IE52007B1 - Chemical compounds - Google Patents

Abstract

Compounds of general formula I 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

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 represents a hydroxy group, an amino group 10 (optionally substituted by an alkgnoyl 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 Rj, which may be the same or different, each represents a halogen atom or a trifluoromethyi, cyano or nitro group, or one of the radicals R2 or Rj represents a hydrogen atom? R4 represents a hydrogen atom or an alkyl group containing 1 to 3 carbon atoms? Rg 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 R, '8 or - E R. wherein Rg 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 Rg and R? together represent a methylenedioxy group; Ηθ 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 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, 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 Rg represents a trifluoromethyl, cyano or nitro group, and/or Rg represents a fluorine atom, and/or R^ represents an alkyl group containing 1 to 3 carbon atoms, and/or Rg 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 S3007 containing 7 to 10 carbon atoms, and/or Rg represents a fluorine or chlorine atom, or an alkylsulfenyl or alkylsulfenyl or alkylsulfinyl group containing 1 to 3 carbcn atans each) E may further represent an ethylene group or {when A represents a methylene group) E may further represent a group of formula — CH-CH2— wherein Rg represents an alkyl group containing 1 to 3 carbon atoms] and aeid 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, benzyl25 amino, 1-phenyleth.ylamino, 2-phenylethylamino, 3phenylpropylamino, dimethylamino, diethylamino, dipropylamino, diisopropylamino, dibenzylamino, di-(2-phenylethyl)amino, di-(3-phenylpropyl)-amino, methyl-ethylamino, methylpropylamino, methyl-isopropylamino, ethyl-isonropylamino, methyl-benzylamino, ethvl-benzylamino, propyl-benzylamino, formylami no, acetylamino, propionyl amino, methoxycarbonylamino, ethoxycarbonylamino, propoxycarbonylamino or isopropoxycarbonylamino group; Rg and Rg, 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 Rg and Rg may represent a hydrogen atom; R^ and Rg, which may be the same or different, may each represent, for example, a hydrogen atom, or a methyl, ethyl, propyl or isopropyl group; R5 may represent, for example, a hydrogen atom or a methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert.butyl, cyclopropyl, eyclobutyl, cyclopentyl, cyclohexyl, allyl, crotyl, pententyl, benzyl, 1-phenylethyl, 2-phenylethyl, 3-phenylpropyl or 4-phenylbutyl group; Rg 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; Ry may represent, for example, a hydrogen atom or a hydroxy, methoxy, ethoxy, propoxy, or isopropoxy group or Rg and Ry together may represent a methylenedioxy group; Rg 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-npropylene, 1-propyl-n-propylene, 1,1-dimethyl-n-propylene, 1,1-diethyl-n-propylene, 1,1-dipropyl-n-propylene, 1methyl-l-ethyl-n-propylene, 1-methyl-l-propyl-n-propylene, 1-ethyl-l-propyl-n-propylene, 1-methy1-n-butylene, or 1-methy1-n-pentylene group.

Preferred compounds of general formula I are those 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; Rg represents a hydrogen, chlorine, bromine or iodine atom or a trifluoromethyl, cyano or nitro group; Rg represents a fluorine, chlorine, or bromine atom or a cyano group; R^ represents a hydrogen atom or a methyl group; Rg 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 or wherein Rg, D and n are as hereinbefore defined; Rg represents a hydrogen, fluorine or chlorine atom or a hydroxy, methoxy, ethoxy, benzyloxy, methylsulfenyl or methylsulfinyl group and R? represents a hydrogen atom or a methoxy group; or Rg and R? together represent a methylenedioxy group; and E represents an n-propylene, 1-raethy1-n-propylene, 1,1dimethyl-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 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 Rg represents a trifluoromethyl, cyano or nitro group; and/or Rg represents a fluorine atom; and/or Rg 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.

Especially preferred compounds of general formula I are those wherein Rj 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; Rg represents a fluorine or chlorine atom or a cyano group; R^ represents a hydrogen atom or a methyl group; Rg 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 R wherein E represents an n-propylene, 1-methy1-n-propylene, 1,1-dimethy1-n-propylene or n-butylene group, or (when R^ represents an ethoxycarbonylamino group and/or R2 represents a cyano group and/or Rj represents a fluorine atom and/or Rg represents an alkyl group containing 1 to 3 carbon atoms op15 tionally substituted by a phenyl group, or an allyl or cyclopropyl group) E may further represent an ethylene group; Rg represents a hydrogen atom or a hydroxy or methoxy group; and Ry represents a hydrogen atom or a methoxy group.

Further classes of especially preferred compounds of general formula I comprise compounds wherein B represents an n-propyl, 1-methyl-n-propyl or 1,1-dimethyl-n-propyl group substituted in the 3-position by a phenyl, 4-hydroxyphenyl, 4-methoxyphenyl or 4chlorophenyl group or represents a 4-(4-methoxyphenyl)-butyl group; and compounds wherein Rq 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 Rg further represents a cyano group; represents a hydrogen atom or a methyl group; R5 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 a 4-(4-methoxyphenyl)-butyl group or (when Rg 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.

Particular especially preferred compounds which may be mentioned are 1-(4-ami no-3,5-di chi orophenyl) (3-phenyl propyl) -2-propyl amino] ethanol and l-(4-amino-3,5-dichlorophenyl)-2- [N- (J, 1-dimethyl 3-(4-hydroxyphenyl)-propyl] -amino] ethanol and physiologically compatible acid addition salts thereof, for example hydrochloric, hydrobromic, sulfuric, phosphoric, fumaric, succinic, lactic, citric, tartaric or maleic acid addition salts thereof.

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 Rp Rg, Rg, Rg and B are as hereinbefore defined) and X represents a group of formula - CO - CH -, OH R4 .- CH - CH -, 0-acyl - CH - CO -, - ch2 - CO -, Z r4 -CH-CH or z - ch-ch2-ch(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, iso10 propanol, trifluoroacetic acid, butanol, diethyl ether, tetrahydrofuran, tetrahydrofuran/water, dioxan or hexamethyl-phosphoric acid triamide, and conveniently at temperatures between -20°C and the boiling point of the reaction mixture, e.g. at temperatures between -20°C and 100°C.

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 53007 formula X, 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 hydride in a solvent such as, for example, methanol, methanol/water, diethyl ether or tetrahydrofuran at -20°C to 50°C; with aluminium isopropylate in isoproanol 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, raneynickel 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-CHR^· group, the reaction is conveniently carried out at temperatures between 0 and 50°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 tetra0-acyl I hydrofuran; if X represents the -CH - CO- 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 lower to slightly elevated temperatures, e.g. at temperatures between 0 and 100°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 pyridine35 borane in a solvent such as, for example, ethanol, isopropanol, tetrahydrofuran, dioxan, trifluoroacetic acid or Γ0 hexamethyl-phosphoric acid triamide and conveniently at temperatures between 0 and 100°C.

If in the compound of general formula II used in the above reduction, X represents the -CHg-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 100°C, the reaction components having been mixed at lower temperatures, e.g. at -10°C; if Z R Z R.

I I * I I * X represents a -CH-CH- or -CH-CHg-CH- 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 100°C. b) Reaction of a carbonyl compound (optionally formed in the reaction mixture) of general formula III K - L ,(111) [Wherein K together with a neighouring hydrogen atcm 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) Rg or represents a group of formula 53007 in which R2, Rg and Rj 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 /“ H - N ,(IV) (wherein M and Q, which are different, represent B and Rg as herein5 before defined, or one of the radicals M or Q represents a group of formula ι in which R^, R2, Rg, R4 and A are as hereinbefore defined) and a reducing agent.

The reaction is preferably carried out in a solvent 10 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 -20°C and the boiling point of the solvent used, e.g. between -20°C and 50°C, preferably, however, at temperatures between 0 and 25°C.

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 cyanoboro20 hydride at pH <7, e.g. at pH 6 - 6.5, and subsequently with sodium borohydride at room temperature.

Where the reaction is carried out with a primary S3007 amine of general formula XV, 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 -20°C and the boiling point of the used solvent, e.g. at temperatures between 0 and 80°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 100°C, preferably, however, at room temperature, and at a hydrogen pressure of 1 to 5 bar.

Methylation of an amine centre may/??e °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 III, wherein L is as defined for Rg, the aforesaid R^ group can also be alkylated at the nitrogen centre, especially when using an excess of the carbonyl compound of general formula III. c) Removal of one or more protective radicals from a compound of general formula V wherein R2, Rj and R^ are as hereinbefore defined; R^' represents Rj 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; Rg' represents Rg as hereinbefore defined or represents a protective radical for an amino group; and B1 represents B as hereinbefore defined or represents a group of formula wherein Rg, D, E and n are as hereinbefore defined; and Rg1 and Ry1, which may be the same or different, are as hereinbefore defined for Rg and Ry respectively or represent hydroxy groups protected by protective radicals, wherein at least one of the radicals , A, Rg* and B1 represent or must contain one of the above-mentioned protective radicals.

Suitable protective radicals include, for exanple, acyl or alkoxyearbonyl radicals such as an ethoxycarbonyl, acetyl, propionyl or benzoyl group or a benzyl group and for A an acetyl, 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 100°C, preferably at the boiling point of the reaction mixture, Tbe cleavage of one or more benzyl greups 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 Dehalogenation of a compound of general formula VI wherein Rp R3, Rp Rg, A and B are as hereinbefore defined and Hal represents a chlorine, bromine or iodine atom.

The dehalogenation may be effected using triphenyl phosphine, hydrogen in the presence of a hydrogenation catalyst or a complex metal hydride, and preferably may 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 a temperature between 0°C and 150°C, e.g. at room temperature or at an elevated temperature, for example at temperatures between 60°C and 150°C, and at a normal pressure or a moderately elevated pressure. When using a 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 ,(VII) wherein R^, Rg, Rg, R4 and A are as hereinbefore defined; Rg is as hereinbefore defined for Rg; and B represents B as hereinbefore defined provided that if Rg does not represent a hydrogen atom, at least one of the radicals Rg or Ry 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 an alkyl halide or alkyl sulfate, for example, methyl iodide, dimethyl sulfate, ethyl bromide, diethyl sulfate, benzyl bromide, 2-phenyl-ethyl bromide or methyl-p-toluene sulfonate, optionally in the presence of a base such as sodium hydroxide or potassium carbonate. Preferred temperatures are those between -10° and 50°C, preferably between 0 and 30°C. The reaction can, however, be carried out wi'hout 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 50°C, preferably, however, at room temperature. 5200? Moreover, the alkylation of a phenolic hydroxy group can be carried out with, for example, a corresponding alkyl halide, alkyl sulphate or diazo alkane in a solvent such as diethyl ether or tetrahydrofuran. Preferred temperatures are those between 0 and 50°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 Rg does not represent a hydrogen atom: Acylation of a compound of general formula VIII B (wherein Rg, Rg with a compound of general formula IX Y - CO - R10 ,(IX) (wherein R1Q 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 such as for example a halogen atom, a nitrophenyl radical, an imidazolyl group or a radical of formula -O-COR^q).

The reaction may, for example, be carried out with acetyl chloride, acetic anhydride, propionic acid anhydride or a corresponding ehloroformate, e.g. ethyl ehloroformate, which simultaneously may serve as asolvent. 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 100°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 Rg, Rg, R^, Rg, Rg, R?, Rg A and n are as before defined and m is 0 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 100°C.

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 0 to 20°C. or in acetone at 0 to 60°C; a peracid such as performic acid in glacial acetic acid or trifluoroacetic acid at 0 to 50°C; m-chloroperbenzoic acid in methylene chloride or chloroform at -20 to 60°C; and sodium metaperiodate in aqueous methanol or ethanol at 15 to 25°C. 53007 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 100°C or in acetone at 0 to 60°C; a peracid such as performic acid or m-chloroperbenzoic acid in glacial acetic acid, trifluoroacetic acid, methylene chloride or chloroform at temperatures between 0 and 60°C; and potassium permanganate in glacial acetic acid, water/sulfuric acid or in acetone at 0 to 20°C. h) For the preparation of compounds of general formula I, as hereinbefore defined, wherein D represents an oxygen or sulfur atom and Rg does not represent a hydrogen atom: Reaction of a compound of general formula XI (wherein Rg, R2, Rg, R4, Rg, Rg 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 D' // ,(XII ) (wherein Rg and R? 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 chloroform, 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 -10°C and the boiling point of the solvent, e.g. at temperatures between -10°C and 100°C, and preferably, at temperatures between 0 and 50°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 X 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, (+)-camphor10-sulfonic acid, L(-)-malic acid, L(+)-mandelic acid, d-abromo-camphor-ft-sulfonic acid or 1-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 -CO-CHRj group, can be obtained, for example, by reaction of an α-halo-ketone with the corresponding amine; compounds of general formula II, wherein X represents the -CHg-CO-group, can be obtained by reaction of a phenyiacetic acid derivative with the corresponding amine.

Compounds of general formula III, wherein A' represents a carbonyl group and 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 ω-phenylalkyl 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-actophenone.

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-Ainino-3,5-dichloro-phenyl)-2-2N-/5-(4-methoxy-phenyl) propyl7amino7ethanol, B = 1-(4-Amino-3-cyano-5-fluoro-phenyl)-2-2N-/3-(4-methoxyphenyl)-propyl7methylamino7ethanol, C = 1-(4-Amino-3,5-dichloro-phenyl)-2-/N-(3-phenyl-propyl)2-propylamino7ethanol hydrochloride, D = 1-(4-Amino-3,5-dichloro-phenyl)-2-/N-/3-(4-hydroxy-phenyl) 15 1 -methyl-propyl7m.ethylamino7ethanol, E = N-/T-Methyl-2-(4-amino-3,5-dichloro-phenyl)-ethyl7-li/3-(4-methoxy-phenyl)-propyl/amine hydrochloride, F = N-22-(4-Amino-3,5-dichloro-phenyl)-ethyl7-N-2J-(4-chlorophenyl)-propyl/isopropylamine, g = N-2?-(4-Chloro-phenyl)-propyl7-N-22-(3,5-dichloro-4-isopropylamino-phenyl)-ethyl/isopropylamine, and H >= N-/2-(4-Amino-3-bromo-5-cyano-phenyl)-ethyl7-N-25-(4-methoxy-phenyl)-butyl7methylamine. 1. Determination of the contractility parameter dp/dt^.^ 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 38°C 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 Is Test compound Increase of dP/dtmax % Half life time in minutes A + 93 38 B + 124 >140 C + 83 112 D + 105 >100 53007 Table II; Test compound Decrease of heart frequency % Half life time 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. saphena) of each test compound (0.1 or 0.2 ml/10 g of body weight) or by administration into the stomach. After an observation time of 14 days the ΙΌ^θ was determined according to the methods described by LITCHFIELD and WILCOXON: Test compound LD-θ mg/kg i.v. 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 X5 invention there are provided pharmaceutical compositions S2007 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.

The following non-limiting examples serve to illustrate the present invention. 1-(4-Amino-3,5-dichloro-phenyl)(4-methoxy-phenyl) propyl7methylamlno7 ethanol Example 1 0.5 g (13.5 m mol) of sodium borohydride were added in portions 5 to a solution of 3.45 g (9 m mol) of 4'-amino-3',5'-dichloro2-/N-/5-(4-methoxy-phenyl)-propyl7methylamino7acetophenone 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 minu10 tes 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 = 19 * 1 as eluent (Macherey and Nagel 70 - 230 mesh ASTM). The fractions containing the desired compound were combined, evaporated and in- vaouo the remaining solvent was removed IR spectrum (methylene chloride): uv spectrum (ethanol): max: from the oil at 40 °s.

OH 3610 cm1 NH2 3400 + 3490 cm’1 CH2 2850 + 2940 cm1 0CH3 2830 c·1 N-alkyl 2800 cm1 C=C 1610 cm1 243 nm (0.23) 280 nm (0.08) 300 nm (0.08) Example 2 - (4-Amino-3,5-dichloro-phenyl) -2-/ΪΤ- (3-phenyl-propyl) -methyl30 amino7ethanol hydrochloride g (0.035 mol) of 4’-amino-2-bromo-3*,5'-dichloro-acetophenone, 6.7 g (0.036 mol) of N-(3-phenyl-propyl)-ethylamine hydrochloride and 10.5 ml (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-pheny1-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 tempera10 ture 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 85°C (under sintering).

Example 3 1-(4-Amlno-3,5-dichloro-phenyl)-2-2H-/J-(4-hydroxy-phenyl)-1methyl-propyl7methvlamlno7ethanol 0.2 mol of sodium borohydride were added in portions to a solution of 0.1 mol of 4'-amino-3’,5'-dichloro-2-/!T-/7-(4-hydroxy-phenyl)1-methyl-propyl7methylaminp7acetophenone 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 1s1 mixture were recrystallized from methy10 lene chloride.

M.p.: 112 - 115°C Example 4 1-(4-Amino-3,5-dichloro-phenyl)-2-/R-/5-(4-methoxy-phenyl)1-methvl-propyl7methylamino7ethanol 0.02 mol of 1-(4-amino-3,5-dichloro-phenyl)-2-/51-/5-(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 icewater 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 75ml 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, - 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. 5200 IR spectrum (methylene chloride): OH nh2 ch2 OCHj N-alkyl C-C C-C + NH2 d UV spectrum (ethanol): *λ max. 244 nm (0.27) 3200 - 3500 cm1 broad (below NH2) 3480 + 3390 cm1 2930, 2850 cm-1 2830 cm1 2800 cm-1 1580, 1510, 1485 cm1 deformation 1620 cm 280 nm (0.08) 300 nm (0.08) Example 5 1-(4-Ethoxycarbonylamino-3-cyano-5-fluoro-phenyl)-2-/R-/5-(4-methoxyphenyl ) -propyl7amlno7ethanol 0.5 g of celite and afterwards 2.5 g (0.01 mol) of 4'-ethoxycarbonylamino-5'-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 60°C under stirring. Subsequently, the reaction mixture was refluxed for 4 horn’s 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’-cyano25 5’-fluoro-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.: 111 - 112°C.

Example 6 1-(4-Ethoxycarhonylamino-3-cyano-5-fluoro-phenyl)-2-/ΊΪ-/5(4-methoxv-phenvl)-propvl7methvlamino7ethanol g (0.06 mol) of 4'-ethoxycarbonylamino-3'-cyano-5’-fluoroacetophenone were added in portions at 60°C 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. .7 g (0.06 mol) of N-2?-(4-methoxy-phenyl)-propyl7methylamine, dissolved in 100 ml of tetrahydrofuran, were added to this so15 lution of 4,-ethoxycarbonylamino-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 N hydrochloric acid. The reaction mixture was allowed to stand 2o 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 700 g of silica gel with ethyl acetate as eluent. The fractions containing the desired compound were combined, evaporated and ln vacuo at 40®C the remaining solvent was removed from the oil obtained.

IR spectrum (methylene chloride): OH 3600 cm” NH 3400 cm1 CH2 2930 cm”1 OCHj 2830 cm”1 N-alkyl 2800 cm”1 CN 2220 cm”1 NHC00C2H5 1735 cm”1 UV spectrum (ethanol)ί max. 228 nm (shoulder; 0.19) 240 nm (shoulder; 0.12) 285 nm (0.06) UV spectrum (ethanol + KOH): 7 max. 223 nm (shoulder; 0.39) 253 - 265 nm (shoulder; 0.1) 318 nm (0.06) Example 7 N-/5-(4-Amino-3-bromo-phenyl)-ethyl7-N-/5-(4-methoxy-phenyl)propyl7methylamine dihydrochloride 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-/?-(4-methoxy-phenyl)-propyl7-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 evaporator. The evaporation product was chromatographed over silica .gel (eluent: methylene chloride : methanol «19 : 1) (Macherey and Nagel, 70 - 230 mesh, ASTM). The fractions containing the desired product were combined and evaporated. The oil obtained was dissolved in little absolute ethanol and hy means of ethanolic hydrochloric acid and addition of ether, the crystalline dihydrochloride was prepared.

M.p.: 168 - 171°C (decomp.).

Example β N-/2-(4-Amino-3,5-dibromo-phenyl)-ethyl7-N-/5-(4-methoxy-phenyl) butyl7methvlamlne 2.9 g (0.077 mol) of lithium aluminium hydride were suspended,, in 5 a nitrogen atmosphere^in 100 ml of absolute tetrahydrofuran. A solution of 15.0 g (0.031 mol) of 4-amino-3,5-dibromo-N-/5-(4methoxy-phenyl)-butyl7-N-methyl-phenylacetamide in 100 ml of absolute tetrahydrofuran was added thereto whilst stirring at room temperature. Subsequently, the reaction mixturewas 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 eva15 poration product was chromatographed over silica gel (Macherey and Nagel, 70 - 230 mesh, ASTM) with methylene chloride : methanol =19 : 1 as eluent. The fractions containing the desired product •were combined and evaporated. The oil obtained was liberated in vacuo at 40° C from the solvent residues.

IR spectrum (methylene chloride): NH, UV spectrum (ethanol): λ max.

N-alkyl OCHj aliphat.

C=C 246 nm (0.24) 281 nm (0.08) 305 nm (0.09). 3380 + 3470 cm' 2790 cm1 2830 cm1 CH, 2850 + 2930 cm' 1610 cm' .-1 Example 9 N-/2-(4-Amino-3-chloro-5-cyano-phenyl)-ethyl7-N-/5-(4-methoxyphenvl)-propyl7methvlamine 6.6 g (0.014 mol) of 1-(ethoxycarbonyloxy)-1-(4-amino-3-chloro5 5-cyano-phenyl) -2-/57-/5- (4-methoxy-phenyl) -propyl7methylamino7ethane 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 10 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 150 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 15 mesh, ASTM) with methylene chloride/methanol -19 : 1 as eluent. The fractions which contained 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): NH2 3400 + 3500 cm 2800 cm1 CHO 2860 + 2940 cm' UV spectrum (ethanol): λ max.

N-alkyl aliphat. aromat. C-C 1600 cm' NHg deformation 1625 cm 244 nm (0.23) 278 nm (0.06) 330 nm (0.13).

Example 10 N-/£-(4-Amino-3-chloro-5-eyano-phenyl)-ethyl7-N-/5~(4-methoxyphenvl) -propyl7methylamine · 1,3 g (0.0027 mol) of 1-(4-amino-3-chloro-5-cyano-phenyl)2-/^-/5-(4-methoxy-phenyl)-propyl7methylamino7ethyl 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 70°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. io Mass spectrum: found M+ 357/59 Molecular weight: 357.8.

Example 11 1-(4-Amino-3-fluoro-phenyl)-2-/N-/3-(4-methoxy-phenyl) -propyl7methylamino7ethanol A solution of 3.9 g (0.0095 mol) of 1-(4-amino-3-bromo-5-fluorophenyl )-2-/N-/3“(4-methoxy-phenyl)-propyl7methylamino7ethanol in 50 ml of methanol was reacted with 2 g of 10% 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 beentaken 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 »19 : 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 offwith suction, washed with little cold isopropanol and dried in vacuo.

M.p.: 110°C (decomp.).

Example 12 1-(4-Ethoxycarbonylamino-3-bromo-phenyl)-2-/^-/4-(4-methoxyphenyl )-butyl7methvlamino7ethanol 1.5 ml (0.015 mol) of ethyl ohloroformate were added under ice5 cooling at 0°C to a solution of 5.1 g (0.0125 mol) of 1-(4-amino3-bromo-phenyl) -2-(4-methoxy-phenyl) -butyl/methylamino/ ethanol in 40 ml of absolute pyridine. The solution obtained was kept over night at +4°C in the refrigerator. Subsequently, the pyridine was distilled off in a rotation evaporator at 50°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 cm1 UV spectrum (ethanol): % max.

NH OCHj N-alkyl aliphat.

C«0 aromat. C-C 224 nm (0.42) 240 nm (0.29) 280 nm (0.04) 3400 cm' 2830 cm-1 2800 cm1 2860 + 2940 cm1 1735 cm1 1610 cm-1 Example 1? Ν-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl7-N-/3-(4-hydroxyphenvl)-1-methyl-propyl7methylamine 0,012 mol of N-/2-(4-amino-3,5-dichloro-phenyl)-ethyl7-N/3-(4-hydroxy-phenyl)-1-methyl-propyl/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 150 ml of tetrahydrofuran. The reaction solution was stirred for 24 hours at room temperature and subsequently extracted twice with 150 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 (Polygosil 60 - 1525; Macherey and Nagel) with methylene chloride : methanol : cone, 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 nh2 ch2 N-alkyl 3580 cm1 3480 + 3380 cm1 2930, 2960, 2850 cm” 2790 cm1 C=C 1580, 1510, 1480 cm' C=C + NH2 deformation 1610 cm' UV spectrum (ethanol): Ά max. 240 nm (0.26; shoulder) 288 nm (0.08) 301 nm (0.08) UV spectrum (ethanol· + KOH): ^-max. 241 nm (0.56) 299 nm (0.17).

Example 14 1-(4-Amino-3,5-dichloro-phenyl)-2-/ΪΪ-/5-(4-methoxy-phenylsulf inyl)-ethyl7methvlamino7ethanol 7.0 g of 1-(4-amino-3,5-dichloro-phenyl)-2-25-/2-(4-methoxy5 phenylsulfenyl)-ethyl7methylamino7ethanol 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: 40 x 200 mm; silica gel 60, of Messrs. E. Merck, grain size: 0.06 - 0.2 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): UV spectrum (ethanol): A max. nh2 ch2 och3 N-alkyl C-C S-0 244 nm (0.54) 300 nm (0.07; shoulder) 3390 + 3480 cm 2940 cm 2840 cm' 2800 cm 1590, 1510 + 1480 cm' 1040 cm (shoulder) ,-1 S3007 Example 15 1-(4-Amino-3,5-diohloro-phenyl)-2-/N-/5-(4-methoxy-phenylsulfonyl)-ethyl7methylamino7ethanol 7.0 g of 1-(4-amino-3,5-dichloro-phenyl)-2-^f-/5-(4-methoxy5 phenylsulfenyl)-ethyl7methylamino7ethanol 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 sdids were filtered off over celite. After removing the dioxan in vacuo the residue was distributed between dichloromethane and water. The evapora15 tion residue of the dried organic phase was purified twice by chromatography (1. column: 60 x 300 mm, AlgO^ II neutral, methy lene chloride : tetrahydrofuran « 5 s 1J 2. column: 35 x 300 mm silica gel 60,'Messrs. E. Merck, grain size: 0.015 - 0.025 mm,· dichloromethane, 8.5' bar). After evaporating the desired frac20 tions in vacuo the title compound was obtained as an oil.

IR spectrum (methylene chloride): NEL, 3395 + 3480 cm ch2 2940 cm1 och3 2840 cm1 N-alkyl 2800 cm1 C«=C 1595, 1520 + 1495 cm-1 so2 .1150 + 1315 cm OT spectrum (ethanol): λ max. 241 nm (0.59) 300 nm (0.09). 53007 Example 16 1-(4-Amino-3,5-dichloro-phenyl)-2-/tT-/5-(4-hydroxy-phenyl)propyl7methvlamino7ethanol 9.2 g of 1-(4-amino-3,5-dichloro-phenyl)-2-/fT-/J-(4-benzyloxyphenyl)-propyl7methylamino7ethanol were dissolved in 150 ml of methanol. The solution was mixed with 1 g of 5 9( 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 40°C. ~ rf IR spectrum (methylene chloride): OH *con — nh2 N-alkyl 3580 cm 3395 + 3495 cm 2800 cm Example 17 1-(4-Amino-3-bromo-phenyl)-2-^f-/5-(4-methoxy-phenyl)-butyl720 methvlamlno7ethanol g of 1-(4-acetamino-3-bromo-phenyl)-2-/iT-/If-(4-methoxy-phenyl)butyl7methylamino7ethanol 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 de30 sired compound, the title compound was obtained by evaporation in vacuo at 40°C. Oil.

IR spectrum (methylene chloride): OH 3590 NH2 3380 N-alkyl 2800 0CH3 2830 aliph. CH2 2850 aromat. C=C 1620 UV spectrum (ethanol): max. 224 mn (0.20) 243 nm (0.14) 280 nm (0.04) 300 nm (0.04) cm + 3470 cm' cm cm' t + 2930 cm cm1 Example 18 1-(4-Amino-3-cyano-5-fluoro-phenyl)-2-/N-/5-(4-methoxy-phenyl)propyl7methylamino7ethanol Prepared analogously to Example 1 from 4'-amino-3'-cyano-5'-fluoro 15 2-/N-/5-(4-methoxyphenyl)propyl7methylamino7acetophenone and sodium borohydride in 90 % methanol.

IR spectrum (methylene chloride): OH nh2 ch2 OCHj N-all C=N NHO deformation 1635 cm' & -1 aromat. C=C 1610 cm UV spectrum (ethanol): Ά max. 242 nm (0.3) 325 nm (0.14). 3590 cm-1 3400 + 3490 cm' 2850 + 2940 cm 2830 cm1 2800 cm”1 2210 cm1 Example 19 1-(4-Amino-3-bromo-5-cyano-phenyl)-2-/N-/5-(4-methoxy-phenyl) propyl7methylamino7ethanol Prepared analogously to Example 1 from 4’ -.amino-3’-bromo-5'30 cyano-2-/N-/5-(4-methoxy-phenyl)-propyl7methylamino7acetophenone and sodium borohydride in 80 % methanol. 53007 IR spectrum (methylene chloride): OH 3590 _·) cm weak nh2 3400 + 3480 cm' ch2 2850 + 2930 cm' C=N 2200 cm-1 C-C 1640 cm-1 UV spectrum (ethanol): max. 243 nm (0.20) 280 nm (0.04) 334 nm (0.12) • Example 20 1- (4-Amino-3,5-dibromo-phenyl)-2-/^-/5-(4-methoxy-phenyl)propvl7methylaminoZethanol Prepared analogously to Example 1 from 4,-amino-3’,5’-dibromo2- 2R-/J-(4-methoxy-phenyl)-propyl7methylamino7acetophenone and sodium borohydride in 80 % methanol.

IR spectrum (methylene chloride): OH 3590 NH2 3380 N-alkyl 2800 OCHj 2830 aliphat. CH2 2850 C-C 1610 UV spectrum (ethanol): λ max. 244 nm (0.16) 303 nm (0.06). cm + 3460 cm cm1 cm1 + 2940 cmcm1 -.1 Example 21 1-(4-Amino-3,5-dichloro-phenyl-2-/R-/T,1-dimethyl-3-(4-methoxyphenyl ) -propyl7amlno7ethanol Prepared analogously to Example 13 from 1-(4-amino-3,5-dichiorophenyl ) -2-2JT-/T, 1 -dimethyl-3- (4-hydroxy-phenyl )-propyl7amino7- ethanol, tetrahydrofuran, sodium ] hydroxide solution and dimethyl- sulfate. Oil. IR spectrum (methylene chloride): OH 3600 -1 cm nh2 3390 + 3490 cm1 ch2 2860 + 2960 cm1 OCHj 2830 cm-1 - C-C 1580 + 1620 cm-1 UV spectrum (ethanol): λ max. 243 nm (0.23) 280 nm (0.08) 300 nm (0.08) Example 22 5 1-(4-Amino-3,5-dichloro-phenyl)-2-/R-/T,1-dimethyl-3-(4-methoxyphenyl ) -propyl7methylamino7ethanol Prepared analogously to Example 13 from 1-(4-amino-3,5-dichlorophenyl )-2-/N-/T,1-dimethyl-3-(4-hydroxyphenyl)-propyl/aminoethanol/, tetrahydrofuran, sodium hydroxide solution, and di10 methylsulfate. Oil.

Calc.: C 61.31 H 6.86 Cl 17.24 N 6.81 Pound: 61.13 6.99 17.25 6.75 Example 23 1-(4-Amino-3-chloro-5-trifluoromethylrphenyl)-2-/N-/5-(4-methoxy15 phenyl )-prop.yl7methylamino7ethanol ~ Prepared analogously to Example 1 from 4’-amino-31-chloro-5'-trif luoromethyl-2-^-/?- (4-methoxy-phenyl) -pr opyl7methylamino7acetophenone and sodium borohydride in 80 % methanol.

IR spectrum (methylene chloride): OH 3590 cm 1 uv spectrum (ethanol): λ max. nh2 N-alkyl och3 2800 cm 2830 cm‘ aliphat.

C»C 225 nm (0.36) 245 nm (0.31) 280 nm (0.05) 310 nm (0.1). 53007 Example 24 1-(3,5-Dichloro-4-hydroxy-phenyl)-2-/ΪΪ-/5-(4-methoxy-phenyl)propvl7methylamino7ethanol Prepared analogously to Example 1 from 3', 5'-dichloro-4’-hydroxy5 2-/N-/3-(4-methoxy-phenyl)-propyl.7niethylamino7acetophenone and sodium borohydride in 80 % methanol.

M.p.; 156 - 157°C.

Example 25 1- (3,5-Dihromo-4-hydroxy-phenyl)-2-£>-(4-methoxy-phenyl)10 propyl7methylamino7ethanol Prepared analogously to Example 1 from 3',5'-dihromo-4’-hydroxy2- /N-/3-(4-methoxy-phenyl)-propyl7methylamino7acetophenone and sodium borohydride in 80 % methanol.

M.p. of the hydrochloride: 159 - 162°C.

Example 26 - (4-Amino-3-bromo-5-f luoro-phenyl)-2-/ΪΪ-/5- (4-methoxy-phenyl) propyl7methvlamino7 ethanol Prepared analogously to Example 1 from 4,-amino-3’-bromo-5'-fl'uoro2-/R-/5-(4-methoxy-phenyl)-propyi7methylamino7acetophenone and sodium borohydride in 80 % methanol.

M.p. of the hydrochloride (amorphous): from 60°C.

Example 27 1- (4-Amino-3-chloro-5-fluoro-phenyl)-2-/ΪΤ-/5- (4-methoxy-phenyl) propyl7methvlamino7ethanol Prepared analogously to Example 1 from 4'-amino-3'-chloro-5'--fluoro2- /ΤΓ-/5-(4-methoxy-phenyl)-propyl7m®thylamino7acetophenone and sodium borohydride in 80 % methanol.

M.p. of the hydrochloride: 103 - 108°C (decomp.).

Example 28 1-(4-Amino-3-chloro-5-cyano-phenyl)-2-2N-/5-(4-methoxy-phenyl)5 propyl7methylamino7ethanol Prepared analogously to Example 1 from 4’-amino-3'-chloro-5'-cyano 2-2N-/5- (4-methoxy-phenyl) -propyl7methylamino7acetophenone and sodium borohydride in 80 % of methanol.

IR spectrum (methylene chloride): OH 3590 10 nh2 3400 N-alkyl 2800 OCHj 2830 aliphat . CH2 2850 CaN 2210 15 C=C 1625 UV spectrum (ethanol): max. 245 nm (0.26) • 278 nm (0.06) 332 nm (0.16).

Example 29 cm + 3500 cm cm cm + 2940 cm' -1 cm -1 cm 1-(4-Amino-3’-chloro-5-nitro-phenyl)—2—/5-(4-methoxy-phenyl)propvl7methylamino7ethanol Prepared analogously to Example 1 from 4’-amino-3'-chloro-5’-nitro 2-2N-/5-(4-methoxy-phenyl)-propyl7methylamino7acetophenone and sod ium borohydride in 80 % methanol. IR spectrum (methylene chloride): OH 3590 cm' NH2 3390 + 3500 cm1 N-alkyl 2800 cm1 OCHj 2830 cm-1 aliphat. 0¾ 2850 + 2940 cm’1 C=C 1630 cm-1 N02 1330 + 1515 cm1 53007 UV spectrum (ethanol): max. 227 nm (0.64) 280 nm (0.16) 400 nm (0.12) Example 30 5 1-(4-Amino-3-chloro-phenyl(4-methoxy-phenyl)-propyl7methylamino7 ethanol Prepared analogously to Example 1 from 4'-amino-3'-chloro-2-/i7/3-(4-methoxy-phenyl)-propyl7methylamino7acetophenone and sodium borohydride IR spectrum in 80 % methanol, (methylene chloride): UV spectrum (ethanol): λ max.

OH 3600 cm' NH2 3380 + 3470 cm1 N-alkyl 2800 cm”1 OCHj 2830 cm1 aliphat. CH2 2850 + 2940 cm1 C=C 1620 cm1 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-/(7-/3-(4-methoxy-phenyl)-propyl7methylamino7ethanol Prepared analogously to Example 1 from 4'-amino-3'-bromo-2-/iT/5-(4-methoxy-phenyl)-propyl7methylamino7acetophenone and sodium borohydride in 80 % methanol.

M.p. of the dihydrochloride: 137°C·(decomp.).

Example 32 - (4-Amino-3,5-dicyano-phenyl) (4-methoxy-phenyl) -propyl7methylamino7 ethanol Prepared analogously to Example 1 from 4'-amino-31,5'-dicyano5 2-/N-/3-(4-methoxy-phenyl )-propyl7iaethylamino7acetophenone and sodium borohydride in 80 % methanol.

M.p. of the hydrochloride: 167 - 170°C.

Example 33 1- (4-Amino-3-bromo-phenyl)-2-ffl- ffl-(4-methoxy-phenyl)-butyl710 methylamlno7ethanol __ Prepared analogously to Example 1 from 4’-amino-3’-bromo2- /N-/?-(4-methoxy-phenyl)-butyl7methylamino7acetophenone and sodium borohydride in 80 % methanol.

IR spectrum (methylene chloride) UV spectrum (ethanol): λ max.

: OH 3590 cm-1 NH2 3380 +3470 cm' N-alkyl 2800 cm-1 OCHj 2830 cm-1 aliphat. CH2 2850 + 2930 cm' C=C 1620 cm-1 224 nm (0.44) · 243 nn (0.28) 280 nm (0.08) 300 zaa (0.06).

Example 34 1_(4-Amino-3-bromo-phenyl)-2-/N-/2-(4-methoxy-phenyl)-ethyl7methvlamino7ethanolPrepared analogously to Example 1 from 4'-amino-3’-bromo-22N-/2-(4-methoxy-phenyl)-ethyl7methylamino7acetophenone and sodium borohydride in 80% methanol.

IR spectrum (methylene chloride): OH 3590 nh2 3380 N-alkyl 2800 OCHj 2830 5 aliphat ;. CH2 2840 C=C 1620 UV spectrum (ethanol): max. 225 nm (0.43) 243 nm (0.36) 280 nm (0.08) 10 296 nm (0.08). a1 34: η1 a1 29' Example 35 1-(4-Amino-3,5-dichloro-phenyl)-2-/^-/5-(4-methoxy-phenyl)butyl7methvlamlno7 ethanol Prepared analogously to Example 1 from 41-amino-3',5'-dichloro2-2Π-/5-(4-methoxy-phenyl)-butyl7methylamino7acetophenone and sodium borohydride in 80 % methanol.

IR spectrum (methylene chloride): UV spectrum (ethanol): λ max.

OH 3590 cm1 NH2 3390 + 3490 cm1 N-alkyl 2800 cm1 OCHj 2830 cm1 aliphat. 0¾ 2850 + 2930 cm1 OC 1610 cm1 245 nm (0.25) 320 nm (0.48).

Example 36 1- (4-Amino-3-bromo-5-cyano-phenyl)-2-2K-/5-(4-methoxy-phenyl)butvl7methylamlno7ethanol Prepared analogously to Example 1 from 41-amino-3’-bromo-5’-cyano2- /ff-/?-(4-methoxy-phenyl)-butyi7methylamino7acetophenone and 30 sodium borohydride in 80 % methanol.

IR spectrum (methylene chloride): UV spectrum (ethanol): max.

OH 3590 cm 1 NH2 3390 + 3490 cm-1 N-alkyl 2800 cm1 OCHj 2830 cm-1 aliphat. CH2 2850 + 2930 cm1 C=N 2210 cm1 C=C 1620 cm1 245 nm (0.27) 278 nm (0.08) 330 nm (0.15).

Example 37 1-(4-Amino-3~bromo-5-cyano-phenyl)-2-/11-/5-(4-methoxy-phenyl)ethyl7methylamino7ethanol Prepared analogously to Example 1 from 4’-amino-3’-hromo-51-cyano 2-/N-/2-(4-methoxy-phenylJ-ethyl/methylamino/acetophenone and sodium borohydride In 80 % methanol.

IR spectrum (methylene chloride): OH ' 3590’ NH2 3390 N-alkyl 2800 OCHj 2830 aliphat. CH2 2850 C=N 2210 C-C 1620 UV spectrum (ethanol): max. 245 nm (0.25) 277 nm (0.09) 331 nm (0.10).

Example 38 1- (4-Amino-3,5-dichloro-phenyl )-2-/(7-/5-(4-methoxy-phenyl)-ethyl/ methylamlno7ethanol Prepared analogously to Example 1 from 4’-amino-3’,5’-dichloro2- /N-/5-(4-methoxy-phenyl)-ethyl7methylamino7acetophenone and cm + 3490 cm’ 1 cm cm' -r + 2950 cm cm cm' Γ1 sodium borohydride in 80 % methanol.

IR spectrum (methylene chloride): OH nh2 N-alkyl OCHj aliphat C-C 3590 cm 3390 + 3490 cm1 2800 cm1 2830 cm1 CH2 2850 + 2930 cm1 1610 cm1 Example 39 1- (4-Amino-3-chloro-5-oyano-phenyl)-2-^-25-(4-methoxy-phenyl)10 butvl7methylamino7ethanol _ Prepared analogously to Example 1 from 4'-amino-3'-chloro-5’-cyano2- (4-methoxy-phenyl) -butyl/methylamino/acetophenone and sodium borohydride in 80 % methanol. 3590 cm1 XR spectrum (methylene chloride): 0Η 15 nh2, 3400 + 3500-cm N-alkyl 2800 cm1 OCHj 2830 cm1 2850 + 2930 cm1 2210 cm1 aliphat. CH2 C-N 20 UV spectrum (ethanol): λ max. c«c 245 nm (0.23) 280 nm (0.05) 332 nm (0.13) 1625 cm1 e Example 40 1-(4-Amino-3-chloro-5-cyano-phenyl)-2-/N-J2-(4-methoxy-phenyl)ethvl7aethylamlno7ethanol Prepared analogously to Example 1 from 4'-amino-3’-chloro-5'-cyano2-2N-/2- (4-methoxy-phenyl) - ethyl7methylamino7acetophenone and sodium borohydride in 80 % methanol.

IR spectrum (methylene chloride): UV spectrum (ethanol): λ max.

OH 3590 cm-1 NH2 3390 + 3490 cm1 N-alkyl 2800 cm1 OCHj 2830 cm1 CH2 2850 + 2940 cm1 C=N 2210 cm1 C=C 1620 cm1 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)-ethyl7methylamino7ethanol Prepared analogously to Example 1 from 4'-amino-3',5’-dichloro15 2-/N-/2-(4-methoxy-phenylsulfenyl)-ethyl/methylamino/acetophenone and sodium borohydride in tetrahydrofuran : water : methanol = 25 : 5 : 10. Oil.

IR spectrum (methylene chloride) 25 UV spectrum (ethanol): λ max.

: OH 3200 - 2500 cm (below NH2) NH2 3480 + 3390 cm1 CH2 2940 cm1 N-alkyl 2800 cm1 OCHj 2830 cm1 C=C 1580 + 1490 cm1 230 mn (0.58j shoulder) 245 nm (0.54) 298 nm (0.14).

Example 42 - (4-Amino-3,5-dichloro-phenyl) -2-/ΪΪ-/2- (4-methoxy-phenoxy) 30 sthyl7methylaminp7 ethanol Prepared analogously to Example 1 from 4'-amino-31,5'-dichloro2-/N-/5- (4-methoxy-phenoxy) -ethyl/methylamino/acetophenone and 53007 sodium borohydride in tetrahydrofuran : water : methanol = 15 : 5 : 3. Oil. IR spectrum (methylene chloride): OH 3200 - 3500 cm1 nh2 (below NH2) 3480 + 3390 c·1 2940 cm1 ch2 N-alkyl 2790 cm1 OCHj 2830 cm1 C=C 1580, 1505 C-O-aryl + 1485 cm-1 1250 cm1 UV spectrum (ethanol): λ 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-/fT-/5- (4-methoxy-phenyl)propvl7amino7propanol-(l) Prepared analogously to Example 1 from 4’-amino-3’,5'-dichloro2- /ET-/5-(4-methoxy-phenyl)-propyl7amino7propiophenone and sodium borohydride.

M.p. of the hydrochloride: 201 - 202°C (decomp.).

Example 44 1-(4-Amino-3,5-dichloro-phenyl)-2-/R-/5-(4-methoxy-phenyl) propyl7-2-propylamino7ethanol Prepared analogously to Example 1 from 4’-amino-3’.,5’-dichloro2-/N-/3-(4-methoxy-phenyl)-propyl7-2-propylamino7acetophenone and sodium borohydride. Oil.

IR spectrum (methylene chloride): UV spectrum (ethanol): max.

OH 3600 -1 cm nh2 OCHj 3400 2830 + 3490 cm' -1 cm 243 nm (0.13) 280 nm (0.03) 300 nm. (0.03) 53007 Example 45 1-(4-Amino-3,5-dichloro-phenyl)-2-^-/5-(4-methoxy-phenyl)propyl7ethylamino7ethanol Prepared analogously to Example 1 from 4*-amino-3’,5'-dichloro 5 2-/fT-/5-(4-methoxy-phenyl)-propyl7ethylamino7acetophenone and sodium borohydride.

IR spectrum (methylene chloride): OH 3600 nh2 3395 och3 2830 UV spectrum (ethanol): λ max. 243 am (0.13) 280 nm (0.04) 300 nm. (0.04) Example 46 - (4-Amino-3,5-dichloro-phenyl) -2-/ΪΤ-/5- (4-methoxy-phenyl) 15 propyl7pr opylamino7 ethanol_' Prepared analogously to Example 1 from 4’-amino-3',5’-dichloro 2-/N-/5~(4-methoxy-phenyl)-propyl7propylamino7acetophenone and sodium borohydride. Oil.

IR spectrum (methylene chloride): OH nh2 3600 3395 och3 2850 UV spectrum (ethanol): λ niax. 245 nm (0.10) 280 nm (0.03) 300 nm. (0.03) Example 47 1-(4-Amino-3,5-dichloro-phenyl)-2-JR-(4-methoxy-phenyl)propvl7cvclopropylamino7ethanol Prepared analogously to Example 1 from 4’-amino-3’,5’-dichloro· Z-/R-£>- (4-methoxy-phenyl) -propyl7oyolopropylamino7acetophenom and sodium borohydride. Oil. IR spectrum (methylene chloride): OH 3590 cm” nh2 3395 + 3495 -1 cm OCHj 2850 UV spectrum (ethanol): max. 245 nm (0.12) 280 nm (0.04) 300 nm. (0.04) Example 45 1-(4-Amino-3,5-dichloro-phenyl)-2-^1-/5-(4-methoxy-phenyl)propvl7methylamlno7propanol-(l), Isomer B Prepared analogously to Example 2 from N-/p-(4-methoxy-phenyl)propyl/methylamine, 4’-amino-2-bromo-3’,5'-dichloro-propiophenone, triethylamine, and sodium borohydride. Oil.

IR spectrum (methylene chloride) UV spectrum (ethanol): max.

OH 3600 + 3680 cm nh2 3390 + 3490 cm' OCHj 2835 + 294.0 cm' aromat 1510, 1585 + 1610 cm' 246 nm (0.14) 278 nm (0.08) 285 nm (0.08) 300 nm (0.08) NMR spectrum (CDClj/E^O): 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-(4-methoxy-phenyl)propvl7methylamino7propanol-(1). Isomer A Prepared analogously to Example 2 from N-/?-(4-methoxy-phenyl)propyl7methylamine, 4’-amino-3’,5’-dichloro-2-bromo-propiophenone, triethylamine, and sodium borohydride.

M.p. of the hydrochloride: 178 - 181 °C.

NMR spectrum of the base (CDCl^/DgO): 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-ffl-ffl- (4-ethoxy-phenyl) propyl7methylamino7ethanol Prepared analogously to Example 2 from 4'-amino-3’,5*-dichloro2-bromo-acetophenone, 1-(4-ethoxy-phenyl)-3-methylamino-propane io hydrochloride, triethylamine, and sodium borohydride. Oil.

IR spectrum (methylene chloride): OH nh2 N-alkyl 3590 3395 2800 UV spectrum (ethanol): /( max. 245 nm (0.13) 280 nm (0.04) 300 nm. (0.04) Example 31 1-(4-Amino-3,5-dichloro-phenyl)-2-ffl-ffl-(4-benzyloxy-phenyl)propyl7methylamino7 ethanol Prepared analogously to Example 2 from 4'-amino-3',5'-dichloro2-bromo-acetophenone, 1-(4-benzyloxy-phenyl)-3-methylamino-propane hydrochloride, triethylamine, IR spectrum (methylene chloride): and sodium borohydride. Oil. OH 3590 cm1 NH2 3395 + 3495 cm N-alkyl 2800 cm1.

Example 52 1-(4-Amino-3-iodo-5-fluoro-phenyl)-2-/R-/3-(4-methoxy-phenyl)propyl7methylamino7ethanol 58007 Prepared analogously to Example 2 from 4'-amino-3’-iodo-5'-fluoro2-bromo-acetophenone, 1-(4-methoxy-phenyl)-3-methylamino-propane hydrochloride, triethylamine, and sodium borohydride. Oil.

IR spectrum (methylene chloride): OH nh2 N-alkyl 3590 cm' 3395 + 3495 cm' 2800 cm1.

Example 53 1- (4-Amino-3-cyano-5-fluoro-phenyl)-2-/!T-/?-(4-methoxy-phenyl)propyl7-2-propylamino7ethanol Prepared analogously to Example 2 from 4’-amino-3'-cyano-5’-fluoro2- bromo-aoetophenone,. 1-(4-methoxy-phenyl)-3-(2-propylamino)15 propane hydrochloride, and sodium borohydride. Oil.

IR spectrum (methylene chloride): OH 3600 NH2 3395 OCHj 2830 N-alkyl 2800 20 C-N 2220 cm1 + 3495 cm' cm1 cm cm Example 54 - (4-Amino-3,5-dichloro-phenyl) -2-/SF-/£- (2-methoxy-phenyl) propyl7methvlamlno7ethanol hydrochloride Prepared analogously to Example 2 from 4*-amino-3’,5'-dichloro25 2-bromo-acetophenone, 1-(2-methoxy-phenyl)-3-methylamino-propane hydrochloride, triethylamine, and sodium borohydride.

M.p.: from 75°C (by sintering). 53007 Example 55 1-(4-Amino-3,5-dichloro-phenyl)-2-^^/3-(3,4-dimethoxy-phenyl)propyl7methylamino7ethanol Prepared analogously to Example 2 from 4'-amino-3',5’-dichloro5 2-bromo-acetophenone, 1-(3,4-dimethoxy-phenyl)-3-methylaminopropane hydrochloride, triethylamine, and sodium borohydride.

IR spectrum (methylene chloride)s OH nh2 OCH.

N-alkyl 3600 cm 3390 + 3485 cm' 2830 cm1 2800 cm .

Example 56 - (4-Amino-3-chloro-5-trif luoromethyl-phenyl) -2-/EF-/2- (4-methoxy phenyl) ethyl7methylamino7ethanol Prepared analogously to Example 1 from 4’-amino-3’-chloro-5'-tri fluoromethyl-2-/N-/2-(4-methoxy-phenyl)-ethyl7methylamino7acetophenone, and sodium borohydride in 80 % methanol.

IR spectrum (methylene chloride): OH 3600 cm”1 nh2 N-alkyl O-CHj aliphat C-C UV spectrum (ethanol): λ max, 225 nm (0.38) 244 nm (0.34) 280 nm (0.07) 307 nm (0.10).

Example 57 - (4-Amino-3,5-dichloro-phenyl)-2-/i?-/J- (4-methoxy-phenyl)propyl7amino7ethanol hydrochloride Prepared analogously to Example 1 from 4'-amino-3’,5'-di5 chloro-2-2R-/3-(4-methoxy-phenyl)-propyl7amino7acetophenone and sodium borohydride in 90 % ethanol.

M.p. of the hydrochloride: 185 - 186°C (ethanol/ether).

Example 58 1- (4-Amino-3,5-dichloro-phenyl)-2-/K-(3-phenyl-propyl)-2-propyl10 amlno7ethanol hydrochloride Prepared analogously to Example 2 from 4'-amino-3',5'-dichloro2- bromo-acetophenone, 1-phenyl-3-(2-propylamino)-propane hydrochloride, triethylamine, and sodium borohydride.

M.p.:. 124 - 128°C.

Example 59 1- (4-Amino-3,5-dichloro-phenyl)-2-^-/5-(4-fluoro-phenyl)-propyl/methylamino7ethanol hydrochloride Prepared analogously to Example 2 from 4'-amino-3’,5’-dichloro2- bromo-acetophenone, 1-(4-fluoro-phenyl)-3-methylamino-propane 20 hydrochloride, triethylamine and sodium borohydride.

M.p.: 185 - 188°C (decomp.).

Example 60 1-(4-Amino-3,5-dichloro-phenyl)-2-/17-/J-(4-hydroxy-phenyl)1- methyl-propyl7amino7ethanol Prepared analogously to Example 4 from 4’-amino-3',5'-diohloro2- /N-/5-(4-hydroxy-phenyl)-1-methyl-propyl7-amino7acetophenone and sodium borohydride in aqueous tetrahydrofuran. As eluent for the chromatographic purufication over silica gel a mixture of dlchloromethane : methanol : cone, ammonia - 19 : 1 : 0.05 was used.

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

IR spectrum (KBr): OH —*1 2300 - 3500 cm (broad, associated) 5 nh2 3460 + 3370 cm1 ch2 2920 + 2960 cm1 c=c 1580, 1510 + 1480 cm1 UV spectrum (ethanol): 'λ max. 244 nm (0.28) 280 nm (0.08) 300 nm (0.08) UV spectrum (ethanol + KOH): λ max. 243 nm (0.54) 299 nm (0.15).

Example 61 1- (4-Amino-3,5-dichloro-phenyl)-2-/IT-/5-(4-methoxy-phenyl)15 1 -methvl-propyl7amino7ethanol ___________________ Prepared analogously·to Example 4.'from 4'-amino-3’,51-dichloro2- /N-/5- (4-methoxy-phenyl )-1 -me'thyl-propyl7amino7acetophenone and sodium borohydride in aqueous tetrahydrofuran.

The compound was abtained as a 1:1 20 rio racemate.

IR spectrum (methylene chloride): UV spectrum (ethanol)s λ max. mixture of the diastereoisome0H 3600 cm1 NH2 3480 + 3390 cm1 CH2 2930 cm1 OCHj 2830 cm1 C-C 1580, 1510 + 1485 cm 244 nm (0.28) 280 nm (0.08) 300 nm (0.09). 53007 Example 62 1-(4-Amino-3-cyano-5-fluoro-phenyl)-2-ffl-ffl-(3,4-dimethoxyphenyl )-ethvl7amlno7ethanol hydrochloride Prepared analogously to Example 5 from 41-amino-3'-fluoro5 5'-cyano-acetophenone, selenium dioxide, 2-(3,4-dimethoxyphenyl )- ethylamine, and sodium borohydride.

M.p.: 196 - 197°C (decomp.).

Example 65 1-(4-Amino-3-fluoro-5-iodo-phenyl)-2-ffl-ffl-(3,4-dimethoxy-phenyl)10 ethyl7amino7ethanol hydrochloride Prepared analogously to Example 5 from 4'-amino-31-fluoro-5'-iodoacetophenone , selenium dioxide, 2-(3,4-dimethoxy-phenyl)-ethylamine, and sodium borohydride.

M.p.: 192 - 193°C (.decomp·.).

Example 64 1-(4-Amino-3-chloro-5-fluoro-phenyl)-2-ffl-ffl-(3,4-dimethbxyphenvl)-ethvl7amino7ethanol hydrochloride Prepared analogously to Example 5 from 4'-amino-3'-chloro5'-fluoro-acetophenone, selenium dioxide, 2-(3,4-dimethoxy20 phenyl)-ethylamine, and sodium borohydride.

M.p.: 184 - 186°C (decomp.).

Example 65 1-(4-Amino-3-bromo-5-fluoro-phenyl)-2-j^i-/5-(3 «4-dimethoxy-phenyl)ethvl7amino7ethanol hydrochloride Prepared analogously to Example 5 from 4'-amino-3'-bromo-5'-fluoroacetophenone , selenium dioxide, 2-(3,4-dimethoxy-phenyl)-ethylamine, S3007 and sodium borohydride.

M.p.: 194 - 195°C (decomp.).

Example 66 1-(4-Amino-3-fluoro-5-cyano-phenyl)-2-£-£-(4-methoxy-phenyl)5 propyl7amino7ethanol Prepared analogously to Example 5 from 4*-amino-3'-fluoro5’-cyano-acetophenone, selenium dioxide, 3-(4-methoxy-phenyl)propylamine, and sodium borohydride.

M.p.: 119 - 121°C.

Example 67 1-(4-Amino-3,5-dichloro-phenyl)-2-/N-(3-phenyl-propyl)-amino7~ 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-ohloro-5-fluoro-phenyl)-2-/N-(1-methyl-2-phenoxyethvl)-amino/ethanol dihydroehloride Prepared analogously to Example 5 from 4'-amino-3'-chlor05'-fluoro-acetophenone, selenium dioxide, 1-methyl-2-phenoxyethylamine, and sodium borohydride.

M.p,: 158 - 16O°C (decong».). 53007 Example 69 1-(4-Amino-3-cyano-5-fluoro-phenyl)-2-/H-(1-methyl-2-phenoxyethyl)-amino7ethanol hydrochloride Prepared analogously to Example 5 from 4'-amino-3'-cyano-5'-fluoro5 acetophenone, selenium dioxide, 1-methyl-2-phenoxy-ethylamine, and sodium borohydride.

M.p.: 178 - 184°C (decomp.).

Example 70 1-(4-Amino-3-bromo-5-fluoro-phenyl)-2-/Sf-(1-methyl-2-phenoxy10 ethvl)-amlno7ethanol dlhydrochloride_ Prepared analogously to Example 5 from 4’-amino-3'-hromo-5’-fluoroacetophenone , selenium dioxide, 1-methyl-2-phenoxy-ethylamine, and sodium borohydride.

M.p.: 156 - 158°C (decomp.). . .

Example 71 N-/2-(4-Amino-3,5-dibromo-phenyl)-ethyi7-N-/5-(4-methoxy-phenyl)propyl7methylamine Prepared analogously to Example 7 from 4-amino-3,5-dibromo-N£j>- (4-methoxy-phenyl )-propyi7-N-methyl-phenyl-acetamide, and lithium aluminium hydride.

M.p. of the hydrochloride: 149 - 153°C.

Example 72 N-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl7-N-/J-(4-methoxy-phenyl)propyl7methylamine Prepared analogously to Example 7 from 4-amino-3,5-dichloro61 53007 N-/3- (4-methoxy-phenyl) -propyl7-N-methyl-phenyl-acetamide, and lithium aluminium hydride.

M.p. of the hydrochloride: 90 - 94°C.

Example 73 5 N-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl7-N-2?-(4-methoxyphenyl) -ethvl7methvlamine Prepared analogously to Example 8 from 4-amino-3,5-dichloroN-/2-(4-methoxy-phenyl)-ethyl7-N-methyl-phenyl-acetamide, and lithium aluminium hydride..

IR spectrum (methylene chloride) UV spectrum (ethanol): λ max.

: NH2 3380 + 3470 cm' N-alkyl 2780 cm1 OCHj 2830 cm-1 aliphat. CHg 2850 + 2930 cm' C=C 1610 cm-1 245 nm (0.24) 281 nm (0.08) • 305 nm (0.07).

Example 74 N-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl7-N-/5-(4-methoxy-phenyl)20 butyl7methylamlne Prepared analogously to Example 8 from 4-amino-3,5-dichloroN-/5-(4-methoxy-phenyl)-butyl7-N-methyl-phenyl-acetamide, and lithium aluminium hydride.

IR spectrum (methylene chloride): UV spectrum (ethanol): λ max.

NH2 3380 + 3480 cm' OCHj 2830 cm“1 aliphat. CHg 2850 + 2930 cm' NH+ 2100 - 2500 cm' C-C 1630 cm-1 245 nm (0.22) 280 nm (0.07) 304 nm (0.08). 53007 Example 75 Ν-/3-(4-Amino-3,5-dichloro-phenyl)-propyl/-2-(5,4-dimethoxyphenyl) -ethylamine hydrochloride Prepared analogously to Example 7 from 3-(4-amino-3,5-dichloro5 phenyl)-Ν-/Σ-(3,4-dimethoxy-phenyl)-ethyl/propionamide, and lithium aluminium hydride.

M.p.: 142 - 145°C.

Example 76 N-/3-(4-Amino-3,5-dichloro-phenyl)-propyl/-N-/2-(3,4-dimethoxy10 Phenyl)-ethyl7methylamine Prepared analogously to Example 8 from 3-(4-amino-3,5-dichlorophenyl )-N-/2-(3,4-dimethoxy-phenyl)-ethyl/-N-methyl-propionarnide, and lithium aluminium hydride. Oil. IR spectrum (methylene chloride): ·· ' ' UV spectrum (ethanol): 'X max.

NH2 3400 + 3500 cm1 OCHj ’ 2835 + 2960 cm1 NCHj 2800 cm1 aromat 1510 + 1590/ 1615 cm1 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-dihromophenyl) -N-/5- (3,4-dimethoxy-phenyl) -ethyl/propionamide, and lithium aluminium hydride.

M.p.: 131 - 134°C.

Example 78 Ν-/5-(4-Amino-3,5-dichloro-phenyl)-ethyl7_N-/J-(4-hydroxy-phenyl) 1 -methyl-propyl7amlne Prepared analogously to Example 8 from 4-amino-3,5-dichloroN-/5- (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 am) with methylene chloride : methanol : cono. ammonia -19 :1 :0.1 as eluent. Foam.

IR spectrum UV spectrum UV spectrum (methylene chloride): OH 3580 cm”1 nh2 3480 + 3385 cm-1 ch2 2920 cm1 C-C 1580, 1510 + 1480 cm (ethanol): Ά max. 242 tub (0.24; shoulder) 280 nm (0.07) 303 nm (0.08) (ethanol + KOH): max. . 242 nm (0.53) - 300 nm (0.16). 2o Example 79 N-/2-(4-Amino-3,5-dichloro-pheayl)-ethyl7-N-/J- (4-methoxy-phenyl)1-methyl-propyl7amine Prepared analogously to Example 8 from 4-amino-3,5-dichloroN-£>-(4-methoxy-phenyl)-1-methyl-propyl7phenylacetamide, and lithium aluminium hydride in tetrahydrofuran. Oil.

ZR spectrum (methylene chloride): NH-1 UV spectrum (ethanol): max. ch2 OCH, 2930 cm' 2830 cm1 C-C 1580, 1510 242 nm (0.25; shoulder) 280 nm (0.07) 302 nm (0.08). + 1485 cm 53007 cample 80 Ν-ffl-(4-Amino-3,5-dichloro-phenyl)-ethyl7-N-/5-(4-benzyloxyphenyl ) -propyl7methylamine___________________«_ Prepared analogously to Example 8 from 4-amino-3,5-dicbloro5 N-/5-(4-benzyloxy-phenyl)-propyl7-N-methyl-phenylacebamide, and lithium aluminium hydride. Oil.

IR spectrum (methylene chloride): nh2 N-alkyl 3390 2800 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)-ethyl7-N-ffl-(3,4-dimethoxyphenyl)-propvl7methvlamine Prepared analogously to Example 8 from 4-amin6-3,5-dichloroN-ffl-(3,4-dimethoxy-phenyl)-propyl7-N-methyl-phenylacetamide, and lithium aluminium hydride. Oil, IR spectrum (methylene chloride): nh2 3395 + 3495 «a OCHj 2830 cm 20 N-alkyl 2800 cm1 UV spectrum (ethanol): 2 max. 230 nm (shoulder; 0.18) 245 nm (shoulder; 0.12) 282 nm (0.04) 302 nm. (0.03) Example 82 N-ffl-(4-Amino-3,5-dichloro-phenyl)-etbyl7-N-/7-(2-methoxy-phenyl)propyl7methylamine hydrochloride Prepared analogously to Example 7 from 4-amino-3,5-dichloro65 53007 '-/5- (2-methoxy-phenyl )-propyl7-N-methyl-phenylacetamide, anri lithium aluminium hydride.

M.p.: 160 - 164°C.

Example 83 N-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl7-N-(3-phenyl-propyl)methylamine Prepared analogously to Example 8 from 4-amino-3,5-dichloroN- (3-phenyl-propyl) -N-rnethyl-phenylacetamide, and lithium aluminium hydride. Oil. io IR spectrum (methylene chloride): NHg 3390 + 3490 cm' N-alkyl 2800 cm”1 OV spectrum (ethanol): 7 max. 245 nm (0.12) 300 nm (0.03) Example 84 propyl7amine hydrochloride Prepared analogously to Example 7 from 4-amino-3»5-dichloroN-£>-(4-methoxy-phenyl)-propyl7phenylacetamide, and lithium aluminium hydride.

M.p.: 203 - 205°C.

Example 85 R-/2- ( 4-Amino-3,5-dichloro-phenyl) -ethyl7-N-/J- (4-methoxy-phenyl) propyl7cyclopropylamine Prepared analogously to Example 8 from 4-amino-3»5-dichloro-.

N-/J-(4-methoxy-phenyl)-propyl7-N-cyclopropyl-phenylacetamide, and lithium aluminium hydride. Oil.

IR spectrum (methylene chloride): NHg 3390 + 3490 cm 2830 cm 53007 UV spectrum (ethanol): 1 max. 245 nm (0.15) 280 nm (0.04) 300 nm (0.05) Example 86 N-/2-(4-Amino-3j5-dichloro-phenyl)-ethyl7-N-^-(4-methoxyphenyl) -propylTpropylamine Prepared analogously to Example 8 from 4-amino-3,5-dichloroN-/5-(4-methoxy-phenyl)-propyl7-N-propyl-phenylacet amide, and lithium aluminium hydride. Oil. IR spectrum (methylene chloride): nh2 3390 + 3490 cm' cm”1 OCHj 2830 N-alkyl 2800 cm”1 UV spectrum (ethanol): max. 243 nm (0.13) 280 nm (0.04) 300 nm (0.04) Example 87 N-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl7-N-/5-(4-methoxyphenvl)-propyl7ethylamlne Prepared analogously to Example 8 N-/3-(4-methoxy-phenyl)-propyl7-Nand lithium aluminium hydride. OilIR spectrum (methylene chloride): UV spectrum (ethanol): max. from 4-amino-3,5-dichloroethyl-phenylacetamide, nh2 OCHj N-alkyl 3390 + 3490 cm' 2830 cm”1 2800 cm”1 243 nm (0.13) 280 nm (0.04) 300 nm (0.04) Example 88 N-/2- (4-Amino-3,5-dichloro-phenyl) -ethyl7-N-{{- (4-methoxyphenyl ) -propYl7-2-propyIamine Prepared analogously to Example 8 from 4-amino-3i5-dichloroN-/J- (4-methoxy-phenyl) -propyl7-N- (2-propyl) -phenylacetamide, and lithium aluminium hydride. Oil.

IR spectrum (methylene chloride): NH2 3390 2830 OCHj UV spectrum (ethanol): λ max. 243 nm (0.13) 280 nm (0.04) 300 nm (0.04) Example 89 Ν-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl/-N-/5-(4-ethoxyphenyl)-propyl7methylamine' Prepared analogously to Example 8 from 4-amino-3,5-dichloro- N-/3-(4-ethoxy-phenyl)-propyl7~N-methyl-phenylacetamide, and lithium aluminium hydride. Oil. IR spectrum (methylene chloride): NH2 3390 + 3490 OCHj 2830 cm-1 N-alkyl 2800 cm1 UV spectrum (ethanol): K max. 245 nm (0.12) 280 nm (0.03) 300 nm (0.04) Example £0 Ν-/Σ-(4-Amino-3,5-dichloro-phenyl)-ethyl7-N-/5- (4-methoxyphenyl)-1-methyl-propyl7methylamlne Prepared analogously to Example 9 from 1-ethoxycarbonyloxy-1(4-amino-3,5-dichloro-phenyl)-2-/77-/5- (4-methoxy-phenyl)1-methyl-propyl/methylamino/ethane, and sodium borohydride in isopropanol. Oil. 53007 IR spectrum (methylene chloride): NHg N-alkyl och3 C-C 3480 + 3380 cm1 2930 cm-1 2790 cm1 2840 cm1 1580, 1510 + 1480 cm1 Example 91 Ν-/Σ- (4-Amino-3-bromo-5-cyano-phenyl)-ethyl7-N-/5-(4-methoxyphenyl)-butyl7methvlamine Prepared analogously to Example 9 from 1-ethoxycarbonyloxy-110 (4-amino-3-bromo-5-cyano-phenyl)-2-/^-/5-(4-methoxy-phenyl )-buty!7methylamino7ethane, and sodium borohydride.

Analysis: Calc.: C 60.6 H 6.3 Br 19.2 N 10.1 Pound: 60.5 6.1 19.2 10.1 15 Example 92 N-/2-(4-Amino-3-chloro-5-cyano-phenyl)-ethyl7-N-/2-(4-methoxyphenyl) - ethvl7methylamine ______________ .

Prepared analogously to Example 9 from 1-ethoxycarbonyloxy-1(4-amino-3-chloro-5-cyano-phenyl)-2-/Π-/Σ-(4-methoxy-phenyl)20 ethyl7methylamino7ethane, and sodium borohydride.

IR spectrum (methylene chloride): NH, 3400 + 3490 cm1 —*1 N-alkyl och3 aliphat C5N C«C UV spectrum (ethanol): max. 244 nm (0.26) 280 nm (0.04) 335 nm (0.15).

Example 95 N-/2-(4-Amino-3-bromo-5-cyano-phenyl)-ethyl7-N-/J-(4-methoxyphenyl )-propyl7methylamine Prepared analogously to Example 9 from 1-ethoxycarbonyloxy-1(4-amino-3-bromo-5-cyano-phenyl)-2-/J?-/J-(4-methoxy-phenyl)propyl/methylamino/ethane, and sodium borohydride.

IR spectrum (methylene chloride): NH.

N-alkyl OCH, 3390 + 3490 cm 3790 cm' UV spectrum (ethanol): max. aliphat C=N C-C 244 nm (0.20) 280 nm (0.04) 334 nm (0.13). 3830 cm' CH2 2850 + “1 2210 cm 1620 cm' 2940 cm' 1 Example 94 N-/2-(4-Amino-3-chloro-5-cyano-phenyl)-ethyl7-N-/?- (4-methoxyphenyl)-hutyl7methvlamine Prepared analogously to Example 9 from 1-ethoxycarbonyloxy-1(4-amino-3-chloro-5-cyano-phenyl)-2-/JT-/5-(4-methoxy-phenyl)-hutyl/ 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-/H-/5-(4-methoxyphenvl) -butvl7methvlamino7ethanol Prepared analogously to Example 1 from 4'-amino-3'-chloro-5'-tri70 fluoromethyl-2-/N-/4-(4-methoxy-phenyl)-butyl7methylamino7acetophenone, and sodium borohydride in 80 % methanol.

IR spectrum (methylene chloride): OH UV spectrum (ethanol): max. nh2 N-alkyl OCHj aliphat. aromat. 225 nm 245 nm 280 nm 308 nm 3590 cm 3410 + 3510 cm' 2800 cm' 2830 cm CH2 2850 + 2930 co' C-C 1630 cm1 (0.32) (0.31) (0.06) (0.10).

Example 96 - (4-Amino-3-cyano-phenyl )-2-(4-methoxy-phenyl)-propyl715 methylamino7ethanol Prepared analogously.to Example 11 from 1-(4-aminp-3-bromo5-cyano-phenyl )-2-/5F-/j- (4-meth0xy-phenyl)-propyl7methylaminci7ethanol in the presence of palladium/charcoal and hydrogen.

IR spectrum (methylene chloride): UV spectrum (ethanol): λ max.

OH 3610 cm NH2 3400 + 3490 cm1 N-alkyl 2800 cm1 OCHj 2830 cm1 C®N 2210 cm1 C-C 1630 cm1 251 nm (0.31) 280 nm (0.60) 328 nm (0.12). 53007 Example 97 N-/2- (4-Amino-3-chloro-phenyl) -ethyl/-N-/5-(4-ben2yloxy-phenyl) propyl7methylamine Prepared analogously to Example 11 from N-/2-(4-amino-3>5-dichloro 5 phenyl )-ethyi7-N-/3-(4-benzyloxy-phenyl )-propyl7methylamine and hydrogen. Oil.

IR spectrum (methylene chloride): NH2 3390 + 3490 cm 1 N-alkyl 2790 cm1.

Example 98 N-[2-(4-Amino-3,5-dichloro-phenyl)-ethyl/-N-/J-(4-hydroxy-phenyl)propyl7methylamine Prepared analogously to Example 16 from N-/2-(4-amino-3,5-dichloro phenyl)-ethyl7-N-£5-(4-benzyloxy-phenyl)-propyl/methylamine and hydrogen. Oil.

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

Example 99 1-(4-Amino-3-fluoro-phenyl)-2-/3-(1-methyl-2-phenoxy-ethyl)20 amino7ethanol tosylate Prepared analogously to Example 17 from 1-(4-acetamino-3-fluorophenyl)-2-/N-(l-methyl-2-phenoxy)-ethyi7amino-ethanol and. sodium hydroxide.

M.p.: 124 - 128°C. 53007 Example 100 N-/5-(4-Amino-3,5-dichloro-phenyl)-ethy!7-N-/?-(4-methoxyphenoxy)-propyl7methylamine 1.74 g (0.014 mol) of 4-methoxy-phenol were dissolved in 60 ml 5 of dry tetrahydrofuran, the solution was cooled to -5°C 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 0°C and the reaction mixture was mixed dropwise with a solution of 4.2 g of N-/5-(4-amino-3,5-dichloro-phenyl)-ethyl710 N-(3-chloro-Rr°py1)-methylamine in 50 ml of dry tetrahydrofuran at the same temperature. After stirring for 18 hours at approx.

°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): NHg CH„ UV spectrum (ethanol): λ max.

N-alkyl C«C 230 nm 246 nm 295 nm 3390 2950 cm 2800 cm' + 3480 cm' 1 1585 + 1560 1505 cm1 (0.18; shoulder) (0.085; shoulder) (0.05).

Example 101 1-(4-Amino-3,5-dichloro-phenyl)-2-/ΪΤ-(3-phenyl-propyl)-ethylamino7ethanol hydrochloride g of 1-(4-amino-3>5-dichloro-phenyl)-2-/ET-(3-phenyl-propy$-aminp7 5 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 fcra fiuther 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 extracted twice with methylene chloride, and the combined methylene 15 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 re20 maining oily residue was crystallised from ethyl acetate; colourless crystals were obtained.

M.p.: 102 - 105°C.

Example 102 1-(4-Ethoxycarbonylamino-3-cyano-5-fluoro-phenyl)-2-/R-/225 (3.4-dimethoxy-phenyl)-ethyl7amino7ethanol -hydrochloride Prepared analogously to Example 4 from 4’-ethoxycarbonylamino3’-cyano-5’-fluoro-acetophenone, selenium dioxide, 2-(3,4-dimethoxy-phenyl)-ethylamine, and sodium borohydride.

M.p.: 190 - 191°C (decomp.). 53007 Example 103 1- (4-Amino-3-cyano-5-fluoro-phenyl)-2-ffl-ffl-(4-methoxy-phenyl)butyl7methylamino7ethanol Prepared analogously to Example 1 from 4'-amino-3’-cyano-5'5 tl.uoro-2-ffl-ffl-(4-methoxy-phenyl)-butyl7methylamino7acetophenone and sodium borohydride in 80 % methanol.

IR spectrum (methylene chloride): UV spectrum (ethanol): λ max.

NH2 3400 + 3490 cm1 N-alkyl 2800 cm-1 0CH3 2830 cm-1 aliphat. CH2 2850 + 2930 cm1 C-N 2210 cm1 C-C 1635 cm1 241 nm (0.27) 280 nm (0.07) 322 nm (0.14).

Example 104 - (4-Acetamino-3-bromo-phenyl )-2-ffl-ffl- (4-methoxy-phenyl)-butyl7methylamlno7 ethanol Prepared analogously to Example 1 from 4'-acetamino-3’-bromo2-ffl-ffl-(4-methoxy-phenyl)-butyl7methylamino7acetophenone and sodium borohydride in 80 % methanol.

IR spectrum (methylene chloride): OH 3590 cm1 NH2 3410 cm1 N-alkyl 2800 cm1 OCHj 2830 cm1 aliphat. CH, 2850 + 2930 cm1 aromat. C-C 1610 cm C-0 1700 cm-1 amide II 1510 cm1 Example 105 Racemates A and B of 1-(4-amino-3,5-dichloro-phenyl)-2-/3^/5-(4-hydroxv-phenyl)-1-methvl-proayl7methylaalao7etfcanol g of 1-(4-amino-3j5-dichloro-pheEyl)-2-/S-/5“(4-hydroxy5 phenyl)-1-methyl-propyl7methylamiao7ethanol (1:1 mixture of the diastereoisomeric racemates A and B) were dissolved is ether and reacted with 0.5 equivalents of 3 H 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 - 249°C (deoonp.). 1^C-MMR spectrum of the base (CDC1-/CD-0D): CHj -CH2-CH2-CH- 37-50 ppm -CH2-CH2-CH- 58.36 ppm ^CH-CH^ -— >- 13-91 ppa 36.33 ppa 20 ^>h-ch2- 61.03 ppa 0H -fe- 68.89 ppm The isoprspanolic 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 - 0.025 mm; ether s methanol 10 :1). The crystalline evaporation residue, was reerystallized from a quantity of ether by concentrating at boiling temperatures.

M.p.: 128 - 131°C. 13C-NMR spectrum (CDClj/CD^OD): CH3 -ch2-ch2-ch- 35.61 ppm CH, ι 3 -CH2-CH2-CH- 59.21 ppm ^>CH-CHg 14.56 PP“ _>N-CH- __2 35.03 PP® ^>n-ch2- ' 63.11 ppm OH -CH- 69.08 ΡΡ» Example 106 1-(4-Amino-3-broao-5-cyano-phenyl)-2-ffl-£4-(4-methoxy-phenyl)butyl7benzylamino7ethanol hydrochloride Prepared analogously to Example 1 from 4'-amino-3'-bromo5,-cyano-2-Jf-/4-(4-methoxy-phenyl)-butyl7benzylamiao7aceto20 phenone and sodium borohydride in 90 % methanol.

M.p. of the hydrochloride: 122 - 126°C.

Example 107 1-(4-Amino-3-bromo-5-oyano-phenyl)-2“/M“/5-(4-Hethoxy-phenyl)butyl7allylamino7ethanol Prepared analogously to Example 1 from 4’-amino-3’-bromo5 5'-cyano-2-/N-/+- (4-methoxy-phenyl)=butyl7allylamiao7acetophenone and sodium borohydride in 90 % methanol. Resin.

IR spectrum (methylene chloride); ifflg 3390 + 3490 cm-1 OCHj 2830 + 2940 ca“1 CN 2210 cm1 «-i aromat. C=C 1610 cm UV spectrum (ethanol); Ά max. 223 nm (0.43) 244 nn (shoulder9 broad; 0.07) 330 nm (broad; 0.05) Example 108 1-(4-Amino-3-bromo-5-cyano-phenyl)-2-/0-/5-(4-methoxy-phenyl).butyl7isopropylamino7ethanol hydrochloride Prepared analogously to Example 1 from 4’-aaino-3'-bromo5’-cyano-2-/N-/5-(4-metho2y-phenyl)-butyl7isopropylanimo7~ acetophenone and sodium borohydride in 90 & aethaaol. 2o M.p. of the hydrochlorides sintering from 40°C.

Calc.; C 55.60 H 6.29 Br 16.20 Cl 2.14 H 8.46 Found; 55-30 6.37 15.40 6.84 8.83 Example 109 - (4-Asnino-3-bromo-5-cyano-phenyl ).-2-/0-/5- (4-aethosy-phenyl)25 butyl7-n-propylamino7ethanol hydrochloride Prepared analogously to Example 1 from 4’-amino-3'-bromo5’-cyano-2-/N-/5-(4-methoxy-phenyl)“butyi7“n“propylaBiEo7·· acetophenone and sodium borohydride in 90 % methanol.

M.p. of the hydrochloride: sintering from 40°C Calc.: Found: C 55.60 55.52 H 6.29 6.32 N 8.46 8.39 5 Example 110 1-(4-Amino-3-bromo-5-cyano-phenyl)-2-/3-/4-(4-methoxy-phenyl)butyl7ethylamino7ethanol hydrochloride Prepared analogously to Example 1 from 4’-amino-3'-bromo5'-cyano-2-/3-/4-(4-methoxy-phenyl)-butyl/ethylamino7aoeto10 phenone and sodium borohydride in 90 % methanol.

M.p. of the hydrochloride: 139 - 142°C.

Example 111 1-(4-Amino-3-bromo-5-trifluoromethyl-phenyl)-2-/3-/5-(4-methoxyphenyl)-propyl7methylamino7ethanol Prepared analogously to Example 1 from 4'-amino-3'-bromo5'-trifluoromethyl-2-/3-/5-(4-methoxy-phenyl)-propyl7methylamino/acetophenone and sodium borohydride in 90 tf methanol. Oil.

IR spectrum (methylene chloride): nh2 OCHj aromat UV spectrum (ethanol): max.

C-C 223 nm (0.26) 244 nm (0.10) 310 nm (very broad; 3400 + 3490 cm 2840 1610 cm + 2940 cm -1 0.04) 52ΘΘ7 Example 112 _ (4-Amino-3-b5r>oao-5“Cjraij.o-pheayl)-2~/ki- (4-phenyl-butyl)methylamino7ethanol hydrochloride Prepared analogously to Example 1 from 4’-amiao=3’”broEio= ’-cyano-2-/N-(4-phenyl-butyl)-aethylaHiao7acetophenQae and sodium borohydride ia 90 % methanol.

M.p. of the hydrochlorides 153 - 155°C.

Example 115 1-(4-Amino-3-cyano-5=fluoro-phenyl)-2-^-22-(A-methosy-phenyl)= ethyl7saethylamino7ethanol hydrochloride Prepared aaalogously to Example 1 from 4'-aaiao-5’»cyaao= 51 -fluoro=2~^'-»/2“(4--aethoxy“phenyl)=ethyl7netb.yianiEo7Eceto· phenone aad sodium borohydride in 90 % methanol.

' M.p. of the hydrochlorides sintering from 68°C._ Calc.: C 60.10 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-/S?~ (3-pheaylsulienyl-propyl)= methylamino/etfaaaol Prepared analogously to Example 2 from 4’-amino=2=broa0=3’, ’-dichloro-acetophenoae, N-/p-(4-nethosy-phesylsulfenyl)-propyl7 methylamine, aad sodium borohydride ia 80 % methanol. Oil.

IR spectrum (methylene chloride); iJHg 3390 ·.· 3490 cn”1 0Ξ 3600 ·;· 3680 en“1 OV spectrum (ethanol) s max. 246 sq (0.18) 300 aa (0.05) Example 115 1-(4-Amino-3,5-dichloro-phenyl )-2-/17-/5-(4-hydroxy-phenyl)propyl7amino7ethanol Prepared analogously to Example 3 from 4'-amino-3’,5'-dichloro2-/57-/5-(4-hydroxy-phenyl)-propyl7amino7acetophenone and sodium borohydride in aqueous tetrahydrofuran. Oil.

IR spectrum (KBr): OH, NH2 3300 - 3600 cm-1 aromat. C-C 1615 cm-1 UV spectrum (ethanol + KOH): max: 244 nm (0.26) 299 nm (0.08) Example 116 1-(4-Amino-3,5-dichloro-phenyl)-2-/Ϊ7-/5-(4-chlorophenyl)propyl7amino7ethanol Prepared analogously to Example 3 from 4’-amino-3',5’-dichloro15' 2-/N-/3-(4-chloro-phenyl)-propyl7amino7acetophenone and sodium' borohydride in aqueous tetrahydrofuran.

M.p.: 103 - 106°C.

Example 117 1- (4-Amino-3,5-dichloro-phenyl)-2-/17-/5-(4-hydroxy-phenyl)20 1-methvl-propyl7isopropYlamino7ethanol Prepared analogously to Example 3 from 4’-amino-3’,5’-dichloro2- fS-(4-hydroxy-phenyl)-1-methyl-propyi7isopropylamino7aeeto- phenone and sodium borohydride. Oil. Calc.: C 61.31 H 6.86 Cl 17.24 N 6.81 25 Found: 61.07 6.86 16.67 6.53 Example 118 1-(4-Amino-3,5-dichloro-phenyl)-2-ffl-ffl-(4-hydroay-pheayl)= 1-methyl-propyl7ethylaiaino7ethanol Prepared analogously to Example 3 from 4'=aHino=3’55’-dichloro 5 2-ffl-ffl-(4-hydro3Ey-phenyl)=1=Hethyl-propyl7ethylaaino7acetophenone and sodium borohydride. Oil.

Calc.: C 60.45 H 6.60 Cl 17.85 U 7.05 Pound: 60.45 6.76 17.70 6.86 Example 119 io 1-( 4-Kethylamino-5,5- dichlore-pheayl )=2=ffl-ffl- (4=hydrexy= phenyl)-1-Bethyl-propyl7aethylamino7ethanol Prepared analogously to Example 3 from 4’-sethylaaino-3’ , 5,“dichloro~2-/N-/3~(4rhydrosy=phenyX)-1-aethyl-prQpyl7~ methylamino7acetophenone and sodium borohydride. Oil.

Calc.: C 60.45 H 6.60 Cl 17.85 IT 7.05 Found: 60.6S 6.73 17.50 6.71 Example 120 1-(4-Dimethylaaino-3,5-dichloro~pheayl)=2=/H=/3“(4=hydr©sy= phenyl)-1-aethyl-propyl7methylanino7ethaaol Prepared analogously to Example 3 from V-diEethylasiso-S’, ’--dichloro-2-/H-_/3-(4-hydrosy-phenyl)-1=Qethyl=propyl7-nethyl· aaino/acetophenone and sodium borohydride. Oil.

Calc.: C 61.31 H 6.86 Cl 17.24 Π 6.81 Found: 61.28 6.57 16.80 6.42 53007 Example 121 - (4-Acetylamino-3,5-dichloro-phenyl )-2-ffl-ffl- (4-hydroxyphenyl )-1 -methvl-propyl7methvlamino7ethanol Prepared analogously to Example 3 from 4 *-acetylamino-31, 5 5'-diehloro-2-/R-/5-(4-hydroxy-phenyl)-1-methyl-propyl7methylamino7acetophenone and sodium borohydride. Foam.

IR spectrum (methylene chloride): OH NH N-alkyl 3580 cm1 3410 cm1 2800 cm1 10 C-0 1700 cm’1 C-C 1610, 1595 cm' Amide II 1515 cm” UV spectrum (ethanol): 7 max. 230 nm (0.30? shoulder) 280 nm (0.04) 15 (Ethanol + KOH): max. 243 nm (0.46) 294 nm (0.08) Example 122 1-(4-Ethoxycarbonylamino-3.5-dichloro-phenyl)-2-ffl-ffl-(4-hydroxyphenyl)-1-methyl-propyl7methylamino7ethanol Prepared analogously to Example 3 from 4'-ethoxycarbonylamino3', 5' -dichloro-2-fflr ffl- (4-hydroxy-phenyl )-1 -methyl-prppyl7methylaminp/acetqphenpne and sodium borohydride. Oil.

Calc.s 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 l-iA-aoino-^cyaso-S-fluoro-ghenyl)»· Prepared analogously to Example 3 fzw. 4’-aEia©-3‘-eye29= '-fluoro“2“/S=/T-Qethyl=3=(4'=h.ydr©27'=fii£ssyl/“ps-epy^betUylamino/acetophenone and sodiun borehydridG. S?.s sistaiasd of the diastereoisomeric raeenates w.c cs?arcvcd by neosc of column chronatography (Si02; nethyleaG ehlerifio s nethosol g cone, ammonia = 50 s 1 s 0.1).

Racemate As M.p.: 161 - 163°C 1^c-®jr spectrum (dg-diEel&yXsaXfosideii ^3 “ΟΗλ ^7 o 17 CHj -CH2-CH2-fe- 57.91 >CH-CB3 13.26 >n~ch3 35.74 Ii-CH2 . 60.SO OH -CH- 63.21 53007 racemate Β; M.p.: 92 - 98°C 1^C-NMR spectrum (dg-dimethylsulfoxide): ?H3 -ch2-ch2-ch- 36.52 ppm CH, -CH2-CH2-CH- 57.78 ppm >CH-CHj 13.19 ppm >n-ch2 61.48 ppa OH . —CH— 69.02 ppa Example 124 1-(4-Ainino-3-cyano-5-fluoro-phenyl)-2-2lJ-/T-methyl-3- (4-aethoxy-phenyl) -propvl7amino7ethanol_______________________.....

Prepared analogously to Example 3 from 4'-amino-3’-cyano5’-fluoro-2-/3-/T-methyl-3-(4-methoxy-phenyl)-propyl7amino7acetophenone and sodium borohydride.

M.p.: 108 - 110°C.

Example 125 1-(4-Amino-3-cyano-5-fluoro-phenyl)-2-/ii-/7-methyl-3-(4-hydroxyphenyl ) -propyl7amino7ethanol Prepared analogously to Example 3 from 4’-amino-3'-cyano5 5'-fluoro-2-/K-/T-methyl-3-(4-hydroxy-phenyl)-propyl7amino7acetophenone and sodium borohydride.

M.p.; 162 - 164°C.

Example 126 1-(4-Amino-3-cyano-5-fluoro-phenyl)-2- /T-/T-methyl-3-(4-meth10 oxy-phenyl)-propyl7methvlamino7ethanol Prepared analogously to Example 4 from 1-(4-amino-3-cyano5-fluoro-phenyl)-2-/H-/T-methyl-3-(4-hydroxy-phenyl)-propyl7methylamino7ethanol and dimethylsulfate/1 N sodium hydroxide solution in tetrahydrofuran. Oil.

IR spectrum (methylene' chloride): UV spectrum (ethanol): λ max. nh2 o-ch3 N-alkyl CBN C-C 3400 + 3500 cm 2830 cm1 2800 cm1 2210 cm1 1580, 1510 cm1 C-C + NH? deformation 1620 cm* 242 nm (0.27) 278 nm (0.05) 286 nm (0.05) 324 nm (0.12) 53007 Example 127 1-(4-Amino-3 >5-dichloro-phenyl)-2-/3-(1-methyl-2-phenoxyethyl)-amino7ethanol hydrochloride Prepared analogously to Example 5 from 4-amino-3',5-dichloroi; acetophenone, selenium dioxide, 1-methyl-2-phenoxy-ethylamine, and sodium borohydride. Amorphous hydrochloride.

IR spectrum (methylene chloride): NHg 3390 + 3490 cm UV spectrum (ethanol): X max 245 nm (0.15) 300 nm (0.04) Example 128 1-(4-Amino-3,5-dichloro-phenyl)-2-/3-/5-(4-fluoro-phenyl)propyl7amino7ethanol hydrochloride Prepared analogously to Example 5 from 4-amino-3', 5-dichloro-aceto phenone, selenium dioxide, 3-(4-fluoro-phenyl)-propylamine, .and sodium borohydride.

M.p. of the hydrochloride: 185 Example 129 1-(4-Amino-3,5-dichloro-phenyl)methylamino7ethanol Prepared analogously to Example : acetophenone, selenium dioxide, and sodium borohydride. Oil.

IR spectrum (methylene chloride) uv spectrum (ethanol): λ max. 187°C (decomp.). ·.-/$- (3-phenyl-1 -methyl-propyl )i from 4’-amino-3',5'-dichloroi-phenyl-1-methyl-propylamine, NH2 3390 + 3490 cm”1 OH 3600 + 3680 cm”1 245 na (0.18) 300 nm (0.06) 530 07 Example 130 - (4-Amino-3,5-dichloro-phenyl )-2-/57- (1 -methyl-2-phenoxy-ethyl) amlno/ethanol hydrochloride Prepared analogously to Example 5 from 4-amino-3',5l-dichloro5 acetophenone, selenium dioxide, 1-methyl-2-phenoxy-ethylamine, and sodium borohydride.

M.p. of the hydrochloride: 122 - 125°C.

Example 131 N-/5-(4-Amino-3-bromo-phenyl)-propyl7-N-/2-(3,4-dimethoxy10 Phenyl) -ethvl7methvlamine hydrochloride_- __ Prepared analogously to Example 7 from N-methyl-N-/2-(3,4-dimethoxy-phenyl) -ethyl/-3- (4-a®iP°-3,5-dibromo-phenyl) -propionamide and lithium aluminium hydride in absolute tetrahydrofuran.

M.p. of the hydrochloride: 70 - 120°C (sintering) IR spectrum (KBr): NH * 2500 - 2650 cm-1 alkyl 2800 - 3000 cm-1 UV spectrum (ethanol): λ max. 234 nm (0.17) 280 nm (0.04) 300 nm (shoulder; 0.03).

Example 132 N-/2-(4-Amino-3-chloro-phenyl)-ethyl7-N-(1-methyl-3-phenylpropyl)-i3opropylamine Prepared analogously to Example 7 from 4-amino-3>5-dichloro25 N-isopropyl-N-(1-methyl-3-phenyl-propyl)-phenylacetamide and lithium aluminium hydride in tetrahydrofuran. Oil.

IR spectrum (methylene chloride): NHg 3390 + 3490 cm-1 UV spectrum (ethanol): max. 241 nm (0.15) 300 nm (0.03) Example 133 Ν-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl/-N-(1-methyl-3-pbenylpropyl) -laopropylamine _____ .

Prepared analogously to Example 7 from 4-amino-3,5-dichloro5 N-isopropyl-N-(1-methyl-3-phenyl-propyl)-phenylacetamide and lithium aluminiumhydride in tetrahydrofuran. Oil.

IR spectrum (methylene chloride): NHg 3390 + 3490 cm1 UV spectrum (ethanol): 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=dichloroN-/J- (4-fluoro-phenyl) -propyl/phenylacetemide and .15 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-methyl3-phenyl-propyl)-methylamine Prepared analogously to Example 7 from 4-amino-3,5-dicbloroN- (1-methyl-3-phenyl-propyl)-phenylacetamide and lithium aluminium hydride in tetrahydrofuran. Oil.

IR spectrum (methylene chloride): NHg 3390 + 3490 cm1 UV spectrum (ethanol): λ max. 243 nm (0.14) ' 300 nm (0.05) Example 136 Ν-/2- (4-Amino-3,5-dichloro-phenyl) -ethyl/-N-/5- (4-methoxyphenyl-sulfenyl)-propvl/methylamine Prepared analogously to Example 7 from 4-amino-3,5-dichloro5 N-/J-(4-methoxy-phenylsulfenyl)-propyl/-N-methyl-phenylacetamide and lithium aluminium hydride in tetrahydrofuran oil.

IR spectrum (methylene chloride): NH2 3390 + 3490 cm' UV spectrum (ethanol)ί λ max. 245 nm (0.16) 300 nm (0.04) Example 137 N-/2-(4-Amino-3-bromo-phenyl)-ethyl/-N-/5-(4-methoxy-phenyl)butyl7methylamine -Prepared analogously to Example 8 from 4-amino-3-bromo-N-/5(4-methoxy-.phenyl)-butyl7-N-metbyl-phenylacetamide 15 and lithium aluminium hydride in absolute tetrahydrofuran.

IR spectrum (methylene chloride): NH2 OCH, 3380 + 3470 cm1 2830 + 2930 cm1 1620 cm1 aromat. C=C NMR spectrum (CDClj/DgO): aromat. H 6.4-7.3 ppm (m, 7H) OCHj 3.7 ppm (s, 3H) NCHj 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)25 ethvl7methylamine ____________________ Prepared analogously to Example 8 from 4-amino-3-bromo-N-/2(4-methoxy-phenyl)-ethyl7-N-methyl-phenylacetami 53007 and lithium aluminium hydride in absolute tetrahydrofuran.

IR spectrum (methylene chloride): NH2 3380 +. 3480 cm-1 OCH, 2840 + 2940 cm’1 aromat. C-C 1620 cm UV spectrum (ethanol): Λ max. 224 na (0.24) 242 no (0.15) 280 na (broad; 0.03) 300 na (broad; 0.03) Example 139 TX-ffl- (4-Amino-3-fluoro-phenyl) -ethyl7-M-ffl- (4-oethoxy-phenyl) propyl7methylamine Prepared analogously to Example 8 froa 4~amino-3-fluoro-Nffl- (4-methoxy-phenyl) -propyl7-N-aethyl-phenylacetamide and lithium aluminium hydride in absolute tetrahydrofuran.

Oil.

IR spectrum (methylene chloride): nh2 3390 + 3490 - .och3 2840 +•2940 aromat. C-C 1610 cm1 UV spectrum (ethanol): Ot max. 227 nm (0.30) 279 nm (0.06) 285 nm (0.06) Example 140 N-/2-(4-Amino-3-chloro-phenyl)-ethyl7~N-/5-(4-methoxy-phenyl)propyl7methylaaine Prepared analogously to Example 8.from 4-amino-3-chloro-N-methylN-ffl- (4-oethoxy-phenyl J-propyl/phenylacetamide and lithium aluminium hydride in absolute tetrahydrofuran. Resin. 53007 IR spectrum (methylene chloride): NH2 OCHj aromat. C-C 1610 cm' OV spectrum (ethanol): λ 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-/5-(4-methoxy10 phenyl)-propyl7amine hydrochloride Prepared analogously to Example 8 from 3-(4-amino-3,5-dichlorophenyl )-N-/5- (4-methoxy-phenyl)-propyl/propionamide and lithium aluminium hydride in absolute tetrahydrofuran.

M.p. of the hydrochloride: 138 - 142°C.

Example 142 N-/3-(4-Amino-3,5-dichloro-phenyl)-propyl/-N-/5-(4-methoxyphenyl)-ethyl7methylamine dihydrochioride Prepared analogously to Example 8 from 3-(4-amino-3.5-dichlorophenyl )-N-methyl-N-/2-(4-methoxy-phenyl)-ethyl/propionamide and lithium aluminium hydride in absolute tetrahydrofuran. M.p. of the dihydrochioride: 147 - 157°C. 53007 Example 143 Ν- /5- (4-Amino-3,5-dichloro-phenyl )-ethyi7-N-/5- (4-methoxyphenyl )-butyl7amlne hydrochloride Prepared analogously to Example 8 from N-/?-(4-amino-3»5-di5 chloro-phenyl)-ethyl7-4-(4-methoxy-phenyl)-butyramide and lithium aluminium hydride in absolute tetrahydrofuran. M.p. of the hydrochloride: 186 - 189°C.

Example 144 N-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl7-N-/J-(4-chloro-phenyl)10 propyl7amine hydrochloride Prepared analogously to Example 8 from 4-amino-3»5-dichloroN-/J-(4-chloro-phenyl)-propyl7phenylacetamide and lithium aluminium hydride in absolute tetrahydrofuran.

' M.p. of the hydrochloride: 186 - 190°C.

Example 145 N-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl7-N-/5- (4-oethoxyphenyl)-butyl7lsopropylamine Prepared analogously to Example 8 from N-/?-(4-amino-3,5-dichloro-phenyl)-ethyl7-N-isopropyl-4-(4-methoxy-phenyl)-butyramide and lithium aluminium hydride in absolute tetrahydrofuran. Oil.

IR spectrum (methylene chloride): NH, C-C 3390 + 3490 2850 + 2930 1610 cm-1 OCHj aromat. 25 UV spectrum (ethanol): λ max. 242 nm (0.12) 280 nm 301 nm (shoulder; 0.04) (0.04) asuu · Example 146 Ν-/Σ-(4-Amino-3,5-dichloro-phenyl)-ethyl/-Ν-/Σ- (4-methoxyphenyl )-ethyl7isopropylamlne Prepared analogously to Example 8 from N-/2-(4-amino-3,5-di5 chloro-phenyl)-ethy3/-N-isopropyl-4-methoxy-phenylacetamide and 1 ~i th i nm aluminiuia hydride in absolute tetrahydrofuran. Oil .

IR spectrum (methylene chloride): NHg 3390 + 3490 cm1 OCH, 2830 + 2960 cm1 Λ aromat. C-C 1610 cm UV spectrum (ethanol): max. 244 zm (shoulder;0.12) 280 nm (shoulder; 0.05) 301 nm (0.05) Example 147 N-/2-(4-Amino-3,5-dichloro-phenyl)-etiiyl/-N-/5-(4-methoxyphenyl)-ethvl7amine hydrochloride Prepared analogously to Example 8 from 4-amino-3,5-dichloroN-/2-(4-methoxy-phenyl)-ethyl/phenylacetamide and lithium aluminium hydride in absolute tetrahydrofuran.

M.p. of the hydrochloride: 206 - 208°C.

Example 148 N-/3-(4-Amlno-3,5-dibromo-phenyl)-propyl/-N-/2-(3»4-dimethoxyphenvl)-ethyl7methvlamine Prepared analogously to Example 8 from N-methylrN-/?-(3,4-di2 5 methoxy-phenyl) -ethyl7-3- (4-amino-3,5-dibromo-phenyl) -propionamide and lithium aluminium hydride in absolute tetrahydrofuran. Oil. 53007 IR spectrum (methylene chloride): NH2 OCH, NMR spectrum (CDClj/DgO): o-ch3 4 n-ch3 2 aromat. H 6 - 7, aliphat, , H 3480 + 3: 580 cm 2840 + 2940 cm' 85 ppm (s, 6H) 25 ppm (s, 3H) 75 ppm (d, 3H) 2 ppm (s, 2H) 1.5 - 2.9 ppm (m, 12H) Example 149 N-£.- (4-Amino-5,5-dichloro-phenyl )-ethyl7-3-phenyl-propylamine hydrochloride Prepared analogously to Example 8 from 4-amino-3,5-dichloroN-(3-phenyl-propyl)-phenylacetamide and lithium aluminium hydride in tetrahydrofuran.

M.p. of the hydrochloride: 197 - 199°C.

Example 150 N-/?-(4-Amino-3-bromo-5-cyano-phenyl)-ethyl7-N-/5-(4-methoxyphenyl )-butyl7benzvlamine Prepared analogously to Example 9 from 1-ethoxycarbonyloxy20 1-(4-amino-3-bromo~5-cyano-phenyl)-2-/iT-/5-(4-methoxy-phenyl)butyl/benzylamino/ethane and sodium borol Oil.

IR spectrum (methylene chloride): NH2 och3 CN aromat UV spectrum (ethanol): A max. 222 nm 244 nm 335 nn xq isopropsnol · 3390 + 3490 cm 2830 + 2930 cm -1 2210 cm . C=C 1620 cm-1 (0.42) (shoulder; 0.09) (broad; 0.05) 53007 Example 151 N-/2-(4-Amino-3-bromo-5-cyano-phenyl)-ethyl7-N-/5- (4-methoxyphenyl)-buty l7allylamine Prepared analogously to Example 9 from 1-ethoxycarbonyloxy5 1_(4-amino-3-bromo-5-cyano-phenyl)-2-ffl-ffl-(4-methoxy-phenyl)butyl7allylamino7ethane and sodium borohydride in isopropanol. Oil.

IR spectrum (methylene chloride): NH2 och3 CN aromat UV spectrum (ethanol): λ max. 222 nm 244 nm 335 nm Example 152 N-/2-(4-Amino-3-bromo-5-cyano-phenyl) -ethyl/-N- ffl- (4-methoxyphenyl)-butyl7ethylamine Prepared analogously to Example 9 from 1-ethoxycarbonyloxy-1(4-amino-3-bromo-5-cyano-phenyl)-2-ffl-ffl-(4-methoxy-phenyl)20 butyl7ethylamino7ethane and sodium borohydride in isopropanol.

Oil. 3390 + 3490 cm 2830 + 2930 cm1 2210 cm1 C=C 1620 cm1 (0.49) (shoulder; 0.1) (broad; 0.06) IR spectrum (methylene chloride): nh2 3390 + 3490 OCH, 2830 + 2960 CN 2210 cm1' 25 aromat. , C=C 1620 cm1 UV spectrum (ethanol): λ max. 222 nm (0.49) 244' nm (shoulder; 0.08) 333 nn (broad; 0.06) Example 153 N-/2-(4-Amino-3-bromo-5-cyano-phenyl)-ethyl7-N-/4-(4-methoxyphenyl)-butyl7isopropylamine Prepared analogously to Example 9 from 1-ethoxycarbonyloxy5 1-(4-amino-3-bramo-5-cyano-phenyl)-2-23-/4-(4-methoxy-phenyl)buty l/i s opr opylamino/e thane and sodium borohydride ia isopropanol. Resin.

IR spectrum (methylene chloride): nh2 3390 + 3490 OCH, 2830 + 2960 10 CN 2210 cm1 aromat. C-C 1620 cm1 UV spectrum (ethanol): λ 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)-ethyl7-N-/4-(4-aethoxyphenyl)-butyl7-n-propylamlne Prepared analogously to Example 9 from 1-ethoxycarhonyloxy1-(4-amino-3-bromo-5-cyano-phenyl)-2-/3-/£-(4-methoxy-phenyl)butyl7-n-propylamino7ethane and sodium borohydride in isopropanol. Oil.

IR spectrum (methylene chloride): OV spectrum (ethanol): Ά max.

NH2 3390 + 3490 ca 1 CN 2210 cm1 OCH- 2830 + 2950 cm-1 aromat. C-C 1620 cm 222 nm (0.46) 244 na (shoulder; 0.08) 330 nm (broad; 0.05) 53007 Example 155 N-/2-(4-Amino-3-bromo-5-cyano-pheayl)-ethyl7-N-(4-phenylbutyl) -methylamine' Prepared analogously to Example 9 from 1-ethoxycarbonyloxy5 1-(4-amino-3-bromo-5-cyano-phenyl)-2~/fT-(4-phenyl-butyl)methylamino7ethane and sodium borohydride in isopropanol. Oil. NMR spectrum (CDCl^): aromat. H 7.0 -7.4 ppm (m, TH) NCHj 2.2 ppm (s, 3H) aliphat. H 1.3 - 2.7 ppm (a, 12H) 1° Example 156 N-/2- (4-Amino-3-cyano-5-f luoro-phenyl) -ethyl/-N-ffl- (4-methoxy-phenyl)-ethyl7methylamine Prepared analogously to Example 9 from 1-ethoxycarbonyloxy1-(4-amino-3-cyano-5-fluoro-phenyl)-2-2iT-27-(4-methoxy-phenyl)15 ethyl7methylamino7ethane and sodium borohydride in isopropanol.

Oil.

NMR spectrum (CDCl^/CH^OD): aromat. H 6.7 - 7.2 ppm (m, 6H) OCHj 3.75 ppm (s, 3H) NCHj 2.3 ppm (s, 3H) 20 aliphat. H 2.4 - 2.7 ppm (m, 8H) Example 157 N-ffl- (4-Amino-3-cyano-5-f luoro-phenyl) -ethyl7-N-ffl- (4-methoxyphenyl)-propyl7methylamlne hydrochloride Prepared analogously to Example 9 from1-ethoxycarbonyloxy25 1-( 4-amino-3-cyano-5-fluoro-phenyl)-2-ffl-ffl- (4-methoxy-phenyl )propyl7methylamino/ethane and sodium borohydride in isopropanol. Hydrochloride as resin.

NMR spectrum (CBClj): aromat. H OCH, a* $ ^CHj aliphat. H 6.7 - 7.2 ppm (a, 6H) 3.75 ppm (s, 3H) 2.8 ppm (s, 3H) 1.5 - 3.5 PP· (a, 10H) Example 158 N-/2-(4-Amino-3-cyano-5-fluoro-phenyl)-ethyl7~N-/5-(4-methoxyphenyl )-butyl7methvlamine Prepared analogously to Example 9 from 1-ethoxycarbonyloxy1-(4-amino-3-cyano-5-fluoro-phenyl)-2-/R-/2i-(4-methoxy-phenyl)10 butyl/methylamino/ethane and sodium borohydride in isopropanol. Resin.

NMR spectrum (CDClj/DgO): aromat. H 7.2 ppm (s, 2H) OCHj NCHj aliphat. H 6.85 ppm (q, 4H) 3.8 ppm (s, 3H) 2.25 ppm (s, 3H) 1.5 - 2.7 ppm ·(,* 12H) Example 159 N-/2-(4-Amino-3-chloro-5-trifluoroaethyl-phenyl)-ethyl/Ν-/ΖΓ-(4-methoxy-phenyl)-butyl/methylamine Prepared analogously to Example 9 from 1-ethoxycarbonyloxy1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-/R-/5- (4-methoxy-phenyl) -butyl7methylamino7ethane and sodium borohydride in isopropanol.

M.p.: 29°C 53007 Example 160 N-/2-(4-Amino-3-chloro-5-trifluoromethyl-phenyl)-ethyl7N-/2-(4-methoxy-phenyl)-ethyl7methylamine Prepared, analogously to Example 9 from 1-ethoxycarhonyloxy1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-/ΕΓ-/Σ- (4-methoxy-phenyl )-ethyl7methylamino/ethane and sodium borohydride in isopropanol. Resin.

IR spectrum (methylene chloride): UV spectrum (ethanol): λ max. 3400 + 3500 cm OCH, 2840 + 2960 cm' Λ aromat. C-C 1610 cm 228 nm (shoulder; 0.10) 244 nm (0.10) 310 nm (0.03) NH.

Example 161 N-(4-Amino-3,5-dichloro-phenyl)-ethyl/-N-/5-(4-fluoro-phenyl)propyl7methvlamine Prepared analogously to Example 9 from 1-ethoxycarbonyloxy1 - (4-amino-3,5-dichloro-phenyl )-2-/R-/5- (4-fluoro-phenyl)-propyl/methylamino/ethane and sodium borohydride in isopropanol. Oil.

IR spectrum (methylene chloride): NH^ 3390 + 3490 cm-1 UV spectrum (ethanol): λ max. 243 nm (0.13) 300 nm (0.03) Example 162 1-(4-Amino-3-trifluoromethyl-phenyl)-2-/N-/5-(4-methoxy25 phenyl)-propvl7methylamino7ethanol 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 100 53007 on barium sulfate in methanol. Oil. NMR spectrum (CDClj/DgO): aromat. H CH-OH OCHj NCHj aliphat. H 6.6 - 7.3 ppm (m, 7H) 4.5 ppm (t, 1H) 3.7 ppm (a, 3H) 2.3 PP· (a, 3H) 2.2 - 2.7 ppm (a, 6H) 1.8 ppm (q, 2H) Example 163 N-/3-(4-Acetamino-3,5-dichloro-phenyl)-propyl7-N~/2-(3»4-di10 methoxy-phenyl)-ethyi7methvlamlne Prepared analogoualy to Example 12 from N-/3-(4-amino-3>5-dichloro phenyl)-propyl7-N-/2-(3,4-dimethoxy-phenyl)-ethyl7methylamine, acetyl chiori.de and triethylamine IR spectrum (methylene chloride) UV spectrum (ethanol: λ max. in toluene. Oil.

NH 3405 cm1 OCHj 2830 + 2940 cm1 CO 1700 cm1 228 nm (shoulder; 0.17) 280 nm (0.04) Example 164 1-(4-Amino-3,5-di chloro-phenyl )-2-/H-/5-(4-hydroxy-phenyl)1-methyl-propyl7allYlamino7gthanol Prepared analogously to Example 13 from 1-(4-amino-3,5-dichloro-phenyl )-2-/77-/5- (4-hydroxy-phenyl)-1-methyl-propyl7~ amino7ethanol with allyl bromide/sodium carbonate in absolute ethanol. Oil.

IR spectrum (methylene chloride): 3580 cm OH nh2 aliphat.

C-C 3390 + 3480 cm' CH2 1850 2930 cm' 1615 cm”1 101 UV spectrum (ethanol): A max. 243 ηιη (0.26) 282 nn (0.08) 300 nn (0.08) (Ethanol + KOH): λ max. 242 nn (0.47) 298 nm (0.19) Example 165 - (4-Amino-3,5-dichloro-phenyl)-2-/3-/5- (4-hydroxy-phenyl)propvl7isopropylamino7e'thanol hydrochloride Prepared analogously to Example 16 from 1-(4-amino-3,5-dilo chloro-phenyl)-2-£1-£>-(4-benzyloxy-phenyl)-propyl/isopropylamino/ethanol and hydrogen in the presence of palladium on charcoal.

M.p. of the hydrochloride: 90 - 110°C.

Example 166 I-(4-Amino-3-chloro-phenyl)-2-/3-/5-(4-hydroxy-phenyl)-propyl/ethylamino/ethanol Prepared analogously to Example 16 from 1-(4-amino-3,5-dichlorophenyl )-2- j8-0- (4-benzyloxy-phenyl) -propyl7ethylamino7ethanol and hydrogen in the presence of palladium on charcoal. Resin.

IR spectrum (methylene chloride): OH 3595 cm'1 3400 + 3490 2840 + 2940 nh2 aliphat. CH2 C=C 1625 cm UV spectrum (ethanol): λ max. 227 nm (0.19) 244 nm (0.17) 290 nm (0.04) (Ethanol + KOH): λ max. 243 nm (0.32) 297 nm (0.08) 102 Example 167 1-(4-Amino-3,5-dichloro-phenyl)-2-£-£-(4-hydroxy-phenyl)propyl7ethylamino7ethanol Prepared analogously to Example 16 from 1-(4-amino-3,5-dichlorophenyl )-2-£-£- (4-benzyloxy-phenyl) -propyl/ethylamino/ethanol and hydrogen in the presence of palladium on charcoal. Resin.

IR spectrum (methylene chloride): OH 3590, 3620 + 3680 cm1 NH„ 3390 + 3480 cm aromat. • C-C 1615 cm”1 UV spectrum (ethanol): A max. 244 nm (0.17) 284 nm (0.06) 200 nm (0.05) (Ethanol + KOH): A max. 243 nm (0.31) 298 nm (0.08) Example 168 U-£- (4-Dimethylamino-3,5-dichloro-phenyl)-propyl/-N-/3(4-methoxy-phenyl)-propyl7methylamine Prepared analogously to Example 101 from 8-£-(4-amino-3,5-di2 0 chloro-phenyl)-propyl/-N-£-(4-methoxy-phenyl)-propy!7amine, paraformaldehyde and sodium cyanoborohydride in ethanol. Oil.

IR spectrum (methylene chloride) NMR spectrum (CDClj/DgO): och3 nch3 2830 + 2940 cm 2790 cm1 nh2 aromat. C-C 161O cm1 aromat. Η 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. Η 2.2 - 2.8 ppm (m,8H) N-CHj 2.2 ppm (s, 3H) -ch2- 1.6 - 1.8 ppm (q,4H) 103 53007 Example 169 N-/J-(4-Amino-3« 5-dichloro-phenyl)-propyl7-N-/J-(4-methoxyphenyl)-propyl7methylamine Prepared analogously to Example 101 from N-/3-(4-amino-3.5-dichloro-phenyl )-propyl7-N-ffl-(4-methoxy-phenyl)-propyl/amine, paraformaldehyde and sodium cyanoborohydride in ethanol. Oil.

IR spectrum (methylene chloride): UV spectrum (ethanol): λ max.

NH2 3390 + 3490 cm ' OCH- 2830 + 2940 cm1 -1 aromat. C»C 1610 cm 230 nm (shoulder; 0.21) 242 nm (0.10) 278 + 285 (broad; 0.03) 302 nm (broad; 0.03) Example 170 N-ffl-(4-Dimethylamino-3,5-dichloro-phenyl)-ethyl7-N-/5- (4-chlorophenyl)-propyl7methylamine Prepared analogously to Example 101 from N-/2-(4-amino-3,5-dichloro-phenyl ) -ethyl7-N-/3- (4-chloro-phenyl) -propyl/amine, paraformaldehyde and sodium cyanoborohydride in ethanol. Oil.

IR spectrum (methylene chloride): NCH^ 2790 cm1 NH UV spectrum (ethanol): λ max. 273 nm (broad; 0.04) 104 53007 Example 171 N-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl7-N-/7-(4-chlorophenyl )-propyl7-2-phenvlethvlamlne hydrochloride Prepared analogously to Example 101 from N-/2-(4-amino-3.5-di5 chloro-phenyl)-ethyl/-N-ffl- (4-chloro-phenyl)-propyl/amine, phenylacetaldehyde and sodium cyanoborohydride in ethanol.

M.p. of the hydrochloride: 158 - 161°C.

Example 172 N-ffl- (4-Amino-3,5-dichloro-phenyl) -ethyl/-IX-ffl- (4-methoxyio Phenyl) -butvl7ethylamine Prepared analogously to Example 101 from N-/2-(4-amino-3«5-dichloro-phenyl ) -ethyl7-N-/£- (4-methoxy-phenyl) -butyl/amine, acetaldehyde and sodium cyanoborohydride in ethanol. Oil.

IR spectrum (methylene chloride): OCH^ 2860 + 2930 cm”115 aromat. C-C 1610 cm1 UV spectrum (ethanol): λ max. 245 nm (0.09) 278 nm (0.02) 282 nm (0.02) 300 nm (0.01) 20 Example 173 N-ffl-(4-Amino-3,5-dichloro-phenyl)-ethyl/-N-ffl-(4-chloro-phenyl)propyl/benzylamine hydrochloride Prepared analogously to Example 101 from N-/5-(4-amino-3»5-dichloro-phenyl )-ethyl7-N-/5-(4-chloro-phenyl)-propylamine, henz25 aldehyde and sodium cyanoborohydride in ethanol.

M.p. of the hydrochloride: 164 - 168°C. 105 53007 Example 174 Ν-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl7-N-/3-(4-chlorophenyl )-propyl7isopropylamine Prepared analogously to Example 101 from Ν-/Σ-(4-amino5 3,5-dichloro-phenyl)-ethyl7-N-/3-(4-chloro-phenyl)-propyl/amine, acetone and sodium cyanoborohydride in absolute methanol. Oil.

IR spectrum (methylene chloride): NHg 3390 + 3480 cm-1 aromat. C-C 1615 cm”1 io UV spectrum (ethanol): max. 241 nm (0.13) 300 nm (0.05) Example 175 N-/T-Methyl-2-(4-amino-3,5-dichloro-phenyl)-ethyl7-N-/5(4-methoxyphenyl)-propyl7amine hydrochloride Prepared analogously to Example 101 from 1-(4*-amino-3’,5’-dichloro-phenyl )-aaetone, 3-(4-methoxyphenyl)-propylamine and sodium cyanoborohydride in ethanol.

M.p. of the hydrochloride: 193 - 195°C.

Example 176 N-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl/-N-/3-(4-chloro-phenyl)propyl7-n-propylamine Prepared analogously to Example 101 from N-/2-(4-amino-3,5-dichloro-phenyl )-ethyl7-N-/3“(4-chloro-phenyl)-propyl/amine, propionaldehyde and sodium cyanoborohydride in ethanol. Oil.

IR spectrum (methylene chloride): NH^ 3380 + 3480 cm”1 aromat. C-C 1610 cm”1 UV spectrum (ethanol): max. 242 nm (0;13) 301 nm (0.05) 106 53007 Sxample 177 N-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl7-N-/J- (4-chloro-phenyl)propyl7ethylamine Prepared analogously to Example 101 from N-/2-(4-aaino-3,5-di5 chloro-phenyl)-ethyl7-N-/J-(4-chloro-phenyl)-propyl7amine, acetaldehyde and sodium cyanoborohydride in ethanol at pH 6 - 6.5. Oil.

IR spectrum (methylene chloride): NHg 3390 + 3480 cm1 aromat. C-C 1615 cm”1 OV spectrum (ethanol): max. 242 nm (0.14) 305 nm (0.04) Example 178 N-/2- (4-Amino-3,5-dichloro-phenyl)-ethyl7-N-/2-(4-methoxyphenyl )-ethyl7ethylamine Prepared analogously to Example 101 from N-/2-(4-amino-3»5-dichloro-phenyl )-ethyl7-N-/2- (4-methoxy-phenyl)-ethyl/amine, acetaldehyde and sodium cyanoborol hydride in ethanol. Oil. IR spectrum (methylene chloride): NH2 3890 + 3480 OCHj 2830 + 2940 aromat. . C-C 1620 cm“1 OV spectrum (ethanol): λ max. 244 nm (0.16) 284 nm (shoulder; 0,04) 300 nm (0.04) Example 179 N-/T-Methyl-2-(4-amino-3,5-dichloro-phenyl)-ethyl7-N-/J-(4-methoxy-phenyl)-propyl7methylamlne Prepared analogously to Example 101 from 1-(41-amino-3'.5'-dichlorophenyl )-acetone, 3-(4-methoxy-phenyl)-N-methyl-propylamine and 107 sodium cyanoborohydride in ethanol. Oil.

IR spectrum (methylene chloride): NH2 3390 + 3480 cm-1 OCH, 2840 + 2940 cm-1 D —1 aromat. C-C 1615 cm UV spectrum (ethanol): λ max. 242 nm (0.14) 280 nm (shoulder; 0.04) 302 nm (0.05) Example 180 N-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl7-N-(3-phenylpropyl)10 isopropylamine hydrochloride Prepared analogously to Example 101 from N-/2-(4-amino-3«5-dichloro-phenyl) -ethyl7-3-phenyl-propylamine, acetone, molecular sieve 3 & and sodium cyanoborohydride in absolute methanol. Foam. IR spectrum (methylene chloride): ΝΗ^ 3390 + 3490 cm-1 _ ΝΗ®> 2300 - 2400 cm1 UV spectrum (ethanol): max. 245 no (0.12) 302 nm (0.04) Example 181 1-(4-Amino-3,5-dichloro-phenyl)-2-/N-(1-methyl-3-phenyl-propyl) 20 methylamino7ethanol hydrochloride Prepared analogously to Example 101 from 1-(4-amino-3,5-dichlorophenyl )-2-/N-(1-methyl-3-phenyl-propyl)-amino/ethanol, paraformaldehyde and sodium cyanoborohydride in ethanol. Oily hydrochloride.

IR spectrum (methylene chloride): NHg 3390 + 3490 cm-1 NH + 2300 - 2400 cm'1 OH 3580 cm1 UV spectrum (ethanol): max. 245 nm (0.12) 302 nm (0.03) 108 53007 Example 182 1-(4-Amino-3,5-dichloro-phenyl)-2-/^-(1-methyl-3-phenylpropyl)-methvlamlno7ethanol hydrochloride Prepared analogously to Example 101 from 1-(4-amino-3,5-di5 chloro-phenyl)-2-/8- (1-methyl-3-phenyl-propyl)-amino/ethanol, paraformaldehyde and sodium cyanoborohydride in absolute ethanol.

M.p. of the hydrochloride: 170 - 173°C.

Example 183 1-(4-Amino-3,5-dichloro-phenyl)-2-/IT-(1-methyl-3-phenylpropyl)-propylamino7ethanol hydrochloride Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro-phenyl)-2-{S- (1-methyl-3-phenyl-propyl)-amino/ethanol, propionaldehyde and sodium cyanoborohydride. Oily hydro-, chloride.

IR spectrum (methylene chloride): NHg UV spectrum (ethanol): λ max.

NH * OH 245 nm (0.12) 302 nm (0.03) 3390 2300 3590 + 3490 cm“ - 2400 cm’1 + 3680 cm' 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-di25 chloro-phenyl)-ethyl7-3-phenyl-propylamine, propionaldehyde and sodium cyanoborohydride in absolute ethanol. Oily hydrochloride.

IR spectrum (methylene chloride): NH^ 3390 + 3490 cm-1 NH® 2300 - 2400 cm-130 OH 3600 + 3650 cm’1 109 UV spectrum (ethanol): X max. 245 nm (0.17) 302 nm (0.05) Example 185 N-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl7-N-(3-phenyl)-propyl)5 ethylamine hydrochloride Prepared analogously to Example 101 from N-/2-(4-amino-3,5-dichloro-phenyl)-ethyl7-3-phenyl-propylamine, acetaldehyde and sodium cyanoborohydride in absolute ethanol. Oily hydrochloride. IR spectrum (methylene chloride): NH, 3390 + 3490 cm-1 NH 2300 - 2400 cm-1 UV spectrum (ethanol): max. 245 nm (0.12) 302 nm (0.04) Example 186 N-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl/-N-(1-methyl-3-phenyl15 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-1 UV spectrum (ethanol): λ max. 243 nm (0.11) 300 nm (0.04) Example 187 1-(4-Amino-3,5-dichloro-phenyl)-2-/0- (1-methyl-2-phenoxy-ethyl)25 ethylamino7ethanol hydrochloride Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro phenyl)-2-/4-(1-methyl-2-phenoxy-ethyl)-amino7ethanol, acetaldeΠ0 53007 hyde and sodium cyanoborohydride in absolute ethanol. Oily hydrochloride.

IR spectrum (methylene chloride): NH^ 3390 + 3490 cm”1 Nh® 2320 - 2460 cm’1 OH 3600 + 3680 cm”1 UV spectrum (ethanol): 3 max. 248 nm (0.12) 300 nm (0.03) Example 188 1-(4-Amino-3-cyano-5-fluoro-phenyl)-2-ffl-ffl-(3,4-diaethoxy10 Phenyl) -ethyl7ethylamino7ethanol Prepared analogously to Example 101 from 1-(4-amino-3-cyano5-f luoro-phenyl )-2-ffl-ffl- (3,4-dime thoxy-phenyl) -ethyl7amino/- ethanol, acetaldehyde and sodium cyanoborohydride in ethanol. Oil. IR spectrum (methylene chloride): nh2 3390 + 3490 cm’ - CN ' 2205 cm1, UV spectrum (ethanol): J 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-^-/2-(3,4-methylenedioxy-phenoxy)-1-methyl-ethvl7ethylamino7ethanol hydrochloride Prepared analogously to Example 101 from 1-(4-amino-3-chloro5-fluoro-phenyl)-2-ffl-ffl-(3,4-methylenedioxy-phenoxy)-1-methyl25 ethyl7amino7ethanol, acetaldehyde and sodium cyanoborohydride in absolute ethanol. Oily hydrochloride. Π1 IR spectrum (methylene chloride): NH, OH UV spectrum (ethanol): λ max. 243 mn (0.17) 287 nm (0.07) 3390 + 3490 cm 2300 - 2450 cm1 3600 + 3680 cm1 Example 190 - (4-Amino-3-bromo-5-fluoro-phenyl)-2-/3- (1 -methyl-2-phenoxyethyl)-ethylamino7ethanol Prepared analogously to Example 101 from 1-(4-amino-3-bromoio 5-fluoro-phenyl)-2-/3-(1-methyl-2-phenoxy-ethyl)-amino/ethanol, acetaldehyde and sodium cyanoborohydride in absolute ethanol. Oil. IR spectrum (methylene chloride): NH2 3390 + 3490 cm 1 UV spectrum (ethanol): 2 max. 240 nm (0.14) 280 - 290 nm (0.03) 15 Example 191 - (4-Amino-3-cyano-5-f luoro-phenyl) -2-/3-/5- (4-methoxy-phenyl)propyl7ethvlamino7ethanol hydrochloride Prepared analogously to Example 101 from 1-(4-amino-3-cyano5-fluoro-phenyl)-2-/3-/5-(4-methoxy-phenyl)-propyl/amino/ethanol, acetaldehyde and sodium cyanoborohydride in absolute ethanol.

Oily hydrochloride.

IR spectrum (methylene chloride): NH„ 3390 + 3490 cm1 UV spectrum (ethanol): λ max. 248 nm (0.11) 2300 - 2500 cm1 2205 cm1 3590 + 3680 cm1 NH CN .OH 280 nm (0.03) 320 nm (0.06) 112 .xample 192 N-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl7-N-/7-(4-fluorophenyl )-propyl7benzylamine hydrochloride Prepared analogously to Example 101 from N-/2-(4-amino-3,5-di5 chloro-phenyl)-ethyl7-N-/?-(4-fluoro-phenyl)-propyl7amine, benzaldehyde and sodium cyanoborohydride in absolute ethanol.

M.p. of the hydrochloride: 118 - 120°C.

Example 193 (4-Amino-3,5-dichloro-phenyl)-ethyl7-N-/5-(4-fluoro10 phenyl)-propyl7-n-propYlamine hydrochloride Prepared analogously to Example 101 from N-/2-(4-amino-3,5-dichloro-phenyl)-ethyl7-N-/J-(4-fluoro-phenyl)-propyl/amine, propionaldehyde and sodium cyanoborohydride in absolute ethanol. ' M.p. of the hydrochloride: 130 - 133°C.

Example 194 N-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl7~N-/5-(4-fluoro-phenyl)propyl7ethylamine hydrochloride Prepared analogously to Example 101 from N-/2-(4-amino-3,5-di2 0 chloro-phenyl)-ethyl7-N~/3-(4-fluoro-phenyl)-propyl/amine, acetaldehyde, molecular sieve 3 2 and sodium cyanoborohydride in absolute methanol.

M.p. of the hydrochloride: 182 - 184°C (decomp.). Π3 53007 Example 195 N-ffl-(4-Amino-3,5-dichloro-phenyl)-ethyl7-N-ffl- (4-fluorophenyl )-propyl7isopropyl-amine hydrochloride Prepared analogously to Example 101 from N-ffl- (4-amino5 3,5-dichloro-phenyl)-ethyl7-N-/7-(4-fluoro-phenyl)-propyl7amine, acetone, molecular sieve 3 £ and sodium cyanohorohydride in absolute methanol.

M.p. of the hydrochloride: 182 - 184°C (decomp.).

Example 196 io 1-(4-Amino-3,5-dichloro-phenyl)-2-ffl-ffl-(4-fluoro-phenyl)propvl7-2-phenvlethylamino7ethanol hydrochloride Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro-phenyl)-2-2N-2J-(4-fluoro-phenyl)-propyl/amino7ethanol, phenylacetaldehyde and sodium cyanohorohydride in absolute 15 ethanol. Amorphous hydrochloride.

IR spectrum (methylene chloride): 3390 + 3490 cm UV spectrum (ethanol): Λ max.

OH 243 nm (0.11) 300 nm (0.04) 3390 + 3490 cm' 2300 - 2500 cm1 3590 + 3680 cm'1 Example 197 1-(4-Amino-3,5-dichloro-phenyl)-2-/N-ffl-(4-fluoro-phenyl)propyl7benzylamino7ethanol hydrochloride Prepared analogously to Example 101 from 1-(4-amino-3,5-di2 5 chioro-phenyl)-2-ffl-ffl-(4-fluoro-phenyl)-propyl7amino7ethanol, benzaldehyde and sodium cyanoborohydride in absolute ethanol.

M.p. of the hydrochloride: 132 - 134°C (decomp.). 114 53007 58007 . Example 198 IR spectrum (methylene chloride): UV spectrum (ethanol): λ max. 1-( 4-Amino-3,5-dichloro-phenyl )-2-/77- //)- (4-f luoro-phenyl) propyl7-n-propylamino7ethanol hydrochloride Prepared analogously to Example 101 from 1-(4-amino-3,5-di5 chloro-phenyl)-2-/17-/5- (4-fluoro-phenyl) -propyl7amino7ethanol, propionaldehyde and sodium cyanoborohydride in absolute ethanol.

M.p. of the hydrochloride: 136 - 138°C (decomp.).

Example 199 1-(4-Amino-3,5-dichloro-phenyl)-2-/77-/5-(4-fluoro-phenyl)propyl7ethylamino7ethanol hydrochloride Prepared analogously to Example 101 from 1-(4-amino-3,5-dicblorophenyl)-2-/N-/5-(4-fluoro-phenyl)-propyl7amino7ethanol, acetaldehyde and sodium cyanoborohydride in absolute ethanol.

M.p. of the hydrochloride: 130 - 134°C.

Example 200 1-(4-Amino-3,5-dichloro-phenyl)-2-/77-(3-phenyl-propyl)-2-phenylethylamino7ethanol hydrochloride Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro2 0 phenyl)-2-/il-(3-phenyl-propyl)-amino/ethanol, phenylacetaldehyde and sodium cyanoborohydride in absolute ethanol. Amorphous hydrochloride .

NIL· 3390 + 3490 cm-1 NH^® 2300 - 250' cm’1 OH 3590 + 3690 cm-1 243 nm (0.12) 300 nm (0.04) 115 1-(4-Amino-3,5-dichloro-phenyl)-2-/N-/3-(4-fluoro-phenyl)propyl7isopropylamino7ethanol hydrochloride Prepared analogously to Example 101 from 1-(4-amino-3,5-di5 chloro-phenyl)-2-/N-/3-(4-fluoro-phenyl)-propyl7amino/ethanol, acetone, molecular sieve 3 8 and sodium cyanoborohydride in absolute methanol.

M.p. of the hydrochloride: 80 - 85°C (decomp.).

Example 202 1-(4-Amino-3,5-dichloro-phenyl)-2-/N-(1-methyl-3-pheny1-propyl) ethylamino7ethanol Prepared analogously to Example 101 from 1-(4-amino-3;5-dichloro-phenyl )-2-/N- (1-methyl-3-phenyl-propyl)-amino7ethanol, acetaldehyde, molecular sieve 3 8 and sodium cyanoborohydride · in absolute ethanol. Oil.

IR spectrum (methylene chloride): NHg 3390 + 3490 cm” UV spectrum (ethanol): 'X max. 245 nm (0.13) 300 nm (0.03) Example 203 20 1—(4-Dimethylamino-3,5-dichloro-phenyl)-2-/N-(3-phenyl-1-methyl propyl)-methylamino7ethanol 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 cm1 UV spectrum (ethanol): λ max. 275 nm (0.03) 116 Example 204 1-(4-Amino-3,5-dichloro-phenyl)-2-/0- (3-phenyl-propyl)benzylamino7ethanol Prepared analogously to Example 101 from 1-(4-amino-3.5-di5 chloro-phenyl)-2-/0-(3-phenyl-propyl)-amino7ethanol, benzaldehyde and sodium cyanoborohydride in absolute ethanol. Oil.

IR spectrum (methylene chloride): NHg 3390 + 3490 co”1 OH 3600 + 3680 co-1 UV spectrum (ethanol): λ max. 245 nm (0.12) 10 300 nm (0.03) Example 205' - (4-Amino-3,5-dichloro-phenyl )-2-/0- £- (4-methylsulf inyl-phenyl) propyl7amino7ethanol 1.5 g (0.0039 mol) of 1-(4-amino-3,5-dichloro-phenyl)-2-/0-/515 (4-methylsulfenylphenyl)-propyl7amino7eth’anol 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 sul25 fate and in vacuo evaporated to dryness. The residue was recrystallized from methanol/ether. Colourless crystals.

M.p.: 127 - 129°C. 117 Example 206 ' - (4-Amino-3,5-dichloro-phenyl) -2-/3-/5- (4-methylsulf enylphenyl )-propyl7amino7ethanol Prepared analogously to Example 5 from 4'-amino-3',5'-dichloro5 acetophenone, selenium dioxide, 3-(4-methylsulfenylphenyl)propylamine and sodium borohydride.

M.p.j 128 - 130°C.

Example 207 1-(4-Amino-3,5-dichloro-phenyl)-2-/3 -/3-(4-methylsulfinyl10 phenyl)-propyl7methylamino7ethanol Prepared analogously to Example 101 from 1-(4-amino-3,5-dichlorophenyl )- 2-/3-/3- (4-methyl. sul finyl.-phenyl.) -ρη-ιργί/ηιηΐ nnjethanol, paraformaldehyde and sodium cyanoborohydride in methanol Foam. —1 IR spectrum (methylene chloride): OH 3660 + 3600 cm NH2 3490 + 3390 cm-1 SO 1050 cm-1 UV spectrum (ethanol): λ max. 242 nm (0.16) 300 nm (0.03) Example 208 1-(4-Amino-3,5-dichloro-phenyl)-2-/3-/5-(4-methylsulfenyl-phenyl) propyl7methylamino7 ethanol Prepared analogously to Example 101 from 1-(4-amino-3,5-dichlorophenyl )-2-/3-/3-(4-methylsulfenyl-phenyl)-propyl/aminc/ethanol, paraformaldehyde and sodium cyanoborohydride in methanol. Colourless oil. —1 IR spectrum (methylene chloride): OH 3690 + 3590 cm NH2 3490 + 3390 cm-1 118 58007 spectrum (ethanol): A max. 245 na (0.23) 295 - 300 nm (0.04) Example 209 - (4-Amino-3,5-dichloro-phenyl)-2-/71-/5- (4-chloro-phenyl) 5 propyl7-n-propylamino7ethanol_ ' Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro-phenyl )-2-/R-/5- (4-chloro-phenyl) -propyl7amino7ethanol, propionaldehyde and sodium cyanoborohydride-in‘ethanol. Oil.

IR spectrum (methylene chloride): NH2 3390, 3490 cm aromat. OC 1620 cm-1 UV spectrum (ethanol): max. 243 nm (0.13) 300 nm (0.04) Example 210 1-(4-Dlmethylamino-3,5-dichloro-phenyl)-2-methyl-2-/H-/?15 (4-methoxy-phenyl)-propyl7methvlamino7ethanol Prepared analogously to Example 101 from 1-(4-amino-3,5-dichlorophenyl )-2-methyl-2-/R-/5-(4-methoxy-phenyl)-propyl7amino7ethanol, paraformaldehyde and sodium cyanoborohydride in ethanol at pH 3 to 7.5. Oil.

* IR spectrum (methylene chloride): OH 3590 cm no SH, NH2 aromat. C-C 1610 cm-1 UV spectrum (ethanol): )) max. 243 nm (0.20) 278 nm (0.06) Π9 53007 Example 211 1-(4-Benzylamino-3,5-dichloro-phenyl )-2-/ΪΤ-/7-(4-chlorophenyl )-propyl7amino7ethanol Prepared analogously to Example 101 from 1-(4-amino-3i5-di5 chloro-phenyl)-2-ffl-ffl-(4-chloro-phenyl)-propyl7amino7ethanol, benzaldehyde and sodium cyanoborohydride in ethanol.

M.p. of the base: 85 - 95°C.

Example 212 1-(4-Amino-3,5-dichloro-phenyl)-2-ffl-ffl-(4-chloro-phenyl)io propyl7benzylamino7ethanol hydrochloride Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro-phenyl )-2-ffl-ffl- (4-chloro-phenyl) -propy!7amino/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-ffl-ffl-(4-chloro-phenyl)propyl7ethylamino7ethanol Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro phenyl)-2-/N-/3-(4-chloro-phenyl)propyl7amino7ethanol, acet20 aldehyde and sodium cyanoborohydride in ethanol. Oil. rf IR spectrum (methylene chloride): NH, 3390, 3490 cm- & rf aromat. C=C 1620 cm UV spectrum (ethanol): A max. 244 nm (0.13) 300 nm (0.04) 120 Example 214 Ν-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl/-N-/7-(4-chlorophenyl)-propyl7methylamlne Prepared analogously to Example 101 from N-/2-(4-amino-3,5-di5 chloro-phenyl)-3-(4-chloro-phenyl)-propylamine, paraformaldehyde and sodium cyanoborohydride in methanol. Oil.

IR spectrum (methylene chloride): NHg 3390, 3490 cm-1 aromat. C»C 1615 ca-1 UV spectrum (ethanol): max. 241 nm (0.10) 10 300 nm (0.04) Example 215 1-(4-Amino-3,5-dichloro-phenyl)-2-/5T-/J-(4-chloro-phenyl)propyl7-2-phenvlethylamino7ethanol hydrochloride Prepared analogously to Example'101 from 1 -,(4-amino-3,5-di 15 chloro-phenyl )-2-/FT-/?- (4-chloro-phenyl) -propyl/amino7ethanol, phenylacetaldehyde and sodium cyanoborohydride in ethanol.

M.p. of the hydrochloride: 103 - 109°C (decomp.).

Example 216 1-(4-Amino-3,5-dichloro-phenyl)-2-/R-/?-(4-chloro-phenyl)-propyl720 aethvlamino7ethanol hydrochloride Prepared analogously to Example 101 from 1-(4-amino-3,5-dichlorophenyl )-2-/Ii-/J- (4-chloro-phenyl )-propyl7amino7ethanol, paraformaldehyde and sodium cyanoborohydride in ethanol.

M.p. of the hydrochloride: 85 - 100°C (decomp.). 121 Example 217 1-(3-Chloro-4-piperidino-phenyl)-2-/^-/J-(4-methoxy-phenyl)propyl7methylamino7ethanol hydrochloride Prepared analogously to Example 1 from 3’-chloro-4'-piperidino5 2-/S-/5-(4-aethoxy-phenyl)-propyl/methylamino/acetophenone and sodium borohydride in methanol. Oily hydrochloride.

IR spectrum (methylene chloride): OH 3600 cm-1 uv spectrum (ethanol): /( max. 258 nm (0.12) 283 nm (shoulder; 0.05) Example 218 1-(4-Amino-3,5-dichloro-phenyl)-2-/R- £5-(3-methoxy-phenyl)propyl7amlno7ethanol Prepared analogously to Example 5 from 4'-amino-3',5'-dichloroacetophenone , selenium dioxide, 3-(3-methoxy-phenyl)-propylamine and sodium borohydride.

M.p.: 124°C.

Example 219 1-(4-Amino-3,5-dichloro-phenyl)-2-/iT-/J-(3-methoxy-phenyl)propyl7ethvlamino7ethanol 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 cm1 nh2 OCHj 122 53007 UV spectrum (ethanol): λ max. 247 nm (0.06) 300 na (0.04) Example 220 - (4-Amino-3,5-dichloro-phenyl )-2-£-£- (3-methoxy-phenyl) 5 propyl7methylamino7ethanol Prepared analogously to Example 101 from 1-(4-amino-3,5-dichlorophenyl )-2-£-£- (3-methoxy-phenyl) -propyl/amino7ethanol, paraformaldehyde and sodium cyanoborohydride in methanol. Oil.

IR spectrum (methylene chloride): OH 3680 + 3620 cm1 nh2 OCHj UV spectrum (ethanol): λ max. 246 nm (0.15) 300 nm (0.04) Example 221 15 1-(3,5-Dichloro-4-isopropylamino-phenyl )-2-£-£- (3-methoxyphenyl)-propyl7i sopropylamlno7ethanol Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro-phenyl) - 2-£-£- (3-methoxy-phenyl) -propyl/amino/ethanol, acetone and sodium cyanoborohydride in methanol. Oil.

IR spectrum (methylene chloride): OH 3600 cm1 3350 cm1 2840 cm’1 NH OCH, UV spectrum (ethanol): max. 250 nm (0.12) 278 - 280 nm (0.03) 123 53007 Example 222 1-(4-Amino-3,5-dichloro-phenyl) -2-/R-/?-(4-chlorophenyl)propyl7i3opropylamino7ethanol Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro-phenyl )-2-/N-/?-(4-chloro-phenyl)-propyl7amino7ethanol, acetone and sodium cyanoborohydride in ethanol. Oil.

IR spectrum (methylene chloride): NH2 aromat. C-C NMR spectrum (CDClj/DgO): aromat. >CH-OH -CH< 3380 + 3480 cm” 1615 cm’1 7.0 - 7.4 ppm (m,6H) 4.4 ppm (dd;1H) 3-0 ppm (dd;1H) aliphat. CH2 2.3 - 2.7 ppm (m;6H) 1.6 - 2.0 ppm (m;2H) isopropyl-CHj 0.8 - 1.2 ppm (dd;6H) Example 223 - (4-Amino-3,5-dichloro-phenyl) -2-/R-/?- (4-chlorophenyl)-propyl7allylamino7ethanol Prepared analogously to Example 13 from 1-(4-amino-3j5-dichloro phenyl)-2-/R-/?- (4-chloro-phenyl)-propyl7amino7ethanol, allyl bromide and triethylamine. Oil.

IR spectrum (methylene chloride): NH„ NMR spectrum (CDClj/D20): 3380 + 3480 cm' aromat. C-C 1610 , cm’1 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) •CH-OH 4.3 - 4.7 ppm (dd;1H) n-ch2- 2.8 - 3.5 ppm (m; 2H) aliphat. CH2 2.2 - 2.7 ppm (m; 6H) 1.5 - 2.0 ppm (m; 2H) 124 53007 Example 224 N-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl7-N-/5-(4-chloro· phenyl)-propyl7allylamine Prepared analogously to Example 13 from N-/5-(4-amino-3,5-dichloro-phenyl )-ethyl7-3-(4-chlorophenyl)-propylamine, allyl bromide and triethylamine. Oil.

IR spectrum (methylene chloride): NH2 aromat. C»C NMR spectrum (CDClj/DgO)s aromat. H olefinic H >n-ch2aliphat. CH2 3380 + 3480 cm”1 1610 cm-1 9- 7.4 ppm ( m; 6H) 6 - 6.1 ppa (m;1H) 0 - 5.3 ppa (m;2H) 0 - 3.3 ppm (di 2H) 7 - 3.3 ppm (m; 8H) 3 - 1.9 ΡΡ» (m; 2H) · Example 225 N-/2-(4-Amino-3,5-dichloro-phenyl)-1-methyl-ethyl7-N-/4-(4-methoxyphenyl) -butyl7methylamine Prepared analogously to Example 101 from 4'-amino-3’,5’-dichloro propiophenone, N-/4-(4-methoxy-phenyl)-butyl7methylamine and sodium cyanoborohydride. Oil.

IR spectrum (methylene chloride): UV spectrum (ethanol): max.

NH2 3380 + 3480 cm aromat C»C 1610 cm”1 245 nm (0.13) 280 nm (broad; 0.04) 300 nm (broad; 0.04) 125 53007 Example 226 N-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl7-N-/3’-(4-methoxyphenyl )-1-methyl-propyl7ethylamine Prepared analogously to Example 13 from N-/2-(4-amino-3,5-dichloro-phenyl ) -ethyl/-N-ffl- (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 Found: 63.17 7.09 17.90 N 7.09 7.15 Example 227 N-/2-(4-Amino-3,5-dichloro-phenyl )-ethyl7-N-/T,1-dimethyl^-( 4-hydroxy-phenyl) -propyl7methylamine. 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-dichlorophenyl )-2-ffl-ffl,1-dimethyl-3-(4-hydroxy-phenyl)-propyl/methylamino/ethanol in 12 ml of trifluoroacetic acid whilst stirring at -10°C. 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 50°C in vacuo, the evaporation residue was mixed with 40 ml of 2 N sodium hydroxide solution and heated for 30 minutes at 120°C. 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 126 - 230 mesh, ASTM), eluene: methylene chloride/methanol »2 : 1. The final purification was carried out using aluminium oxide (neutral, activity step III), The eluent used was ether/ n-hexane = 2:1. After a short time the oily evaporation re5 sidue crystallized.

M.p.: 122 - 124°C.

Example 228 N-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl7-N-/J-(4-hydroxyphenyl)-1-methvl-propyl7ethylamine 10 Prepared analogously to Example 227 from 4'-amino-2-bromo3',5'-dichloro-acetophenone, N-/J-(4-hydroxy-phenyl)-1methyl-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 III). Eluent: ether/petroieum ether =2:1.

Oil.

IR spectrum (methylene chloride): OH 3590 cm1 3480 + 3390 nh2 20 CHg, CHj 2960 + 2930 Λ + 2860 cm N-alkyl 2810 cm1 C=C 1585 + 1510 + 1485 cm”1 25 OT spectrum (ethanol): A max. 241 nm (0.28 shoulder) 280 - 302 nm (0.08) (Ethanol + KOH): Ί max. 241 nm (0.56) 298 nm (0.17) Example 229 JO 1-(4~Amino~3,5-di chloro-phenyl )-2-/FT-/T,1-dimethyl-3-(4-hydroxyphenyl) -propyl7methylamino7ethanol Prepared analogously to Example 3 from 4'-amino-2-bromo-3’, 127 ’-dichloro-acetophenone, N-/T, 1-dimethyl-3-(4-hydroxy-phenyl)propyl7methylamine, 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). Eluei£s ether/ tetrahydrofuran »3:1 and then methylene chloride/ methanol / cone, ammonia = 30 : 1 : 0.3.

M.p.: 155 -158°C.

Example 230 1-(4-Amino-3,5-dichloro-phenyl)-2-/0-/T,1-dimethyl-3(4-hydroxy-phenyl)-propyl7amlno7ethanol Prepared analogously to Example 3 from 4'-amino-2-bromo-3’, ’-dichloro-acetophenone, 1,1-dimethyl-3-(4-hydroxy-phenyl)propylamine, sodium carbonate and reduction with sodium boro15 hydride in aqueous tetrahydrofuran. The purification was carried out using akca gel 60 (Macherey ahd-Nagel, 70 - 230 mesh, ASTM). Eluent: a mixture of methylene chloride/methanol/conc. ammonia = 25 : 1 : 0.2.

M.p.: 142 - 144°C. 9nExample 231 N-/3-(4-Chlorophenyl)-propyl7-N-/5-(3,5-dichloro-4-isopropylamino-phenvl) -ethyl7isopropylamine Prepared analogously to Example 101 from N-/5-(4-amino-3,5-dichlorophenyl )-ethyl7-/3-(4-chloro-phenyl)-propyl7amine, acetone and sodium cyanoborohydride. Oil.

NMR spectrum (CDClj): aromat. H >CH>CH- aliphat. H 7 - 7.3 ppm (m; 6H) 3-5 - 4.1 ppm (m; 1H) approx. 3 ppm (m; 1H) 2.3 - 2.7 ppm (m; 8H) 30 1.5 - 2.0 ppm (m; 2H) 0.9 - 1.3 ppm (dd; 12H) 128 53007 Example 232 N-22-(4-Amino-3,5-dichloro-phenyl)-ethyl7-N-(1-methyl-3phenvl-propvlJ-methylamine Prepared analogously to Example 101 from N-/T-(4-amino5 3,5-dichloro-phenyl)-ethyl7-N-(1-methyl-3-phenyl-propyl)amine, paraformaldehyde and sodium cyanoborohydride. Oily hydrochloride.

IR-spectrum (methylene chloride J: NHg 3390 + 3490 cm 1 CH2 2930 cm-1 UV-spectrum (ethanol): max. 243 nm (0.12) 300 nm (0.04) Example 233 w-/2-(4-Amino-3(5-dichloro-phenyl)-ethyl7-N-(1-methyl-3phenvl-propyl )-n-propylamlne Prepared analogously to Example 101 from N-22-(4-amino3,5-dichloro-phenyl)-ethyl7-N-(1-methy1-3-pheny1-propyl)amine, propionaldehyde and sodium cyanoborohydride. Oily hydrochloride.

IR-spectrum (methylene chloride): NHg 3390 + 3490 cm” 20 CHg 2930 cm-1 UV-spectrum (ethanol):^ max. 245 nm (0.11) 300 nm (0.04) 129 Example A Tablets containing 25 mg of l-(4-amino-3,5-dichloro-phenyl)2-/IT- (3—phenyl-propyl)-2-propylamino7ethanol hydrochloride Composition: 1 tablet contains: Active ingredient 25-0 mg Corn starch 30.0 mg Lactose 61.5 mg Gelatine 3.0 mg io 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 Diameter Weight: and a facet on both sides 7 mm 120 mg.

Example B Coated tablets containing 10 mg of 1-(4-amino-3,5-dichlorophenyl)-2-/N-(3-phenyl-propyl)-2-propylamino7ethanol hydrochloride 1 coated tablet core contains: Active ingredient Cora starch Lactose Gelatine Magnesium stearate 120.0 mg .0 mg .0 mg 71.5 mg 3.0 mg 0.5 mg 130 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 sub5 sequently coated with pure sugar syrup up to a weight of 165 mg and polished.

Example C Capsules containing 20 mg of 1-(4-aaino-3,5-dichloro-phenyl)2-ZR-(3-phenvl-propyl)-2-propylamino7ethanol 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 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 filling machine. Capsule shot weight: 200 mg. 131 53007 Example D Drops containing 20 mg/5 ml of 1-(4-amino-3,5-dichloro-phenyl)2-/N-(3-phenyl-propyl)-2-propylamlno7ethanol -hydrochloride 100 ml of drop solution contain: Active ingredient 0.4 g Hydroxyethyl cellulose 0.15 g Tartaric acid 0.1 g Sorbite solution 70 % dry 30.0 g Glycerine 10.0 g10 Benzoic acid 0.15 g 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 70°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-propylamino7ethanol hydrochloride Suppository contains: Active ingredient 0.05 g Hard fat (e.g. Witepsol W 45) 1.65 g 1.70 g 132 53007 Method of preparation; The hard fat was melted. At 38°C the pulverized active ingredient was dispersed in the melt. The liquid mixture thus formed was cooled to 35°C and poured into slightly pre-cooled suppo5 sitory 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-propylamino7ethanol 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 5i0 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 (65)

1. CLAIMS ,(1) [wherein Rj 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; K 2 and Rj, which may be the same or different, each represents a halogen atom or a trifluoromethyi, cyano or nitro group, or one of the radicals R 2 or Rj represents a hydrogen atom; R^ represents a hydrogen atom or an alkyl group containing 1 to 3 carbon atoms; Rg 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 134 or 58007 wherein R g 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 R g and Ry together represent a methylenedioxy group; R g 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 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, 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 R 2 represents a trifluoromethyl, cyano or nitro group, and/or Rg represents a fluorine atom, and/or R 4 represents an alkyl group containing 1 to 3 carbon atoms, and/or Rg 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 R g 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 -CH — CH 2 135 53007 wherein R g represents an alkyl group containing 1 to 3 carbon atoms1 and acid addition salts thereof.

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 hydro5 chloric, hydrobromic, sulfuric, phosphoric; furmaric, succinic, lactic, citric, tartaric or maleic acid.

4. Compounds as claimed in any one of the preceding claims, wherein Rg represents an amino group (optionally substituted by a benzyl group or an alkoxyearbonyl group containing 2 to 10 4 carbon atoms) or an alkylamino or dialkylamino group in which each alkyl part may contain from 1 to 3 carbon atoms; R 2 represents a hydrogen, chlorine, bromine, or iodine atom or a trifluoromethyl, cyano or nitro group; Rg represents a fluorine or bromine atom or a cyano group; represents a 15 hydrogen atom or a methyl group; Rg represents a hydrogen atom, an alkyl group containing 1 to 3 carbon atoms (optionally substituted by a phenyl group) or an allyl or cycloprcpyl group ; A represents a methylene, ethylene or hydroxymethylene group; and B represents a group of formula or wherein R g , D and n are as defined in claim 1; R g represents a hydrogen, fluorine or chlorine atom or a hydroxy, methoxy, ethoxy, benzyloxy, methylsulfenyl or methylsulfinyl group and 25 Ry represents a hydrogen atom or a methoxy group, or R g and R? together represent a methylenedioxy group; and E represents an n-propylene, 1-methyl-n-propylene, 1,1-dimethy1-n136 53007 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 R 2 represents a trifluoromethyi, cyano or nitro group, and/or Rj represents a fluorine atom, and/or Rg 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; R 2 represents a hydrogen, chlorine or bromine atom or a cyano group; R. represents a fluorine or chlorine atom or a cyano group; R 4 represents a hydrogen atom or a methyl group; Rg 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-methy1-n-propylene, 1,1-dimethy1-n-propylene or n-butylene group, or (when R^ represents an ethoxycarbonylamino group, and/or R 2 represents a cyano group, and/or Rj represents a fluorine atom, and/or Rg 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; Rg represents a hydrogen atom or a hydroxy or methoxy group, 137 and Ry 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; Rg represents a 5 chlorine or bromine atom; Rg represents a fluorine or chlorine atom, or one of the radicals Rg or Rg further represents a cyano group; R^ represents a hydrogen atom or a methyl group; Rg represents a hydrogen atom, an alkyl group containing 1 to 3 carbon atoms or an allyl group; A repre10 sents a methylene or hydroxymethylene group; and B represents an n-propyl, 1-methy1-n-propyl or 1,1-dimethy1-npropyl group (each of which is substituted in the 3-position by a phenyl, 4-hydroxyphenyl, 4-methoxyphenyl or 4-chlorophenyl group) or a 4-(4-methoxyphenyl)-butyl group or (when 15 Rg represents an alkyl group containing 1 to 3 carbon atoms or an allyl group and/or Rg 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-propyl, 1-methy1-n-propyl or 1,1-dimethy1-n-pro20 pyl group substituted in the 3-position by a phenyl, 4hydroxyphenyl, 4-methoxyphenyl, 4-chlorophenyl or

8. 1-(4-Amino-3,5-dichloro-phenyl)-2-[N-(3-pheny12ί» propyl) -2-propylamino] ethanol.

9. 1-(4-Amino-3,5-dichloro-phenyl)-2-[Ν-[1,1-dimethy13- (4-hydroxy-phenyl)-propyl]amino]ethanol.

10. Physiologically compatible acid addition salts of compounds as claimed in claim 8 or claim 9. 30

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 as herein described in any one of the examples.

13. A process for the preparation of compounds as claimed in claim 1 which comprises reducing a compound of general formula II. 138 53007 ,(ii) wherein R^, Rg, Rg, Rg and B are as defined in claim 1, and X represents a group of formula *4 - CO - CH -, OH R 4 5 - CH - CH -, 0-acyl -CH-CO -, - ch 2 - CO -, Z r 4 - CH - CH or z r 4 - ch-ch 2 -ch10 wherein R 4 is as defined in claim 1, acyl represents an organic acyl group, and 1 represents a reductively cleavable group.

14. A process as claimed in claim 13 wherein Z represents a bromine or iodine atom or a carbonic ester radical.

1515. A process as claimed in claim 13 or claim 14 wherein the reaction is carried out in a solvent at temperatures between -20°C and the boiling point of the reaction mixture. 139

16. A process as claimed in any one of claims 13 to 15 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.

17. A process as claimed in claim 16 Eor 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.

18. A process as claimed in claim 16 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.

19. A process as claimed in claim 18 in which the said complex metal hydride is sodium borohydride, sodium cyanoborohydride arlithium aluminium hydride.

20. A process as claimed in claim 16 for the preparation of compounds as claimed in claim 1 wherein A represents a methylene or ethylene group, wherein the reduction is effected using pyridine-borane.

21. 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 R g or represents a group of formula 140 53007 wherein R^, R 2 , Rj and R^ 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 z 5 H-N ,(IV) (wherein M and Q, which are different, represent B and Rg as defined in claim 1, or one of the radicals M or Q represents a group of formula -OH- IO wherein Rj, R 2 , κ R 4 and A areas defined in claim 1) and with a reducing agent.

22. A process as claimed in claim 21 wherein the reac- ·> tion is carried out in a solvent at temperatures between -20 and the boiling point of the solvent used.

15. 23. A process as claimed in claim 21 or claim 22 wherein the reduction is effected using a complex metal hydride or catalytically activated hydrogen.

24. A process as claimed in claim 21 or claim 22 wherein an amine centre is methylated using formic acid and formaldehyde. 141 53007

25. A process as claimed in any one of claims 21 to 24 wherein the reaction is carried out at the boiling point of the reaction mixture. gg. 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 Rg, Rg and R^ are as defined in claim 1} R^'·represents Rg 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; Rg' represents Rg 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 p. g , D, E and n are as defined in claim 1; and R g * and R?', which may be the same or different, represent R g and Ry respectively as defined in claim 1 or eaoh represents

16. 20 a hydroxy group protected by a protective radical, wherein 142 at least one of the radicals R^’, A, Rg' and/or B 1 represents or must contain one of the above-mentioned protective radicals.

27. A process as claimed in claim 26 wherein the reaction is carried out in a solvent at temperatures between 0 and 100°C.

28. A process as claimed in claim 26 or 27 wherein the protecting group or groups is/are chosen from acyl or alkoxycarbonyl or benzyl groups.

29. A process as claimed in claim 28 wherein one or more acyl or alkoxycarbonyl groups used as protecting groups is/are removed hydrolytically using an acid or base.

30. A process as claimed in claim 29 when carried out in an agueous medium.

31. A process as claimed in claim 28 wherein one or more benzyl groups used as protecting groups is/are removed hydroaenolytically.

32. A process for the preparation of compounds as claimed in claim 1, which comprises dehalogenating a compound of general formula VI wherein R^, Rg, R 4 , Rg, A and B are as defined in claim 1; and Hal represents a chlorine, bromine or iodine atom.

33. a process as claimed in claim 32 wherein the reaction is carried out in a solvent.

34. A process as claimed in claim 32 or 33 wherein the dehalogenation is effected using triphenylphosphine, using hydrogen in the presence of a hydrogenation catalyst or using a complex metal hydride. 143

35. A process as claimed in any one of claims 32 to 34 wherein the reaction is carried out at temperatures between 0 and 150°C.

36. A process for the preparation of compounds as claimed in claim 1, which comprises alkylating a compound of general formula VII wherein R^, R 2 , Rg, R 4 and A are as defined in claim 1; Rg represents Rg as defined in claim 1 and B represents B as defined in claim 1 whereby, if Rg does not represent a hydrogen atom, at least one of the radicals R g or R? must represent a hydroxy group or R^ must represent ai 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.

37. A process as claimed in claim 36 wherein the reaction is carried out in a solvent at temperatures between -10 and 50°C.

38. A process as claimed in claim 36 or claim 37 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.

39. . A process as claimed in claim 36 or 37 wherein the alkylation of a phenolic hydroxy group is effected using the corresponding alkyl halide,alkyl sulfate or diazoalkane.

40. a process for the preparation of compounds as claimed in claim 1 wherein 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, 144 53007 and Rg does not represent a hydrogen atom, which comprises reacting a compound of general formula VIII A - CH - N (wherein Rg, Rg, R 4 , Rg, A and B are with a compound of formula IX as defined in claim 1), Ϊ - CO - R 10 , (IX) (wherein Rg g 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).

41. A process as claimed in claim 40 wherein Y represents a halogen atom, a nitrophenyl radical, an imidazolyl group or a group of formula -O-CORgg wherein Rg Q is as defined in claim 40.

42. A process as claimed in claim 40 or claim 41 wherein the reaction is carried out in a solvent.

43. A process as claimed in any one of claims 40 to 42 wherein the reaction is carried out at temperatures from 0 to 100°C.

44. A process as claimed in any one of claims 36 to 43 wherein the reaction is carried out in the presence of a base.

45. 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 145 53007 wherein R^, Rg, Rg, R^, Rg, Rg, R ? , Rg, A and n are as defined in.claim 1; and m is 0 or 1.

46. A process as claimed in claim 45 wherein the reac5 tion is carried out in a solvent at temperatures between -80 and 100°C.

47. A process as claimed in claim 45 or claim 46 for the preparation of compounds as claimed in claim 1 wherein D represents a sulfinyl group, wherein the oxidation 10 is carried out with an equimolar amount of the oxidixing agent.

48. A process as claimed in claim 45 or claim 46 for the preparation of compounds as claimed in claim 1 wherein D represents a sulfonyl group, wherein the oxidation is car15 ried out with one or with two or more moles of oxidising agent per mole of the compound of formula X.

49. A process for the preparation of compounds as claimed in claim 1 wherein D represents an oxygen or sulfur atom and Rg is as defined in claim 1, with the exception of 20 a hydrogen atom, which comprises reacting a compound of general fonnula XX, 146 53007 (wherein R 2 , Rj, R 4 , Rg, Rg and n are as defined in claim 1, V represents a nucleophilically exchangeable group and A 1 represents a methylene or ethylene group) with a compound of general formula XIX (wherein R g and R? 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.

50. A process as claimed in claim 49 wherein the reaction is carried out in a solvent.

51. A process as claimed in claim 50 wherein the reaction is carried out at temperatures between -10°C and the boiling point of the solvent used.

52. A process as claimed in claim 51 wherein the reaction is carried out at temperatures between -10 and 50°C.

53. A process as claimed in any one of claims 13 to 52 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.

54. A process as claimed in any one of claims 13 to 53 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.

55. A process for the preparation of compounds as claimed in claim 1 substantially as herein described in any one of the Examples. 147 53007

56. Compounds as claimed in claim 1 when prepared by a process as claimed in any one of claims 13 to 55.

57. Pharmaceutical compositions comprising as active ingredient at least one compound of formula I as defined in claim 1 or a 5 physiologically compatible acid addition salt thereof, in association with one or more pharmaceutical carriers or excipients.

58. Compositions as claimed in claim 57 in a form suitable for oral, rectal or parenteral administration.

59. Compositions as claimed in claim 57 or claim 58 in the form of 10 tablets, coated tablets, capsules, drops, suppositories or ampoules.

60. Compositions as claimed in any one of claims 57 to 59 in the form of dosage units.

61. Compositions as claimed in claim 60 wherein each dosage unit contains from 5 to 75 mg of active ingredient. 15

62. Compositions as claimed in claim 61 wherein each dosage unit contains from 10 to 50 mg of active ingredient.

63. Pharmaceutical compositions as claimed in claim 57 substantially as herein described.

64. Pharmaceutical compositions substantially as herein described 20 in any one of Examples A to F.

65. 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.