2 2850+2930 cm- C#N 2210 cm- C=C 1625 cm- UV spectrum (ethanol): A max. 245 nm (0.23) 280 nm (0.05) 332 nm (0.13).

Example 40 1 -(4-Amino-3-chloro-5-cyano-phenyl)-2-[N-[2-(4-methoxy-phenyl)-ethyl] methyla mino] ethanol Prepared analogously to Example 1 from 4'-amino-3'-chloro-5'-cyano-2-[N-[2-(4-methoxy- phenyl)-ethyl]methylamino]acetophenone and sodium borohydride in 80% methanol.

IR spectrum (methylene chloride): OH 3590 cm- NH2 3390+3490 cm- N-alkyl 2800 cm-' OCH3 2830 cm-' CH2 2850+2940 cm-' C#N 2210 cm- C=C 1620 cm- UV spectrum (ethanol): A max. 245 nm (0.24) 280 nm (0.04) 332 nm (0.13).

Example 41 1 -(4-Amino-3,5-dichloro-phenyl )-2-[N-[2-(4-methoxy-phenylsulfenyl)-ethyl] methyl amino]ethanol Prepared analogously to Example 1 from 4'-amino-3',5'-dichloro-2-[N-[2-(4-methoxy-phenyl- sulfenyl)-ethyl]methylamino]acetophenone and sodium borohydride in tetrahydrofuran:water:methanol=25:5.10. Oil.

IR spectrum (methylene chloride): OH 3200-2500 cm- (below NH2) NH2 3480+3390 cm- CH2 2940 cm- N-alkyl 2800 cm- OCH3 2830 cm- C=C 1580+1490 cm- UV spectrum (ethanol): A max. 230 nm (0.58; shoulder) 245 nm (0.54) 298 nm (0.14) Example 42 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-[2-(4-methoxy-phenoxy)ethyl]methylamino]ethanol Prepared analogously to Example 1 from 4'-amino-3',5'-dichloro-2-[N-[2-(4-methoxy-phenoxy)- ethyl]methylamino]acetophenone and sodium borohydride in tetrahydrofuran: water:methanol=15:5:3. Oil.

IR spectrum (methylene chloride): OH 3200-3500 cm- (below NH2) NH2 3480+3390 cm- CH2 2940 cm- N-alkyl 2790 cm- OCH3 2830 cm- C=C 1580, 1505+1485 cm- C-O-aryl 1250 cm- UV spectrum (ethanol): A max. 230 nm (0.32; shoulder) 244 nm (0.26; shoulder) 294 nm (0.12).

Example 43 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-methoxy-phenyl)-propyl]amino]propanol-(1) Prepared analogously to Example 1 from 4'-amino-3',5'-dichloro-2-[N-[3-(4-methoxy-phenyl)- propyl]amino]propiophenone and sodium borohydride.

M.p. of the hydrochloride:201 -202"0 (decomp.).

Example 44 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-methoxy-phenyl)propyl]-2-propylamino]ethanol Prepared analogously to Example 1 from 4'-amino-3',5'-dichloro-2-[N-[3-(4-methoxy-phenyl)- propyl]-2-propylamino]acetophenone and sodium borohydride. Oil.

IR spectrum (methylene chloride): OH 3600 cm- NH2 3400+3490 cm- OCH3 2830 cm- UV spectrum (ethanol): A max. 243 nm (0.13) 280 nm (0.03) 300 nm. (0.03) Example 45 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-methoxy-phenyl)propyl]ethylamino]ethanol Prepared analogously to Example 1 from 4'-amino-3',5'-dichloro-2-[N-[3-(4-methoxy-phenyl)- propyl]ethylamino]acetophenone and sodium borohydride.

IR spectrum (methylene chioride): OH 3600 cm-' NH2 3395+3490 cm-' OCH3 2830 cm- UV spectrum (ethanol): A max. 243 nm (0.13) 280 nm (0.04) 300 nm (0.04).

Example 46 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-methoxy-phenyl)propyl]propylamino]ethanol Prepared analogously to Example 1 from 4'-amino-3',5'-dichloro-2-[N-[3-(4-methoxy-phenyl)- propyl]propylamino]acetophenone and sodium borohydride. Oil.

IR spectrum (methylene chloride): OH 3600 cm-1 NHS 3395+3495 cm- OCH3 2850 cm-' UV spectrum (ethanol): A max. 245 nm (0.10) 280 nm (0.03) 300 nm (0.03) Example 47 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-methoxy-phenyl)-propyl]cyclopropylamino]ethanol Prepared analogously to Example 1 from 4'-amino-3',5'-dichloro-2-[N-[3-(4-methoxy-phenyl)- propyl]cyclopropylamino]acetophenone and sodium borohydride. Oil.

IR spectrum (methylene chloride): OH 3590 cm-' NH2 3395+3495 cm- OCH3 2850 cm-' UV spectrum (ethanol): A max. 245 nm (0.12) 280 nm (0.04) 300 nm (0.04).

Example 48 1-(4-Amino-3,5-dichloro-phenyl-2-[N-[3-(4-methoxy-phenyl)propyl]methylamino]propanol-(1).

Isomer B Prepared analogously to Example 2 from N-[3-(4-methoxy-phenyl)propyl]methylamine, 4'- amino-2-bromo-3',5'-dichloro-propiophenone, triethylamine, and sodium borohydride. Oil.

IR spectrum (methylene chloride): OH 3600+3680 cm~ NH2 3390+3490 cm- OCH3 2835+2940 cm~ aromat 1510, 1585+1610 cm- UV spectrum (ethanol): A max. 246 nm (0.14) 278 nm (0.08) 285 nm (0.08) 300 nm (0.08) NMR spectrum (CDCID2O): signal of the proton at the carbon atom 1 of the propanol part: doublet at 4.1 ppm (J=10 Hz).

Example 49 1 -(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-methoxy-phenyl)propyl] methyla mino]propanol-( I), Isomer A Prepared analogously to Example 2 from N-[3-(4-methoxy-phenyl)-propyl]methylamine, 4'- amino-3',5'-dichloro-2-bromo-propiophenone, triethylamine, and sodium borohydride.

M.p. of the hydrochloride: 178-181 OC.

NMR spectrum of the base (CDClD2O): signal of the proton at the hydrogen atom 1 of the propanol part: doublet at 4.6 ppm (J=4.5 Hz).

Example 50 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-ethoxy-phenyl)propyl]methylamino]ethanol Prepared analogously to Example 2 from 4'-amino-3',5'-dichloro-2-bromo-acetophenone, 1-(4ethoxy-phenyl)-3-methylamino-propane hydrochloride, triethylamine, and sodium borohydride. Oil.

IR spectrum (methylene chloride): OH 3590 cm- NH2 3395+3495 cm~ N-alkyl 2800 cm- UV spectrum (ethanol): A max. 245 nm (0.13) 280 nm (0.04) 300 nm (0.04).

Example 51 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-benzyloxy-phenyl)propyl]methylamino]ethanol Prepared analogously to Example 2 from 4'-amino-3',5'-dichloro-2-bromo-acetophenone, 1-(4- benzyloxy-phenyl)-3-methylamino-propane hydrochloride, triethylamine, and sodium borohydride. Oil.

IR spectrum (methylene chloride): OH 3590 cm- NH2 3395+3495 cm~ N-alkyl 2800 cm~1.

Example 52 I -(4-Am ino-3-iodo-5-fluoro-phenyl)-2-[N-[3-(4-methoxy-phenyl)-propyl] methylamino]ethanol Prepared analogously to Example 2 from 4'-amino-3'-iodo-5'-fluoro-2-bromo-acetophenone, 1 - (4-methoxy-phenyl)-3-methylamino-propane hydrochloride, triethylamine, and sodium borohydride.

Oil.

IR spectrum (methylene chloride): OH 3590 cm- NH2 3395+3495 cm- N-alkyl 2800 cm~1.

Example 53 1-(4-Amino-3-cyano-5-fluoro-phenyl)-2-[N-[3-(4-methoxy-phenyl)propyl]-2-propylamino]ethanol Prepared analogously to Example 2 from 4'-amino-3'-cyano-5'-fluoro-2-bromo-acetophenone, 1-(4-methoxy-phenyl)-3-(2-propylamino)-propane hydrochloride, and sodium borohydride. Oil.

IR spectrum (methylene chloride): OH 3600 cm- NH2 3395+3495 cm~ OCH3 2830 cm-' N-alkyl 2800 cm- C=-N 2220 cm-' Example 54 1 -(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(2-methoxy-phenyl)propyl] methylamino]ethanol Hydrochloride Prepared analogously to Example 2 from 4'-amino-3',5'-dichloro-2-bromo-acetophenone,1 -(2methoxy-phenyl)-3-methylamino-propane hydrochloride, triethylamine, and sodium borohydride.

M.p.: from 750C (by sintering).

Example 55 1 -(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(3,4-dimethoxy-phenyl)propyl] methyla mino]ethanol Prepared analogously to Example 2 from 4'-amino-3',5'-dichloro-2-bromo-acetophenone, 1 (3,4-dimethoxy-phenyl)-3-methylamino-propane hydrochloride, triethylamine, and sodium borohydride.

IR spectrum (methylene chloride): OH 3600 cm- NH2 3390+3485 cm~ OCH3 2830 cm- N-alkyl 2800 cm-' Example 56 1 -(4-Amino-3-chloro-5-trifluoromethyl-phenyl)-2-[N-[2-(4-methoxyphenyl)ethyl] methyl amino]ethanol Prepared analogously to Example 1 from 4'-amino-3'-chloro-5'-trifluoromethyl-2-[N-[2-(4methoxy-phenyl)-ethyl]methylamino]acetophenone, and sodium borohydride in 80% methanl.

IR spectrum (methylene chloride): OH 3600 cm- NH2 3410+3510 cm- N-alkyl 2800 cm- O-CH3 2830 cm~ aliphat. CH2 2850+2940 cm-' C=C 1630 cm- UV spectrum (ethanol): A max. 225 nm (0.38) 244 nm (0.34) 280 nm (0.07) 307 nm (0.10).

Example 57 1 -(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-methoxy-phenyl)propyl]amino]ethanol Hydrochloride Prepared analogously to Example 1 from 4'-amino-3',5'-dichloro-2-[N-[3-(4-methoxy-phenyl)propyl]amino]acetophenone and sodium borohydride in 90% ethanol.

M.p. of the hydrochloride: 185-1 860C (ethanol/ether).

Example 58 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-(3-phenyl-propyl)-2-propylamino]ethanol Hydrochloride Prepared analogously to Example 2 from 4'-amino-3',5'-dichloro-2-bromo-acetophenone, 1phenyl-3-(2-propylamino)-propane hydrochloride, triethylamine, and sodium borohydride.

M.p.: 124-1280C.

Example 59 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-fluoro-phenyl)-propyl]methylamino]ethanol Hydrochloride Prepared analogously to Example 2 from 4'-amino-3',5'-dichloro-2-bromo-acetophenone,1 -(4fluoro-phenyl)-3-methylamino-propane hydrochloride, triethylamine and sodium borohydride.

M.p.; 185-188 C (decomp.).

Example 60 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-hydroxy-phenyl)-1-methyl-propyl]amino]ethanol Prepared analogously to Example 4 from 4'-amino-3',5'-dichloro-2-[N-[3-(4-hydroxy-phenyl)-1- methyl-propyl]-amino]acetophenone and sodium borohydride in aqueous tetrahydrofuran. As eluent for the chromatographic purification over silica gel a mixture of dichloromethane:methanol:conc.

ammonia=19:1:0.05 was used.

(Oil: 1:1 mixture of the diastereoisomeric racemates).

IR spectrum (KBr): OH 2300-3500 cm- (broad, associated) NH2 3460+3370 cm~ CH2 2920+2960 cm~1 C=C 1580,1510+1480 cm~' UV spectrum (ethanol): ,t max. 244 nm (0.28) 280 nm (0.08) 300 nm (0.08) UV spectrum (ethanol+KOH): # max. 243 nm (0.54) 299 nm (0.15).

Example 61 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-methoxy-phenyl)-1-methyl-propyl]amino]ethanol Prepared analogously to Example 4 from 4'-amino-3',5'-dichloro-2-[N-[3-(4-methoxy-phenyl)-1 methyl-propyl]aminojacetophenone and sodium borohydride in aqueous tetrahydrofuran.

The compound was obtained as a 1:1 mixture of the diastereoisomeric racemate.

IR spectrum (methylene chloride): OH 3600 cm- NH2 3480+3390 cm~' CH2 2930 cm- OCH3 2830 cm~1 C=C 1580, 1510+1485 cm- UV spectrum (ethanol): A max. 244 nm (0.28) 280 nm (0.08) 300 nm (0.09).

Example 62 1-(4-Amino-3-cyano-5-fluoro-phenyl)-2-[N-[2-(3,4-dimethoxyphenyl)-ethyl]amino]ethanol Hydrochloride Prepared analogously to Example 5 from 4'-amino-3'-fluoro-5'-cyano-acetophenone, selenium dioxide, 2-(3,4-dimethoxyphenyl)-ethylamine, and sodium borohydride.

M.p.: 196-1 970C (decomp.).

Example 63 1-(4-Amino-3-fluoro-5-iodo-phenyl)-2-[N-[2-(3,4-dimethoxy-phenyl)ethyl]amino]ethanol Hydrochloride Prepared analogously to Example 5 from 4'-amino-3'-fluoro-5'-iodoacetophenone, selenium dioxide, 2-(3,4-dimethoxy-phenyl)-ethylamine, and sodium borohydride.

M.p.: 1 92-1 930C (decomp.).

Example 64 1-(4-Amino-3-chloro-5-fluoro-phenyl)-2-[N-[2-(3,4-dimethoxyphenyl)-ethyl]amino]ethanol Hydrochloride Prepared analogously to Example 5 from 4'-amino-3'-chloro-5'-fluoro-acetophenone, selenium dioxide, 2-(3,4-dimethoxyphenyl)-ethylamine, and sodium borohydride.

M.p.: 184-1 860C (decomp.).

Example 65 1 -(4-Amino-3-bromo-5-fluoro-phenyl)-2-[N-[2-(3,4-dimethoxy-phenyl)ethyl]amino]ethanol Hydrochloride Prepared analogously to Example -5 from 4'-amino-3'-bromo-5'-fluoroacetophenone, selenium dioxide, 2-(3,4-dimethoxy-phenyl)-ethylamine, and sodium borohydride.

M.p.: 194-195 C (decomp.).

Example 66 1 -(4-Amino-3-fiuoro-5-cyano-phenyl )-2-[N--(4-methoxy-phenyl )propyl]amino]ethanol Prepared analogously to Example 5 from 4'-amino-3'-fluoro-57-cyano-acetophenone, selenium dioxide, 3-(4-methoxy-phenyl)propylamine, and sodium borohydride.

M.p.: 119-1210C.

Example 67 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-(3-phenyl-propyl)-amino]ethanol Hydrochloride Prepared analogously to Example 5 from 4'-amino-3',5'-dichloroacetophenone, selenium dioxide, 3-phenyl-propylamine, and sodium borohydride.

M.p.:180-181 C (decomp.).

Example 68 1 -(4-Amino-3-chlo ro-5-fl uoro-phenyl)-2-[N-( 1 -methyl-2-phenoxy-ethyl)-amino]ethanol Dihydrochloride Prepared analogously to Example 5 from 4'-amino-3'-chloro-5'-fluoro-acetophenone, selenium dioxide, 1-methyl-2-phenoxy-ethylamine, and sodium borohydride.

M.p.: 1 58-1 600C (decomp.).

Example 69 1-(4-Amino-3-cyano-5-fluoro-phenyl)-2-[N-(1-methyl-2-phenoxy-ethyl)-amino]ethanol Hydrochloride Prepared analogously to Example 5 from 4'-amino-3'-cyano-5'-fluoro-acetophenone, selenium dioxide, 1 -methyl-2-phenoxy-ethylamine, and sodium borohydride.

M.p.: 178-1 840C (decomp.).

Example 70 1-(4-Amino-3-bromo-5-fluoro-phenyl)-2-[N-(1-methyl-2-phenoxy-ethyl)-amino]ethanol Dihydrochloride Prepared analogously to Example 5 from 4'-amino-3'-bromo-5'-fluoro-acetophenone, selenium dioxide, 1 -methyl-2-phenoxy-ethylamine, and sodium borohydride.

M.p.: 156-1 580C (decomp.).

Example 71 N-[2-(4-Amino-3,5-dibromo-phenyl)-ethyl]-N-[3-(4-methoxy-phenyl)propyl]methylamine Prepared analogously to Example 7 from 4-amino-3,5-dibromo-N-[3-(4-methoxy-phenyl) propyl]-N-methyl-phenyl-acetamide, and lithium aluminium hydride.

M.p. of the hydrochloride: 149-1 530C.

Example 72 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4-methoxy-phenyl)propyl] methylamine Prepared analogously to Example 7 from 4-amino-3 ,5-dichloro-N-[3-(4-methoxy-phenyl)- propyl]-N-methyl-phenyl-acetamide, and lithium aluminium hydride.

M.p. of the hydrochloride: 90--940C.

Example 73 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[2-(4-methoxyphenyl)-ethyl]methylamine Prepared analogously to Example 8 from 4-amino-3,5-dichloro-N-[2-(4-methoxy-phenyl)-ethyl]- N-methyl-phenyl-acetamide, and lithium aluminium hydride.

IR spectrum (methylene chloride): NH2 3380+3470 cm- N-alkyl 2780 cm-' OCH3 2830 cm- aliphat. CH2 2850+2930 cm- C=C 1610 cm- UV spectrum (ethanol): # max. 245 nm (0.24) 281 nm (0.08) 305 nm (0.07).

Example 74 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[4-(4-methoxy-phenyl)butyl]methylamine Prepared analogously to Example 8 from 4-amino-3,5-dichloro-N-[4-(4-methoxy-phenyl)-butyl]- N-methyl-phenyl-acetamide, and lithium aluminium hydride.

IR spectrum (methylene chloride): NH2 3380+3480 cm- OCH3 2830 cm- aliphat. CH2 2850+2930 cm-1 NH+ 2100-2500 cm- C=C 1630 cm-' UV spectrum (ethanol): max. 245 nm (0.22) 280 nm (0.07) 304 nm (0.08).

Example 75 N-[3-(4-Amino-3,5-dichloro-phenyl)-propyl]-2-(3,4-dimethoxyphenyl)-ethylamine Hydrochloride Prepared analogously to Example 7 from 3-(4-amino-3,5-dichlorophenyl)-N-[2-(3,4-dimethoxy phenyl)-ethyl]propionamide, and lithium aluminium hydride.

M.p.: 142-1450C.

Example 76 N-[3-(4-Amino-3,5-dichloro-phenyl)-propyl]-N-[2-(3,4-dimethoxyphenyl)-ethyl]methylamine Prepared analogously to Example 8 from 3-(4-amino-3,5-dichlorophenyl)-N-{2-(3,4-dimethoxy- phenyl)-ethyl]-N-methyl-propionamide, and lithium aluminium hydride. Oil.

IR spectrum (methylene chloride): NH2 3400+3500 cm~ OCH3 2835+2960 cm- NCH3 2800 cm- aromat 1510+ 1590/1615 cm~' UV spectrum (ethanol): A max. 239 nm (shoulder) 281 nm(0.11) 300 nm (0.08).

Example 77 N-[3-(4-Amino-3-bromo-phenyl)-propyl]-2-(3,4-dimethoxy-phenyl)-ethylamine Hydrochloride Prepared analogously to Example 7 from 3-(4-amino-3,5-dibromophenyl)-N-[2-(3,4-dimethoxy- phenyl)ethyl]propionamide, and lithium aluminium hydride.

M.p.: 131-1340C.

Example 78 N-[2-(4-Amino-3,5-dichloro-phenyl}-ethyl]-N-[3 -methyl-propyl]amine Prepared analogously to Example 8 from 4-amino-3,5-dichloro-N-[3(4-hydroxy-phenyl)-1- methyl-propyl]phenyl-acetamide, and lithium aluminium hydride in tetrahydrofuran. The chromatographic purification was carried out by means of medium pressure chromatography on silica gel (grain size: 0.015-0.025 mm) with methylene chloride:methanol:conc. ammonia=19:1:0.1 as eluent. Foam.

IR spectrum (methylene chloride): OH 3580 cm- NH2 3480+3385 cm- CH2 2920 cm- C=C 1580, 1510+1480 cm- UV spectrum (ethanol): A max. 242 nm (0.24: shoulder) 280 nm (0.07) 303 nm (0.08) UV spectrum (ethanol+KOH): max. 242 nm (0.53) 300 nm (0.16).

Example 79 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4-methoxy-phenyl)-1 -methyl-propyl]amine Prepared analogously to Example 8 from 4-amino-3,5-dichloro-N-[3-(4-methoxy-phenyl)-1 methyl-propyl]phenylacetamide, and lithium aluminium hydride in tetrahydrofuran. Oil.

IR spectrum (methylene chloride): NH2 3480+3385 cm~' CH2 2930 cm- OCH3 2830 cm- C=C 1580,1510+ 1485 cm~ UV spectrum (ethanol): # max. 242 nm (0.25; shoulder) 280 nm (0.07) 302 nm (0.08).

Example 80 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4-benzyloxy-phenyl)-propyl]methylamine Prepared analogously to Example 8 from 4-amino-3,5-dichloro-N-[3-(4-benzyloxy-phenyl)- propyl]-N-methyl-phenylacetamide, and lithium aluminium hydride. Oil.

IR spectrum (methylene chloride): NH2 3390+3490 cm- N-alkyl 2800 cm-' UV spectrum (ethanol): A max. 245 nm (0.10) 280 nm (0.04) 300 nm (0.04).

Example 81 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(3,4-dimethoxy-phenyl)-propyl]methylamine Prepared analogously to Example 8 from 4-amino-3,5-dichloro-N-[3-(3,4-dimethoxy-phenyl)- propyl]-N-methyl-phenylacetamide, and lithium aluminium hydride. Oil.

IR spectrum (methylene chloride): NH2 3395+3495 cm-' OCH3 2830 cm~ N-alkyl 2800 cm- UV spectrum (ethanol): max. 230 nm (shoulder; 0.18) 245 nm (shoulder; 0.12) 282 nm (0.04) 302 nm (0.03).

Example 82 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(2-methoxy-phenyl)propyl]methylamine Hydrochloride Prepared analogously to Example 7 from 4-amino-3,5-dichloro-N-[3-(2-methoxy-phenyl)- propyl]-N-methyl-phenylacetamide, and lithium aluminium hydride.

M.p.: 160-1 640 C.

Example 83 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-(3-phenyl-propyl]-methylamine Prepared analogously to Example 8 from 4-amino-3,5-dichloro-N-(3-phenyl-propyl)-N-methyl phenylacetamide, and lithium aluminium hydroxide. Oil.

IR spectrum (methylene chloride): NH2 3390+3490 cm- N-alky 2800 cm- UV spectrum (ethanol): max. 245 nm (0.12) 300 nm (0.03) Example 84 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4-methoxy-phenyl )propyl]amine Hydrochloride Prepared analogously to Example 7 from 4-amino-3,5-dichloro-N-[3-(4-methoxy-phenyl)- propyl]phenylacetamide, and lithium aluminium hydride.

M.p.: 203-205 C.

Example 85 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4-methoxy-phenyl)propyl]cyclopropylamine Prepared analogously to Example 8 from 4-amino-3,5-dichloro-N-[3-(4-methoxy-phenyl)- propyl]-N-cyclopropyl-phenylacetamide, and lithium aluminium hydride. Oil.

IR spectrum (methylene chloride): NH2 3390+3490 cm- OCH3 2830 cm-t UV spectrum (ethanol): A max. 245 nm (0.15) 280 nm (0.04) 300 nm (0.05) Example 86 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4-methoxyphenyl)-propyl]propylamine Prepared analogously to Example 8 from 4-amino-3,5-dichloro-N-[3-(4-methoxy-phenyl)- propyl]-N-propyl-phenylacetamide, and lithium aluminium hydride. Oil.

IR spectrum (methylene chloride): NH2 3390+3490 cm~ OCH3 2830 cm- N-alkyl 2800 cm-l UV spectrum (ethanol): A max. 243 nm (0.13) 280 nm (0.04) 300 nm (0.04) Example 87 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4-methoxyphenyl)-propyl]ethylamine Prepared analogously to Example 8 from 4-amino-3,5-dichloro-N-[3-(4-methoxy-phenyl)- propyl]-N-ethyl-phenylacetamide, and lithium aluminium hydride. Oil.

IR spectrum (methylene chloride): NH2 3390+3490 cm- OCH3 2830 cm~ N-alkyl 2800 cm-' UV spectrum (ethanol): A max. 243 nm (0.13) 280 nm (0.04) 300 nm (0.04) Example 88 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4-methoxy-phenyl)-propyl]-2-propylamine Prepared analogously to Example 8 from 4-amino-3,5-dichloro-N-[3-(4-methoxy-phenyl)- propyl]-N-(2-propyl)-phenylacetamide, and lithium aluminium hydride. Oil.

iR spectrum (methylene chloride): NH2 3390+3490 cm~ OCH3 2830 cm- UV spectrum (ethanol): A max. 243 nm (0.13) 280 nm (0.04) 300 nm (0.04) Example 89 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4-ethoxy-phenyl)-propyl]methylamine Prepared analogously to Example 8 from 4-amino-3,5-dichloro-N-[3-(4-ethoxy-phenyl)-propyl]- N-methyi-phenylacetamide, and lithium aluminium hydride. Oil.

IR spectrum (methylene chloride): NH2 3390+3490 cm- OCH3 2830 cm- N-alkyl 2800 cm-' UV spectrum (ethanol): A max. 245 nm (0.12) 280 nm (0.03) 300 nm (0.04) Example 90 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4-methoxy-phenyl)-1 -methylpropyl]methylamine Prepared analogously to Example 9 from 1 -ethoxywarbonyloxy-1 -(4-amino-3,5-dichloro-phenyl) 2-[N-[3-(4-methoxy-phenyl)-l -methyl-propyl]methylamino]ethane, and sodium borohydride in isopropanol. Oil.

IR spectrum (methylene chloride): NH2 3480+3380 cm- CH2 2930 cm- N-alkyl 2790 cm- OCH3 2840 cm- C=C 1580, 1510+1480 cm- Example 91 N-[2-(4-Amino-3-bromo-5-cyano-phenyl)-ethyl]-N-[4-(4-methoxy-phenyl)-butyl]methylamine Prepared analogously to Example 9 from 1 -ethoxycarbonyloxy-1 -(4-amino-3-bromo-5-cyano phenyl)-2-[N-[4-(4-methoxy-phenyl)-butyl]-methylamino]ethane, and sodium borohydride.

Analysis: Calc.: C 60.6 H 6.3 Br 19.2 N 10.1 Found: 60.5 6.1 19.2 10.1 Example 92 N-[2-(4-Amino-3-chloro-5-cyano-phenyl)-ethyl]-N-[2-(4-methoxy-phenyl)-ethyl] methyla mine Prepared analogously to Example 9 from 1 -ethoxycarbonyloxy- 1 -(4-amino-3-chloro-5-cyanophenyl-2-[n-[2-(4-methoxy-phenyl)ethyl]methylamino]ethane, and sodium borohydride.

IR spectrum (methylene chloride): NH2 3400+3490 cm- N-alkyl 3790 cm-' OCH3 2830 cm-' aliphat. CH2 2850+2940 cm-' C#N 2210 cm- C=C 1620 cm- UV spectrum (ethanol): A max. 244 nm (0.26) 280 nm (0.04) 335 nm (0.15).

Example 93 N-[2-(4-Amino-3-bromo-5-cyano-phenyl)-ethyl]-N-[3-(4-methoxy-phenyl )-propyl] methylamine Prepared analogously to Example 9 from 1 -ethoxycarbonyloxy-1 -(4-amino-3-bromo-5-cyanophenyl)-2-[N-[3-(4-methoxy-phenyl)-propyl]methylamino]ethane, and sodium borohydride.

IR spectrum (methylene chloride): NH2 3390+3490 cm- N-alkyl 3790 cm-' OCH3 3830 cm- aliphat. CH2 2850+2940 cm- C#N 2210 cm- C=C 1620 cm- UV spectrum (ethanol): # max. 244 nm (0.20) 280 nm (0.04) 334 nm (0.13).

Example 94 N-[2-(4-Am ino-3-chloro-5-cyano-phenyl)-ethyl]-N-[4-(4-methoxy-phenyl)-butyl] methyl a mine Prepared analogously to Example 9 from I -ethoxycarbonyloxy-1 -(4-amino-3-chloro-5-cyanophenyl)-2-[N-[4-(4-methoxy-phenyl)-butyl]-methylamino]ethane, and sodium borohydride.

Analysis: Calc.: C 67.5 H 7.3 Cl 9.53 N 11.25 Found: 67.5 7.14 9.65 11.34 Example 95 1-(4-Amino-3-chloro-5-trifluoromethyl-phenyl)-2-[N-[4-(4-methoxy-phenyl)-butyl]methylamino]ethanol Prepared analogously to Example 1 from 4'-amino-3'-chloro-5'-trifluoromethyl-2-[N-[4-(4- methoxy-phenyl)-butyl]methylamino]acetophenone, and sodium borohydride in 80% methanol.

IR spectrum (methylene chloride): OH 3590 cm- NH2 3410+3510 cm~ N-alkyl 2800 cm- OCH3 2830 cm- aliphat. CH2 2850+2930 cm- aromat. C=C 1630 cm-' UV spectrum (ethanol): # max. 225 nm (0.32) 245 nm (0.31) 280 nm (0.06) 308 nm (0.10).

Example 96 1-(4-Amino-3-cyano-phenyl)-2-[N-[3-(4-methoxy-phenyl)-propyl]-methyalmino]ethanol Prepared analogously to Example 11 from 1-(4-amino-3-bromo-5-cyano-phenyl)-2-[N-[3-(4- methoxy-phenyl)-propyl]methylamino]-ethanol in the presence of palladium/charcoal and hydrogen.

IR spectrum (methylene chloride): OH 3610 cm- NH2 3400+3490 cm~ N-alkyl 2800 cm- OCH3 2830 cm~ C#N 2210 cm- C=C 1630 cm- UV spectrum (ethanol): A max. 251 nm (0.31) 280 nm (0.60) 328 nm (0.12).

Example 97 N-[2-(4-Amino-3-chloro-phenyl)-ethyl]-N-[3-(4-benzyloxy-phenyl)-propyl]methylamine Prepared analogously to Example 11 from N-[2-(4-amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4- benzyloxy-phenyl)-propyl]methylamine and hydrogen. Oil.

IR spectrum (methylene chloride): NH2 3390+3490 cm~ N-alkyl 2790 cm~1.

Example 98 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4-hydroxy-phenyl)-propyl]methylamine Prepared analogously to Example 16 from N-[2-(4-amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4- benzyloxy-phenyl)-propyl]methylamine and hydrogen. Oil.

IR spectrum (methylene chloride): OH 3580 cm- NH2 3390+3490 cm~ N-alkyl 2800 cm~1.

Example 99 1-(4-Amino-3-fluoro-phenyl)-2-[N-(1-methyl-2-phenoxy-ethyl)-amino]ethanol Tosylate Prepared analogously to Example 17 from 1-(4-acetamino-3-fluoro-phenyl)-2-[N-(1-methyl-2phenoxy)-ethyl]amino-ethanol and sodium hydroxide.

M.p.: 124-1280C.

Example 100 N-[2-(4-Amino-3,5-dichloro-phenyl )-ethyl]-N-[3-(4-methoxy-phenoxy)-propyl] methylamine 1.74 g (0.014 mol) of 4-methoxy-phenol were dissolved in 60 ml of dry tetrahydrofuran, the solution was cooled to -50C and under stirring 0.67 g (0.014 mol) of a 50% suspension of sodium hydride in oil were added thereto. Stirring was continued for 2 hours at OOC and the reaction mixture was mixed dropwise with a solution of 4.2 g of N-[2-(4-amino-3,5-dichloro-phenyl)-ethyl]-N-(3-chloro- propyl)-methylamine in 50 ml of dry tetrahydrofuran at the same temperature. After stirring for 1 8 hours at approx. 200 C, the reaction mixture was evaporated in vacuo, and the evaporation residue was distributed between ether and water.The phases were separated and the aqueous layer was extracted thrice with ether. The ether extracts were washed with water, combined, dried, and evaporated in vacuo. The oily evaporation residue was purified by chromatography over a silica gel column (eluent:ether), and after evaporating the desired fractions, the title compound was obtained as an oil.

IR spectrum (methylene chloride): NH2 3390+3480 cm-l CH2 2950 cm- N-alkyl 2800 cam~' C=C 1585+1560+1505 cm~' UV spectrum (ethanol): A max. 230 nm (0.18; shoulder) 246 nm (0.085; shoulder) 295 nm (0.05).

Example 101 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-(3-phenyl-propyl)-ethyl-amino]ethanol Hydrochloride 2 g of 1-(4-amino-3,5-dichloro-phenyl)-2-[N-(3-phenyl-propyl)-amino]-ethanol hydrochloride were dissolved in 50 ml of ethanol. To this solution 0.4 ml of acetaldehyde and subsequently whilst stirring at room temperature 1.2 g of sodium cyanoborohydride were added, maintaining a pH value of 6-6.5 by addition of 2 N hydrochloric acid. The mixture was stirred for a further 2 hours at this pH value. The solution was poured into water and acidified with 2 N hydrochloric acid to destroy the excess sodium cyanoborohydride.Then 2 N sodium hydroxide solution was added until alkaline, the reaction mixture was extracted twice with methylene chlorjde, and the combined methylene chloride phases were washed with water, dried over sodium sulfate, and evaporated in vacuo to dryness. A nearly colourless oil was obtained, which was dissolved in ethanol. This ethanolic solution was acidified with ethereal hydrochloric acid up to pH 5 and in vacuo in a rotation evaporator the solvent was removed. The remaining oily residue was crystallised from ethyl acetate; colourless crystals were obtained.

M.p.: 102-1050C.

Example 102 1-(4-Ethoxycarboxylamino-3-cyano-5-fluoro-phenyl)-2-[N-[2-(3,4-dimethoxy-phenyl)ethyl]amino]ethanol Hydrochloride Prepared analogously to Example 4 from 4'-ethoxycarbonylamino-3'-cyano-5'-fluoro- acetophenone, selenium dioxide, 2-(3,4-dimethoxy-phenyl)-ethylamine, and sodium borohydride.

M.p.: 190-191 C (decomp.).

Example 103 1 -(4-Amino-3-cyano-5-fluoro-phenyl)-2-[N-[4-(4-methoxy-phenyl)-butyl] methylamino]ethanol Prepared analogously to Example 1 from 4'-amino-3'-cyano-5t-fluoro-2-[N-[4-(4-methoxy- phenyl)-butyl]methylamino]acetophenone and sodium borohydride in 80% methanol.

IR spectrum (methylene chloride): OH 3590 cm- NH2 3400+3490 cm-l N-alkyl 2800 cam~' OCH3 2830 cm- aliphat. CH2 2850+2930 cam~' C#N 2210 cm- C=C 1635 cm- UV spectrum (ethanol): max. 241 nm (0.27) 280 nm (0.07) 322 nm (0.14).

Example 104 1 -(4-Acetam ino-3-bromo-phenyl )-2-[N-[4-(4-methoxy-phenyl)-butyl]-methylamino]ethanol Prepared analogously to Example 1 from 4'-acetamino-3'-bromo-2-[N-[4-(4-methoxy-phenyl)- butyl]methylamino]acetophenone and sodium borohydride in 80% methanol.

IR spectrum (methylene chloride): OH NH2 3590 cm- N-alkyl 3410 cm- OCH3 2800 cm- aliphat. CH2 2850+2930 cm-' aromat. C=C 1610 cm- 2830 cm- C=O 1700 cm- amide II 1510 cm- Example 105 Racemates A and B of 1-(4-amino-3,5-dichloro-phenyl)-2-[N-[3-(4-hydroxy-phenyl)-1-methylpropyl]methylamino]ethanol 36 g of 1-(4-amino-3,5-dichloro-phenyl)-2-[N-[3-(4-hydroxy-phenyl)-1-methyl-propyl]methylamino]ethanol (1:1 mixture of the diastereoisomeric racemates A and B) were dissolved in ether and reacted with 0.5 equivalents of 3 N hydrogen chloride in ether. The crude crystalline product of the hydrochloride of the racemate A thus obtained was recrystallized first from isopropanol and then by dissolving in a large quantity of methanol and subsequent evaporation until crystallization began.

M.p. of the hydrochloride: 248-2490C (decomp.).

13C-NMR spectrum of the base (CDCI3/CD30D):

37.50 ppm 58.36 ppm 13.91 ppm 36.33 ppm 61.03 ppm 68.89 ppm The isopropanolic mother liquor was evaporated and distributed between ether and 2 N ammonia. The evaporation residue of the dried organic phase was separated by means of HPLC, the racemate A being retained, to isolate the racemate B (SiO2 60; Merck; 0.015-0.05 mm; ether:methanol=10:1), The crystalline evaporation residue was recrystallized from a quantity of ether by concentrating at boiling temperatures.

M.p.: 128-1310C.

13C-NMR spectrum (CDCI3/CD30D):

35.61 ppm 59.21 ppm 14.56 ppm 35.03 ppm 63.11 ppm 69.08 ppm Example 106 1 -(4-Arnino-3-bromo-5-cyano-phenyl)-2-[N-[4-(4-methoxy-phenyl)-butyl]benzylamino]ethanol Hydrochloride Prepared analogously to Example 1 from 4'-amino-3'-bromo-5'-cyano-2-[N-[4-(4-methoxy- phenyl)-butyl]benzylamino]acetophenone and sodium borohydride in 90% methanol.

M.p. of the hydrochloride: 122-1 260 C.

Example 107 1 -(4-Amino-3-bromo-5-cyano-phenyl)-2-[N-[4-(4-methoxy-phenyl)-butyl]allylamino]ethanol Prepared analogously to Example I from 4'-amino-3'-bromo-5'-cyano-2-[N-[4-(4-methoxy- phenyl)-butyl]allylamino]acetophenone and sodium borohydride in 90% methanol. Resin.

IR spectrum (methylene chloride): NH2 3390+3490 cm- OCH3 2830+2940 cm- CN 2210 cm- aromat. C=C 1610 cm- UV spectrum (ethanol): A max. 223 nm (0.43) 244 nm (shoulder, broad; 0.07) 330 nm (broad; 0.05) Example 108 1 -(4-Amino-3-bromo-5-cyano-phenyl)-2-[N-[4-(4-methoxy-phenyl)-butyl] isopropylamino]ethanol Hydrochloride Prepared analogously to Example 1 from 4'-amino-3'-bromo-5'-cyan-2-[N-[4-(4-methoxy- phenyl)-butyl]isopropylamino]acetophenone and sodium borohydride in 90% methanol.

M.p. of the hydrochloride: sintering from 400C.

Calc.: C 55.60 H 6.29 Br 16.20 CI 2.14 N 8.46 Found: 55.30 6.37 15.40 6.84 8.83 Example 109 1 -(4-Amino-3-bromo-5-cyano-phenyl )-2-[N-[4-(4-methoxy-phenyl)-butyl]-n-propylamino]- ethanol Hydrochloride Prepared analogously to Example 1 from 4'-amino-3'-bromo-5'-cyano-2-[N-[4-(4-methoxy- phenyl)-butyl]-n-propylamino]acetophenone and sodium borohydride in 90% methanol.

M.p. of the hydrochloride: sintering from 400C Calc.: C 55.60 H 6.29 N 8.46 Found: 55.52 6.32 8.39 Example 110 1-(4-Amino-3-bromo-5-cyano-phenyl)-2-[N-[4-(4-methoxy-phenyl)-butyl]ethylamino]ethanol Hydrochloride Prepared analogously to Example 1 from 4'-amino-3'-bromo-5'-cyano-2-[N-[4-(4-methoxy- phenyl)-butyl]ethylamino]acetophenone and sodium borohydride in 90% methanol.

M.p. of the hydrochloride: 139-1 420C.

Example 111 1-(4-Amino-3-bromo-5-trifluoromethyl-phenyl)-2-[N-[3-(4-methoxy-phenyl)-propyl]methylamino]ethanol Prepared analogously to Example 1 from 4'-amino-3'-bromo-5'-trifluoromethyl-2-[N-[3-(4- methoxy-phenyl)-propyl]methylamino]acetophenone and sodium borohydride in 90% methanol. Oil.

IR spectrum (methylene chloride): NH2 3400+3490 cm-1 OCH3 2840+2940 cm-l aromat. C=C 1610 cm- UV spectrum (ethanol): max. 223 nm (0.26) 244 nm (0.10) 310 nm (very broad; 0.04) Example 112 1-(4-Amino-3-bromo-5-cyano-phenyl)-2-[N-(4-phenyl-butyl)-methylamino]ethanol Hydrochloride Prepared analogously to Example 1 from 4'-amino-3'-bromo-5'-cyano-2-[N-(4-phenyl-butyl)- methylamino]acetophenone and sodium borohydride in 90% methanol.

M.p. of the hydrochloride: 153-155 C.

Example 113 1 -(4-Amino-3-cyano-5-fluoro-phenyl)-2-[N-[2-(4-methoxy-phenyl)-ethyl] methyla mino]ethanol Hydrochloride Prepared analogously to Example 1 from 4'-amino-3'-cyano-5t-fluoro-2-[N-[2-(4-methoxy- phenyl)-ethyl]methylamino]acetophenone and sodium borohydride in 90% methanol.

M.p. of the hydrochloride: sintering from 680C.

Calc.: C60.10 H 6.12 Cl 9.35 N 11.05 Found: 59.91 6.07 9.40 10.69 Example 114 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-(3-phenylsulfenyl-propyl)-methylamino]ethanol Prepared analogously to Example 2 from 4'-amino-2-bromo-3',5'-dichloro-acetophenone, N-[3 (4-methoxy-phenylsulfenyl)-propyl]-methylamine, and sodium borohydride in 80% methanol. Oil.

IR spectrum (methylene chloride): NH2 3390+3490 cm~' OH 3600+3680 cm~ UV spectrum (ethanol): A max. 246 nm (0.18) 300 nm (0.05) Example 115 1 -(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-hydroxy-phenyl)-propyl]amino]ethanol Prepared analogously to Example 3 from 4'-amino-3',5'-dichloro-2-[N-[3-(4-hydroxy-phenyl)- propyl]amino]acetophenone and sodium borohydride in aqueous tetrahydrofuran. Oil.

IR spectrum (KBr): OH, NH2 3300-3600 cm-' aromat. C=C 1615 cm-l UV spectrum (ethanol+KOH): A max. 244 nm (0.26) 299 nm (0.08) Example 116 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-chlorophenyl)-propyl]amino]ethanol Prepared analogously to Example 3 from 4'-amino-3',5'-dichloro-2-[N-[3-(4-chloro-phenyl)propylamino]acetophenone and sodium borohydride in aqueous tetrahydrofuran.

M.p.: 103-1060C.

Example 117 1 -(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-hydroxy-phenyl)-1 -methyl-propyl] isopropylamino]ethanol Prepared analogously to Example 3 from 4'-amino-3',5'-dichloro-2-[N-[3-(4-hydroxy-phenyl)-1 methyl-propyl]isopropylamino]acetophenone and sodium borohydride. Oil.

Calc.: C 61.31 H 6.86 Cl 17.24 N 6.81 Found: 61.07 6.86 16.67 6.53 Example 118 1 -(-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-hydroxy-phenyl)-1 -methyl-propyl]ethylamino]ethanol Prepared analogously to Example 3 from 4'-amino-3',5'-dichloro-2-[N-[3-(4-hydroxy-phenyl)-1- methyl-propyl]ethylamino]acetophenone and sodium borohydride. Oil.

Calc.: C 60.45 H 6.60 CI 17.85 N 7.05 Found: 60.45 6.76 17.70 6.86 Example 119 1 -(4-Methyla mino-3,5-dichloro-phenyl)-2-[N-[3-(4-hydroxy-phenyl)-1 -methyl-propyl] methylamino]ethanol Prepared analogously to Example 3 from 4'-methylamino-3',5'-dichloro-2-[N-[3-(4-hydroxy- phenyl)-1 -methyl-propyl]-methylamino]acetophenone and sodium borohydride. Oil.

Calc.: C 60.45 H 6.60 CI 17.85 N 7.05 Found: 60.68 6.73 17.50 6.71 Example 120 1 -(4-Dimethylamino-3,5-dichloro-phenyl)-2-[N-[3-(4-hydroxy-phenyl)-1 -methyl-propyl] methylamino]ethanol Prepared anaiogously to Example 3 from 4'-dimethylamino-3',5'-dichloro-2-[N-[3-(4-hydroxy- phenyl)-1 -methyl-propyl]-methylamino]acetophenone and sodium borohydride. Oil.

Calc.: C 61.31 H 6.86 CI 17.24 N 6.81 Found: 61.28 6.57 16.80 6.42 Example 121 1 -(4-Acetyla mino-3,5-dichloro-phenyl )-2-[N-[3-(4-hydroxy-phenyl)-1 -methyl-propyl] methyl amino]ethanol Prepared analogously to Example 3 from 4'-acetylamino-3',5'-dichloro-2-[N-[3-(4-hydroxyphenyl)-1-methyl-propyl]methylamino]acetophenone and sodium borohydride. Foam.

IR spectrum (methylene chloride): OH 3580 cm-' NH 3410 cm-' N-alkyl 2800 cm-' C=O 1700 cm-' C=C 1610,1595cm-1 Amid 11 1515 cm-' UV spectrum (ethanol): max. 230 nm (0.30; shoulder) 280 nm (0.04) (Ethanol+KOH): max. 243 nm (0.46) 294 nm (0.08) Example 122 1 -(4-Ethoxycarbonylamino-3,5-dichloro-phenyl)-2-[N-[3-(4-hydroxy-phenyl)-1 -methylpropyl]methylamino]ethanol Prepared analogously to Example 3 from 4'-ethoxycarbonylamino-3',5'-dichloro-2-[N-[3-(4- hydroxy-phenyl)-1-methyl-propyl]-methylamino]acetophenone and sodium borohydride. Oil.

Calc.: C 58.02 H 6.20 Cl 15.57 N 6.15 Found: 58.20 6.32 15.32 6.03 Example 123 Racemates A and B of 1-(4-amino-3-cyano-5-fluoro-phenyl)-2-[N-[1-methyl-3-(4-hydroxy- phenyl)-propyl] methylamino]ethanol Prepared analogously to Example 3 from 4'-amino-3'-cyano-5'-fluoro-2-[N-[ 1 -methyl-3-(4- hydroxy-phenyl)-propyl]methylamino]acetophenone and sodium borohydride. The obtained mixture of the diasteroisomeric racemates was separated by means of column chromatography (SiO2; methylene chloride:methanol:conc. ammonia=50:1:0.1).

Racemate A: M.p.: 161-1630C 13C-NMP spectrum (d6-dimethylsulfoxide):

37.17 ppm 57.91 ppm 13.26 ppm 35.74 ppm 60.90 ppm 69.21 ppm Racemate B: M.p.: 92-980C 13C-NM P spectrum (d6-dimethylsulfoxide):

36.52 ppm 57.78 ppm

13.19 ppm 61.48ppm 69.02 ppm Example 124 1 -(4-Amino-3-cyano-5-fluoro-phenyl)-2-[N-[1 -methyl-3-(4-methoxy-phenyl)-propyl]amino]ethanol Prepared analogously to Example 3 from 4'-amino-3'-cyano-5'-fluoro-2-[N-[1 -methyl-3-(4 methoxy-phenyl)-propyl]a mino]-acetophenone and sodium borohydride.

M.p.: 108-1100C.

Example 125 1 -(4-Amino-3-cyano-5-fluoro-phenyl)-2-[N-[1 -methyl-3-(4-hydroxy-phenyl)-propyl]amino]ethanol Prepared analogously to Example 3 from 4'-amino-3'-cyano-5'-fluoro-2-[N-[1 -methyl-3-(4hydroxy-phenyl)-propyl]amino]-acetophenone and sodium borohydride.

M.p.: 162-164 C.

Example 126 1-(4-Amino-3-cyano-5-fluoro-phenyl)-2-[N-[1-methyl-3-(4-methoxy-phenyl)-propyl]methylamino]ethanol Prepared analogously to Example 4 from 1-(4-amino-3-cyano-5-fluoro-phenyl)-2-[N-[1-methyl3-(4-hydroxy-phenyl)-propyl]methylamino]ethanol and dimethylsulfate/1 N sodium hydroxide solution in tetrahydrofuran. Oil.

IR spectrum (methylene chloride): NH2 3400+3500 cm~ O-CH3 2830 cm- N-alkyl 2800 cm- C#N 2210 cm- C=C. 1580,1510 cm~' C=C+NH2 deformation 1620 cm- UV spectrum (ethanol): A max. 242 nm (0.27) 278 nm (0.05) 286 nm (0.05) 324 nm (0.12) Example 127 1 -(4-Amino-3,5-dichloro-phenyl)-2-[N-( 1 -methyl-2-phenoxy-ethyl)-amino]ethanol Hydrochloride Prepared analogously to Example 5 from 4'-amino-3',5'-dichloroacetophenone, selenium dioxide, 1 -methyl-2-phenoxy-ethylamine, and sodium borohydride. Amorphous hydrochloride.

IR spectrum (methylene chloride): NH2 3390+3490 cm- UV spectrum (ethanol): A max. 245 nm (0.15) 300 nm (0.04) Example 128 1 -(4-Amino-3,5-dichloro-phenyl )-2-[N-[3-(4-fluoro-phenyl)-propyl]amino]ethanol Hydrochloride Prepared analogously to Example 5 from 4'-amino-3',5'-dichloro-acetophenone, selenium dioxide, 3-(4-fluoro-phenyl)-propylamine, and sodium borohydride.

M.p. of the hydrochloride: 1 65-1 870C (decomp.).

Example 129 1 -(4-Amino-3,5-dichloro-phenyl)-2-[N-(3-phenyl-1 -methyl-propyl)-methylamino]ethanol Prepared analogously to Example 5 from 4'-amino-3',5'-dichloroacetophenone, selenium dioxide, 3-phenyl-1-methyl-propylamine, and sodium borohydride. Oil.

IR spectrum (methylene chloride): NH2 3390+3490 cm~1 OH 3600+3680 cm~' UV spectrum (ethanol): A max. 245 nm (0.18) 300 nm (0.06) Example 130 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-(1-methyl-2-phenoxy-ethyl)-amino]ethanol Hydrochloride Prepared analogously to Example 5 from 4'-amino-3',5'-dichloroacetophenone, selenium dioxide, 1-methyl-2-phenoxy-ethylamine, and sodium borohydride.

M.p. of the hydrochloride: 122-1 250C.

Example 131 N-[3-(4-Amino-3-bromo-phenyl)-propyl]-N-[2-(3,4-dimethoxyphenyl)-ethyl]methylamine Hydrochloride Prepared analogously to Example 7 from N-methyl-N-[2-(3,4-dimethoxy-phenyl)-ethyl]-3-(4- amino-3,5-dibromo-phenyl)-propionamide, and lithium aluminium hydride in absolute tetrahydrofuran.

M.p. of the hydrochloride: 70-1 200C (sintering) IR spectrum (KBr): NH# 2500-2650 cm- alkyl 2800-3000 cm-l UV spectrum (ethanol): A max. 234 nm (0.17) 280 nm (0.04) 300 nm (shoulder; 0.03).

Example 132 N-[2-(4-Amino-3-chloro-phenyl)-ethyl]-N-(1-methyl-3-phenyl-propyl)-isopropylamine Prepared analogously to Example 7 from 4-amino-3,5-dichloro-N-isopropyl-N-( 1 -methyl-3- phenyl-propyl)-phenylacetamide and lithium aluminium hydride in tetrahydrofuran. Oil.

IR spectrum (methylene chloride): NH2 3390+3490 cm- UV spectrum (ethanol): .1 max. 241 nm(0.15) 300 nm (0.03) Example 133 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-(1 -methyl-3-phenyl-propyl)-isopropylamine Prepared analogously to Example 7 from 4-amino-3,5-dichloro-N-isopropyl-N-( 1 -methyl-3- phenyl-propyl)-phenylacetamide and lithium aluminiumhydride in tetrahydrofuran. Oil.

IR spectrum (methylene chloride): NH2 3390+3490 cm-l UV spectrum (ethanol): A max. 245 nm (0.15) 302 nm (0.04).

Example 134 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-3-(4-fluoro-phenyl)-propylamine Hydrochloride Prepared analogously to Example 7 from 4-amino-3,5-dichloro-N-[3-(4-fluoro-phenyl)- propyl]phenylacetamide and lithium aluminium hydride in tetrahydrofuran.

M.p. of the hydrochloride: 205-206 C.

Example 135 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-( 1 -methyl-3-phenyl-propyl )-methylamine Prepared analogously to Example 7 from 4-amino-3,5-dichloro-N-( 1 -methyl-3-phenyl-propyl)phenylacetamide and lithium aluminium hydride in tetrahydrofuran. Oil.

IR spectrum (methylene chloride): NH2 3390+3490 cm-' UV spectrum (ethanol): A max. 243 nm (0.14) 300 nm (0.05) Example 136 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4-methoxy-phenyl-sulfenyl)-propyl]methylamine Prepared analogously to Example 7 from 4-amino-3,5-dichloro-N-[3-(4-methoxy-phe sulfenyl)-propyl]-N-methyl-phenylacetamide and lithium aluminium hydride in tetrahydrofuran oil.

IR spectrum (methylene chloride): NH2 3390+3490 cm UV spectrum (ethanol): A max. 245 nm (0.16) 300 nm (0.04) Example 137 N-[2-(4-Amino-3-bromo-phenyl)-ethyl]-N-[4-(4-methoxy-phenyl)-butyl]methylamine Prepared analogously to Example 8 from 4-amino-3-bromo-N-[2-(4-methoxy-phenyl)-butyl]-N- methyl-phenylacetamide and lithium aluminium hydride in absolute tetrahydrofuran.

IR spectrum tmethylene chloride): NH2 3380+3470 cm- OCH3 2830+2930 cm- aromat. C=C 1620 cm-' NMR spectrum (CDC13/D2O): aromat. H 6.4-7.3 ppm (m, 7H) OCH3 3.7 ppm (s, 3H) NCH3 2.2 ppm (s 3H) aliph. H 1.3-2.8 ppm (m, 8H) Example 138 N-[2-(4-Amino-3-bromo-phenyl)-ethyl]-N-[2-(4-methoxy-phenyl)-ethyl]methylamine Prepared analogously to Example 8 from 4-amino-3-bromo-N-[2-(4-methoxy-phenyl)-ethyl]-N- methyl-phenylacetamide and lithium aluminium hydride in absolute tetrahydrofuran.

IR spectrum (methylene chloride): NH2 3380+3480 cm-' OCH3 2840+2940 cm- aromat. C=C 1620 cm-' UV spectrum (ethanol): A max. 224 nm (0.24) 242 nm (0.15) 280 nm (broad; 0.03) 300 nm (broad; 0.03) Example 139 N-[2-(4-Amino-3-fluoro-phenyl)-ethyl]-N-[3-(4-methoxy-phenyl)-propyl]methylamine Prepared analogously to Example 8 from 4-amino-3-fluoro-N-[3-(4-methoxy-phenyl)-propyl]-N- methyl-phenylacetamide and lithium aluminium hydride in absolute tetrahydrofuran. Oil.

IR spectrum (methylene chloride): NH2 3390+3490 cm- OCH3 2840+2940 cm- aromat. C=C 1610 cm- UV spectrum (ethanol): A max. 227 nm (0.30) 279 nm (0.06) 285 nm (0.06) Example 140 N-[2-(4-Amino-3-chloro-phenyl )-ethyl]-N-[3-(4-methoxy-phenyl)-propyl] methylamine Prepared analogously to Example 8 from 4-amino-3-chloro-N-methyl-N-[3-(4-methoxy-phenyl)- propyl]phenylacetamide and lithium aluminium hydride in absolute tetrahydrofuran. Resin.

IR spectrum (methylene chloride): NH2 3390+3470 cm-1 OCH3 2840+2940 cm-' aromat. C=C 1610 cm-' UV spectrum (ethanol): A max. 224 nm (0.25) 240 nm (0.18) 280 nm (0.04) 300 nm (0.03).

Example 141 N-[3-(4-Amino-3,5-dichloro-phenyl)-propyl]-N-[3-(4-methoxy-phenyl)-propyl]amine Hydrochloride Prepared analogously to Example 8 from 3-(4-amino-3,5-dichlorophenyl)-N-[3-(4-methoxy- phenyl)-propyl]propionamide and lithium aluminium hydride in absolute tetrahydrofuran.

M.p. of the hydrochloride: 1 38-1 420C.

Example 142 N-[3-(4-Amino-3,5-dichloro-phenyl)-propyl]-N-[2-(4-methoxy-phenyl)-ethyl]methylamine Di hydrochloride Prepared analogously to Example 8 from 3-(4-amino-3,5-dichloro-phenyl)-N-methyl-N-[2-(4- methoxy-phenyl)-ethyl]propionamide and lithium aluminium hydride in absolute tetrahydrofuran.

M.p. of the dihydrochloride: 147-1 570C.

Example 143 N-[2-(4-Amino-3,5-dichloro-phenyl)ethyl]-N-[4-(4-methoxy-phenyl)-butyl]amine Hydrochloride Prepared analogously to Example 8 from N-[2-(4-amino-3,5-dichloro-phenyl)-ethyl]-4-(4- methoxy-phenyl)-butyramide and lithium aluminium hydride in absolute tetrahydrofuran.

M.p. of the hydrochloride: 186-1 890C.

Example 144 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4-chloro-phenyl)-propyl]amine Hydrochloride Prepared analogously to Example 8 from 4-amino-3,5-dichloro-N-[3-(4-chloro-phenyl)propyl]phenylacetamide and lithium aluminium hydride in absolute tetrahydrofuran.

M.p. of the hydrochloride: 1 86-1 900C.

Example 145 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-(4-methoxy-phenyl)-butyl]isopropylamine Prepared analogously to Example 8 from N-[2-(4-amino-3,5-dichloro-phenyl)-ethyl]-N-isopropyl- 4-(4-methoxy-phenyl)-butyramide and lithium aluminium hydride in absolute tetrahydrofuran. Oil.

IR spectrum (methylene chloride): NH3 3390+3490 cm-l OCH3 2850+2930 cm- aromat. C=C 1610 cm-l UV spectrum (ethanol): A max. 242 nm (0.12) 280 nm (shoulder; 0.04) 301 nm (0.04) Example 146 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[2-(4-methoxy-phenyl)-ethyl]isopropylamine Prepared analogously to Example 8 from N-[2-(4-amino-3,5-dichloro-phenyl)-ethyl]-N-isopropyl4-methoxy-phenylacetamide and lithium aluminium hydride in absolute tetrahydrofuran. Oil.

IR spectrum (methylene chioride): NH2 3390+3490 cm~' OCH3 2830+2960 cm-l aromat. C=C 1610cm-' UV spectrum (ethanol): A max. 244 nm (shoulder; 0.12) 280 nm (shoulder; 0.05) 301 nm (0.05) Example 147 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[2-(4-methoxy-phenyl)-ethyl]amine Hydrochloride Prepared analogously to Example 8 from 4-amino-3,5-dichloro-N-[2-(4-methoxy-phenyl)ethyl]phenylacetamide and lithium aluminium hydride in absolute tetrahydrofuran.

M.p. of the hydrochloride: 206-2080C.

Example 148 N-[3-(4-Amino-3,5-dibromo-phenyl)-propyl]-N-[2-(3,4-dimethoxy-phenyl)-ethyl]methylamine Prepared analogously to Example 8 from N-methyl-N-[2-(3,4-dimethoxy-phenyl)-ethyl]-3-(4amino-3,5-dibromo-phenyl)-propionamide and lithium aluminium hydride in absolute tetrahydrofuran.

Oil.

IR spectrum (methylene chloride): NH2 3480+3380 cm~' OCH3 2840+2940 cm- NMR spectrum (CDCI3/D2O): O-CH3 4.85 ppm (s, 6H) N-CH3 2.25 ppm (s, 3H) aromat. H 6.75 ppm (d, 3H) 7.2 ppm (s, 2H) aliphat. H 1.5-2.9 ppm (m, 12H) Example 149 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-3-phenyl-propylamine Hydrochloride Prepared analogously to Example 8 from 4-amino-3,5-dichloro-N-(3-phenyl-propyl)phenylacetamide and lithium aluminium hydride in tetrahydrofuran.

M.p. of the hydrochloride: 197-1 990C.

Example 150 N-[2-(4-Amino-3-bromo-5-cyano-phenyl)-ethyl]-N-[4-(4-methoxy-phenyl)-butyl]benzylamine Prepared analogously to Example 9 from 1-ethoxycarbonyloxy-1-(4-amino-3-bromo-5-cyanophenyl)-2-[N-[4-(4-methoxy-phenyl)-butyl]=benzylamino]ethane and sodium borohydride in isopropanol. Oil.

IR spectrum (methylene chloride): NH2 3390+3490 cm-1 OCH3 2830+2930 cm- CH 2210 cm- aromat. C=C 1620 cm- UV spectrum (ethanol): A max. 222 nm (0.42) 244 nm (shoulder; 0.09) 335 nm (broad; 0.05) Example 151 N-[2-(4-Amino-3-bromo-5-cyano-phenyl)-ethyl]-N-[4-(4-methoxy-phenyl)-butyl]allylamine Prepared analogously to Example 9 from 1-ethoxycarbonyloxy-1-(4-amino-3-bromo-5-cyanophenyl)-2-[N-[4-(4-methoxy-phenyl)-butyl]allylamino]ethane and sodium borohydride in isopropanol.

OIl.

IR spectrum (methylene chloride): NH2 3390+3490 cm~ OCH3 2830+2930 cm- CN 2210 cm- aromat. C=C 1620 cm- UV spectrum (ethanol): A max. 222 nm (0.49) 244 nm (shoulder; O.1) 335 nm (broad; 0.06) Example 152 N-[2-(4-Amino-3-bromo-5-cyano-phenyl)-ethyl]-N-[4-(4-methoxy-phenyl)-butyl]ethylamine Prepared analogously to Example 9 from 1 -ethoxycarbonyloxy-1 -(4-amino-3-bromo-5-cyanophenyl)-2-[N-[4-(4-methoxy-phenyl)-butyl]ethylamino]ethane and sodium borohydride in isopropanol.

Oil.

IR spectrum (methylene chloride): NH2 3390+3490 cm- OCH3 2830+2960 cm~ CH 2210 cm- aromat. C=C 1620 cm-' UV spectrum (ethanol): A max. 222 nm (0.49) 244 nm (shoulder; 0.08) 333 nm (broad; 0.06) Example 153 N-[2-(4-Amino-3-bromo-5-cyano-phenyl)-ethyl]-N-[4-(4-methoxy-phenyl)-butyl]isopropylamine Prepared analogously to Example 9 from 1 -ethoxycarbonyloxy-1 -(4-amino-3-bromo-5-cyanophenyl)-2-[N-[4-(4-methoxy-phenyl)-butyl]isopropylamino]ethane and sodium borohydride in isopropanol. Resin.

IR spectrum (methylene chloride): NH2 3390+3490 cm~ OCH3 2830+2960 cm- CN 2210 cm- aromat. C=C 1620 cm- UV spectrum (ethanol): A max. 221 nm (0.53) 244 nm (shoulder: 0.1) 330 nm (broad; 0.07) Example 154 N-[2-(4-Amino-3-bromo-5-cyano-phenyl)-ethyl]-N-[4-(4-methoxy-phenyl)-butyl]-n-propylamine Prepared analogously to Example 9 from 1 -ethoxycarbonyloxy-1-(4-amino-3-bromo-5-cyanophenyl)-2-[N-[4-(4-methoxy-phenyl)-butyl]-n-propylamino]ethane and sodium borohydride in isopropanol. Oil.

IR spectrum (methylene chloride): NH2 3390+3490 cm- CN 2210 cm- OCH3 2830+2950 cm~ aromat. C=C 1620 cm-' UV spectrum (ethanol): A max. 222 nm (0.46) 244 nm (shoulder; 0.08) 330 nm (broad; 0.05) Example 155 N-[2-(4-Amino-3-bromo-5-cyano-phenyl)-ethyl]-N-[4-phenyl-butyl)-methylamine Prepared analogously to Example 9 from 1 -ethoxywarbonyloxy-1 -(4-amino-3-bromo-5-cyano phenyl)-2-[N-(4-phenyl-butyl)-methylamino]ethane and sodium borohydride in isopropanol. Oil.

NMR spectrum (CDCl3): aromat. H 7.0-7.4 ppm (m, 7H) NCH3 2.2 ppm (s, 3H) aliphat. H 1.3-2.7 ppm (m, 1 2H) Example 156 N-[2-(4-Amino-3-cyano-5-fluoro-phenyl)-ethyl]-N-[2-(4-methoxy-phenyl)-ethyl]methylamine Prepared analogously to Example 9 from 1 -ethoxycarbonyloxy-1 -(4-amino-3-cyano-5-fluoro phenyl)-2-[N-[2-(4-methoxy-phenyl)-ethyl]methylamino]ethane and sodium borohydride in isopropanol. Oil.

NMR spectrum 9CDCl3/CH3OD): aromat. H 6.7-7.2 ppm (m, 6H) OCH3 3.75 ppm (s, 3H) NCH3 2.3 ppm (s, 3H) aliphat. H 2.4-2.7 ppm (m, 8H) Example 157 N-[2-(4-Amino-3-cyano-5-fluoro-phenyl)-ethyl]-N-[3-(4-methoxy-phenyl)-propyl]methylamine Hydrochloride Prepared analogously to Example 9 from 1-ethoxycarbonyloxy-1-(4-amino-3-cyano-5-fluorophenyl)-2-[N-[3-(4-methoxy-phenyl)-propyl]methylamino]ethane and sodium borohydride in isopropanol. Hydrochloride as resin.

NMR spectrum (CDCI3): aromat. H 6.7-7.2 ppm (m, 6H) OCH3 3.75 ppm (s. 3H) #NCH3 2.8 ppm (s 3H) aliphat. H 1.5-3.5 ppm (m, 1 OH) Example 158 N-[2-(4-Amino-3-cyano-5-fluoro-phenyl)-ethyl]-N-[4-(4-methoxy-phenyl)-butyl]methylamine Prepared analogously to Example 9 from 1 -ethoxywarbonyloxy-1 -(4-amino-3-cyano-5-fluorophenyl)-2-[N-[4-(4-methoxy-phenyl)-butyl]methyl]amino]ethane and sodium borohydride in isopropanol. Resin.

NMR spectrum (CDClWD2O): aromat. H 7.2 ppm (s, 2H) 6.85 ppm (q, 4H) OCH3 3.8 ppm (s 3H) NCH3 2.25 ppm (s 3H) aliphat. H 1.5-2.7 ppm (m, 1 2H) Example 159 N-[2-(4-Amino-3-chloro-5-trifluoromethyl-phenyl)-ethyl]-N-[4-(4-methoxy-phenyl)-butyl]- methylamine Prepared analogously to Example 9 from 1 -ethoxycarbonyloxy-1 -(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-[N-[4-(4-methoxy-phenyl)-butyl]methylamino]ethane and sodium borohydride in isopropanol.

M.p.: 290C.

Example 160 N-[2-(4-Amino-3-chloro-5-trifluoromethyl-phenyl)-ethyl]-N-[2-(4-methoxy-phenyl)-ethyl]methylamine Prepared analogously to Example 9 from 1 -ethoxycarbonyloxy-1 -(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-[N-[2-(4-methoxy-phenyl)-ethyl]methylamino]ethane and sodium borohydride in isopropanol. Resin.

IR spectrum (methylene chioride): NH2 3400+3500 cm- OCH3 2840+2960 cm- aromat. C=C 1610 cm- UV spectrum (ethanol): A max. 228 nm (shoulder; 0.10) 244 nm (0.10) 310 nm (0.03) Example 161 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4-fluoro-phenyl)-propyl]methylamine Prepared analogously to Example 9 from 1 -ethoxycarbonyloxy-1 -(4-amino-3,5-dichloro-phenyl)2-[N-[3-(4-fluoro-phenyl)-propyl]-methylamino]ethane and sodium borohydride in isopropanol. Oil.

IR spectrum (methylene chloride): NH2 3390+3490 cm~ UV spectrum (ethanol): A max. 243 nm (0.13) 300 nm (0.03) Example 162 1 -(4-Amino-3-trifluoromethyl-phenyl)-2-[N-[3-(4-methoxy-phenyl)-propyl] methylamino]ethanol Prepared analogously to Example 11 from 1 -(4-amino-3-bromo-5-trifluoromethylphenyl)-2-[N [3-(4-methoxy-phenyl)-propyl]methylamino]ethanol and hydrogen in the presence of palladium oxide on barium sulfate in methanol. Oil.

NMR spectrum (CDCID2O): aromat. H 6.6-7.3 ppm (m, 7H) CH-OH 4.5 ppm (t, 1 H) OCH3 3.7 ppm (s, 3H) NCH3 2.3 ppm (s, 3H) aliphat. H 2.2-2.7 ppm (m, 6H) -CH2- 1.8 ppm (q, 2H) Example 163 N-[3-(4-Acetamino-3,5-dichloro-phenyl)-propyl]-N-[2-(3,4-dimethoxy-phenyl)-ethyl]methylamine Prepared analogously to Example 12 from N-[3-(4-amino-3,5-dichloro-phenyl)-propyl]-N-[2- (3,4-dimethoxy-phenyl)-ethyl]methylamine, acetyl chloride and triethylamine in toluene. Oil.

IR spectrum (methylene chloride): NH 3405 cm- OCH3 2830+2940 cm- CO 1700 cm- UV spectrum (ethanol): A max. 228 nm (shoulder; 0.17) 280 nm (0.04) Example 164 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-hydroxy-phenyl)-1-methyl-propyl]allylamino]ethanol Prepared analogously to Example 13 from 1 -(4-amino-3,5-dichloro-phenyl)-2-[N-[3-(4-hydroxy- phenyl]-1-methyl-propyl]amino]ethanol with allyl bromide/sodium carbonate in absolute ethanol. Oil.

IR spectrum (methylene chloride): OH 3580 cm- NH2 3390+3480 cm- aliphat. CH2 1850+2930 cm- C=C 1615 cm- UV spectrum (ethanol): A max. 243 nm (0.26) 282 nm (0.08) 300 nm (0.08) (Ethanol+KOH): A max. 242 nm (0.47) 298 nm (0.19) Example 165 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-hydroxy-phenyl)-propyl]isopropylamino]ethanol Hydrochloride Prepared analogously to Example 16 from 1-(4-amino-3,5-dichloro-phenyl)-2-[N-[3-(4- benzyloxy-phenyl)-propyl]isopropylamino]ethanol and hydrogen in the-presence of palladium on charcoal.

M.p. of the hydrochloride: 90-11 10 C.

Example 166 1-(4-Amino-3-chloro-phenyl)-2-[N-[3-(4-hydroxy-phenyl)-propyl]-ethylamino]ethanol Prepared analogously to Example 16 from 1 -(4-aminol-3,5-dichlorophenyl)-2-[N-[3-(4-benzyloxy- phenyl)-propyl]ethylamino]ethanol and hydrogen in the presence of palladium on charcoal. Resin.

IR spectrum (methylene chloride): OH 3595 cm- NH2 3400+3490 cm- aliphat. CH2 2840+2940 cm- C=C 1625 cm- UV spectrum (ethanol): # max. 227 nm (0.19) 244 nm (0.17) 290 nm (0.04) (Ethanol+KOH): A max. 243 nm (0.32) 297 nm (0.08) Example 167 1 -(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-hydroxy-phenyl)-propyl]ethylamino]ethanol Prepared analogously to Example 16 from 1 -(4-amino-3,5-dichloro-phenyl)-2-[N-[3-(4- benzyloxy-phenyl)-propyl]ethylamino]ethanol and hydrogen in the presence of palladium on charcoal.

Resin.

IR spectrum (methylene chloride): OH 3590, 3620+3680 cm- NH2 3390+3480 cm- aromat. C=C 1615 cm- UV spectrum (ethanol): Xmax. 244 nm (0.17) 284 nrn (0.06) 200 nm (0.05) (Ethanol+KOH): A max. 243 nm (0.31) 298 nm (0.08) Example 168 N-[3-(4-Dimethylamino-3,5-dichloro-phenyl)-propyl]-N-[3-(4-methoxy-phenyl)-propyl]methylamine Prepared analogously to Example 101 from N-[3-(4-amino-3,5-dichloro-phenyl)-propyl]-N-[3-(4- methoxy-phenyl)-propyl]amine, paraformaldehyde and sodium cyanoborohydride in ethanol. Oil.

IR spectrum (methylene chloride): OCH3 2830+2940 cm- NCH3 2790 cm- NH2 aromat. C=C 1610 cm- NMR spectrum (CDCl3/D2O): aromat. H 7.0 ppm (q, 4H) 7.1 ppm (s 2H) OCH3 3.75 ppm (s, 3H) N(CH3)2 2.85 ppm (s 6H) aliphat, H 2.2-2.8 ppm (m, 8H) N-CH3 2.2 ppm (s, 3H) -CH2- 1.6-1.8 ppm (q, 4H) Example 169 N-[3-(4-Amino-3,5-dichloro-phenyl)-propyl]-N-[3-(4-methoxy-phenyl)-propyl] methylamine Prepared analogously to Example 101 from N-[3-(4-amino-3,5-dichloro-phenyl)-propyl]-N-[3-(4- methoxy-phenyl)-propyl]amine, paraformaldehyde and sodium cyanoborohydride in ethanol Oil.

IR spectrum (methylene chloride): NH2 3390+3490 cm-' OCH3 2830+2940 cm- aromat. C=C 1610 cm- UV spectrum (ethanol): A max. 230 nm (shoulder; 0.21) 242 nm (0.10) 278+285 (broad; 0.03) 302 nm (broad; 0.03) Example 170 N-[2-(4-Dimethylamino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4-chloro-phenyl)-propyl]methylamine Prepared analogously to Example 101 from N-[2-(4-amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4chloro-phenyl)-propyl]amine, paraformaldehyde and sodium cyanoborohydride in ethanol. Oil.

IR spectrum (methylene chloride): NCH3 2790 cm~ NH2 NH UV spectrum (ethanol): A max. 273 nm (broad; 0.04) Example 171 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4-chloro-phenyl)-propyl]-2-phenylethylamine Hydrochloride Prepared analogously to Example 101 from N-[2-(4-a mino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4- chloro-phenyl)-propyl]amine, phenylacetaldehyde and sodium cyanoborohydride in ethanol.

M.p. of the hydrochloride: 158-161 OC.

Example 172 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[4-(4-methoxy-phenyl)-butyl]ethylamine Prepared analogously to Example 101 from N-[2-(4-amino-3,5-dichloro-phenyl)-ethyl]-N-[4-(4methoxy-phenyl)-butyl]amine, acetaldehyde and sodium cyanoborohydride in ethanol. Oil.

IR spectrum (methylene chloride): OCH3 2860+2930 cm-' aromat. C=C 1610 cm-' UV spectrum (ethanol): A max. 245 nm (0.09) 278 nm (0.02) 282 nm (0.02) 300 nm (0.01) Example 173 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4-chloro-phenyl)-propyl]benzylamine Hydrochloride Prepared analogously to Example 101 from N-[2-(4-amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4- chloro-phenyl)-propylamine, benzaldehyde and sodium cyanoborohydride in ethanol.

M.p. of the hydrochloride: 1 64-1 680C.

Example 174 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4-chlorophenyl)-propyl]isopropylamine Prepared analogously to Example 101 from N-[2-(4-amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4- chloro-phenyl)-propyl]-amine, acetone and sodium cyanoborohydride in absolute methanol. Oil.

IR spectrum (methylene chloride): NH2 3390+3480 cm~' aromat. C=C 1615 cm- UV spectrum (ethanol): A max. 241 nm (0.13) 300 nm (0.05) Example 175 N-[1 -Methyl-2-(4-a mino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4-methoxyphenyl)-propyl]amine Hydrochloride Prepared analogously to Example 101 from 1-(4'-amino-3',5'-dichloro-phenyl)acetone, 3-(4methoxyphenyl)-propylamine and sodium cyanoborohydride in ethanol.

M.p. of the hydrochloride: 193-1950C.

Example 176 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4-chloro-phenyl)-propyl]-n-propylamine Prepared analogously to Example 101 from N-[2-(4-amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4chloro-phenyl)-propyl]amine, propionaldehyde and sodium cyanoborohydride in ethanol. Oil.

IR spectrum (methylene chloride): NH2 3380+3480 cm~' aromat. C=C 1610 cm- UV spectrum (ethanol): A max. 242 nm (O.13) 301 nm (0.05) Example 177 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4-chloro-phenyl)-propyl]ethylamine Prepared analogously to Example 101 from N-[2-(4-amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4chlor-phenyl)-propyl]amine, acetaldehyde and sodium cyanoborohydride in ethanol at pH 6-6.5. Oil.

IR spectrum (methylene chloride): NH2 3390+3480 cm~' aromat. C=C 1615 cm- UV spectrum (ethanol: A max. 242 nm (0.14) 305 nm (0.04) Example 178 N-[2-(4-Amino-3,5-dichloor-phenyl)-ethyl]-N-[2-(4-methoxy-phenyl)-ethyl]ethylamine Prepared analogously to Example 101 from N-[2-(4-amino-3,5-dichloro-phenyl)ethyl]-N-[2-(4methoxy-phenyl)-ethyl]amine, acetaldehyde and sodium cyanoborohydride in ethanol. Oil.

IR spectrum (methylene chloride): NH2 3890+3480 cm- OCH3 2830+2940 cm- aromat. C=C 1620 cm- UV spectrum (ethanol): A max. 244 nm (0.16) 284 nm (shoulder; 0.04) 300 nm (0.04) Example 179 N-[1-Methyl-2-(4-amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4-methoxy-phenyl)-propyl]methylamine Prepared analogously to Example 101 from 1-(4'-amino-3',5'-dichloro-phenyl)-acetone, 3-(4methoxy-phenyl)-N-methyl-propylamine and sodium cyanoborohydride in ethanol. Oil.

IR spectrum (methylene chloride): NH2 3390+3480 cm- OCH3 2840+2940 cm~' aromat. C=C 1615 cm-' UV spectrum (ethanol): A max. 242 nm (0.14) 280 nm (shoulder; 0.04) 302 nm (0.05) Example 180 N-[2-(4-Amino-3,5-dichyloro-phenyl)-ethyl]-N-(3-phenylpropyl)-isopropylamine Hydrochloride Prepared analogously to Example 101 from N-[2-(4-amino-3,5-dichloro-phenyl)-ethyl]-3-phenylpropylamine, acetone, molecular sieve 3 and sodium cyanoborohydride in absolute methanol. Foam.

IR spectrum (methylene chloride): NH2 3390+3490 cm~1 NH# 2300-2400 cm- UV spectrum (ethanol): A max. 245 nm (0.12) 302 nm (0.04) Example 181 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-(1-methyl-3-phenyl-propyl)-methylamino]ethanol Hydrochloride Prepared analogously to Example 101 from 1-(4-amino-3,5-dichlorophenyl)-2-[N-(1-methyl-3phenyl-propyl)-amino]ethanol, paraformaldehyde and sodium cyanoborohydride in ethanol. Oil hydrochloride.

IR spectrum (methylene chloride): NH2 3390+3490 cm- NH+ 23O0-240Ocm1 OH 3580 cm- UV spectrum (ethanol:) A max. 245 nm (0.12) 302 nm (0.03) Example 182 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-(1-methyl-3-phenyl-propyl)-methylamino]ethanol Hydrochloride Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro-phenyl)-2-[N-(1-methyl-3phenyl-propyl)-amino]ethanol, paraformaldehyde and sodium cyanoborohydride in absolute ethanol.

M.p. of the hydrochloride: 170-1 730C.

Example 183 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-(1-methyl-3-phenyl-propyl)-propylamino]ethanol Hydrochloride Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro-phenyl)-2-[N-(1-methyl-3phenyl-propyl)-amino]ethanol, propionaldehyde and sodium cyanoborohydride. Oil hydrochloride.

IR spectrum (methylene chloride): NH2 3390+3490 cm- NH+ 2300-2400 cm- OH 3590+3680 cm- UV spectrum (ethanol): A max. 245 nm (0.12) 302 nm (0.03) Example 184 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-(3-phenyl-propyl)-n-propylamine Hydrochloride Prepared analogously to Example 101 from N-[2-(4-amino-3,5-di propylamine, propionaldehyde and sodium cyanoborohydride in absolute ethanol. Oily hydrochloride.

IR spectrum (methylene chloride): NH2 3390+3490 cm~' NH# 2300-2400 cm- OH 3600+3650 cm~ UV spectrum (ethanol): A max. 245 nm (0.17) 302 nm (0.05) Example 185 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-(3-phenyl)-propyl)-ethylamine Hydrochloride Prepared analogously to Example 101 from N-[2-(4-amino-3,5-dichloro-phenyl)-ethyl]-3-phenyl- propylamine, acetaldehyde and sodium cyanoborohydride in absolute ethanol. Oily hydrochloride.

IR spectrum (methylene chloride): NH2 3390+3490 cm~' NH3 2300-2400 cm- UV spectrum (ethanol): A max. 245 nm (0.12) 302 nm (0.04) Example 186 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-(1 -methyl-3-phenyl-propyl)-ethylamine Hydrochloride Prepared analogously to Example 101 from N-[2-(4-amino-3,5-dichloro-phenyl)-ethyl]-N-(1- methyl-3-phenyl-propyl]amine, acetaldehyde and sodium cyanoborohydride in absolute ethanol. Oily hydrochloride.

IR spectrum (methylene chloride): NH2 3390+3490 cm-l UV spectrum (ethanol): A max. 243 nm (0.11) 300 nm (0.04) Example 187 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-(1-methyl-2-phenoxy-ethyl)-ethylamino]ethanol Hydrochloride Prepared analogously to Example 101 from 1-(4-amino-3,5-dichlorophenyl)-2-[N-(1-methyl-2- phenoxy-ethyl)-amino]ethanol, acetaldehyde and sodium cyanoborohydride in absolute ethanol. Oily hydrochloride.

IR spectrum (methylene chloride): NH2 3390+3490 cm- NH# 2320-2468 cm- OH 3600+3680 cm~' UV spectrum (ethanol): A max. 248 nm (0.12) 300 nm (0.03) Example 188 1-(4-Amino-3-cyano-5-fluoro-phenyl)-2-[N-[2-(3,4-dimethoxy-phenyl)-ethyl]ethylamino]ethanol Prepared analogously to Example 101 from 1-(4-amino-3-cyano-5-fluoro-phenyl)-2-[N-[2-(3,4- dimethoxy-phenyl)-ethyl]amino]ethanol, acetaldehyde and sodium cyanoborohydride in ethanol. Oil.

IR spectrum (methylene chloride): NH2 3390+3490 cm~' CN 2205 cm- UV spectrum (ethanol): A max. 240 nm (shoulder; 0.16) 280 nm (0.04) 325 nm (0.06) Example 189 1-(4-Amino-3-chloro-5-fluoro-phenyl)-2-[N-[2-(3,4-methylene-dioxy-phenoxy)-1-methylethyl]ethylamino]ethanol Hydrochloride Prepared analogously to Example 101 from 1-(4-amino-3-chloro-5-fluoro-phenyl)-2-[N-[2-(3,4- methylenedioxy-phenoxy)-1-methyl-ethyl]amino]ethanol, acetaldehyde and sodium cyanoborohydride in absolute ethanol. Oily hydrochloride.

IR spectrum (methylene chloride): NH2 3390+3490 cm- NH# 2300-2450 cm- OH 3600+3680 cm~ UV spectrum (ethanol): A max. 243nm(0.17) 287 nm (0.07) Example 190 1-(4-Amino-3-bromo-5-fluoro-phenyl)-2-[N-(1-methyl-2-phenoxy-ethyl)-ethylamino]ethanol Prepared analogously to Example 101 from 1 -(4-amino-3-bromo-5-fluoro-phenyl)-2-[N-( 1 - methyl-2-phenoxy-ethyl)-amino]ethanol, acetaldehyde and sodium cyanoborohydride in absolute ethanol. Oil.

IR spectrum (methylene chloride): NH2 3390+3490 cm~ UV spectrum (ethanol): A max. 240 nm (0.14) 280-290 nm (0.03) Example 191 1-(4-Amino-3-cyano-5-fluoro-phenyl)-2-[N-[3-(4-methoxy-phenyl)-propyl]ethylamino]ethanol Hydrochloride Prepared analogously to Example 101 from 1 -(4-amino-3-cyano-5-fluoro-phenyl)-2-[N-[3-(4- methoxy-phenyl)-propyl]amino]ethanol, acetaldehyde and sodium cyanoborohydride in absolute ethanol. Oily hydrochloride.

IR spectrum (methylene chloride): NH2 3390+3490 cm~' NH# 2300-2500 cm- CN 2205 cm-l OH 3590+3680 cm- UV spectrum (ethanol): Amax. 248 nm (0.11) 280 nm (0.03) 320 nm (0.06) Example 192 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4-fluoro-phenyl)-propyl]benzylamine Hydrochloride Prepared analogously to Example 101 from N-[2-(4-amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4- fluoro-phenyl)-propyl]amino, benzaldehyde and sodium cyanoborohydride in absolute ethanol.

M.p. of the hydrochloride: 118-1 200C.

Example 193 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4-fluoro-phenyl)-propy]-n-propylamine Hydrochloride Prepared analogously to Example 101 from N-[2-(4-amino-3,5-dichloro-phenyl)-ethyl]-N [3-(4- fluoro-phenyl)-propyl]amine, propionaldehyde and sodium cyanoborohydride in absolute ethanol.

M.p. of the hydrochloride: 13O1330 C.

Example 194 N-[2-(4-Amino-3,5-dichloor-phenyl)-ethyl]-N-[3-(4-fluoro-phenyl)-propyl]ethylamine Hydrochloride Prepared analogously to Example 101 from N-[2-(4-amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4- fluoro-phenyl)-propyl]amine, acetaldehyde, molecular sieve 3A and sodium cyanoborohydride in absolute methanol.

M.p. of the hydrochloride: 1 82-1 840C (decomp.).

Example 195 n-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4-fluoro-phenyl)-propyl]isopropyl-amine Hydrochloride Prepared analogously to Example 101 from N-[2-(4-amino-3,5-dichloro-phenyl)-ethylj-N-[3-(4- fluoro-phenyl)-propyl]-amine, acetone, molecular sieve 3A and sodium cyanoborohydride in absolute methanol.

M.p. of the hydrochloride: 182-1840C (decomp.).

Example 196 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-fluoro-phenyl)-propyl]-2-phenylethylamino]ethanol Hydrochloride Prepared analogously to Example 101 from 1 -(4-amino-3,5-dichloro-phenyl)-2-[N-[3-(4-fluoro- phenyl)-propyl]amino]ethanol, phenylacetaldehyde and sodium cyanoborohydride in absolute ethanol.

Amorphous hydrochloride.

IR spectrum (methylene chloride): NH2 3390+3490 cm~1 NH0 2300 -3500 cm-' OH 3590+3680 cm~ UV spectrum (ethanol): A max. 243 nm (0.11) 300 nm (0.04) Example 197 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-fluoro-phenyl)-propyl]benzylamino]ethanol Hydrochloride Prepared analogously to Example 101 from 1 -(4-amino-3,5-dichloro-phenyl)-2-[N-[3-(44luoro- phenyl)-propyl]aminoethanol, benzaldehyde and sodium cyanoborohydride in absolute ethanol.

M.p. of the hydrochloride: 132-1 340C (decomp.).

Example 198 1 -(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-fluoro-phenyl)-propyl]-n-propylamino]ethanol Hydrochloride Prepared analogously to Example 101 from 1 -(4-amino-3,5-dichloro-phenyl)-2-[N-[3-(44luoro- phenyl)-propyl]amino]ethanol, propionaldehyde and sodium cyanoborohydride in absolute ethanol.

M.p. of the hydrochloride: 136-1 380C (decomp.).

Example 199 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-fluoro-phenyl)-propyl]ethylamino]ethanol Hydrochloride Prepared analogously to Example 101 from 1 -(4-amino-3,5-dichloro-phenyl)-2-[N-[3-(4-fluoro- phenyl)-propyl]amino]ethanol, acetaldehyde and sodium cyanoborohydride in absolute ethanol.

M.p. of the hydrochloride: 130-1 340 C.

Example 200 1 -(4-Amino-3,5-dichloro-phenyl)-2-[N-(3-phenyl-propyl )-2-phenyl-ethylamino]ethanol Hydrochloride Prepared analogously to Example 101 from 1 -(4-amino-3,5-dichloro-phenyl)-2-[N-(3-phenyl- propyl)-amino]ethanol, phenylacetaldehyde and sodium cyanoborohydride in absolute ethanol.

Amorphous hydrochloride.

IR spectrum (methylene chloride): NH2 3390+3490 cm- NH 2300--2500cm-' OH 3590+3690 cm- UV spectrum (ethanol): R max. 243 nm (0.12) 300 nm (0.04) Example 201 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-fluoro-phenyl)-propyl]isopropylamino]ethanol Hydrochloride Prepared analogously to Example 101 from 1 -(4-amino-3,5-dichloro-phenyl)-2-[N-[3-(44luoro- phenyl)-propyl]amino]ethanol, acetone, molecular sieve 3A and sodium cyanoborohydride in absolute methanol.

M.p. of the hydrochloride: 80-850C (decomp.).

Example 202 1 -(4-Amino-3,5-dichloro-phenyl)-2-[N-( 1 -methyl-3-phenyl-propyl )-ethylamino]ethanol Prepared analogously to Example 101 from 1 -(4-amino-3,5-dichloro-phenyl)-2-[N-( 1 -methyl-3- phenyl-propyl)-amino]ethanol, acetaldehyde, molecular sieve 3A and sodium cyanoborohydride in absolute ethanol. Oil.

IR spectrum (methylene chloride!: NH2 3390+3490 cm- UV spectrum (ethanol): A max. 245 nm (0.13) 300 nm (0.03) Example 203 1 -(4-Di methylamino-3,5-dichloro-phenyl)-2-[N-(3-phenyl-1 -methyl-propyl)-methylamino]ethanol Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro-phenyl)-2-[N-(3-phenyl-1- methyl-propyl)-amino]ethanol, formaldehyde and sodium cyanoborohydride in absolute ethanol. Oil.

IR spectrum (methylene chloride): OH 3600+3680 cm- N-alkyl 2800 cm- UV spectrum (ethanol): A max. 275 nm (0.03) Example 204 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-(3-phenyl-propyl)-benzylamino]ethanol Prepared analogously to Example 101 from 1 -(4-amino-3,5-dichloro-phenyl)-2-[N-(3-phenyl- propyl)-amino]ethanol, benzaldehyde and sodium cyanoborohydride in absolute ethanol. Oil.

IR spectrum (methylene chloride): NH2 3390+3490 cm-l OH 3600+3680 cm~ UV spectrum (ethanol): A max. 245 nm (0.12) 300 nm (0.03) Example 205 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-methylsulfinyl-phenyl)-propyl]amino]ethanol 1.5 g (0.0039 mol) of 1-(4-amino-3,5-dichloro-phenyl)-2-[N-[3-(4-methylsulfenylphenyl)- propyl]amino]ethanol and 639 mg (0.0078 mol) of anhydrous sodium acetate were dissolved in 60 ml of 50% acetic acid. A solution of 622 mg (0.0039 mol) of bromine in 3 ml of 50% acetic acid was dropped slowly into this solution whilst stirring at room temperature. When the addition was finished the light-brown solution was allowed to stand for 1 hour at room temperature and then was poured into water.The reaction mixture was basified with ammonia up to pH 8.5 whilst cooling with ice and exhaustively extracted with methylene chloride. The combined methylene chloride extracts were dried over sodium sulfate and in vacuo evaporated to dryness. The residue was recrystallized from methanol/ether. Colourless crystals.

M.p.: 127-1290C.

Example 206 1 -(4-Amino-3,5-dichloro-phenyl)- 2-[N-[3-(4-methylsulfenylphenyl)-propyl]amino]ethanol Prepared analogously to Example 5 from 4'-amino-3',5'-dichloroacetophenone, selenium dtoxide, 3-(4-methylsulfenylphenyl)-propylamine and sodium borohydride.

M.p.: 128-1300C.

Example 207 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-methylsulfinylphenyl)-propyl]methylamino]ethanol Prepared analogously to Example 1Q1 from 1 -(4-amino-3,5-dichlorophenyl)-2-[N-[3-(4- methylsulfinyl-phenyl)-propyl]amino]ethanol, paraformaldehyde and sodium cyanoborohydride in methanol. Foam.

IR spectrum (methylene chloride): OH 3660+3600 cm~' NH2 3490+3390 cm- SO 1050 cm- UV spectrum (ethanol): Amax. 242 nm (0.16) 300 nm (0.03) Example 208 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-methylsulfenyl-phenyl)-propyl]methylamino]ethanol Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro-phenyl)-2-[N-[3-(4methylsulfenyl-phenyl)-propyl]amino]ethanol, paraformaldehyde and sodium cyanoborohydride in methanol. Colourless oil.

IR spectrum (methyiene chloride): OH 3690+3590 cm- NH2 3490+3390 cm~' UV spectrum (ethanol): A max. 245 nm (0.23) 295-300 nm (0.04) Example 209 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-chloro-phenyl)-propyl]-n-propylamino]ethanol Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro-phenyl)-2-[N-[3-(4-chlorophenyl)-propyl]amino]ethanol, propionaldehyde and sodium cyanoborohydride in ethanol. Oil.

IR spectrum (methylene chloride): NH2 3390, 3490 cm- aromat. C=C 1620 cm-' UVspectrum (ethanol): A max. 243 nm (0.13) 300 nm (0.04) Example 210 1-(4-Dimethylamino-3,5-dichloro-phenyl)-2-methyl-2-[N-[3-(4-methoxy-phenyl)-propyl]methylamino]ethanol Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro-phenyl)-2-methyl-2-[N-[3-(4methoxy-phenyl)-propyl]amino]ethanol, paraformaldehyde and sodium cyanoborohydride in etnaol at pH 3 to 7.5. Oil.

IR spectrum (methylene chloride): OH 3590 cm-' no NH, NH2 aromat. C=C 1610 cm-' UV spectrum (ethanol): A max. 243 nm (0.20) 278 nm (0.06) Example 211 1-(4-Benzylamino-3,5-dichloro-phenyl)-2[N-[3-(4-chloro-phenyl)-propyl]amino]ethanol Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro-phenyl)-2-[N-[3-(4-chlorophenyl)-propyl]amino]ethanol, benzaldehyde and sodium cyanoborohydride in ethanol.

M.p. of the base: 85-950C.

Example 212 1 -(4-Amino-3,5-dichloro-phenyl )-2-[N-[3-(4-chloro-phenyl )-propyl]benzylamino]ethanol Hydrochloride Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro-phenyl)-2-[N-[3-(4-chlorophenyl)-propyl]amino]ethanol, benzaldehyde and sodium cyanoborohydride in ethanol.

M.p. of the hydrochloride: 110-114 C.

Example 213 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-chloro-phenyl)-propyl]ethylamino]ethanol Prepared analogously to Example 101 from 1 -(4-amino-3,5-dichloro-phenyl)-2-[N-[3-(4-chloro- phenyl)-propyl]amino]ethanol, acetaldehyde and sodium cyanoborohydride in ethanol. Oil.

IR spectrum (methylene chloride): NH2 3390, 3490 cm-' aromat. C=C 1620 cm-' UV spectrum (ethanol): #max 244 nm (0.13) 300 nm (0.04) Example 214 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4-chloro-phenyl)-propyl]methylamine Prepared analogously to Example 101 from N-[2-(4-amino-3,5-dichloro-phenyl)-3-(4-chloro- phenyl)-propylamine, paraformaldehyde and sodium cyanoborohydride in methanol. Oil.

IR spectrum (methylene chloride): NH2 3390,3490 cm-l aromat. C=C 1615 cm-' UV spectrum (ethanol): A max. 241 nm (0.10) 300 nm (0.04) Example 215 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-chloro-phenyl)-propyl]-2-phenylethylamino]ethanol Hydrochloride Prepared analogously to Example 101 from 1 -(4-amino-3,5-dichloro-phenyl)-2-[N-[3-(4-chloro- phenyl)-propyl]amino]ethanol, phenylacetaldehyde and sodium cyanoborohydride in ethanol.

M.p. of the hydrochloride: 103-1 090C (decomp.).

Example 216 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-chloro-phenyl)-propyl]methylamino]ethanol Hydrochloride Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro-phenyl)-2-[N-[3-(4-chloro- phenyl)-propyl]amino]ethanol, paraformaldehyde and sodium cyanoborohydride in ethanol.

M.p. of the hydrochloride: 85-1 000C (decomp.).

Example 217 1 -(3-Chloro-4-piperidino-phenyl)-2-[N-[3-(4-methoxy-phenyl)-propyl] methyla mi no] ethanol Hydrochloride Prepared analogously to Example 1 from 3'-chloro-4'-piperidino-2-[N-[3-(4-methoxy-phenyl)- propyl]methylamino]acetophenone and sodium borohydride in methanol. Oily hydrochloride.

IR spectrum (methylene chloride): OH 3600cm-' OCH3 2840 cm-' NHs 23O0-27O0cm1 UV spectrum (ethanol): A max. 258 nm (0.12) 283 nm (shoulder: 0.05) Example 218 1 -(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(3-methoxy-phenyl)-propyl]amino]ethanol Prepared analogously to Example 5 from 4'-amino-3',5'-dichloro-acetophenone, selenium dioxide, 3-(3-methoxy-phenyl)-propylamine and sodium borohydride.

M.p.: 1240C.

Example 219 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(3-methoxy-phenyl)-propyl]ethylamino]ethanol Prepared analogously to Example 101 from 1 -(4-amino-3,5-dichloro-phenyl)-2-[N-[3-(3- methoxy-phenyl)-propyl]amino]ethanol, acetaldehyde and sodium cyanoborohydride in methanol. Oil.

IR spectrum (methylene chloride): OH 3580 cm- NH2 3490+3390 cm- OCH3 2830 cm- UV spectrum (ethanol): A max. 247 nm (0.06) 300 nm (0.04) Example 220 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(3-methoxy-phenyl)-propyl]methylamino]ethanol Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro-phenyl)-2-[N-[3-(3- methoxy-phenyl)-propyl]amino]ethanol, paraformaldehyde and sodium cyanoborohydride in methanol.

Oil.

IR spectrum (methylene chloride): OH 3680+3620 cm- NH2 3490+3390 cm- OCH3 2840 cm- UV spectrum (ethanol): A max. 246nm(0.15) 300 nm (0.04) Example 221 1 -(3,5-Dichloro-4-isopropyla mino-phenyl-2-[N-[3-(3-methoxy-phenyl)propyl isopropylamino]ethanol Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro-phenyl)-2-[N-[3-(3methoxy-phenyl)-propyl]amino]ethanol, acetone and sodium cyanoborohydride in methanol. Oil.

IR spectrum (methylene chloride): OH 3600 cm-' NH 3350 cm- OCH3 2840 cm- UV spectrum (ethanol): # max. 250 nm (0.12) 278-280 nm (0.03) Example 222 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-chlorophenyl)-propyl]isopropylamino]ethanol Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro-phenyl)-2-[N-[3-(4-chloro- phenyl)-propyl]amino]ethanol, acetone and sodium cyanoborohydride in ethanol. Oil.

IR spectrum (methylene chloride): NH2 3380+3480 cm- aromat. C=C 1615 cm- NMR spectrum (CDCl3/D2O): aromat. H 7.0-7.4 ppm (m, 6H)

4.4 ppm (dd; 1 H) 3.0 ppm (dd; 1 H) aliphat. CH2 2.3-2.7 ppm (m; 6H) 1.6-2.0 ppm (m; 2H) isopropyl-CH3 0.8-1.2 ppm (dd; 6H) Example 223 1 -(4-Amino-3,5-dichloro-phenyl)-2-[N-[3-(4-chlorophenyl)-propyl]-allylamino]ethanol Prepared analogously to Example 13 from 1 -(4-amino-3,5-dichlorophenyl)-2-[N-[3-(4-chloro- phenyl)-propyl]amino]ethanol, ally bromide and triethylamine. Oil.

IR spectrum (methylene chloride): NH2 3380+3480 cm-' aromat. C=C 1610 cm- NMR spectrum (CDCl3/D2O): aromat. H 7.0-7.4 ppm (m; 6H) olefinic H 5.5-6.1 ppm (m; 1H) 5.0-5.3 ppm (m; 2H)

4.3-4.7 ppm (dd; 1 H) 2.8-3.5 ppm (m; 2H) aliphat. CH2 2.2-2.7 ppm (m; 6H) 1.5-2.0 ppm (m; 2H) Example 224 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-n-[3-(4-chloro-phenyl)-propyl]allylamine Prepared analogously to Example 13 from N-[2-(4-amino-3,5-dichloro-phenyl)-ethyl]-3-(4- chlorophenyl)-propylamine, allyl bromide and triethylamine. Oil.

IR spectrum (methylene chloride): NH2 3380+3480 cm-' aromat. C=C 1610 cm-' NMR spectrum (CDCID2O): aromat. H 6.9-7.4 ppm (m; 6H) olefinic H 5.6-6.1 ppm (m; 1 H) 5.0-5.3 ppm (m; 2H)

3.0-3.3 ppm (d; 2H) aliphat. CH2 2.7-3.3 ppm (m; 8H) 1.3-1.9 ppm (m; 2H) Example 225 N-[2-(4-Amino-3,5-dichloro-phenyl)-1-methyl-ethyl]-N-[4-(4-methoxy-phenyl)-butyl]methyl amine Prepared analogously to Example 101 from 4'-amino-3',5'-dichloro-propiophenone, N-[4-(4methoxy-phenyl)-butyl]methylamine and sodium cyanoborohydride. Oil.

IR spectrum (methylene chloride): NH2 3380+3480 cm- aromat C=C 1610 cm-' UV spectrum (ethanol): # max. 245 nm (0.13) 280 nm (broad; 0.04) 300 nm (broad; 0.04) Example 226 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4-methoxy-phenyl)-1-methyl-propylethylamine Prepared analogously to Example 13 from N-[2-(4-amino-3 ,5-dichloro-phenyl)-ethyl]-N-[3-(4- hydroxy-phenyl)-1-methyl-propyl]-ethylamine in tetrahydrofuran with sodium hydroxide solution and dimethyl sulfate. The purification was carried out using aluminium oxide (neutral, activity step I) eluted with ether:petroleum ether=1 :1.5. Oil.

Calc.: C 63.79 H 7.14 Cl 17.94 N 7.09 Found: 63.17 7.09 17.90 7.15 Example 227 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[1,1-dimethyl-3-(4-hydroxy-phenyl)-propyl]methylamine 1.8 ml (0.018 mol) of pyridine borane were added dropwise to a solution of 3 g (0.0075 mol) of 1 -(4-amino-3,5-dichloro-phenyl)-2-[N-[1,1 -dimethyl-3-(4-hydroxy-phenyl)-propyl] methylamino]ethanol in 12 ml of trifluoroacetic acid whilst stirring at --100C. After removing the cooling bath the reaction solution warmed up to room temperature within 30 minutes and was subsequently heated on the steam bath for 60 minutes.After evaporating the trifluoroacetic acid in a rotation evaporator at 500C in vacuo, the evaporation residue was mixed with 40 ml of 2 N sodium hydroxide solution and heated for 30 minutes at 1 200C. After cooling the reaction mixture was carefully acidified with hydrochloric acid and mixed with concentrated ammonia until basic and subsequently extracted twice with 75 ml portions of ether. The ether extracts obtained were washed twice with each 50 ml of water, after combination dried with magnesium sulfate, and in vacuo in a rotation evaporator evaporated to dryness.The evaporation residue was first purified over silica gel 60 (Macherey and Nagel 70-230 mesh, ASTM), eluent:methylene chloride/methanol=2:1. The final purification was carried out using aluminium oxide (neutral, activity step Ill). The eluent used was ether/n-hexane=2:1. After a short time the oily evaporation residue crystallized.

M.p.: 122-1240C.

Example 228 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-[3-(4-hydroxy-phenyl)-1 -methyl-propyl]ethylamine Prepared analogously to Example 227 from 4'-amino-2-bromo-3',5'-dichloro-acetophenone, N [3-(4-hydroxy-phenyl)-1 -methyl-propyl]ethylamine, sodium carbonate in aqueous tetrahydrofuran and subsequent reaction of the obtained reaction product with pyridine-borane in trifluoroacetic acid. The purification was carried out over aluminium oxide (neutral, activity step Ill). Eluent:ether/petroleum ether=2:1. Oil.

IR spectrum (methylene chloride): OH 3590cm-' NH2 3480+3390cm-1 CH2, CH3 2960+2930+2860 cm-' N-alkyl 2810 cm- C=C 1585+1510+1485cm-' UV spectrum (ethanol): A max. 241 nm (0.28 shoulder) 280-302 nm (0.08) (Ethanol+KOH): A max. 241 nm (0.56) 298 nm (0.17) Example 229 1 -(4-Amino-3,5-dichloro-phenyl)-2-tN-[1,1 -dimethyl-3-(4-hydroxy-phenyl)-propyl] methyl- amino]ethanol Prepared analogously to Example 3 from 4'-amino-2-bromo-3',5'-dichloro-acetophenone, N [1,1-dimethyl-3-(4-hydroxy-phenyl)-propyl]methylamine, sodium carbonate and subsequent reduction with sodium borohydride in aqueous tetrahydrofuran. The two purification stages were carried out using silica gel 60 (Macherey and Nagel, 70-230 mesh, ASTM). Eluents ether/tetrahydrofuran=3:1 and then methylene chloride/methanol/conc. ammonia=30:1 :0.3.

M.p.: 155-1580C.

Example 230 1 -(4-Amino-3,5-dichloro-phenyl)-2-[N-[1 1 -dimethyl-3-(4-hydroxy-phenyl)-propyl]amino]ethanol Prepared analogously to Example 3 from 4'-amino-2-bromo-3',5'-dichloro-acetophenone,1.1- dimethyl-3-(4-hydroxy-phenyl)-propylamine, sodium carbonate and reduction with sodium borohydride in aqueous tetrahydrofuran. The purification was carried out using silica gel 60 (Macherey and Nagel, 70-230 mesh, ASTM). Eluent: a mixture of methylene chloride/methanol/conc.

ammonia=25:1 :0.2.

M.p.: 142-1440C.

Example 231 N-[3-(4-Chlorophenyl)-propyl]-N-[2-(3,5-dichloro-4-isopropyl-amino-phenyl)-ethyl]isopropylamine Prepared analogously to Example 101 from N-[2-(4-amino-3,5-dichlorophenyl)-ethyl]-[3-(4- chloro-phenyl)-propyl]amine, acetone and sodium cyanoborohydride. Oil.

NMR spectrum (CDCl3): aromat. H 7-7.3 ppm (m; 6H)

3.5-4.1 ppm (m; 1 H) approx. 3 ppm (m; 1 H) aliphat. H 2.3-2.7 ppm (m; 8H) 1.5-2.0 ppm (m; 2H) 0.9-1.3 ppm (dd; 12H) Example 232 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-(1 -methyl-3-phenyl-propyl)-methylamine Prepared analogously to Example 101 from N-[2-(4-amino-3,5-dichloro-phenyl)-ethyl]-N-( 1 - methyl-3-phenyl-propyl)-amine, paraformaldehyde and sodium cyanoborohydride. Oily hydrochloride.

IR-spectrum (methylene chloride): NH2 3390+3490 cm- CH2 2930 cm- UV-spectrum (ethanol): A max. 243 nm (0.12) 300 nm (0.04) Example 233 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl]-N-(1-methyl-3-phenyl-propyl]-n-propylamine Prepared analogously to Example 101 from N-[2-(4-amino-3,5-dichloro-phenyl)-ethyl]-N-(1- methyl-3-phenyl-propyl)-amine, propionaldehyde and sodium cyanoborohydride. Oily hydrochloride.

IR-spectrum (methylene chloride): NH2 3390+3490 cm- CH2 2930 cm- UV-spectrum (ethanol): A max. 245 nm (0.11) 300 nm (0.04) Example A Tablets containing 25 mg of 1 -(4-amino-3,5-dichloro-phenyl)-2-[N-(4-phenyl-propyl)-2- propylamino]ethanol Hydrochloride Composition: 1 tablet contains: Active ingredient 25.0 mg Corn starch 30.0 mg Lactose 61.5 mg Gelatine 3.0 mg Magnesium stearate 0.5 mg 120.0 mg Method of Preparation: The active ingredient, corn starch and lactose were mixed, homogeneously moistened with an aqueous gelatine solution and granulated. After drying in a circulating drier and screening (1.5 mm mesh size) the lubricant was mixed thereto. The mixture thus obtained was pressed into tablets.

Form: biplanar with a dividing slot on one side and a facet on both sides Diameter: 7 mm Weight: 120 mg.

Example B Coated Tablets containing 10 mg of 1 -(4-a mino-3,5-dichloro-phenyl)-2-[N-(3-phenyl-propyl)-2- propylamino]ethanol Hydrochloride 1 coated tablet core contains: Active ingredient 10.0 mg Corn start 35.0 mg Lactose 71.5 mg Gelatine 3.0 mg Magnesium stearate 0.5 mg 120.0 mg Method of Preparation: Prepared analogously to Example A.

The mixture obtained was pressed into cores, which were then coated with a sugar paste up to a weight of 160 mg, and subsequently coated with pure sugar syrup up to a weight of 1 65 mg and polished.

Example C Capsules containing 20 mg of 1 -(4-a mino-3,5-dichloro-phenyl)-2-[N-(3-phenyl-propyl)-2-propyl- amino]ethanol Hydrochloride 1 Capsule contains: Active ingredient 20.0 mg Lactose pulverized 114.0 mg Corn starch 60.0 mg Soluble starch 5.0 mg Magnesium stearate 1.0 mg 200.0 mg Method or Preparation: The active ingredient was homogeneously mixed with the other auxiliary products and the mixture obtained was filled into gelatine capsules by means of a capsule filiing machine.

Capsule shot weight: 200 mg.

Example D Drops containing 20 mg/5 ml of 1-(4-amino-3,5-dichloro-phenyl)-2-[N-(3-phenyl-propyl)-2- propylamino]ethanol Hydrochloride 100 ml of drop solution contain: Active ingredient 0.4 g Hydroxyethyl cellulose 0.15g Tartaric acid 0.1 g Sorbite solution 70% dry 30.0 g Glycerine 10.0 g Benzoic acid 0.159 Water distilled ad 100.0 ml Method of Preparation: The hydroxyethyl cellulose, as well as the benzoic acid and tartaric acid were dissolved whilst stirring in the water heated up to 700 C. The solution obtained was cooled to room temperature and the glycerine and the sorbite solution were added with stirring. The active ingredient was added at room temperature, whereby stirring was continued until it was completely dissolved. The resultant juice was deaerated in vacuo under stirring.

Example E Suppositories containing 50 mg of 1-(4-amino-3,5-dichloro-phenyl)-2-[N-(3-phenyl-propyl)-2- propylamine]ethanol Hydrochloride 1 Suppository contains: Active ingredient 0.05 g Hard fat (e.g. Witepsol W 45) 1.65 g 1.70 g Method of Preparation: The hard fat was melted. At 380C the pulverized active ingredient was dispersed in the melt. The liquid mixture thus formed was cooled to 350C and poured into slightly pre-cooled suppository moulds.

Weight of suppository: 1.7 g.

Example F Ampoules containing 20 mg of 1 -(4-amino-3,5-dichloro-phenyl)-2-[N-(3-phenyl-propyl)-2- propylamino]ethanol Hydrochloride 1 Ampoule contains: Active ingredient 20.0 mg Citric acid 12.5 mg Sodium monohydrogen phosphate 37.5 mg Sorbite 36.5 mg Water for injection ad 5.0 ml Method of Preparation: The active ingredient, citric acid and sodium monohydrogen phosphate and sorbite were successively dissolved in the water for injection at room temperature.

After filling up to the calibration mark the solution was filtered through a membranous filter and filled into cleaned and sterilized ampoules.

Sterilisation: 20 minutes at 121 C.

Claims

1. Compounds of general formula I

[wherein R, represents a hydroxy group, an amino group (optionally substituted by an alkanoyl group containing 1 to 3 carbon atoms or an alkoxycarbonyl group containing 2 to 4 carbon atoms) or an alkylamino or dialkylamino group in which each alkyl part may contain from 1 to 3 carbon atoms and may each optionally be substituted by a phenyl group; R2 and R3, which may be the same or different, each represents a halogen atom or a trifluoromethyl, cyano or nitro group, or one of the radicals R2 or R3 represents a hydrogen atom;R4 represents a hydrogen atom or an alkyl group containing 1 to 3 carbon atoms; P5 represents a hydrogen atom, a straight-chained or branched alkyl group containing 1 to 4 carbon atoms, a cycloalkyl group containing 3 to 6 carbon atoms, an alkenyl group containing 2 to 5 carbon atoms or an aralkyl group containing 7 to 10 carbon atoms; A represents a methylene, ethylene or hydroxymethylene group; and B represents a group of formula

wherein R6 represents a hydrogen or halogen atom, a hydroxy group, an alkoxy group containing 1 to 3 carbon atoms optionally substituted by a phenyl group, or an alkylsulfenyl or alkylsulfinyl group containing 1 to 3 carbon atoms and R7 represents a hydrogen atom, a hydroxy group or an alkoxy group containing 1 to 3 carbon atoms, or R6 and R7 together represent a methylenedioxy group;R8 represents a hydrogen atom or an alkyl group containing 1 to 3 carbon atoms; D represents an oxygen or sulfur atom, or a sulfinyl or sulfonyl group; n is 1 or 2; and E represents a straight-chained alkylene group containing 3 to 5 carbon atoms optionally substituted by one or two alkyl groups containing 1 to 3 carbon atoms each, or (when A represents a methylene or ethylene group, and/or R1 represents an amino group substituted by an alkanoyl group containing 1 to 3 carbon atoms or by an alkoxycarbonyl group containing 2 to 4 carbon atoms, a hydroxy group or an alkylamino or dialkylamino group in which each alkyl part may contain from 1 to 3 carbon atoms and each may optionally be substituted by a phenyl group, and/or R2 represents a trifluoromethyl, cyano or nitro group, and/or R3 represents a fluorine atom, and/or R4 represents an alkyl group containing 1 to 3 carbon atoms, and/or R5 represents an alkyl group containing 1 to 4 carbon atoms, a cycloalkyl group containing 3 to 6 carbon atoms, an alkenyl group containing 2 to 5 carbon atoms, or an aralkyl group containing 7 to 10 carbon atoms, and/or R6 represents a fluorine or chlorine atom, or an alkylsulfenyl or alkylsulfinyl group containing 1 to 3 carbon atoms each) E may further represent an ethylene group or (when A represents a methylene group) E may further represent a group of formula

2. Physiologically compatible acid addition salts of compounds of formula I as defined in claim 1.

3. Salts as claimed in claim 2 formed with hydrochloric, hydrobromic, sulfuric, phosphoric, furmaric, succinic, lactic, citric, tartaric or maleic acid.

4. Compounds as claimed in any one of the preceding claims, wherein R, represents an amino group (optionally substituted by a benzyl group or an alkoxycarbonyl group containing 2 to 4 carbon atoms) or an alkylamino or dialkylamino group in which each alkyl part may contain from 1 to 3 carbon atoms; R2 represents a hydrogen, chlorine, bromine, or iodine atom or a trifluoromethyl, cyano or nitro group; R3 represents a fluorine or bromine atom or a cyano group; R4 represents a hydrogen atom or a methyl group; P5 represents a hydrogen atom, an alkyl group containing 1 to 3 carbon atoms (optionally substituted by a phenyl group) or an allyl or cyclopropyl group;A represents a methylene, ethylene or hydroxymethylene group; and B represents a group of formula

wherein R8, D and n are as defined in claim 1; R6 represents a hydrogen, fluorine or chlorine atom or a hydroxy, methoxy, ethoxy, benzyloxy, methylsulfenyl or methylsulfinyl group and R7 represents a hydrogen atom or a methoxy group, or R6 and R7 together represent a methylenedioxy group; and E represents an n-propylene, 1 -methyl-n-propylene, 1,1 -dimethyl-n-propylene or n-butylene group or (when A represents a methylene or ethylene group, and/or R, represents an amino group optionally substituted by a benzyl group or an alkoxycarbonyl group containing 2 to 4 carbon atoms or an alkylamino or dialkylamino group, wherein each alkyl part may contain from 1 to 3 carbon atoms, and/or R2 represents a trifluoromethyl, cyano or nitro group, and/or R3 represents a fluorine atom, and/or P5 represents an alkyl group containing 1 to 3 carbon atoms optionally substituted by a phenyl group, or an alkyl or cyclopropyl group) E may further represent an ethylene group.

5. Compounds as claimed in claim 4, wherein R, represents an amino group (optionally substituted by an ethoxycarbonyl group), or an alkylamino or dialkylamino group in which each alkyl part may contain from 1 to 3 carbon atoms; R2 represents a hydrogen, chlorine or bromine atom or a cyano group; R3 represents a fluorine or chlorine atom or a cyano group; R4 represents a hydrogen atom or a methyl group; P5 represents a hydrogen atom, an alkyl group containing 1 to 3 carbon atoms (optionally substituted by a phenyl group) or an allyl or cyclopropyl group;A represents a methylene or hydroxymethylene group; and B represents a group of formula

wherein E represents an n-propylene, l-methyl-n-propylene, 1 ,1-dimethyl-n-propylene or n-butylene group, or (when R, represents an ethoxycarbonylamino group, and/or R2 represents a cyano group, and/or R3 represents a fluorine atom, and/or P5 represents an alkyl group containing 1 to 3 carbon atoms optionally substituted by a phenyl group, or an allyl or cyclopropyl group) E may further represent an ethylene group; R6 represents a hydrogen atom or a hydroxy or methoxy group, and R7 represents a hydrogen atom or a methoxy group.

6. Compounds as claimed in claim 4 wherein R, represents an amino, dimethylamino or alkylamino group containing 1 to 3 carbon atoms in the alkyl part; R2 represents a chlorine or bromine atom; R3 represents a fluorine or chlorine atom or one of the radicals R2 or P3 further represents a cyano group; R4 represents a hydrogen atom or a methyl group; P5 represents a hydrogen atom, an alkyl group containing 1 to 3 carbon atoms or an allyl group;A represents a methylene or hydroxymethylene group; and B represents an n-propyl, 1 -methyl-n-propyl or 1,1 -dimethyl-n-propyl group each of which is substituted in the 3-position by a phenyl, 4-hydroxyphenyl, 4-methoxyphenyl or 4-chlorophenyl group) or (when P5 represents an alkyl group containing 1 to 3 carbon atoms or an allyl group and/or R2 represents a cyano group) B may further represent a 2-(3,4-dimethoxyphenyl)-ethyl group.

7. Compounds as claimed in claim 6 wherein B represents an n-propyi, l-methyl-n-propyl or 1,1dimethyl-n-propyl group substituted in the 3-position by a phenyl, 4-hydroxyphenyl, 4-methoxyphenyl, 4-chlorophenyl or a 4-(4-methoxyphenyl)-butyl group.

8. 1 -(4-Amino-3,5-dichloro-phenyl)-2-[N-(3-phenyl-propyl)-2-propylamino]ethanol.

9. 1 -(4-Amino-3,5-dichloro-phenyl)-2-[N-[ 1,1 -dimethyl-3-(4-hydroxy-phenyl)-propyl]amino]ethanol.

10. Physiologically compatible acid addition salts of compounds as claimed in claim 8 or claim 9.

11. Hydrochloric, hydrobromic, sulphuric, phosphoric, fumaric, succinic, lactic, citric, tartaric or maleic acid addition salts of compounds as claimed in claim 8 or claim 9.

12. Compounds as claimed in claim 1 wherein R, represents a hydroxy group, or an amino group optionally substituted by an alkanoyl group containing 1 to 3 carbon atoms or by an alkoxycarbonyl group containing 2 to 4 carbon atoms; P5 represents a hydrogen atom, a straight-chained or branched alkyl group containing 1 to 4 carbon atoms, a cycloalkyl group containing 3 to 6 carbon atoms or an aralkyl group containing 7 to 10 carbon atoms; and R6 represents a hydrogen or halogen atom, a hydroxy group, or an alkoxy group containing 1 to 3 carbon atoms optionally substituted by a phenyl group and R7 represents a hydrogen atom a hydroxy group or an alkoxy group containing 1 to 3 carbon atoms or R6 and R, together represent a methylenedioxy group; and E represents a straight-chained alkylene group containing 3 to 5 carbon atoms optionally substituted by an alkyl group containing 1 to 3 carbon atoms or (when A represents a methylene or ethylene group, and/or R, represents an amino group substituted by an alkanoyl group containing 1 to 3 carbon atoms or an alkoxycarbonyl group containing 2 to 4 carbon atoms in total, and/or R2 represents a trifluoromethyl, cyano or nitro group, and/or R3 represents a fluorine atom, and/or R4 represents an alkyl group containing 1 to 3 carbon atoms, and/or P5 represents an alkyl group containing 1 to 4 carbon atoms, a cycloalkyl group containing 3 to 6 carbon atoms or an aralkyi group containing 7 to 10 carbon atoms and/or R6 represents a fluorine or a chlorine atom) E may further represent an ethylene group, or (when A represents a methylene group) E may further represent a group of formula

wherein P9 represents an alkyl group containing 1 to 3 carbon atoms.

13. Compounds as claimed in claim 1 as herein described in any one of the examples.

14. Compounds as claimed in claim 1 as herein described in any one of Examples 1 to 20 and 23 to 104.

1 5. A process for the preparation of compounds as claimed in claim 1, which comprises reducing a compound of general formula II.

wherein R1, R2, R3, P5 and B are as defined in claim 1, and X represents a group of formula

-CH2-CO-,

wherein R4 is as defined in claim 1, acyl represents an organic acyl group, and Z represents a reductively cleavable group.

1 6. A process as claimed in claim 1 5 wherein Z represents a bromine or iodine atom or a carbonic ester radical.

1 7. A process as claimed in claim 1 5 or claim 16 wherein the reaction is carried out in a solvent at temperatures between -200C and the boiling point of the reaction mixture.

18. A process as claimed in any one of claims 1 5 to 17 wherein the reduction is carried out using a hydride, aluminium isopropylate in the presence of a primary or secondary alcohol, catalytically activated hydrogen, or nascent hydrogen.

1 9. A process as claimed in claim 1 8 for the preparation of compounds as claimed in claim 1 wherein A represents a hydroxymethylene group, wherein the reduction is effected using a complex metal hydride, aluminium isopropylate, catalytically activated hydrogen, or nascent hydrogen.

20. A process as claimed in claim 1 8 for the preparation of compounds as claimed in claim 1 wherein A represents a methylene or ethylene group, wherein the reduction is effected using a complex metal hydride.

21. A process as claimed in claim 20 in which the said complex metal hydride is sodium borohydride, sodium cyanoborohydride or lithium aluminium hydride.

22. A process as claimed in claim 18 for the preparation of compounds as claimed in claim 1 wherein A represents a methylene or ethylene group, wherein the reduction is effected using pyridineborane.

23. A process for the preparation of compounds as claimed in claim 1 which comprises reacting a carbonyl compound, optionally formed in the reaction mixture, of general formula III K-L, (III) (wherein K together with a neighbouring hydrogen atom in the alkyl part of the radical L represents an oxygen atom;L has one of the meanings listed in claim 1 for B or (with the exception of a hydrogen atom) for R5 or represents a group of formula

wherein P1, R2, R3 and R4 are as defined in claim 1, and A' represents a carbonyl, methylene or ethylene group) or an aldehyde hydrate thereof with an amine of general formula IV

(wherein M and Q,which are different, represent B and R5 as defined in claim 1, or one of the radicals M or 0 represents a group of formula

wherein P1, R2, R3, R4 and A are as defined in claim 1) and with a reducing agent.

24. A process as claimed in claim 23 wherein the reaction is carried out in a solvent at temperatures between -20 and the boiling point of the solvent used.

25. A process as claimed in claim 23 or claim 24 wherein the reduction is effected using a complex metal hydride or catalytically activated hydrogen.

26. A process as claimed in claim 23 or claim 24 wherein an amine centre is methylated using formic acid and formaldehyde.

27. A process as claimed in any one of claims 23 to 26 wherein the reaction is carried out at the boiling point of the reaction mixture.

28. A process for the preparation of compounds as claimed in claim 1, which comprises removing one or more protecting groups from a compound of general formula V

wherein R2, R3 and R4 are as defined in claim 1; P1, represents R1 as defined in claim 1 or a hydroxy or amino group protected by a protective radical;A" represents A as defined in claim 1 or a hydroxymethylene group protected by a protective radical; P5, represents P5 as defined in claim 1 or a protective radical for an amino group; and B' represents B as defined in claim 1 or a group of formula

wherein R8, D, E and n are as defined in claim 1; and P6, and R7', which may be the same or different, represent R6 and R7 respectively as defined in claim 1 or each represents a hydroxy group protected by a protective radical, wherein at least one of the radicals R,', A", P5, and/or B' represents or must contain one of the above-mentioned protective radicals.

29. A process as claimed in claim 28 wherein the reaction is carried out in a solvent at temperatures between 0 and 100 C.

30. A process as claimed in claim 28 or 29 wherein the protecting group or groups is/are chosen from acyl or alkoxycarbonyl groups.

31. A process as claimed in claim 30 wherein one or more acyl or alkoxycarbonyl groups used as protecting groups is/are removed hydrolytically using an acid or base.

32. A process as claimed in claim 31 when carried out in an aqueous medium.

33. A process as claimed in claim 30 wherein one or more benzyl groups used as protecting groups is/are removed hydrogenolytically.

34. A process for the preparation of compounds as claimed in claim 1, which comprises dehalogenating a compound of general formula VI

wherein R,, R3, R4, RE, A and B are as defined in claim 1; and Hal represents a chlorine, bromine or iodine atom.

35. A process as claimed in claim 34 wherein the reaction is carried out in a solvent.

36. A process as claimed in claim 34 or 35 wherein the dehalogenation is effected using triphenylphosphine, using hydrogen in the presence of a hydrogenation catalyst or using a complex metal hydride.

37. A process as claimed in any one of claims 34 to 36 wherein the reaction is carried out at temperatures between 0 and 1 500C.

38. A process for the preparation of compounds as claimed in claim 1, which comprises alkylating a compound of general formula VII

wherein R1, R2, R3, R4 and A are as defined in claim 1; P5'I represents P5 as defined in claim 1 and B" represents B as defined in claim 1 whereby, if P5,, does not represent a hydrogen atom, at least one of the radicals R6 or R7 must represent a hydroxy group or R1 must represent an amino group optionally substituted by an alkyl group containing 1 to 3 carbon atoms, which alkyl group may optionally be substituted by a phenyl group.

39. A process as claimed in claim 38 wherein the reaction is carried out in a solvent at temperatures between -10 and 500 C.

40. A process as claimed in claim 38 or claim 39 wherein the alkylation of a nitrogen atom is effected by means of the corresponding alkyl halide or alkyl sulfate, by means of a corresponding carbonyl compound and a complex metal hydride, or by means of formaldehyde and formic acid.

41. A process as claimed in claim 38 or 39 wherein the alkylation of a phenolic hydroxy group is effected using the corresponding alkyl halide, alkyl sulfate or diazoalkane.

42. A process for the preparation of compounds as claimed in claim 1 wherein R1 represents an amino group substituted by an alkanoyl group containing 1 to 3 carbon atoms or an alkoxycarbonyl group containing 2 to 4 carbon atoms, and R5 does not represent a hydrogen atom, which comprises reacting a compound of general formula VIII

(wherein R2, R3, R4, R,, A and B are as defined in claim 1), with a compound of formula IX Y-CO-R10, (IX) (wherein R10 represents a hydrogen atom, a methyl or ethyl group or an alkoxy group containing 1 to 3 carbon atoms; and Y represents a nucleophilically exchangeable group).

43. A process as claimed in claim 42 wherein Y represents a halogen atom, a nitrophenyl radical, an imidazolyl group or a group of formula --OO-COR,, wherein R10 is as defined in claim 42.

44. A process as claimed in claim 42 or claim 43 wherein the reaction is carried out in a solvent.

45. A process as claimed in any one of claims 42 to 44 wherein the reaction is carried out at temperatures from 0 to 100 C.

46. A process as claimed in any one of claims 38 to 45 wherein the reaction is carried out in the presence of a base.

47. A process for the preparation of compounds as claimed in claim 1 wherein D represents a sulfinyl or sulfonyl group, which comprises oxidizing a compound of general formula X

wherein R1, R2, R3, R4, R,, R6, R7, R8, A and n are as defined in claim 1; and m is O or 1.

48. A process as claimed in claim 47 wherein the reaction is carried out in a solvent at temperatures between -80 and 100 C.

49. A process as claimed in claim 47 or claim 48 for the preparation of compounds as claimed in claim 1 wherein D represents a sulfinyl group, wherein the oxidation is carried out with an equimolar amount of the oxidising agent.

50. A process as claimed in claim 49 wherein the reaction is carried out at temperatures between -20 and 600C.

51. A process as claimed in claim 47 or claim 48 for the preparation of compounds as claimed in claim 1 wherein D represents a sulfonyl group, wherein the oxidation is carried out with one or with two or more moles of oxidising agent per mole of the compound of formula X.

52. A process for the preparation of compounds as claimed in claim 1 wherein D represents an oxygen or sulfur atom and R5 is as defined in claim 1 , with the exception of a hydrogen atom, which comprises reacting a compound of general formula Xl,

(wherein R1, R2, R3, R4, R5, R8 and n are as defined in claim 1, V represents a nucleophilically exchangeable group and A''' represents a methylene or ethylene group) with a compound of general formula XII

(wherein R6 and R7 are as defined in claim 1 and D' represents an oxygen or sulfur atom) or an alkali metal salt or alkaline earth metal salt thereof.

53. A process as claimed in claim 52 wherein the reaction is carried out in a solvent.

54. A process as claimed in claim 53 wherein the reaction is carried out at temperatures between --1 OOC and the boiling point of the solvent used.

55. A process as claimed in claim 54 wherein the reaction is carried out at temperatures between -10 and 500C.

56. A process as claimed in any one of claims 15 to 55 wherein a compound of formula I containing one or more chiral centres initially obtained is subsequently resolved into its optical isomers and diastereoisomeric racemates and their optical enantiomers.

57. A process as claimed in any one of claims 15 to 56 wherein a compound of formula I initially obtained is subsequently converted into an acid addition salt thereof or an acid addition salt of a compound of formula I initially obtained is subsequently converted into a compound of formula I.

58. A process as claimed in any one of claims 1 5 to 57 for the preparation of compounds as claimed in claim 12.

59. A process for the preparation of compounds as claimed in claim 1 substantially as herein described in any one of the Examples.

60. A process for the preparation of compounds as claimed in claim 12 substantially as herein described in any one of Examples 1 to 20 and 23 to 104.

61. Compounds as claimed in claim 1 when prepared by a process as claimed in any one of claims 1 5 to 60.

62. Compounds as claimed in claim 12 when prepared by a process as claimed in claim 58 or claim 60.

63. Pharmaceutical compositions comprising as active ingredient at least one compound of formula I as defined in claim 1 or a physiologically compatible acid addition salt thereof, in association with one or more pharmaceutical carriers or excipients.

64. Compositions as claimed in claim 63 in a form suitable for oral, rectal or parenteral administration.

65. Compositions as claimed in claim 63 or claim 64 in the form of tablets, coated tablets, capsules, drops, suppositories or ampoules.

66. Compositions as claimed in any one of claims 63 to 65 in the form of dosage units.

67. Compositions as claimed in claim 66 wherein each dosage unit contains from 5 to 75 mg of active ingredient.

68. Compositions as claimed in claim 67 wherein each dosage unit contains from 10 to 50 mg of active ingredient.

69. Compositions as claimed in any one of claims 63 to 68 wherein the compound of formula I is as defined in claim 12.

70. Pharmaceutical compositions as claimed in claim 63 substantially as herein described.

71. Pharmceutical compositions substantially as herein described in any one of Examples A to F.

72. Compounds of general formula i as claimed in claim 1 and physiologically compatible acid addition salts thereof for use in a method of treatment of patients suffering from cardiovascular diseases.

73. A method of treating patients suffering from, or susceptible to, cardiovascular diseases which comprises administering to the said patient an effective amount of a compound of formula I as defined in claim 1 or a physiologically compatible acid addition salt thereof.

74. Each and every novel method, process, compound or composition herein disclosed.