NZ199215A - Secondary or tertiary omega-phenylalkylamines - Google Patents

Description

New Zealand Paient Spedficaiion for Paient Number 1 99215 !/ Priority Date(s): /Q..{p?.8Q, Complete Specification Filed: 9.. ci.SE CQ aca^-...cff/cs3; Publication Date: .... .01]. JJE-Jt-. ]??$) PiO. Journal, No: . '992 J 5 HO DM ,n Patents Form No. 5 NEW ZEALAND PATENTS ACT 1953 COMPLETE SPECIFICATION "CHEMICAL COMPOUNDS" -i/WE DR. KARL THOMAE GESELLSCHAFT MIT BESCHRANKTER HAFTUNG a Body Corporate organised under the laws of the Federal Republic of Germany Qf Biberach an der Riss, Federal Republic of Germany hereby declare the invention, for which -I/we pray that a patent may b® granted to hv&/us, and the method by which it is to be performed, to be particularly described in and by the following statement (followed by page I A.) \ 199215 This invention relates to new phenylalkylamines, to processes for their preparation and to pharmaceutical compositions containing them, and to their use in the 5 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 alk^noyl 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 15 group; R2 and R^, which may be the same or different, each represents a halogen atom or a trifluoromethyl, cyano or nitro group, or one of the radicals R£ or R^ represents a hydrogen atom; represents a hydrogen atom or an alkyl group containing 1 to 3 carbon atoms; Rrj 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 25 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 - la- Chemical Compounds 2 I ?92l 5 R 8 -CH-(CH2)n-D R 7 or < R 6 - E R 7 wherein Rg represents a hydrogen or halogen atom, a 5 hydroxy group, an alkoxy group containing 1 to 3 carbon atoms optionally substituted by a phenyl group, or an alkyl-sulfenyl 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 10 Rg and R^ together represent a methylenedioxy group; Rg 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^ 20 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 25 be substituted by a phenyl group, and/or R2 represents .a trifluoromethyl, cyano or nitro group, and/or represents a fluorine atom, and/or represents an alkyl group containing 1 to.3 carbon atoms, and/or R- represents a_ st/tn qh-fc-cAai^ieet cr brtxs\cJ\ 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 20 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, methyl-amino, ethylamino, propylamino, isopropylamino, benzyl-25 amino, 1-phenylethylamino, 2-phenylethylamino, 3- phenylpropylamino, dimethylamino, diethylamino, dipropyl-amino, diisopropvlamino, dibenzylamino, di-(2-phenylethyl)-amino, di-(3-phenylpropyl)-amino, methyl-ethylamino, methyl-propylamino, methyl-isopropylamino, ethyl-isopropylamino, 30 methyl-benzylamino, ethvl-benzylamino, propyl-benzylamino, /pyrrolidine, piperidino,—hcxamefehyleneimino/ formylamino, acetylamino, propionylamino, methoxycarbonylamino, ethoxycarbonylamino, propoxycarbonylamino or isoprcpoxycarbonylamino group; . 4 - 199215 R2 and , which may be the same or different, may each represent, for example, a fluorine, chlorine, bromine or iodine atom or a trifluoromethyl, cyano or nitro group, or one of R2 and R^ may represent a hydrogen atom; 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; Rc- may represent, for example, a hydrogen atom or a methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert.-10 butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oMtenw i allyl, crotyl, kentenryi, 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, 15 propoxy, isopropoxy, methylsulfenyl, ethylsulfenyl, methylsulfinyl, propylsulfinyl, benzyloxy, 2-phenylethoxy or 3-phenylpropoxy group; R^ may represent, for example, a hydrogen atom or a hydroxy, methoxy, ethoxy, propoxy, or isopropoxy group or Rg and 20 R7 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-n-25 propylene,.1-propyl-n-propylene, 1,1-dimethyl-n-propylene, 1,1-diethyl-n-propylene, 1,1-dipropyl-n-propylene, 1-methyl-l-ethyl-n-propylene, 1-methyl-l-propyl-n-propylene, 1-ethyl-l-propyl-n-propylene, 1-methyl-n-butylene, or 1-methyl-n-pentylene group. 3 0 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 35 from 1 to 3 carbon atoms; R^ represents a hydrogen, chlorine, bromine or iodine atom or a trifluoromethyl, cyano or nitro group; R^ represents a fluorine, chlorine, or bromine atom or a cyano group; R^ represents a hydrogen atom or a methyl group; R_ represents a hydrogen atom, . .. ■ o Y.< » 199215 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 hydroxy-methylene group; and B represents a group of formula Rfi • J -CH-(CW2)n-D// or - E 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-methyl-n-propylene, 1,1-dimethyl-n-propylene or n-butylene group or (when A represents a methylene or ethylene group; and/or R^ represents 15 an amino group optionally substituted by a benzyl group or by an alkoxycarbonyl group containing 2 to 4 carbon atoms, or an alkylamino or dialkylamino group in which each alkyl part may contain from 1 to 3 carbon atoms; and/or R2 represents a trifluoromethyl, cyano or nitro group; and/or R^ 20 represents a fluorine atom; and/or R^ 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 25 I are those wherein R^ represents an amino group optionally substituted by an ethoxycarbony1 group, or an alkylamino or dialkylamino group in which each alkyl part may contain 199215 from 1 to 3 carbon atoms; R2 represents a hydrogen, chlorine or bromine atom or a cyano group; R^ represents a fluorine or chlorine atom or a cyano group) represents a hydrogen atom or a methyl group; R,. 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 - E wherein E represents an n-propylene, 1-methyl-n-propylene, \ 1,1-dimethyl-n-propylene or n-butylene group, or (when R^ represents an ethoxycarbonylamino group and/or R^ represents a cyano group and/or R^ represents a fluorine atom and/or R^ represents an alkyl group containing 1 to 3 carbon atoms op-15 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 R^ represents a hydrogen atom or a methoxy group.

The compounds of general formula I may, for example, 20 be prepared by the following processes, which processes constitute further features of the present invention: a) Reduction of a compound of general formula II . R„ X - N B »(II) (.wherein R, , 1f R2f R3 and R^ are as hereinbefore defined) and 25 either B^ represents a group of formula 199215 and X represents a group of formula R4 ii I i " - A -CH - or is as, hereinbefore defined for B and X represents 5 a group of formula R4 OH r4 O-acyl - CO - CH . -, - CH - CH - CH - CO ? ?4 ? ?4 - A"' - CO - CH - CH. - or - CH-CH2-CH- (wherein R^, R^ and R^ are as hereinbefore defined, A"' represents a methylene or ethylene group, k is 1, 2 or 3, 10 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 re duction may, for example, be carried out in a solvent such as methanol, methanol/water, ethanol, ethanol/water, iso-propanol, trifluoroacetic acid, butanol, diethyl ether, tetrahydrofuran, tetrahydrofuran/water, dioxan or hexa-2o methyl-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 25 primary or secondary alcohol, catalytically activated hydrogen or nascent hydrogen.

For the preparation of compounds of general W-'JTT. ■ iy- .. 1 992 1 5 formula I, wherein A represents a hydroxymethylene group, the reduction is appropriately carried out, for example, with a complex metal hydride such as sodium borohydride or lithium aluminium hydride in a solvent such as, for example, 5 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 10 catalyst such as for example platinum, palladium, raney- nickel or raney-cobalt at room temperature and at a hydrogen pressure of 1 to 5 bar* or with nascent hydrogen, e.g. from activated metallic aluminium and water or zinc and hydrochloric acid, at temperatures up to the boiling temperature 15 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 20 borohydride in methanol/water, ethanol/water or isopropanol or with lithium aluminium hydride in diethyl ether or tetra- O-acyl I hydrofuran; if X represents the -CH - CO- group, the reaction is preferably carried out with a hydride in a solvent such 25 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 pyridine-35 borane in a solvent such as, for example, ethanol, isopropanol, tetrahydrofuran, dioxan, trifluoroacetic acid or 199215 a 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 -J\».\-CO- group or represents the -CO- CCH2)k group, the reaction is preferably ?« or -CH-CH2~CH- group, the reaction carried out at elevated temperatures, e.g, with lithium aluminium hydride in tetrahydrofuran at the boiling temperature of the reaction mixture; if X repre-10 sents 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 ii* i X represents a -CH-CH-15 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. 2 0 b) Reaction of a carbonyl compound (optionally formed in the reaction mixture) of general formula III K ~ L , (HI) [wherein K together with a neighouring hydrogen atom in the alkyl part of the radical L represents an oxygen atom; and L has 25 one of the meanings hereinbefore recited for B or (with the exception of a hydrogen atom) formula R,.

Rj. or represents a group of - CH - A' 199215 in which R,, R~, R_ and R. are as hereinbefore defined; and J_ £ J 4 cuy A' represents a carbonyl, methylene or ethylene group] or ' hydrate thereof with an amine of general formula IV H - N ,(IV) Q (wherein M and Q, which are different, represent B and R^ as herein- before defined, or one of the radicals M or Q represents a group of formula in which R^, R2, R^r R^ 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 the: p<*-"tr oj the ScrU/lsit, uSd-dm €■ G • bctk/etyi -3C anct SO between -20 C and pO y, preferably, however, at temperatures between 0 and 25°C. Suitable reducing agents include, 15 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 cyanoboro-2 0 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 rro w&t 199215 amine of general formula IV, the Schiff's base formed in the reaction mixture is preferably reduced with a complex metal hydride such as sodium borohydride or lithium aluminium hydride in a solvent such as, for example, 5 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, 10 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. also Methylation of an amine centre may^be carried out using formaldehyde and formic acid as the reducing agent at 15 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 represents an amino or alkylamino group containing 1 to 3 carbon atoms, and with a car-20 bonyl compound of general formula III, wherein L is as defined for R^, 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 com-25 pound of general formula V wherein R2, R^ and R^ are as hereinbefore defined; R^' represents R^ as hereinbefore defined or represents a hydroxy or amino group protected by a protective radical; A" represents 30 A as hereinbefore defined or represents a hydroxymethylene 199215 group protected by a protective radical; R,. 1 represents R,. as hereinbefore defined or represents a protective radical for an amino group; and B' represents B as hereinbefore defined or represents a group of formula R8 or -CH-(CH2)n-D ■ * fJ2.fc*TENT omej 0 JANi985 3 'VP* wherein Rg, D, E and n are as hereinbefore defined; and Rg' and R^', which may be the same or different, are as herein-10 before defined for Rg and R^ respectively or represent hydroxy groups protected by protective radicals, wherein at least one of the radicals R^1, A", R^1 and B1 represent or must contain one of the above-mentioned protective radicals.

Suitable protective radicals include, for example, acyl 15 or alkoxycarbonyl radicals such as an ethoxycarbonyl, acetyl, propionyl or benzoyl group or a benzyl group and for A" an acetyl, methoxycarbony1 or ethoxycarbonyl group.

The cleavage of one or more of the above-mentioned acyl and/or alkoxy carbonyl radicals is preferably carried 20 out hydrolytically in an aqueous solvent, e.g. in water, iso-propanol/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 25 and 100°C, preferably at the boiling point of the reaction mixture. ^ trio ft The cleavage of ^ benzyl yadi ral/ is preferably carried out hydrogenolytically, e.g. with hydrogen in the presence of a catalyst such as, for example, palladium/charcoal, 199215 conveniently in a solvent such as methanol, ethanol, ethyl acetate or glacial acetic acid and optionally under addition of an acid such as hydrochloric acid at temperatures between 0 and 50°C, preferably, however# at room temperature and at a hydrogen pressure of 1 to 7 bar, preferably 3 to 5 bar. d) For the preparation of compounds of general formula I, wherein R2 represents a hydrogen atom: Dehalogenation of a compound of general formula VI Hal A - CH - N ^ 5 , (VI) B wherein R^, R^, R^, A and B are as hereinbefore defined, R'^ represents a halogen atari or a trifluorcmethy^ cyano or nitro group and Hal represents a chlorine, bromine or iodine atom. wherein R^j j n^y A and D age ao hereinbefore defined ■and nal rcprcocnta a ohlorinej bromine or iodine afeo»y The dehalogenation may be effected using tri- phenyl phosphine, hydrogen in the presence of a hydrogen-ation 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, 20 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 25 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 raney-nickel or palladium/charcoal the dehalogenation may, for example, be 30 carried out at room temperature and at normal pressu^fa £N^ e) Reaction of a compound of general formula VII Va O V 199215 R 2 A - CH.- N ,(VII) B" R (wherein R^, R2 , R^, R^ and A are as hereinbefore defined; Rc" is as hereinbefore defined for Rc; and B" represents B b d as hereinbefore defined provided that if R^" does not repre-5 sent a hydrogen atom, at least one of the radicals Rg or R7 must represent a hydroxy group or R^ must represent an amino group optionally substituted by an alkyl group containing 1 to 3 carbon atoms, which alkyl group may additionally be substituted by a phenyl radical) with an appropriate alkylating agent 10 whereby the desired compound is obtained. vent e.g. in water/methanol/ ethanol/water, tetrahydrofuran/ dioxan, acetone or dimethylsulfoxide/ with an alkylating methyl iodide, dimethyl sulfate, ethyl bromide, diethyl sulfate, benzyl bromide, 2-phenyl-ethyl bromide or methvl-p-toluene sulfonate, optionally in the presence of a base such as sodium hydroxide or potassium carbonate. Preferred temperatures are those between -10°C and 50°C, preferably between 0 and 30°C. The 20 reaction can, however, be carried out without a solvent. ried out using formaldehyde/formic acid, generally at elevated tanpera-tures, 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.

The reaction is preferably carried out in a sol- agent such as an alkyl halide or alkyl sulfate, for example/ The alkylation of a nitrogen atom can also be car // v ' 1&9Z1S Moreover, the alkylation of a phenolic hydroxy group can be carried out with, for example a corresponding alkyl halide, alkyl sulfate or diazoalkane, preferably in a solvent such as diethyl ether or tetrahydrofuran. Preferred temperatues 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 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 R^ does not represent a hydrogen atom: Acylation of a compound of general formula VIII ^ S" A - CH - N ,IVIII) B (wherein R2, R3, R4, A and B are as hereinbefore defined and R5'1 is as hereinbefore defined for Rg other than a hydrogen atari) with a compound of general formula IX Y - CO - R , (IX) (wherein R^q 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 imida- zolyl group or a radical of formula -O-COR^q where R1Q is as defined above) The reaction may, for example, be carried out with acetyl chloride, acetic anhydride, propionic acid anhydride or a corresponding chloroformate, e.g. ethyl chloroformate, 25 which simultaneously may serve as a solvent. The reaction is optionally effected in the presence of a solvent such as, water/tetrahydrofuran, diethyl ether, tetrahydrofuran 'v ' £ 2 2 APR 1986J 'SiHl 1 9 92 1 5 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 A - r CH - N CH I R8 " (CH2)n - S0m wherein R.

R-.» R4' R5' '1' 2' "3 defined and m is 0 or 1.

R.

R-7 / R 8, A and n are as before The oxidation is preferably carried out in a solvent, e.g. in water, water/pyridine, ethanol, methanol, 15 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 20 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 25 peracid such as performic acid in glacial acetic acid or tri- fluoroacetic 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. 199215 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, tri-fluoroacetic acid or formic acid at 20 to 100°C or in acetone at 0 to 60°Cj 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 R,. does not represent a hydrogen atom: Reaction of a compound of general formula XI R2 An' ~ CH ~ N CH - (CH ) - V 1 2 n 8 ,(XI) (wherein R^ R2, ^3' ^4 > r 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 H - D< ,(xn; 199215 (wherein R, and R_. are as hereinbefore defined and D' repre- b / sents 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 5 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 10 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. 15 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 20 general formula I may conveniently be carried out by fractional crystallisation of the diastereoisomeric salts formed by the said compound and an optically active acid such as, for example, D(-)-tartaric acid, L(+)-tartaric acid, diben-zoy1-D-tartaric acid, dibenzoy1-L-tartaric acid, (+)-camphor-25 10-sulfonic acid, L(-)-malic acid, L(+)-mandelic acid, d-a-bromo-camphor-"j|^-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 30 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 35 prepared as hereinbefore disclosed may optionally be converted with inorganic or organic acids into their physiologically compatible acid addition salts, for example by 1 9 92 1 5 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 5 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-CHR^ group, can be obtained, for example, by reaction of an a-halo-ketone with the corresponding amine; compounds of general formula II, wherein X represents the -Cl^-CO-group, can be obtained by reaction of a phenyl-15 acetic acid derivative with the corresponding amine.

Compounds of general formula III, wherein A1 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 20 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, 25 for example, by reaction of an u-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 phenylalkyl-35 amine.

The compounds of general formula I possess 199215 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 5 and slight side-effects.

For example the following compounds have been tested with regard to their biological properties: A = 1-(4-Amino-3,5-dichloro-phenyl)-2-/N-/5-(4-methoxy-phenyl) propyl7amino7 ethanol, B = 1-(4-Amino-3-cyano-5-fluoro-phenyl)-2-/N-/5-(4-methoxy-phenyl )-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) 1-methyl-propyl7mo"thylainin£7e'thanol, » • E = N-/T-Methyl-2-(4-amino-3,5-dichloro-phenyl)-ethyl7-N-/3-(4-methoxy-phenyl)-propylamine hydrochloride, F = N-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl7-N-/3-(4-chloro-phenyl)-propyl7isopropylamine, G = N-/3-(4-Chloro-phenyl)-propyl7-N-/2-(3f5-dichloro-4-iso-propylamino-phenyl)-ethyl7lsopropylamine, and H *= N-/2-(4-Amino-3~bromo-5-cyano-phenyl)-ethyl7-N-/£-(4-methoxy-phenyl )-butyl7methylamine. 19921 1. Determination of the contractility parameter dp/dtmax or heart frequency in narcotized cats Male and female cats having a body weight of approx. 2 to 4 kg were narcotized with pentobarbital sodium 5 (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 3 8°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 3 50), 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 15 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. 20 All substances were injected into the V.saphena as solution (water or polyethylene glycol 200) . Each dose was 0.3 mg/kg i.v. The maximum activity and the time after application at which the activity was reduced to half of the maximum were measured.

The following tables show the results: Table I: Test compound Increase of dP/dtmax % Half life time in minutes A + 93 38 B + 124 >140 C + 00 OJ 112 D + 105 >100 19921 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 5 or 0.2 ml/10 g of body weight) or by administration into the stomach. After an observation time of 14 days the LD^q was determined according to the methods described by LITCHFIELD and WILCOXON: Test LD50 mg/kg compound i.v. p.o.

A 19 >100 C 32 250 The compounds of general formula I are suitable 10 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 15 invention there are provided pharmaceutical compositions 1992.15 comprising, as active ingredient, at least one compound of general formula I as hereinbefore defined or a physiologically compatible salt thereof, in associationowith 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 10 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 ex-15 cipients 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 de- . rivatives, glycols, various wetting, dispersing or emulsify-20 ing 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 7 5 mg, preferably 10 to 25 50 mg, of active ingredient according to the invention. Such dosage units may, for example, be administered 1 to 4 times daily. The total daily dosage may, however, be varied according to the compound used, the subject treated and the complaint concerned.

According to a still.further feature of the present ' (or^erVt?ii)ta<^lH1)ere is Provided a method of treating a patient ^suffering from or susceptible to cardiovascular diseases which comprises administering to the said patient an effective amount of a compound of formula I, as hereinbefore de-35 fined, or a physiologically compatible acid addition salt thereof. 0 JAM935 199215 The following non-limiting examples serve to illustrate the present invention. - 25 -Example 1 1 9 92 1 5 1-(4-Amino-3,5-dichloro-phenyl)-2-/N-/5-(4-methoxy-phenyl)-propyl7methvlamino7ethanol ___ 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-31»51-dichloro- 2-/N-/3-(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 minu- 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 15 methylene chloride : methanol =19 : 1 as eluenfe (Macherey and Nagel 70 - 230 mesh ASTM). The fractions containing the desired compound were combined, evaporated and in- vacuo the remaining solvent was removed from the oil at 40°s. IR spectrum (methylene chloride): uv spectrum (ethanol): max: oh 3610 cm~^ nh2 3400 + 3490 ch2 2850 + 2940 A 0ch3 N-alkyl 2830 2800 cm" cm"1 c=c 1610 cm"1 243 nm (0.23) 280 nm (0.08) 300 nm (0.08) ,-1 -1 Example 2 1-(4-Amino-3,5-dichloro-phenyl)-2-/N-(3-phenyl-propyl)-methyl-30 amino7ethanol hydrochloride g (0.035 mol) of 4l-amino-2-bromo-3l,5 *-dichloro-acetophenone, 6.7 g (0.036 mol) of N-(3-phenyl-propyl)-ethylamine hydrochloride J 9 92 1 5 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, 5 and evaporated in a rotation evaporator. The oily residue, which consisted of 4'-amino-3!,5'-dichloro-2-/N-(3-phenyl-propyl)-methyl-amino/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 tempera-10 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 15 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, 2 0 crystalline product was obtained. -M.p.: from 85°C (under sintering).

Example 3 1-(4-Amino-3,5-dichloro-phenyl)-2-^ff-/5-(4-hydroxy-phenyl)-1-methyl-propvl7methvlamino7ethanol 0.2 mol of sodium borohydride were added in portions to a solution of 0.1 mol of 4,-amino-3l,5,-dichloro-2-/K-/5-(4-hydroxy-phenyl)-1-methyl-propyl7methylamino7acetophenone 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 ©titer extracts were washed • 7 19 92 1 5 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 5 of methylene chloride : methanol = 30 : 1 was used. The residue, which was obtained after fractionation and evaporation in a rotation evaporator, crystallized after addition of a smaLl amount of previously prepared compound. The obtained diastereoisomeric crystals in a 1:1 mixture were recrystallized from methy-10 lene chloride.

M.p.: 112 - 115°C Example 4 1-(4-Amino-3»5-dichloro-phenyl)-2-/f?-/5-(4-methoxy-phenyl)-1-methvl-propyl7methvlamlno7ethanol 0.02 mol of 1-(4-amino-3,5-dichloro-phenyl)-.2-/R-/5-(4-hydroxy-phenyl)-1-methyl-propyl7methylamino7ethanol were dissolved in 22 ml of 1 N sodium hydroxide solution and 10 ml of water. To this solution were dropped under stirring and cooling with ice-water 0.022 mol of dimethyl sulfate and the reaction solution 2 0 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 2 5 evaporated in a rotation evaporator and the residue was purified over silica gel 60 (Macherey and Nagel, 70 - 230 mesh, ASTM) (eluent: methylene chloride : methanol =30 : 1). The obtained oily evaporation residue was liberated from the solvent residues in vacuo over sulfuric acid. The oil 3 0 obtained was a 1:1 mixture of the diastereoisometric racemates.

IR spectrum (methylene chloride): OH nh2 ch2 och- UV spectrum (ethanol): 'A max. 199215 3200 - 3500 cm (below NH2) 3480 + 2930, -1 broad '3 N-alkyl C=C C=C + NH2 244 nm (0.27) 280 nm (0.08) 300 nm (0.08) 3390 cm-1 2850 cm"1 2830 cm"1 2800 cm"1 -1 1580, 1510, 1485 cm deformation 1620 cm -1 Example 5 1-(4-Ethoxycarbonylamino-3-cyano-5-fluoro-phenyl)-2-/N-/3-(4-methoxy-phenvl) -propyl7amino7ethanol 0.5 g of celite and afterwards 2.5 g (0.01 mol) of 4'-ethoxy-carbonylamino-31-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 hours 20 and the undissolved solids were filtered off. Into this solution were dropped after cooling and external cooling with ice, 2.01 g (0.01 mol) of 3-(4-methoxy-phenyl)-propylamine hydrochloride and 1.01 g (0.01 mol) of triethylamine, dissolved in 12 ml of ethanol. The solution containing the crude 4,-ethoxycarbonylamino-3'-cyano-25 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 30 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). 199215 The fractions containing . the desired compound were evaporated and a colourless crystalline product was obtained. m.p.: 111 - 112°c.

Example 6 1-(4-Ethoxycarbonylamino-3-cyano-5-fluoro-phenyl)-2-/N-/3-(4-methoxv-phenvl)-pror?vl7methvlamino7ethanol g (0.06 mol) of 4'-ethoxycarbonylamino-3'-cyano-5'-fluoro-acetophenone 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 10 2 ml of water whilst stirring. Subsequently, the reaction mixture was refluxed for 4 hours, then diluted with 100 ml of tetrahydrofuran and filtered off from the undissolved solids. 10.7 g (0.06 mol) of N-/5-(4-methoxy-phenyl)-propyi7methylamine, dissolved in 100 ml of tetrahydrofuran, were added to this so-15 lution of 41-ethoxycarbonylamino-3'-cyano-51-fluoro-phenylglyoxal after cooling at room temperature. The solution obtained was mixed in portions with 8 g (0.13 mol) of sodium cyanoborohydride, the solution being kept at pH 6 by dropwise addition of 2 N hydrochloric acid. The reaction mixture was allowed to 20 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 25 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 in vacuo at 40°C 30 the remaining solvent was removed from the oil obtained.

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

UV spectrum (ethanol + KOH): ^ 1 9 92 1 5 oh nh ch2 och, 3 n-alkyl cn nhcooc2h5 3600 cm" 3400 cm" 2930 cm" 2830 cm" 2800 cm" 2220 cm" 1735 cm" 228 nm (shoulder; 0.19) 240 nm (shoulder; 0.12) 285 nm (0.06) 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 dlhvdrochloride ' 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-/5-(4-me- 2 0 thoxy-phenyl)-propyl7-N-methyl-phenylacetamide in 100 ml of absolute tetrahydrofuran was dropped thereto whilst stirring at room temperature., Subsequently, the reaction mixture was re-fluxed for 1 hour, the excess lithium aluminium hydride was decomposed with ethyl acetate and water, 10 n sodium hydroxide so- lution 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 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 by means of ethanolic hydrochloric acid and addition of ether, the crystalline dihydro-chloride was prepared.

M.p.: 168 - 171°C (decomp.).

Example 8 1 992 1 5 N-/2-(4-Amino-3,5-dibromo-phenyl)-ethyl7-N-/Z£-(4-methoxy-phenyl)-butvl7methylamine 2.9 g (0.077 mol) of lithi-um 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-/Zf-(4-methoxy-phenyl)-butyl7-N-methyl-phenylacetamide in 100 ml of absolute tetrahydrofuran was added thereto whilst stirring at room temperature. Subsequently, the reaction mixture was refluxed 10 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 eva-15 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. ~~ a 2 0 IR spectrum (methylene chloride): NHg 3380 + 3470 cm N-alkyl och3 2790 cm"1 2830 cm"1 aliphat. CH£ c=c 2850 + 2930 cm"1 1610 cm"1 UV spectrum (ethanol):^ max. 246 nm (0.24) 281 nm (0.08) 305 nm (0.09) Example 9 199215 N-/2- (4-Amino-3-chloro-5-cyano-phenyl) -ethyl7-N-/3- (4-methoxy-phenvl)-propyl7methvlamlne 6.6 g (0.014 mol) of 1-(ethoxycarbonyloxy)-1-(4-amino-3-chloro-5 5-cyano-phenyl)-2-/fT-/5-(4-methoxy-phenyl)-propyl7methylamino7-ethane were dissolved in 70 ml of isopropanol and stirred overnight with 5.5 g (0.14 mol) of sodium borohydride at room temperature. The solution obtained was evaporated to dryness and taken up in 100 ml of water. The excess sodium borohydride was destroyed 10 with 50 ml of 2 n hydrochloric acid. Subsequently, the reaction mixture was basified with 100 ml of 2 n ammonia, and ex tracted 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. — 1 IR spectrum (methylene chloride): NHg 3400 + 3500 cm" 2 0 N-alkyl 2800 cm"1 aliphat. CH2 2860 + 2940 cm"1 aromat. C=C 1600 cm"1 * NH2 deformation 1625 cm UV spectrum (ethanol): \ max. 244 nm (0.23) 25 278 nm (0.06) 330 nm (0,13).

Example 10 N -/2- ( 4-Amino-3-chloro-5- cyano -phenyl) - ethyl7-N-( 4-me thoxy-phenvl) -propyl7methvlamlne • 1.3 g (0.0027 mol) of 1-(4-amino-3-chloro-5-cyano-phenyl)- 2-/R-/3-(4-methoxy-phenyl)-propyi7methylamino7ethyl iodide were dissolved in 30 ml of hexamethyl phosphoric acid triamide. 0.25 g 199215 (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 5 was washed with water, dried over sodium sulfate, and evaporated to dryness in vacuo. The remaining oily residue was chromatographed over silica gel (eluent: methylene chloride : methanol =20 : 1). The oily evaporation residue obtained was liberated in vacuo from the solvent residues.

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

Example 11 1-(4-Amino-3-fluoro-phenyl)-2-/N-/3-(4-methoxy-phenyl)-propyl7-methylamino7 ethanol A solution of 3.9 g (0.0095 mol) of 1-(4-amino-3-bromo-5-fluoro-phenyl)-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 2 0 been taken up, the catalyst was filtered off and the filtrate was evaporated in a rotation evaporator. The 4 g of oil thus obtained was chromatographed (Macherey and Nagel, 70 - 230 mesh, ASTM) with chloroform : methanol =19 : 1 as eluent. The fractions4 containing . the desired compound were combined and evaporated. 2 5 The oil obtained was dissolved in isonropanol and the hydrochloride was precipitated with isopropanoxic hydrochloric acid and ethyl acetate. The crystals were filtered off with suction, washed with little cold isopropanol and dried in vacuo.

M.p.: 110°C (decomp.). \ 34 1 992 1 5 Example 12 1-(4-Ethoxycarbonylamino-3-bromo-phenyl)-2-/N-/5-(4-methoxy-phenvl)-butvl7methvlamino7ethanol 1.5 ml (0.015 mol) of ethyl chloroformate were added under ice-5 cooling at 0°C to a solution of 5.1 g (0.0125 mol) of 1-(4-amino-3-bromo-phenyl)-2-/N-/5-(4-methoxy-phenyl)-butyl7methylamino7-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 10 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 15 : methanol » 9 : 1 as eluent. The fractions containing the desired compound were combined and evaporated. The oil obtained was liberated in vacuo at 40°C from the solvent residues. IR spectrum (methylene chloride): OH 3610 cm" nh och3 N-alkyl aliphat. CHg c=0 aromat. c=c 224 nm (0.42) 240 nm (0.29) 280 nm (0.04) 3400 cm 2830 cm"1 2800 cm"1 2860 + 2940 cm"1 1735 cm"1 1610 cm"1 UV spectrum (ethanol): \ max 1 9 92 1 5 Example 13 N-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl7-N-/3-(4-hydroxy-phenyl)-1-methvl-propyl7methvlamine 0.012 mol of N-/2-(4-amino-3»5-dichloro-phenyl)-ethyl7-N-5 /3-(4-hydroxy-phenyl)-1-methyl-propyl7amine 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 tetra-10 hydrofuran. 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 15 60 - 1525; Macherey and Nagel) with methylene chloride : methanol : conc. ammonia = 19 s 1 : 0.1 as eluent. The oily evaporation residue was removed from the solvent residues in vacuo over potassium hydroxide.

IR spectrum (methylene chloride): OH 3580 cm 2 0 NH2 3480 + 3380 cm"1 CH2 2930, 2960, 2850 cm"1 N-alkyl 2790 cm"1 C=C 1580, 1510, 1480 cm'1 C=C + NH2 deformation 1610 cm'1 25 UV spectrum (ethanol): "X 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). - 36 -Example 14 J 992 15 1-(4-Amino-3,5-dichloro-phenyl)-2-/!T-/2-(4-methoxy-phenylsul-f inyl)-ethvl7methvlamino7ethanol 7.0 g of 1-(4-amino-3,5-dichloro-phenyl)-2-/N-/£-(4-methoxy-5 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 10 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 15 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. —*1 ' IR spectrum (methylene chloride): NH2 3390 + 3480 cm" CH2 2940 cm"1 OCH^ 2840 cm"1 N-alkyl 2800 cm"1 C=C 1590, 1510 + 1480 cm _ A S=0 1040 cm" (shoulder) UV spectrum (ethanol): \ max. 244 nm (0.54) 300 nm (0.07; shoulder) Example 15 19921 1-(4-Amino-3,5-dichloro-phenyl)-2-/N-/2-(4-methoxy-phenyl-sulfonvl)-ethvl7methvlamino7ethanol 7.0 g of 1-(4-amino-3,5-dichloro-phenyl)-2-/N-/2-(4-methoxy-5 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 10 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 evapora-15 tion residue of the dried organic phase was purified twice by chromatography (1. column: 60 x 300 mm, AlgO^ II neutral, methylene chloride : tetrahydrofuran = 5 : 1; 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 frac-2 0 tions in vacuo the title compound was obtained as an oil. _ A IR spectrum (methylene chloride): NH2 3395 + 3480 cm CH2 2940 cm"1 OCH, 2840 cm"1 A3 N-alkyl 2800 cm C=C 1595, 1520 + -1 0 + -1 '2 UV spectrum (ethanol): \ max. 241 nm (0.59) 300 nm (0.09). 1495 cm" S0o .1150+1315 cm"1 - 38' -Example 16 J 992 is 199215 1-(4-Amino-3,5-dichloro-phenyl) -2-/N-/3- (4-hydroxy-phenyl)-propvl7methvlamino7ethanol 9.2 g of 1-(4-amino-3,5-dichloro-phenyl)-2-/N-/3-(4-benzyloxy-5 phenyl)-propyl7methylamino7ethanol were dissolved in 150 ml of methanol. The solution was mixed with 1 g of 5 % palladium/ charcoal and hydrogenated at room temperature under a hydrogen pressure of 5 bar. After taking up the calculated amount of hydrogen, the catalyst was filtered off, the solution was evapo-10 rated 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.

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

Example 17 1-(4-Amino-3-bromo-phenyl)-2-^R-/5- (4-methoxy-phenyl )-butyl7-methvlamino7ethanol 3 g of 1-(4-acetamino-3-bromo-phenyl)-2-/!T-i/5-(4-methoxy-phenyl)-butyi7methylamino7ethanol were refluxed in 100 ml of semi-concen-trated 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 de-30 sired compound, the title compound was obtained by evaporation in vacuo at 40°C. Oil. 1 992 1 5 IR spectrum (methylene chloride): UV spectrum (ethanol): \ Example 18 oh nh2 N-alkyl och, 3590 cm -1 3380 + 3470 cm 2800 cm-1 2830 cm-1 -1 2850 + 2930 cm -1 aliph. CH2 aromat. C=C 1620 cm max. 224 nm (0.20) 243 nm (0.14) 280 nm (0.04) 300 nm (0.04) -1 1-(4-Amino-3-cyano-5-fluoro-phenyl)-2-/N-/3-(4-methoxy-phenyl)-propvl7methvlamino7ethanol Prepared analogously to Example 1 from 4f-amino-3'-cyano-5'-fluoro-2-/N-/5-(4-methoxyphenyl)propyl7me"t*iylamino7acetophenone and sodium borohydride in 90 % methanol.

IR spectrum (methylene chloride): uv spectrum (ethanol): ^ max.

OH nh2 ch2 och3 N-alkyl C=N NH -1 3590 cm 3400 + 3490 cm + 2940 cm -1 2850 2830 cm -1 -1 2800 cm 2210 cm -1 -1 2 deformation 1635 cm aromat. c=c 1610 cm"1 242 nm (0.3) 325 nm (0.14). -1 Example 19 1 - (4-Amino-3-bromo-5-cyano-phenyl)-2-/N-/5- (4-methoxy-phenyl) propyl7methvlamino7 ethanol Prepared analogously to Example 1 from 41-amino-3'-bromo-5'-cyano-2-/F-/5-(4-methoxy-phenyl)-propyl7methylamino7acetophenone and sodium borohydride in 80 94 methanol.

IR spectrum (methylene chloride): OH 35 3^0 NH2 3400 + 3480 cm"1 CH2 2850 + 2930 cm"1 C=N 2200 cm"1 C=C 1640 cm"1 UV spectrum (ethanol): *X max. 243 nm (0.20) 280 nm (0.04) 334 nm (0.12).

Example 20 1-(4-Amino-3,5-dibromo-phenyl)-2-/N-/3-(4-methoxy-phenyl)-propyl7methvlamlno7ethanol Prepared analogously to Example 1 from 4'-amino-3',5'-dibromo- 2-/N-/3-(4-methoxy-phenyl)-propyl/methylaminojacetophenone and sodium borohydride in 80 % methanol.

IR spectrum (methylene chloride): OH 3590 cm nh2 3380 + 3460 cm"1 N-alkyl 2800 cm"1 OCHj 2830 cm"1 aliphat. CH2 2850 + 2940 cm"1 C=C 1610 cm"1 UV spectrum (ethanol): A max. 244 nm (0.16) 303 nm (0.06), Example 21 1-(4-Amino-3»5-dichloro-phenyl-2-^Ef-/T,1-dimethyl-3-(4-methoxy-phenvl)-propvl7amlno7ethanol Prepared analogously to Example 13 from 1-(4-amino-3,5-dichloro-phenyl ) -2-/H-/T, 1 -dimethyl-3- (4-hydroxy-phenyl) -propyl7amino7-ethanol, tetrahydrofuran, sodium hydroxide solution and dimethyl sulfate. Oil. ir spectrum (methylene chloride): oh 3600 cm" NH2 3390 + 3490 cm"1 ch2 2860 + 2960 cm"1 och, 2830 cm-1 c«c 1580 + 1620 cm-1 UV spectrum (ethanol): A max. 243 nm (0.23) 280 nm (0.08) 300 nm (0.08) 199215 Example 22 1-(4-Amino-3,5-dichloro-phenyl)-2-/fi-/T,1-dimethyl-3-(4-methoxy-phenvl)-propvl7methvlamlno7ethanol Prepared analogously to Example 13 from 1-(4-amino-3,5-dichloro-phenyl )-2-/N-/T,1-dimethyl-3-(4-hydroxyphenyl)-propyl7amino-ethanol7» tetrahydrofuran, sodium hydroxide solution, and di-10 methylsulfate. Oil.

Calc.: C 61.31 H 6.86 CI 17.24 N 6.81 Found: 61.13 6.99 17.25 6.75 Example 23 1-(4-Amino-3-chloro-5-trifluoromethyl r-phenyl)-2-/N-/3-(4-methoxy-15 phenyl) -propyl7methylamino7ethanol .

Prepared analogously to Example 1 from 4'-amino-3'-chloro-5!-tri-f luoromethyl-2-/H- 0- (4-methoxy-phenyl) -propy^^^y^s^insJ-acetophenone and sodium borohydride in 80 % methanol.

IR spectrum (methylene chloride): OH 3590 cm" 2 0 NH2 3410 + 3510 cm"1 N-alkyl 2800 cm"1 OCHj 2830 cm"1 aliphat. CH2 2850 + 2940 cm"1 C»C 1630 cm"1 uv spectrum (ethanol): max. 225 nm (0.36) . 245 nm (0.31) 280 nm (0.05) 310 nm (0.1).

Example 24 1 9 92 1 5 1-(3»5-Dichloro-4-hydroxy-phenyl)-2-/N-/5-(4-methoxy-phenyl)-propyl7methylamino7ethanol Prepared analogously to Example 1 from 3',5'-dichloro-4f-hydroxy- 2-/N-/3-(4-methoxy-phenyl)-propyl7methylamino7acetophenone and sodium borohydride in 80 % methanol.

M.p.: 156 - 157°C.

Example 25 1-(3,5-Dibromo-4-hydroxy-phenyl)-2-/N-/3-(4-methoxy-phenyl)-propvl7m ethylamino7ethano1 Prepared analogously to Example 1 from 31,51-dibromo-41-hydroxy- 2-/N-/3-(4-methoxy-phenyl)-propyl7methylamino7acetophenone and sodium borohydride in 80 % methanol.

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

Example 26 1-(4-Amino-3-bromo-5-fluoro-phenyl)-2-/N-/5-(4-methoxy-phenyl)-propyl7methvlamino7ethanol Prepared analogously to Example 1 from 4'-amino-3'-bromo-5'-fluoro- 2-/!T-/5-(4-methoxy-phenyl)-propyl7methylamin£7acetophenone 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-/N-/5-(4-methoxy-phenyl)-propyl7methvlamino7ethano1 Prepared analogously to Example 1 from 4'-amino-31-chloro-51-fluoro-(4-methoxy-phenyl)-propyl7methylamino7acetophenone and • HI 9 92 1 5 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-./IT-/3-(4-methoxy-phenyl )-5 propyl7methvlamino7ethanol Prepared analogously to Example 1 from 4'-amino-3'-chloro-5'-cyano-2-/N-/3-(4-methoxy-phenyl)-propyl7methylamino7acetophenone and sodium borohydride in 80 % of methanol.

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

OH NH CH, 2 N-alkyl och3 aliphat.

C=N C=C 245 nm (0.26) 278 nm (0.06) 332 nm (0.16). 3590 cm 3400 2800 cm 2830 cm 2850 2210 cm -1 + 3500 cm -1 -1 -1 + 2940 cm -1 -1 1625 cm -1 Example 29 2 0 1-(4-Amino-3-chloro-5-nitro-phenyl)-2-/n-/5-(4-methoxy-phenyl)-propyl7methvlamino7ethanol Prepared analogously to Example 1 from 4'-amino-3'-chloro-5'-nitro-z-3-3- (4-methoxy-phenyl)-propyl7methylamino7acetophenone and sodium borohydride in 80 % methanol.

* IR spectrum (methylene chloride): OH 3590 cm NH2 3390 + 3500 cm"1 N-alkyl 2800 cm"1 OCH^ 2830 cm"1 aliphat. CH2 2850 + 2940 cm"1 C=C 1630 cm"1 N0o 1330 + 1515 cm"1 UV spectrum (ethanol): *"X max. 227 nm (0.64) 280 nm (0.16) 400 nm (0.12) t 9 92 1 5 Example 30 1_(4-Amino-3-chloro-phenyl)-2-/N-/3-(4-methoxy-phenyl)-propyl7-methvlamlno7ethanol Prepared analogously to Example 1 from 4l-amino-3l-chloro-2-_/!T-/3-(4-methoxy-phenyl)-propyl7methylamino7acetophenone and sodium borohydride in 80 % methanol.

IR spectrum (methylene chloride): UV spectrum (ethanol): A max. oh . nh2 N-alkyl och3 aliphat. CH2 c=c 225 nm (0.44) 243 nm (0.36) 280 nm (0.09) 295 nm (0.08) 3600 cm 3380 2800 cm 2830 cm 2850 1620 cm -1 + 3470 cm -1 -1 + 2940 cm -1 -1 -1 Example 31 1 - (4-Amino-3-bromo-phenyl)-2-/N-/3- (4-methoxy-phenyl)-propyl7-methylamino7ethanol Prepared analogously to Example 1 from 4l-amino-3'-bromo-2-/IT-D- (4-methoxy-phenyl)-propyl7methylamino7acetophenone and sodium 25 borohydride in 80 % methanol.

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

I " Example 32 1 - (4-Amino-3,5-dicyano-phenyl)-2-/N-/5- (4-methoxy-phenyl )-propyl7-methvlamlno7ethanol 199215 Prepared analogously to Example 1 from 4,-amino-3l,5'-dicyano-5 2-/N-/3-(4-methoxy-phenyl)-propyl7methylamino7acetophenone and sodium borohydride in 80 % methanol.

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

Example 33 1-(4-Amino-3-bromo-phenyl)-2-/N-/5-(4-methoxy-phenyl)-butyl/-10 methylamino7ethanol Prepared analogously to Example 1 from 4'-amino-3'-bromo- 2-/N-/5-(4-methoxy-phenyl)-butyl7methylamin£7acetophenone and sodium borohydride in 80 # methanol.

^ A IR spectrum (methylene chloride): OH 3590 cm * NH2 3380 +3470 cm"1 N-alkyl 2800 cm"1 0CH3 2830 cm"1 aliphat. CH2 2850 + 2930 cm"1 C=c 1620 cm"1 UV spectrum (ethanol): A max. 224 nm (0.44) 243 nn (0.28) 280 nm (0.08) 300 nm (0.06).

Example 34 2 5 1_(4-Amino-3-bromo-phenyl)-2-/N-/2-(4-methoxy-phenyl)-ethyl/-methvlamino7ethanol Prepared analogously to Example 1 from 4'-amino-3'-bromo-2-_/N-/5- (4-methoxy-phenyl )-ethyl7methylamino7acetophenone and sodium borohydride in 80% methanol.

IR spectrum (methylene chloride): UV spectrum (ethanol): "X max. 199215 oh nh2 N-alkyl och 3590 cm -1 3380 + 3470 cm 2800 cm"1 2830 cm"1 -1 3 -1 aliphat. CH2 2840 + 2940 cm C=C 1620 cm"1 225 nm (0.43) 243 nm (0.36) 280 nm (0.08) 296 nm (0.08).

Example 35 1-(4-Amino-3,5-dichloro-phenyl)-2-/N-/£-(4-methoxy-phenyl)■ butvl7methvlamino7ethano1 Prepared analogously to Example 1 from 4'-amino-3',5'-dichloro-2-^N-fpt-(4-methoxy-phenyl)-butyl/methylamino7acetophenone and sodium borohydride in 80 % methanol.

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

OH NH 2 N-alkyl och3 aliphat.

C=C 245 nm (0.25) 320 nm (0.48). 3590 cm 3390 + 2800 cm -1 3490 cm -1 -1 -1 CH, 2830 cm 2850 + 2930 cm 1610 cm"1 -1 Example 36 1-(4-Amino-3-bromo-5-cyano-phenyl)-2-/F-/5-(4-methoxy-phenyl)-butvl7methvlamino7ethanol Prepared analogously to Example 1 from 4'-amino-3'-bromo-51-cyano- 2-/N-/£-(4-methoxy-phenyl)-butyl7methylamino7acetophenone and sodium borohydride in 80 % methanol. 199215 IR spectrum (methylene chloride): OH 3590 cm" NH2 3390 + 3490 cm"1 N-alkyl 2800 cm"1 OCH^ 2830 cm"1 aliphat. CH2 2850 + 2930 cm"1 C=N 2210 cm"1 C=C 1620 cm"1 UV spectrum (ethanol): max. 245 nm (0.27) 278 nm (0.08) 330 nm (0.15).

Example 37 1-(4-Amino-3-bromo-5-cyano-phenyl)-2-/N-/2-(4-methoxy-phenyl)- ethvl7methvlamino7ethanol - Prepared analogously to Example 1 from 4'-amino-3'-bromo-51-cyano-15 2-,/!T-/2-(4-methoxy-phenyl )-ethyl7methylamino7acetophenone and sodium borohydride in 80 % methanol. * — 1 IR spectrum (methylene chloride): OH 3590 cm NH2 3390 + 3490 cm"1 N-alkyl 2800 cm"1 2 0 0CH3 2830 cm'1 aliphat. CH2 2850 + 2950 cm"1 C=N 2210 cm"1 C=C 1620 cm"1 UV spectrum (ethanol): ^ max. 245 nm (0.25) 25 277 nm (0.09) 331 nm (0.10).

Example 38 1-(4-Amino-3,5-dichloro-phenyl)-2-/IT-/5-(4-methoxy-phenyl)-ethyl7 -methvlamino7ethanol Prepared analogously to Example 1 from 4'-amino-3f>5'-dichloro- 2-/N-/5- (4-methoxy-phenyl )-ethyl7methylamino7acetophenone and sodium borohydride in 80 % methan IR spectrum (methylene chloride): f 9 92 1 5 -1 oh 3590 cm"1 nh2 3390 + 3490 cm cm"1 N-alkyl 2800 och3 2830 -1 cm aliphat. ch2 2850 + 2930 cm c=c 1610 -1 cm Example 39 1-(4-Amino-3-chloro-5-cyano-phenyl)-2-/N-/5-(4-methoxy-phenyl)-butvl7methvlamino7ethanol Prepared analogously to Example 1 from 4'-amino-3'-chloro-5'-cyano- 2-/N-/2+-(4-methoxy-phenyl)-butyl7methylamino7acetophenone and sodium borohydride in 80 % methanol.

A IR spectrum (methylene chloride): OH 3590 cm" NH2. 3400 + 3500-cm"1 N-alkyl 2800 cm"1 OCHj 2830 cm"1 aliphat. CH2 2850 + 2930 cm"1 C=N 2210 cm"1 C=C 1625 cm"1 UV spectrum (ethanol): A max. 245 nm (0.23) 280 nm (0.05) 332 nm (0.13).

Example 40 1-(4-Amino-3-chloro-5-cyano-phenyl)-2-/N-/2-(4-methoxy-phenyl)-ethyl7methvlamlno7ethanol Prepared analogously to Example 1 from 4*-amino-31-chloro-5'-cyano- 2-/5-(4-methoxy-phenyl)-ethyl7methylamino7acetophenone and sodium borohydride in 80 % methanol.

IR spectrum (methylene chloride): UV spectrum (ethanol): !X max. oh nh2 N-alkyl och3 ch2 C=N 19^215 3590 cm 3390 + 2800 cm 2830 cm 2850 + 2210 cm c=c 245 nm (0.24) 280 nm (0.04) 332 nm (0.13). 1620 cm 3490 cm -1 -1 2940 cm -1 -1 -1 -1 Example 41 1-(4-Amino-3,5-dichloro-phenyl)-2-/N-/2-(4-methoxy-phenylsul-fenvl)-ethvl7methvlamino7ethanol Prepared analogously to Example 1 from 4'-amino-31,5l-dichloro-2-/N-/5-(4-methoxy-phenylsulfenyl)-ethyl7Ine"thylamino7aceto-phenone and sodium borohydride in tetrahydrofuran : water. : . methanol =25 : 5 : 10. Oil.

IR spectrum (methylene chloride): uv spectrum (ethanol): ^ max. oh nh2 ch2 N-alkyl och3 c=c 3200 - 2500 cm (below NH2) 3480 + 3390 cm 2940 cm'1 2800 cm'1 2830 cm'1 1580 + 1490 cm -1 -1 -1 230 nm (0.58; shoulder) 245 nm (0.54) 298 nm (0.14).

Example 42 1-(4-Amino-3,5-dichloro-phenyl)-2-/JT-/2-(4-methoxy-phenoxy)-30 ethvl7methylamino7ethanol Prepared analogously to Example 1 from 4'-amino-3',5'-dichloro-2-/N-/5- (4-methoxy-phenoxy) -ethyl/methylamino/acetophenone and sodium borohydride in tetrahydrofuran = 15 : 5 : 3. Oil.

IR spectrum (methylene chloride): OH NH, CH: UV spectrum (ethanol): /\ max.

N-alkyl och3 c=c 1 992 1 5 water : methanol 3200 - 3500 cm (below NH2) 3480 + 3390 cm 2940 cm"1 2790 cm"1 2830 cm"1 1580, 1505 + 1485 cm"1 1250 cm"1 -1 -1 C-O-aryl 230 nm (0.32; shoulder) 244 nm (0.26; shoulder) 294 nm (0.12).

Example 43 1-(4-Amino-3,5-dichloro-phenyl)-2-/IT-/5-(4-methoxy-phenyl) ■ propyl7amino7propanol-(1) Prepared analogously to Example 1 from 4'-amino-31>5'-dichloro-2-^T-/3-(4-methoxy-phenyl)-propyl7amino7propiophenone and 2 0 sodium borohydride.

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

Example 44 1-(4-Amino-3,5-dichloro-phenyl)-2-/lT-/5-(4-methoxy-phenyl)-25 propvl7-2-propylamino7ethanol Prepared analogously to Example 1 from 4'-amino-3't5'-dichloro- 2-/N-/3- (4-methoxy-phenyl) -pr opyl7-2-pr opylamino7ac etophenone and sodium borohydride. Oil. -1 -1 IR spectrum (methylene chloride): oh 3600 nh2 3400 och3 2830 UV spectrum (ethanol): max. 243 nm (0.13) 280 nm (0.03) 300 nm. (0.03) + 3490 cm -1 • 51 199215 Example 45 1-(4-Amino-3,5-dichloro-phenyl)-2-/F-/5-(4-methoxy-phenyl)-propyl7ethvlamino7ethanol Prepared analogously to Example 1 from 4*-amino-3',51-dichloro- 2-/N-/5-(4-methoxy-phenyl)-propyl/ethylamino7acetophenone and sodium borohydride.

IR spectrum (methylene chloride): OH nh2 OCH, A D UV spectrum (ethanol): A max. 243 nm 280 nm 300 nm.

Example 46 1-(4-Amino-3,5-dichloro-phenyl)-2-/^-/5-(4-methoxy-phenyl)-propvl7propvlamino7ethanol . 3600 cm -1 3395 + 3490 cm 2830 cm"1 -1 (0.13) (0.04) (0.04) Prepared analogously to Example 1 from 41-amino-31,5'-dichloro-2-/F-/5- (4-methoxy-phenyl) -propyl7propylamino7acetophenone and sodium borohydride. Oil.

IR spectrum (methylene chloride): OH 3600 cm" NH2 3395 + 3495 cm"1 0CH5 2850 cm"1 UV spectrum (ethanol): % max. 245 nm (0.10) 280 nm (0.03) 300 nm. (0.03) Example 47 1 - (4-Amino-3,5-dichloro-phenyl )-2-/IT-/3- (4-methoxy-phenyl) -propvl7cvclopropvlamino7ethanol Prepared analogously to Example 1 from 4'-amino-3'»51-dichloro-2-/ff-/?- (4-methoxy-phenyl) -propyl/cyclopropylamino7acetophenone t 9 92 1 5 and. sodium borohydride. Oil. a"1 3495 cm-1 -1 IR spectrum (methylene chloride): oh 3590 nh2 3395 0ch, 2850 UV spectrum (ethanol): max. mJ 245 nm (0.12) 280 nm (0.04) 300 nm. (0.04) Example 48 1-(4-Amino-3,5-dichloro-phenyl)-2-/N-/5-(4-methoxy-phenyl)-10 propvl7methvlamlno7propanol-(1). Isomer B Prepared analogously to Example 2 from N-/5-(4-methoxy-phenyl)-propyl/methylamine, 4'-amino-2-bromo-3',5'-dichloro-propio-phenone, triethylamine, and sodium borohydride. Oil. 3680 cm"1 3490 cm 2940 cm"1 1510, 1610 cm"1 ir spectrum (methylene chloride): oh 3600 + nh2 3390 + och3 2835 + aromat 1585 + uv spectrum (ethanol): \ max. 246 nm (0.14) 278 nm (0.08) 285 nm (0.08) 0 0 10 (0.08) NMR spectrum (CDC13/D20): 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-/IT-/5- (4-methoxy-phenyl)-propvl7methvlamino7propanol-(1). Isomer A Prepared analogously to Example 2 from N-/5-(4-methoxy-phenyl)-propyl/methylamine, 41-amino-31,5'-dichloro-2-bromo-propiophenone, 30 triethylamine, and sodium borohydride. 1992 M.p. of the hydrochloride: 178 - 181°C.

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

Example 50 1-(4-Amino-3,5-dichloro-phenyl)-2-/N-/5-(4-ethoxy-phenyl)-propyl7methylamino7ethanol Prepared analogously to Example 2 from 4'-amino-31,5'-dichloro- 2-bromo-acetophenone, 1-(4-ethoxy-phenyl)-3-methylamino-propane hydrochloride, triethylamine, and sodium borohydride. Oil.

IR spectrum (methylene chloride): OH 3590 cm NH2 3395 + 3495 cm" N-alkyl 2800 cm"1 UV spectrum (ethanol): max. 245 nm (0.13) 280 nm (0.04) 300 nm. (0.04) Example 51 1-(4-Amino-3»5-dichloro-phenyl) - 2-/IT-£5-(4-b enzyloxy-phenyl)-propyl7methvlamino7ethanol Prepared analogously to Example 2 from 4'-amino-31,5'-dichloro- 2-bromo-acetophenone, 1-(4-benzyloxy-phenyl)-3-methylamino-pro-pane hydrochloride, triethylamine, and sodium borohydride. Oil. IR spectrum (methylene chloride): OH 3590 cm"1 NH2 3395 + 3495 cm" N-alkyl 2800 cm"1. - 54 Example 52 t 9 9215 1-(4-Amino-3-iodo-5-fluoro-phenyl)-2-/N-/3-(4-methoxy-phenyl)-propyl7methylamino7ethanol Prepared analogously to Example 2 from 4'-amino-3'-iodo-5'-fluoro- 2-bromo-acetophenone, 1-(4-methoxy-phenyl)-3-methylamino-propane hydrochloride, triethylamine, and sodium borohydride. Oil. _ A IR spectrum (methylene chloride): OH 3590 cm" NH2 3395 + 3495 cm"1 N-alkyl 2800 cm"1.

Example 53 1-(4-Amino-3-cyano-5-fluoro-phenyl)-2-/!T^/5-(4-methoxy-phenyl)-propvl7-2-propylamino7ethanol Prepared analogously to Example 2 from 4'-amino-3'-cyano-5'-fluoro* 2-bromo-acetophenone,. 1-(4-methoxy-phenyl)-3-(2-propylamino)-15 propane hydrochloride, and sodium borohydride. Oil. — 1 IR spectrum (methylene chloride): OH 3600 cm NH2 3395 + 3495 cm"1 0CH3 2830 cm"1 N-alkyl 2800 cm"1 C=N 2220 cm"1 Example 54 1-(4-Amino-3,5-dichloro-phenyl)-2-/N-/5-(2-methoxy-phenyl) ■ propyl7methvlamino7ethanoI hydrochloride Prepared analogously to Example 2 from 4'-amino-3',5'-dichloro-25 2-bromo-acetophenone, 1-(2-methoxy-phenyl)-3-methylamino-propane hydrochloride, triethylamine, and sodium borohydride.

M.p.: from 75°C (by sintering).

Example 55 1 9 92 1 5 1-(4-Amino-3,5-dichloro-phenyl)-2-/N-/3-(3,4-dimethoxy-phenyl)-propvl7methvlamino7ethanol _ Prepared analogously to Example 2 from 41-amino-3',5'-dichloro- 2-bromo-acetophenone, 1-(3,4-dimethoxy-phenyl)-3-methylamino-propane hydrochloride, triethylamine, and sodium borohydride. IR spectrum (methylene chloride): t0H 3600 cm NH2 3390 + 3485 cm"1 0CH3 2830 cm"1 N-alkyl 2800 cm"1.

Example 56 1-(4-Amino-3-chloro-5-trifluoromethyl-phenyl)-2-/N-/2-(4-methoxy-phenyl)ethvl7methvlamlno7ethanol Prepared analogously tp Example 1 from 4'-amino-3'-chloro-5f-tri ■ fluoromethyl-2-/N-/2-(4-methoxy-phenyl)-ethyl7methylamino7acetophenone, and sodium borohydride in 80 % methanol.

IR spectrum (methylene chloride): OH 3600 cm NH2 3410 + 3510 cm"1 N-alkyl 2800 cm"1 0-CH3 2830 cm"1 aliphat. CH2 2850 + 2940 cm"1 C«C 1630 cm"1 UV spectrum (ethanol): % max. 225 nm (0.38) 244 nm (0.34) 280 nm (0.07) 307 nm (0.10).

Example 57 199215 1-(4-Amino-3,5-dichloro-phenyl)-2-/N-/5-(4-methoxy-phenyl)-propvl7amino7ethano1 hydrochloride Prepared analogously to Example 1 from 4*-amino-31,5'-di-chloro- 2-Z&-Z3 -(4-methoxy-phenyl)-propyl7ainin£7acetophenone 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(3-phenyl-propyl)-2-propyl-amlno7ethanol hydrochloride Prepared analogously to Example 2 from 4'-amino-3',5'-dichloro- 2-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-/N-/3-(4-fluoro-phenyl)-propyl7-methylamino7ethanol hydrochloride Prepared analogously to Example 2 from 4'-amino-3',5'-dichloro- 2-bromo-acetophenone, 1-(4-fluoro-phenyl)-3-methylamino-propane hydrochloride, triethylamine and sodium borohydride.

M.p.: 185 - 188°C (decomp.).

Example 60 1-(4-Amino-3 > 5-dichloro-phenyl)-2-/IT-/5-(4-hydroxy-phenyl)- 1-methyl-propyl7amino7ethanol Prepared analogously to Example 4 from 4'-amino-3'»5'-dichloro- 2-/N-/5-(4-hydroxy-phenyl)-1-methyl-propyl7-aniino7acetophenone and sodium borohydride in aqueous tetrahydrofuran. As eluent for the chromatographic purufication over silica gel a mixture of ,t %%L 1 5 dichloromethane : methanol : conc. ammonia =19 was used.

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

IR spectrum (KBr): OH 2300 - 3500 cm" (broad, associa ted) NH2 3460 + 3370 cm"1 CH2 2920 + 2960 cm"1 C=C 1580, 1510 + 1480 cm"1 UV spectrum (ethanol): A max. 244 nm (0.28) 280 nm (0.08) 300 nm (0.08) UV spectrum (ethanol + KOH): A max. 243 nm (0.54) 299 nm (0.15).

^ Example 61 1-(4-Amino-3,5-dichloro-phenyl)-2-/3-(4-methoxy-phenyl)-15 1-methyl-propyl7amino7ethanol Prepared analogously to Example 4. from 4'-amino-3',5'-dichloro- 2-/N-/5- (4-methoxy-phenyl )-1 -methyl-propyl7amino7 acetophenone and sodium borohydride in aqueous tetrahydrofuran.

The compound was ©btained as a 1:1 mixture of the diastereoisome-2 0 ric racemate.

IR spectrum (methylene chloride): UV spectrum (ethanol): X max. oh 3600 -1 cm nh2 ch2 3480 2930 + 3390 cm"1 -1 cm -1 cm och. 2830 c-c 1580, 1510 + 1485 244 nm (0.28) 280 nm (0.08) 300 nm (0.09) • Example 62 19921 5 1-(4-Amino-3-cyano-5-fluoro-phenyl)-2-/N-/2-(3,4-dimethoxy-phenvl)-ethvl7amino7ethanol hydrochloride Prepared analogously to Example 5 from 4'-amino-3'-fluoro-5'-cyano-acetophenone, selenium dioxide, 2-(3»4-dimethoxy-phenyl )-ethylamine, and sodium borohydride.

M.p.: 196 - 197°C (decomp.).

Example 63 1-(4-Amino-3-fluoro-5-iodo-phenyl)-2-(3»4-dimethoxy-phenyl)-ethvl7amino7ethanol hydrochloride Prepared analogously to Example 5 from 4'-amino-3'-fluoro-5'-iodo-acetophenone, 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-/N-/S-(3,4-dimethoxy-phenvl)-ethvl7amino7ethano1 hydrochloride Prepared analogously to Example 5 from 4'-amino-3'-chloro-5'-fluoro-acetophenone, selenium dioxide, 2-(3,4-dimethoxy-phenyl )-ethylamine, and sodium borohydride.

M.p.: 184 - 186°C (decomp.).

Example 63 1-(4-Amino-3-bromo-5-fluoro-phenyl)-2-/N-/5-(3»4-dimethoxy-phenyl)-ethvl7amino7ethanol hydrochloride Prepared analogously to Example 5 from 4'-amino-3'-bromo-51-fluoro-acetophenone, selenium dioxide, 2-(3,4-dimethoxy-phenyl)-ethylamine, 199215 and sodium borohydride. M.p.: 194 - 195°C (decomp.).

Example 66 1-(4-Amino-3-fluoro-5-cyano-phenyl)-2-/N-/3-(4-methoxy-phenyl) propvl7amino7ethanol Prepared analogously to Example 5 from 4'-amino-3'-fluoro-5'-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)-amino/-ethanol hydrochloride ; —, Prepared analogously to Example 5 from 4'-amino-3',5'-dichloro-acetophenone, selenium dioxide, 3-phenyl-propylamine, and sodium borohydride.

M.p.: 180 - 181°C (decomp.).

Example 68 1-(4-Amino-3-chloro-5-fluoro-phenyl)-2-/N-(1-methyl-2-phenoxy-ethvl)-amino/ethanol dihvdrochloride Prepared analogously to Example 5 from 4'-amino-3'-chloro-5'-fluoro-acetophenone, selenium dioxide, 1-methyl-2-phenoxy-ethylamine, and sodium borohydride.

M.p.: 158 - 160°C (decomp.).

Example 69 I 9 92 1 5 1-(4-Amino-3-cyano-5-fluoro-phenyl)-2-/N-(l-methyl-2-phenoxy-ethvl)-amino7ethanol hydrochloride Prepared analogously to Example 5 from 4'-amino-3'-cyano-5'-fluoro-acetophenone , selenium dioxide, 1-methyl-2-phenoxy-ethylamine, and sodium borohydride.

M.p.: 178 - 184°C (decomp.).

Example 70 1-(4-Amino-3-bromo-5-fluoro-phenyl)-2-/17-(1-methyl-2-phenoxy-ethvl )«»amino7ethanol dlhydrochloride Prepared analogously to Example 5 from 4'-amino-3'-bromo-5'-fluoro-acetophenone, selenium dioxide, 1-methyl-2-phenoxy-ethylamine, and sodium borohydride.

M.p.: 156 - 158°C (decomp.). ' Example 71 N-/2-(4-Amino-3,5-dibromo-phenyl)-ethyl7~N-/3-(4-methoxy-phenyl)-propyl7methylamine Prepared analogously to Example 7 from 4-amino-3,5-dibromo-N-/3- (4-methoxy-phenyl )-propyl7-N-methyl-phenyl-acetamide, and lithium aluminium hydride.

M.p. of the hydrochloride1 149 - 153°C.

Example 72 N-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl7-N-/5-(4-methoxy-phenyl)-propyl7methvlamine Prepared analogously to Example 7 from 4-amino-3»5-dichloro- si 9 92 1 5 N-/3- (4-methoxy-phenyl)-propyl7-n-methyl-phenyl-acetamide, and lithium aluminium hydride.

M.p. of the hydrochloride: 90 - 94°C.

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

IR spectrum (methylene chloride): NH2 3380 + 3470 cm-1 N-alkyl 2780 cm'1 0CH3 2830 cm"1 aliphat. CH2 2850 + 2930 cm"1 C=C 1610 cm"1 UV spectrum (ethanol): A max. 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 )< butvl7methvlamine Prepared analogously to Example 8 from 4-amino-3»5-dichloro-N-/5- (4-methoxy-phenyl) -butyl7-N-methyl-phenyl-acetairn.de , and lithium aluminium hydride. — 1 IR spectrum (methylene chloride): NH2 3380 + 3480 cm" 0CH3 2830 cm"1 aliphat. CH2 2850 + 2930 cm"1 NH+ 2100 - 2500 cm"1 C=C 1630 cm"1 UV spectrum (ethanol): ^ max. 245 nm (0.22) 280 nm (0.07) 304 nm (0.08).

Example 75 1992 15 n-/3-(4-Amino-3,5-dichloro-phenyl)-propyl7-2-(3,4-dimethoxy-phenvl)-ethylamine hydrochloride Prepared analogously to Example 7 from 3-(4-amino-3,5-dichloro-5 phenyl) -N-/2"- (3,4-dimethoxy-phenyl)-ethyl/Pr°Pionamide / and lithium aluminium hydride.

M.p.: 142 - 145°C.

Example 76 \ N-/3-(4-Amino-3,5-dichloro-phenyl)-propyl/-N-/2-(3,4-dimethoxy-10 phenyl)-ethvl7methylamine Prepared analogously to Example & from 3-(4-amino-3,5-dichloro-phenyl )-N-/2-(3,4-dimethoxy-phenyl)-ethyl/-N-methyl-propionamide, and lithium aluminium hydride. Oil. — 1 IR .spectrum (methylene chloride): NHL, 3400 + 3500 cm" OCH, 2835 + 2960 cm"1 NCH, 2800 cm"1 3 3 aromat 1510 + 1590/ 1615 cm"1 UV spectrum (ethanol): max. 239 nm (shoulder) 20 , 281 nm (0.11) 300 nm (0.08).

Example 77 N-/5-(4-Amino-3-bromo-phenyl)-propyl/-2-(3,4-dimethoxy-phenyl) ■ ethvlamlne hydrochloride Prepared analogously to Example 7 from 3-(4-amino-3>5-dibromo-phenyl) -N-/2- (3,4-dimethoxy-phenyl) -ethyl/propionamide, and lithium aluminium hydride.

M.p.: 131 - 134°C.

I 9 92 1 5 Example 78 1 N-/5- (4-Amino-3»5-dichloro-phenyl )-ethyl7-N-/5- (4-hydroxy-phenyl)-1-methvl-propyl7amine Prepared analogously to Example 8 from 4-amino-3,5-dichloro-N-/3- (4-hydroxy-phenyl) -1 -methyl-propyl/phenyl-acetamide, and lithium aluminium hydride in tetrahydrofuran. The chromatographic purification was carried out by means of medium pressure chromatography on silica gel (grain size: 0.015 — 0.025 mm) with methylene chloride : methanol : cone, ammonia = 19 : 1 : 0.1 as eluent. Foam.

IR spectrum (methylene chloride): OH 3580 cm NH2 3480 + 3385 cm"1 CH2 2920 cm"1 C=C 1580, 1510 + 1480 cm UV spectrum (ethanol): max. 242 nm (0.24; shoulder) 280 nm (0.07) 303 nm (0.08) UV spectrum (ethanol + K0H): X max. 242 nm (0.53) 300 nm (0.16).

Example 79 N-/2- (4-Amino-3»5-dichloro-phenyl )-ethyl7-N-/5- (4-methoxy-phenyl)-1 -methyl-propyl7amlne Prepared analogously to Example 8 from 4-amino-3,5-dichloro-N-/5-(4-methoxy-phenyl)-1-methyl-propyl/phenylacetamide, and lithium aluminium hydride in tetrahydrofuran. Oil. _ A IR spectrum (methylene chloride): NH2 3480 + 3385 cm CH2 2930 cm"1 OCHj 2830 cm"1 C-C 1580, 1510 + 1485 cm UV spectrum (ethanol): % max. 242 nm (0.25; shoulder) 280 nm (0.07) 302 nm (0.08). " - 64 - J 9 92 1 5 Example 80 1 N-/2- (4-Amino-3,5-dichloro-phenyl )-ethyl7-N-/3- (4-benzyloxy-phenvl)-propvl7methvlamine Prepared analogously to Example 8 from 4-amino-3,5-dichloro-N-/5- (4-benzyloxy-phenyl)-propyl7-N-methyl-phenylacetamide, and lithium aluminium hydride. Oil.

IE spectrum (methylene chloride): NH2 3390 + 3490 cm N-alkyl 2800 cm"1 UV spectrum (ethanol): /I 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- jj>- (3,4-dimethoxy-phenvl)-propvl7methvlamlne Prepared analogously to Example 8 from 4-amino-3,5-dichloro-N-/5- (3,4-dimethoxy-phenyl) -propyl7-N-methyl-phenylacetamide, and lithium aluminium hydride. Oil.

IR spectrum (methylene chloride): NHg 3395 + 3495 cm 0CH3 2830 cm"1 N-alkyl 2800 cm"1 UV spectrum (ethanol): A max. 230 nm (shoulder; 0.18) 245 nm (shoulder; 0.12) 282 nm (0.04) 302 nm. (0.03) Example 82 N-/5- (4- Amino-3»5-dichloro-phenyl )-ethyl7-N-/5-(2-methoxy-phenyl )■ propvl7methvlamlne hydrochloride Prepared analogously to Example 7 from 4-amino-3»5-dichloro- ' 199215 N-/3- (2-methoxy-phenyl )-propyl7-N-methyl-phenylacetamide, and lithium aluminium hydride.

M.p.: 160 - 164°C.

Example 85 N-/2-(4-Amino-3»5-dichloro-phenyl)-ethyl7-N-(3-phenyl-propyl)-methylamine Prepared analogously to Example 8 from 4-amino-3,5-dichloro-N- (3-phenyl-propyl) -N-methyl-^phenylacetamide, and lithium aluminium hydride. Oil.

IR spectrum (methylene chloride): NH2 3390 + 3490 cm N-alkyl 2800 cm"1 UV spectrum (ethanol): ^ max. 245 nm (0.12) 300 nm (0.03) Example 84 N-/2- (4-Amino-3,5-dichloro-phenyl)-ethyl7-N-/5- (4-methoxy-phenyl)-propyl7amine hydrochloride Prepared analogously to Example 7 from 4-amino-3»5-dichloro-N-/5- (4-methoxy-phenyl)-propyl7phenylacetamide, and lithium aluminium hydride.

M.p.: 203 - 205°C.

Example 85 N-/2- (4-Amino-3»5-dichloro-phenyl )-ethyl7-N-/5- (4-methoxy-phenyl)-propyl7cvclopropylamlne .

Prepared analogously to Example 8 from 4-amino-3»5-dichloro-. 25 N-/5-(4-methoxy-phenyl)-propyl7-N-cyclopropyl-phenylacetamide, and lithium aluminium hydride. Oil. —1 IR spectrum (methylene chloride): NHg 3390 + 3490 cm 0CH, 2830 cm"1 .199215 UV spectrum (ethanol): "k max. 245 nm (0.15) 280 nm (0.04) 300 nm (0.05) Example 86 » N-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl7-N-/5-(4-methoxy-phenvl)-propvl7propvlamine Prepared analogously to Example 8 from 4-amino-3,5-dichloro-N-/5-(4-methoxy-phenyl)-propyl7-N-propyl-phenylacet amide, and lithium aluminium hydride. Oil.

IR spectrum (methylene chloride): NH2 3390 + 3490 cm"1 0CH3 2830 cm"1 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-/3- (4-methoxy-phenvl)-propvl7ethylamine Prepared analogously to Example 8 from 4-amino-3»5-dichloro- N-/3-(4-methoxy-phenyl)-propyl7-N-ethyl-phenylacet amide, and "lithium aluminium hydride. Oil.

) IR spectrum (methylene chloride): NH2 3390 + 3490 cm 0CH3 2830 cm"1 N-alkyl 2800 cm"1 UV spectrum (ethanol): 7i max. 243 nm (0.13) 280 nm (0.04) 300 nm (0.04) -1 67 19 9215 Example 88 N-/2-(4-Amino-3,5-dichloro-phenyl) -ethyl7-N-/3- (4-methoxy-phenvl)-propyl7-2-propylamine Prepared analogously to Example 8 from 4-amino-3,5-dichloro-N-/5- (4-methoxy-phenyl) -propyl7-N-(2-propyl)-phenylacetamide, and lithium aluminium hydride. Oil.

IR spectrum (methylene chloride): NH2 3390 + 3490 cm" OCHj 2830 cm"1 UV spectrum (ethanol): /\ max. 243 nm (0.13) Example 89 N-/5- (4-Amino-3,5-dichloro-phenyl )-ethyl7-N-/5- (4-ethoxy • Prepared analogously to Example 8 from 4-amino-3,5-dichloro- N-/5-(4-ethoxy-phenyl)-propyl7-N-methyl-phenylacetamide, and lithium aluminium hydride. Oil.

Example 90 N-/5- (4-Amino-3»5-dichloro-phenyl)-ethyl7-N-/5-(4-methoxy-phenyl)-1-methyl-propyl7methylamine Prepared analogously to Example 9 from 1-ethoxycarbonyloxy-1-(4-amino-3,5-dichloro-phenyl)-2-/ff-/3-(4-methoxy-phenyl)-1-methyl-propyl/nethylamino/ethane, and sodium borohydride in isopropanol. Oil. 280 nm (0.04) 300 nm (0.04) phenyl)-propyl7methylamine IR spectrum (methylene chloride): NH2 och3 N-alkyl UV spectrum (ethanol): ^ max. 245 nm 280 nm 300 nm (0.12) (0.03) (0.04) 1 9 92 t 3480 + 3380 cm"1 2930 cm"1 2790 cm"1 2840 cm"1 1580, 1510 + 1480 c: Example 91 N-/2-(4-Amino-3-bromo-5-cyano-phenyl)-ethyl/-N-/£-(4-methoxy-phenvl)-butvl7methYlamlne Prepared analogously to Example 9 from 1-ethoxycarbonyloxy-1-(4-amino-3-bromo-5-cyano-phenyl)-2- (4-methoxy-phenyl)-butyl/- methylamino7ethane, and sodium borohydride.

Analysis: Calc.: C 60.6 H 6.3 Br 19.2 N 10.1 Found: 60.5 6.1 19.2 10.1 Example 92 N-/2-(4-Amino-3-chloro-5-cyano-phenyl)-ethyl7-N-/2-(4-methoxy-phenvl)-ethvl7methvlamine Prepared analogously to Example 9 from 1-ethoxycarbonyloxy-1-(4-amino-3-chloro-5-cyano-phenyl)-2-/R-/2-(4-methoxy-phenyl)-ethyl7methylamino7ethane, and sodium borohydride.

IR spectrum (methylene chloride): NH2 3400 + 3490 cm"1 N-alkyl 3790 cm"1 0CH3 2830 cm"1 aliphat. CH2 2850 + 2940 cm"1 C=N 2210 cm"1 C=C 1620 cm"1 UV spectrum (ethanol): ^ max. 244 nm (0.26) 280 nm (0.04) 335 nm (0.15).

IR spectrum (methylene chloride): NH 2 ch2 N-alkyl och3 oc V .) 1 K ^ • 69 J9 9215 Example 93 N-/2-(4-Amino-3-bromo-5-cyano-phenyl)-ethyl7-N-/5-(4-methoxy-phenvl)-propyl7methvlamine Prepared analogously to Example 9 from 1-ethoxycarbonyloxy-1-(4-amino-3-bromo-5-cyano-phenyl)-2-/N-/3-(4-methoxy-phenyl)-propyl7methylamino7ethane, and sodium borohydride.

IR spectrum (methylene chloride): NH~ 3390 + 3490 cm"1 2 -1 N-alkyl 3790 cm 1 OCH, 3830 cm"1 3 -1 aliphat. CH9 2850 + 2940 cm * -1 C5N 2210 cm C«C 1620 cm"1 UV spectrum (ethanol): A max. 244 nm (0.20) 280 nm (0.04) 334 nm (0.13).

Example 94 N-/2- (4-Amino-3-chloro-5-cyano-phenyl )-ethyl7-N-/5- (4-methoxy-phenvl)-butvl7methvlamine Prepared analogously to Example 9 from 1-ethoxycarbonyloxy-1- (4-amino-3-chloro-5-cyano-phenyl)-2- /fT- (4-methoxy-phenyl)-butyl/-methylamino/ethane, and sodium borohydride.

Analysis: Calc.: C 67.5 H 7.3 CI 9.53 N 11.25 25 Found: 67.5 7.14 9.65 11.34 Example 95 phenyl) -butvl7methylamino7ethanol Prepared analogously to Example 1 from 4'-amino-31-chloro-5'-tri- •i ') fc $ 992 1 5 fluoromethyl-2-/N-/£-(4-methoxy-phenyl)-butyl/methylamino/aceto-phenone, and sodium borohydride in 80 % methanol.

IR spectrum (methylene chloride): .10 UV spectrum (ethanol): ^ max. 2 N-alkyl OCH, OH 3590 cm NH„ 3410 2800 cm 2830 cm aliphat. CH2 2850 aromat. OC 1630 cm 225 nm (0.32) 245 nm (0.31) 280 nm (0.06) 308 nm (0.10). -1 + 3510 cm -1 -1 -1 + 2930 cm -1 -1 Example 96 1 - (4-Amino-3-cyano-phenyl) -2-/]?- Jj>- (4-methoxy-phenyl) -propyl/-methylamlno7ethanol Prepared analogously to Example 11 from 1-(4-amino-3-bromo-5-cyano-phenyl) -2-/fT- (4-methc>xy-phenyl) -propyl7methylamino7 -ethanol in the presence of palladium/charcoal and hydrogen.

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

OH NH 2 N-alkyl 0CH-X C»N c=c 251 nm (0.31) 280 nm (0.60) 328 nm (0.12). 3610 cm 3400 2800 cm -1 + 3490 cm -1 -1 2830 cm 2210 cm 1630 cm -1 -1 -1 I *) i"J » -71 - 1 9 921 5 Example 97 N-/2- (4-Amino-3-chloro-phenyl )-ethyl/-N-/5- (4-benzyloxy-phenyl )-propvl7methylamine Prepared analogously to Example 11 from N-/2-(4-amino-3,5-dichloro-5 phenyl )-ethyl/-N-/5-( 4-benzyloxy-phenyl)-propyl/methylamine and hydrogen. Oil. — 1 IR spectrum (methylene chloride): NH2 3390 + 3490 cm N-alkyl 2790 cm"1.

Example 98 _lo N-/2-(4-Amino-3»5-dichloro-phenyl)-ethyl/-N-/3-(4-hydroxy-phenyl)-propylTmethvlamlne Prepared analogously to Example 16 from N-/2-(4-amino-3»5-dichloro-phenyl )-ethyl/-N-/J- (4-benzyloxy-phenyl)-propyl/methylamine and hydrogen. Oil.

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

Example 99 1-(4-Amino-3-fluoro-phenyl)-2-/1T- (1-methyl-2-phenoxy-ethyl)-2 0 amlno/ethanol tosvlate Prepared analogously to Example 17 from 1-(4-acetamino-3-fluoro-phenyl)-2-/N-(l-methyl-2-phenoxy)-ethyl/amino-ethanol and sodium hydroxide.

M.p.: 124 - 128°C. -> I o :*y Example 100 199215 n-/2- (4- Amino-3»5-dichloro-phenyl)-ethyl7-n-/5- (4-methoxy-phenoxy)-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 imder 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-/j?-( 4-amino-3»5-dichloro-phenyl)-ethyl7-10 n-(3-chloro-Pr°PY1)-methylamine in 50 ml of dry tetrahydrofuran at the same temperature. After stirring for 18 hours at approx. 20°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 15 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): nh, ch! 2 N-alkyl c«c 3390 + 3480 cm 2950 cm~1 2800 cm"1 1585 + 1560 + -1 -1 UV spectrum (ethanol): % max. 1505 cm 230 nm (0.18; shoulder) 246 nm (0.085; shoulder) 295 nm (0.05). 199215 Example 101 1-(4-Amino-3,5-dichloro-phenyl)-2-/!T-(3-phenyl-propyl)-ethyl-amino7ethanol hydrochloride 2 g of 1-(4-amino-3>5-dichloro-phenyl)-2-/f?-(3-phenyl-propy$-amino7-ethanol hydrochloride were dissolved in 50 ml of ethanol. To this solution 0.4 ml of acetaldehyde and subsequently whilst stirring at room temperature 1.2 g of sodium cyanoborohydride were.added, maintaining a pH value of 6 - 6.5 by addition of 2 n hydrochloric acid. The mixture was stirred for a fiirther 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 chloride phases were washed with water, dried over sodium sulfate, and evaporated in vacuo to dryness. A nearly colourless oil was obtained, which was dissolved in ethanol. This ethanolic solution was acidified with ethereal hydrochloric acid up to pH 5 and in vacuo in a rotation evaporator the solvent was removed. The remaining oily residue was crystallised from ethyl acetate; eoiourless crystals were obtained.

M.p.: 102 - 105°C.

Example 102 1 - (4-Ethoxycarbonylamino-3-cyano-5-f luoro-phenyl)-2-/W-/2-(3.4-dimethoxv-phenvl)-ethvl7amlno7ethanol hydrochloride Prepared analogously to Example 4 from 41-ethoxycarbonylamino-3'-cyano-5'-fluoro-acetophenone, selenium dioxide, 2-(3,4-di-methoxy-phenyl)-ethylamine, and sodium borohydride.

M.p.: 190 - 191°C (decomp.).

Example 103 199215 1-(4-Amino-3-cyano-5-fluoro-phenjyl)-2-/N-/5-(4-methoxy-phenyl) butvl7methvlamino7 ethanol Prepared analogously to Example 1 from 4'-amino-31-cyano-51-fluoro-2-/N-/5-(4-methoxy-phenyl)-butyl7methylamino7acetophenone and sodium borohydride in 80 % methanol.

IR spectrum (methylene chloride): OH 3590 cm NH2 3400 + 3490 cm"1 N-alkyl 2800 cm"1 0CH3 2830 cm"1 aliphat. CH2 2850 + 2930 cm"1 C5N 2210 cm"1 C=C 1635 cm"1 UV spectrum (ethanol): A max. 241 nm (0.27) 280 nm (0.07) 322 nm (0.14).

Example 104 1 - (4-Acetamino-3^bromo-phenyl )-2-/!?- (4-methoxy-phenyl) -butyl/-methvlamino7ethanol Prepared analogously to Example 1 from 4'-acetamino-31-bromo-(4-methoxy-phenyl) -butyl7methylamino7 ac etophenone and sodium borohydride in 80 % methanol.

IR spectrum (methylene chloride): OH 3590 cm NH2 3410 cm"1 N-alkyl 2800 cm"1 0CH3 2830 cm"1 aliphat. CH9 2850 + 2930 cm"1 — 1 aromat. C«C 1610 cm C-0 1700 cm"1 amide II 1510 cm"1 "" ' 199215 Racemates A and B of 1-(4-amino-3,5-dichloro-phenyl)-2-/Ii-/5-(4-hvdroxv-phenvl)-1-methvl-propvl7methvlamlno7ethanol 36 g of 1-(4-amino-3,5-dichloro-phenyl)-2-/?f-/5-(4-hydroxy-5 phenyl)-1-methyl-propyl7methylamino7ethanol (1:1 mixture of the diastereoisomeric racemates A and B) were dissolved in ether and reacted with 0.5 equivalents of 3 ,N hydrogen chloride in ether. The crude crystalline product of the hydrochloride of the racemate.A thus obtained was recrystallized 10 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 (decomp.). 13C-NMR spectrum of the base (CDCl^/CD^OD): ch3 -CH2-CH2-CH- 37.50 ppm CH, t 3 -CHo-CH^-CH- 58.36 ppm ^CH-CH, 13.91 ppm :N-CH3 36.33 ppm ^>N-CH2- 61.03 ppm OH -CH- 68.89 ppm The isoprepanolic mother liquor was evaporated and distributed between ether and 2 n ammonia. The evaporation residue of the 25 dried organic phase was separated by means of HPLC, the racemate A being retained, to isolate the racemate B (SiC^ 60; Merck; • 76 9 9921 5 0.015 - 0.025 mm; ether : methanol » 10 :1). The crystalline evaporation residue was recrystallized from a quantity of ether by concentrating at boiling temperatures.

M.p.: 128 - 131°C. 13C-NMR spectrum (CDClj/CD^OD): .61 ppm 59.21 ppm 14.56 ppm 35.03 ppm « 63.11 ppm OH -CH- 69.08 ppm Example 106 1-(4-Amino-3-bromo-5-cyano-phenyl)-2-/N-/5-(4-methoxy-phenyl) butvl7benzvlamlno7ethanol hydrochloride Prepared analogously to Example 1 from 4'-amino-3'-bromo-5'-cyano- 2-4T-tfE- (4-methoxy-phenyl)-butyl7benzylamin£7 acetophenone and sodium borohydride in 90 % methanol.

M.p. of the hydrochlorides 122 - 126°C. ch3 -ch2-ch2-ch- ch3 -ch2-ch2-ch- :CH-CH :n-ch, n-ch2- ► 7 199215 Example 1Q7 1-(4-Amino-3-bromo-5-cyano-phenyl)-2-/N-/5-(4-methoxy-phenyl)-butvl7allylamino7ethanol Prepared analogously to Example 1 from 41-amino-3'-bromo-5'-cyano-2-/N-/Ji- ( 4-methoxy-phenyl) -butyl/allylamino7acetophenone and sodium borohydride in 90 % methanol. Resin.

IR spectrum (methylene chloride): NH2 3390 + 3490 cm OCHj 2830 + 2940 cm"1 CN 2210 cm"1 aromat. C=C 1610 cm UV spectrum (ethanol): *X max. 223 nm (0.43) 244 nm (shoulder, broad; 0.07) 330 nm (broad; 0.05) Example 108 1-(4-Amino-3-bromo-5-cyano-phenyl)-2-/N-/5-(4-methoxy-phenyl)-butyl7lsopropylamino7ethanol hydrochloride Prepared analogously to Example 1 from 41-amino-3'-bromo-5 • -cyano-2-/N-/£- (4-methoxy-phenyl )-butyl/i sopropylamino/-acetophenone and sodium borohydride in 90 % methanol.

M.p. of the hydrochloride: sintering from 40°C.

Calc.: C 55.60 H 6.29 Br 16.20 CI 2.14 N 8.46 Found: 55.30 6.37 15.40 6.84 8.83 Example 109 1 - (4-Amino-3-bromo-5-cyano-phenyl )-2- J 99215 acetophenone and sodium borohydride in 90 % methanol.

M.p. of the hydrochloride: sintering from 40°C Calc.: C 55.60 H 6.29 N 8.46 Found: 55.52 6.32 8.39 Example 110 1-(4-Amino-3-bromo-5-cyano-phenyl)-2-/N-/5- (4-methoxy-phenyl)-butvl7ethylamino7ethano1 hydrochloride Prepared analogously to Example 1 from 4'-amino-3'-bromo-5 • -cyano-2-/Sr-/5- (4-methoxy-phenyl)-butyl7ethylamino7aceto-phenone and sodium borohydride in 90 96 methanol.

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

Example 111 1-(4-Amino-3-bromo-5-trifluoromethyl-phenyl)-2- M.p. of the hydrochloride: 153 - 155°C.

Example 113 1-(4-Amino-3-cyano-5-fluoro-phenyl)-2-/IT-/2-(4-methoxy-phenyl)-ethyl7methylamino7ethanol hydrochloride Prepared analogously to Example 1 from 4'-amino-3'-cyano- '-fluoro-2-/N-/2-(4-methoxy-phenyl)-ethyl/methylamino/aceto- phenone and sodium borohydride in 90 % methanol.

M.p. of the hydrochloride: sintering from 68°C.

Calc.: C 60.10 ' H 6.12 CI 9.35 N 11.05 Found: 59.91 6.07 9.40 10.69 Example 114 1-(4-Amino-3 * 5-dichloro-phenyl)-2-/H-(3-phenylsulfenyl-propyl)-methvlamino7ethanol Prepared analogously to Example 2 from 4•-amino-2-bromo-3'» 5'-dichloro-acetophenone, N-/5-(4-methoxy-phenylsulfenyl)-propyl7-methylamine, and sodium borohydride in 80 % methanol. Oil. IR spectrum (methylene chloride): NHg 3390 + 3490 cm~ OH 3600 + 3680 cm"1 UV spectrum (ethanol): 'X max. 246 nm (0.18) 300 nm (0.05) 4992 1 5 Example 115 1-(4-Amino-3,5-dichloro-phenyl)-2-/N-/5-(4-hydroxy-phenyl)-propyl7amino7ethanol Prepared analogously to Example 3 from 4'-amino-31,5'-dichloro- 2-/FT-/5-(4-hydroxy-phenyl)-propyl7amino7acetophenone and sodium borohydride in aqueous tetrahydrofuran. Oil.

IR spectrum (KBr): OH, NH« 3300 - 3600 cm-1 — 1 aromat. C=C 1615 cm UV spectrum (ethanol + KOH): "X max: 244 nm (0.26) 299 nm (0.08) Example 116 1 - (4-Amino-3,5-dichloro-phenyl)-2-/ff-/5- (4-chlorophenyl)-propyl7amino7ethanol Prepared analogously to Example 3 from 4*-amino-3',5'-dichloro-2-/fT-/5- (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-/5-(4-hydroxy-phenyl)- 1-methvl-propvl7isopropYlamino7ethano l Prepared analogously to Example 3 from 4'-aaino-3',5'-dichloro- 2-(4-hydroxy-phenyl) -1 -methyl-propyl/ isopropylamino/aceto phenone and sodium borohydride. Oil.

Calc.: C 61.31 H 6.86 CI 17.24 N 6.81 Found: 61.07 6.86 16.67 6.53 J 9921 5 Example 118 1-(4-Amino-3»5-dichloro-phenyl)-2-/N-/3-(4-hydroxy-phenyl)- 1-methvl-propyl7ethvlamino7ethano l Prepared analogously to Example 3 from 41-amino-3',51-dichloro- 2-3-D- (4-hydroxy-phenyl) -1 -methyl-propyl/ethylamino/aceto-phenone and sodium borohydride. Oil.

Calc.: C 60.45 H 6.60 CI 17.85 N 7.05 Found: 60.45 6.76 17.70 6.86 Example 119 1-(4-Methylamino-3,5-dichloro-phenyl)-2-/N-/3-(4-hydroxy-phenvl) -1 -methyl-propyl7methvlamino7ethanol Prepared analogously to Example 3 from 4'-methylamino-3'» 5'-dichloro-2-/N-/3-(4-hydroxy-phenyl)-1-methyl-propyl.7-methylamino7acetophenone and sodium borohydride. Oil.

Calc.: C 60.45 H 6.60 CI 17.85 N 7.05 Found: 60.68 6.73 17.50 6.71 Example 120 1-(4-Dimethylamino-3»5-dichloro-phenyl)-2-/51-/3-(4-hydroxy-phenvl) -1 -methyl-propvl7methvlamino7ethanol Prepared analogously to Example 3 from 4,-dimethylamino-31» 5'-dichloro-2-/N-/3-(4-hydroxy-phenyl)-1-methyl-propyl7-methyl-amino/acetophenone and sodium borohydride. Oil.

Calc.: C 61.31 H 6.86 CI 17.24 N 6.81 Found: 61.28 6.57 16.80 6.42 | • " " - 82 - Example 121 199215 1-(4-Acetylamino-3,5-dichloro-phenyl)-2-/N-/5-(4-hydroxy-phenyl )-1-methvl-propyl7methvlamino7ethanol Prepared analogously to Example 3 from 41-acetylamino-31» 5' -dichloro-2-/N-/5- (4-hydroxy-phenyl) -1 -methyl-propyl7-methylamino7acetophenone and sodium borohydride. Foam. ••1 IR spectrum (methylene chloride): OH 3580 cm NH 3410 cm"1 N-alkyl 2800 cm"1 C=0 1700 cm"1 C=C 1610, 1595 cm Amide II 1515 cm"1 UV spectrum (ethanol): max. 230 nm (0.30; shoulder) 280 nm (0.04) (Ethanol + K0H): ^ max. 243 nm (0.46) 294 nm (0.08) Example 122 -1 1 - (4-Ethoxycarbonylamino-3.5-dichloro-phenyl)-2-/N-/5- (4-hydroxy-phenyl)-1-methyl-propyl7methylamino7ethanol Prepared analogously to Example 3 from 4'-ethoxycarbonylamino-3', 5'-dichloro-2-/N-/5- (4-hydroxy-phenyl )-1 -methyl-propyl7-methylamino7acetophenone and sodium borohydride. Oil.

Calc.: C 58.02 H 6.20 CI 15.57 N 6.15 Found: 58.20 6.32 15.32 6.03 0 83 d 992 1 5 Example 123 Racemates A and B of 1-(4-amino-3-cyano-5-fluoro-phenyl)-2-/N-/T-methyl-3-(4-hvdroxv-phenvl)-propyl7met.hyiflmino7ethanol Prepared analogously to Example 3 from 4,-amino-3'-cyano-5 5'-fluoro-2-/ff-/T-methyl-3-(4-hydroxy-phenyl)-propyl7methyl-amino7acetophenone and sodium borohydride. The obtained mixture of the diastereoisomeric racemates was separated by means of column chromatography (Si02; methylene chloride : methanol : conc. ammonia =50 : 1 : 0.1).

Racemate A: M.p.: 161 - 163°C ^3r>_WMD C-NMR spectrum (dg-dimethylsulfoxide): ch3 -ch2-ch2-ch- 37.17 ppm ch3 -ch2-ch2-ch- 57.91 ppm > ch-ch3 13.26 ppm .74 ppm > n-ch2 60.90 ppm oh -ch - 69.21 ppm J 99215 Racemate B: M.p.: 92 - 98°C 15 C-NMR spectrum (d^-dimethylsulfoxide): CHj -ch2-ch2-ch- ch3 -ch2-ch2-ch- >ch-ch, > n-ch, oh —ch- 36.52 ppm 57.78 ppm 13.19 ppm 61.48 ppm 69.02 ppm Example 124 1-(4-Amino-3-cyano-5-fluoro-phenyl)-2-/ffl-/T-methyl-3-(4-meth-oxv-phenvl) -propyl7amino7ethanol ■ Prepared analogously to Example 3 from 41-amino-3'-cyano-51 -fluoro-2-/N-/T-methyl-3- ( 4-methoxy-phenyl) -propyl/amino/-acetophenone and sodium borohydride.

M.p.: 108 - 110°C.

J 992 1 5 Example 125 1-(4-Amino-3-cyano-5-fluoro-phenyl)-2-i/i7-/T-methyl-3-(4-hydroxy-phenvl)-propyl7amino7ethanol Prepared analogously to Example 3 from 4'-amino-31-cyano-5' -f luoro-2-/il-/T-methyl-3- (4-hydroxy-phenyl) -propyl7amino7-acetophenone and sodium borohydride.

M.p.: 162 - 164°C.

Example 126 1 - (4-Amino-3-cyano-5-f luoro-phenyl)-2-/H-/T-methyl-3-(4-aeth-^LO oxv-phenvl)-propvl7methylamino7ethanol Prepared analogously to Example 4 from 1-(4-amino-3-cyano-5-fluoro-phenyl)-2-/R-/T-methyl-3-(4-hydroxy-phenyl)-propyl7-methylamino7ethano1 and dimethylsulfate/1 N sodium hydroxide solution in tetrahydrofuran. Oil.

IR spectrum (methylene'chloride): NHg 3400 + 3500 cm"1 0-CHj 2830 cm"1 N-alkyl 2800 cm"1 CSN 2210 cm"1 C-C 1580, 1510 cm"1 C=C + NH2 deformation 1620 cm"1 UV spectrum (ethanol): A max. 242 nm (0.27) 278 nm (0.05) 286 nm (0.05) 324 nm (0.12) Example 127 1-(4-Amino-3,5-dichloro-phenyl)-2-/N-(1-methyl-2-phenoxy ethyl)-amino7ethanol hydrochloride Prepared analogously to Example 5 from 4-amino-3\5-dichlfiro-5 acetophenone, selenium dioxide, 1-methyl-2-phenoxy-ethylflmine, 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) -1 ic Example 128 1-(4-Amino-3,5-dichloro-phenyl)-2-/N-/5-(4-fluoro-phenyl)-propyl7amino7ethanol hydrochloride , \ Prepared analogously to Example 5 from 4-amino-3\5-dichlo|*o-aceto-phenone, selenium dioxide, 3-(4-fluoro-phenyl)-propylamine, .and 15 sodium borohydride.

M.p. of the hydrochloride: 185 - 187°C (decomp.). ' / Example 129 1 - (4-Amino-3,5-dichloro-phenyl )-2-/fT- (3-phenyl-1 -methyl-propyl)-methyl amino7ethanol , ^ . •20 Prepared analogously to Example 5 from 4'-amino-3',5'-diohloro- acetophenone, selenium dioxide, 3-phenyl-1-methyl-propylamine, and sodium borohydride. Oil.

IR spectrum (methylene chloride): NHg 3390 + 3+90 cm OH 3600 + 3^80 cm uv spectrum (ethanol): X max. 245 nm (0.18) 300 nm (0.06) -1 -1 199215 Example 130 1-(4-Amino-3,5-dichloro-phenyl)(1-methyl-2-phenoxy-ethyl)-amino7ethano1 hydrochloride Prepared analogously to Example 5 from 4-amino-31,5Ldichloro-acetophenone, selenium dioxide, 1-methyl-2-phenoxy-ethylamine, and sodium borohydride.

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

Example 131 N-/3- (4-Amino-3-bromo-phenyl)-propyl7-N-/2- (3, 4-dimethoxy-phenyl)-ethyl7methylamlne hydrochloride Prepared analogously to Example 7 from N-methyl-H-/2-(3»4-di-methoxy-phenyl)-ethyl7-3-(4-amino-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): A 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-phenyl-propyl)-isopropylamine Prepared analogously to Example 7 from 4-amino-3»5-dichloro-N-i sopropyl-N-(1-methyl-3-phenyl-propyl)-phenylacet amide and lithium aluminium hydride in tetrahydrofuran. Oil.

IR spectrum (methylene chloride): NH2 3390 + 3490 cm"1 UV spectrum (ethanol): A 241 nm (0.15) 300 nm (0.03) Example 133 *1992 1 5 N-/2-(4-Amino-3»5-dichloro-phenyl)-ethyl7-N-(1-methyl-3-phenyl-propyl)-isopropylamlne Prepared analogously to Example 7 from 4-amino-3,5-dichloro- N-isopropyl-N-(1-methyl-3-phenyl-propyl)-phenylacetamide and lithium aluminiurahydride in tetrahydrofuran. Oil.

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

Example 134 N-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl7-3-(4-fluoro-phenyl)-propylamine hydrochloride Prepared analogously to Example 7 from 4-amino-3»5^dichloro-N-/3- (4-fluoro-phenyl)-propyl/phenylacetamide and lithium aluminium . hydride in tetrahydrofuran.

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

Example 135 N-[ji- (4-Amino-3,5-dichloro-phenyl) -ethyl7-N- (1 -methyl-3-phenyl-propyl)-methylamine Prepared analogously to Example 7 from 4-amino-3,5-dichloro-N-(1-methyl-3-phenyl-propyl)-phenylacetamide and lithium aluminium hydride in tetrahydrofuran. Oil.

IR spectrum (methylene chloride): NHg 3390 + 3490 cm"*1 UV spectrum (ethanol): A max. 243 nm (0.14) 300 nm (0.05) 499215 Example 136 N-/2-(4-Amino-3»5-dichloro-phenyl)-ethyl/-N-/5-(4-methoxy-phenvl-sulfenvl)-propyl7methvlamine Prepared analogously to Example 7 from 4-amino-3,5-dichloro-5 N-/J-(4-methoxy-phenylsulfenyl)-propyl/-N-methyl-phenylacet- amide and lithium aluminium hydride in tetrahydrofuran oil. IR spectrum (methylene chloride): NH2 3390 + 3490 cm"1 UV spectrum (ethanol): X max. 245- nm (0.16) 300 nm (0.04) Example 137 N-/2- (4-Amino-3-bromo-phenyl) - e thy 1/-N-/7- (4-methoxy-phenyl) -butvl7methylamins - Prepared analogously to Example 8 from 4-amino-3-bromo-N-/2-(4-methoxy-;phenyl)-butyl7-N-methyl-phenylacetamide 15 and lithium aluminium hydride in absolute tetrahydrofuran.

IR spectrum (methylene chloride): NH2 3380 + 3470 cm 0CH, 2830 + 2930 cm"1 3 —1 aromat. C«C 1620 cm NMR spectrum (CDC13/D20): aromat. H 6.4-7.3 ppm (m, 7H) 0CH3 3.7 ppm (s, 3H) NCH3 2.2 ppm (s, 3H) aliph. H 1.3-2.8 ppm (m, 8H) Example 138 N-/2-(4-Amino-3-bromo-phenyl)-ethyl/-N-/5-(4-methoxy-phenyl)- ethvl/methvlamine .

Prepared analogously to Example 8 from 4-amino-3-bromo-N-/5-(4-methoxy-phenyl)-ethyl/-N-methyl-phenylacetamide 199215 and lithium aluminium hydride in absolute tetrahydrofuran.

IR spectrum (methylene chloride): NH2 3380 +• 3480 cm OCH-z 2840 + 2940 cm'1 —1 aromat. C=C 1620 cm 5 UV spectrum (ethanol): 2 max. 224 nm (0.24) 242 nm (0.15) 280 nm (broad; 0.03) 300 nm (broad; 0.03) Example 139 N-/2- (4-Amino-3-fluoro-phenyl )-ethyl7-N-/5- (4-methoxy-phenyl) ■ propvl7methvlamine Prepared analogously to Example 8 from 4-amino-3-fluoro-N-jj>- (4-methoxy-phenyl )-propyl7-N-methyl-phenylacetamide and lithium aluminium hydride in absolute tetrahydrofuran.

Oil. 1 IR spectrum (methylene chloride): NH2 3390 + 3490 cm' . 0CH-, 2840 + -2940 cm"1 3 aromat. C=C 1610 cm UV spectrum (ethanol): A max. 227 nm (0.30) 2 0 279 nm (0.06) -1 285 nm (0.06) Example 140 N-/2-(4-Amino-3-chloro-phenyl)-ethyl7-N-/5-(4-methoxy-phenyl) ■ propyl7methvlamine Prepared analogously to Example 8 from 4-amino-3-chloro-N-methyl-N-/3-(4-methoxy-phenyl)-propyl7phenylacetamide and lithium aluminium hydride in absolute tetrahydrofuran. Resin.

J 99215 —-1 IR spectrum (methylene chloride): NHg 3390 + 3470 cm" OCH, 2840 + 2940 cm"1 J A aromat. C=C 1610 cm UV spectrum (ethanol); A max. 224 nm (0.25) 240 nm (0.18) 280 nm (0.04) 300 nm (0.03).

Example 141 N-/3- (4-Amino-3,5-dichloro-phenyl) -propyl7-N-/5- ( 4-m ethoxy-10 phenyl) -propylamine hydrochloride Prepared analogously to Example 8 from 3-(4-amino-3,5-dichloro-phenyl ) -N-/5- (4-methoxy-phenyl) -propyl/propion amide 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 )-propyl7-N-/2- (4-methoxy-phenyl)-ethyl7methylamlne dihydrochloride Prepared analogously to Example 8 from 3-(4-amino-3»5-dichloro-phenyl )-N-methyl-N-/2-(4-methoxy-phenyl)-ethyl7propionamide 2 0 and lithium aluminium hydride in absolute tetrahydrofuran.

• M.p. of the dihydrochloride: 147 - 157°C. - 92 - (199215 Example 145 N-/2-(4-Amino-3»5-dichloro-phenyl)-ethyl7-N-^f-(4-methoxy-phenyl ) -butvl7amlne hydrochloride Prepared analogously to Example 8 from N-/2-(4-amino-3»5-di-5 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-/5-(4-chloro-phenyl)-10 propylamine hydrochloride Prepared analogously to Example 8 from 4-amino-3,5-dichloro-N-/3-(4-chloro-phenyl)-propyl7pkenylacetamide 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-/7-(4-methoxy-phenyl)-butyl7isopropylamine Prepared analogously to Example 8 from N-/2-(4-amino-3,5-dichloro-phenyl )-ethyl7-N-isopropyl-4- (4-methoxy-phenyl ) -butyramide and lithium aluminium hydride in absolute tetrahydrofuran. Oil.

A IR spectrum (methylene chloride): NEL, 3390 + 3490 cm" OCH, 2850 + 2930 cm"1 3 A aromat. C«C 1610 cm 25 uv spectrum (ethanol): A max. 242 nm (0.12) 280 nm (shoulder; 0.04) 301 nm (0.04) Example 146 J 99215 N-/2- (4-Amino-3»5-dichloro-phenyl)-ethyl7-N-/2- (4-methoxy-phenyl )-ethyl7isopropvlamlne Prepared analogously to Example 8 from N-/2-(4-amino-3,5-di-chloro-phenyl)-ethyl7-N-isopropyl-4-methoxy-phenylacetamide and lithium aluminium hydride in absolute tetrahydrofuran. Oil . _ -4 IR spectrum (methylene chloride): NHg 3390 + 3490 cm OCH, 2830 + 2960 cm~1 aromat. OC 1610 cm UV spectrum (ethanol): A max. 244 nm (shoulder;0.12) 280 nm (shoulder; 0.05) 301 nm (0.05) Example 147 N-/2- (4- Amino-3,5-dichloro-phenyl )-ethyl7-N-/2- (4-methoxy-phenvl)-ethyl7amine hydrochloride Prepared analogously to Example 8 from 4-amino-3,5-dichloro-N-/2-(4-methoxy-phenyl) -ethyl/phenylacetamide and lithium aluminium hydride in absolute tetrahydrofuran.

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

Example 148 N-/3- (4-Amino-3,5-dibromo-phenyl) -propyl7~N-/2- (3»4-dimethoxy-phenyl)-ethyl7methylamine Prepared analogously to Example 8 from N-methylr-N-/2-(3,4-di-methoxy-phenyl) -ethyl/-3- (4-amino-3,5-dibromo-phenyl )-propion?mide and lithium aluminium hydride in absolute tetrahydrofuran. Oil. - 94 -■ 199215 IR spectrum (methylene chloride): NHg 3480 + 3380 cm -1 -1 0CH3 2840 + 2940 cm NMR spectrum (CDCl^/DgO): 0-CH^ 4.85 ppm (s, 6H) N-CH3 2.25 ppm (s, 3H) aromat. H 6.75 ppm (d, 3H) 7.2 ppm (s, 2H) aliphat. H 1.5-2,9 ppm (m, 12H) Example 149 N-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl7-3-phenyl-propylam in e hydrochloride Prepared analogously to Example 8 from 4-amino-3»5-dichloro-N-(3-phenyl-propyl)-phenylacetamide and lithium aluminium hydride in tetrahydrofuran.

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

Example 150 N-/2-(4-Amino-3-bromo-5-cyano-phenyl)-ethyl7-N-]]+-(4-methoxy-phenyl) -butyl7benzvl amine Prepared analogously to Example 9 from 1-ethoxycarbonyloxy-1-(4-amino-3-bromo-5-cyano-phenyl)-2-(4-methoxy-phenyl)-butyl7benzylamino7ethane and sodium borohydride in isopropanol. Oil. — 1 IR spectrum (methylene chloride): NH2 3390 + 3490 cm 0CH3 2830 + 2930 cm"1 CN 2210 cm"1 aromat. C=C 1620 cm UV spectrum (ethanol): A max. 222 nm (0.42) 244 nm (shoulder; 0.09) 335 nn (broad; 0.05) 49921 5 Example 151 N-/2- (4-Amino-3-bromo-5-cyano-phenyl )-ethyl7-N-/£- (4-methoxy- phenyl ) -butvl7allylamine Prepared analogously to Example 9 from 1-ethoxycarbonyloxy- 1 - (4-amino-3-bromo-5-cyano-phenyl (4-methoxy-phenyl)- butyl/allylamino/ethane and sodium borohydride in isopropanol.

Oil. , IR spectrum (methylene chloride): NH2 3390 + 3490 cm OCH^ 2830 + 2930 cm"1 CN 2210 cm"1 aromat. C=C 1620 cm"1 UV spectrum (ethanol): ^ max. 222 nm (0.49) 244 nm (shoulder; 0.1) 335 nm (broad; 0.06) Example 152 4* N-/2- (4-Amino-3-bromo-5-cyano-phenyl )-ethyl7-N-/£- (4-methoxy-phenyl)-butyl7ethvlamine Prepared analogously to Example 9 from 1-ethoxycarbonyloxy-1-(4-amino-3-bromo-5-cyano-phenyl) -2-/N-/5- (4-methoxy-phenyl) -butyl7ethylamino7ethane and sodium borohydride in isopropanol. Oil.

IR spectrum (methylene chloride): NH2 3390 + 3490 cm-1 0CH3 2830 + 2960 cm"1 CN 2210 cm"1 aromat. C=C 1620 cm UV spectrum (ethanol): A max. 222 nm (0.49) 244 nm (shoulder; 0.08) 333 nn (broad; 0.06) 199215 Example 155 N-/2- (4-Amino-5-bromo-5-cyano-phenyl )-ethyl7-N-/5- (4-methoxy-phertvl) -butvl7isopropvlamine Prepared analogously to Example 9 from 1-ethoxycarbonyloxy-5 1_(4-amino-5-bromo-5-cyano-phenyl) -2-/N-(4-methoxy-phenyl)-butyl/isopropylamino/ethane and sodium borohydride in isopropanol. Resin.

* IR spectrum (methylene chloride); NH2 3390 + 3490 cm 0CH3 2830 + 2960 cm"1 CN 2210 cm"1 aromat. C=C 1620 cm"1 UV spectrum (ethanol): A max. 221 nm (0.53) 244 nm (shoulder; 0.1) 330 nm (broad; 0.07) Example 154 N-/2-(4-Amino-3-bromo-5-cyano-phenyl)-ethyl7-N-/£-(4-methoxy^ phenyl)-butvl7-n-propylamine ~y Prepared analogously to Example 9 from 1-ethoxycarbonyloxy-1-(4-amino-3-bromo-5-cyano-phenyl)-2-/H- fU-(4-mesfchoxy-phenyl)-2 0 butyl7-n-propylamino7ethane and sodium borohydride in isopropanol. Oil. _ A IR spectrum (methylene chloride): NH2 3390 + 3490 cm" CN 2210 cm"1 OCH, 2830 + 2950 cm"1 * -1 aromat. C=C 1620 cm UV spectrum (ethanol): A max. 222 nm (0.46) 244 nm (shoulder; 0.08) 330 nm (broad; 0.05) Example 155 4992 1 5 N-/2-(4-Amino-3-bromo-5-cyano-phenyl)-ethyl7-N-(4-phenyl-butvl) -methvlamine Prepared analogously to Example 9 from 1-ethoxycarbonyloxy-1 - (4-amino-3-bromo-5-cyano-phenyl )-2-/8F- (4-phenyl-butyl)-methylamino/ethane and sodium borohydride in isopropanol. Oil. NMR spectrum (CDCl^): aromat. H 7.0 - 7.4 ppm (m, 7H) NCH3 2.2 ppm (s, 3H) aliphat. H 1.3 - 2.7 ppm (m, 12H) Example 156 N-/2-(4-Amino-3-cyano-5-fluoro-phenyl)-ethyl7-N-/£-(4-meth-oxv-phenyl )-ethyl7methylamine Prepared analogously to Example 9 from 1-ethoxycarbonyloxy-1 - (4-amino-3-cyano-5-;f luoro-phenyl)-2-/H-/2- (4-methoxy-phenyl) -ethyl7methylamino7ethane said sodium borohydride in isopropanol. Oil. " NMR spectrum (CDCl^/CH^GD): aromat. H 6.7 - 7.2 ppm (m, 6H) 0CH3 3.75 ppm (s, 3H) NCH3 2.3 ppm (s, 3H) aliphat. H 2.4 - 2.7 ppm (m, 8H) Example 157 N-£1- (4-Amino-3-cyano-5-f luoro-phenyl) - ethyl/-N-(4-methoxy-phenyl)-propyl7methylamine hydrochloride Prepared analogously to Example 9 from 1-ethoxycarbonyloxy- 1 - (4-amino-3-cyano-5-f luoro-phenyl)-2-/TT-/5-(4-methoxy-phenyl)- propyl/methylamino/ethane and sodium borohydride in isopropanol. Hydrochloride as resin. 98 II9 92 1 5 NMR spectrum (CDCl^): aromat. H nrw 6.7 - 7;2 ppm (m, 6H) 3.75 ppm (s, 3H) 2.8 ppm (s, 3H) 1.5 - 3.5 ppm (m» 10H) aliphat. H Example 158 N-/2-(4-Amino-3-cyano-5-fluoro-phenyl)-ethyl7-N-/5-(4-methoxy-phenyl)-butyl7methylamine Prepared analogously to Example 9 from 1-ethoxycarbonyloxy-1 - (4-amino-3-cyano-5-f luoro-phenyl)-2-/!f-/?f-(4-methoxy-phenyl)-butyl/methylamino/ethane and sodium borohydride in isopropanol. Resin.

NMR spectrum (CDC13/D20): aromat. H 7.2 ppm (s, 2H) Example 159 N-/2-(4-Amino-3-chloro-5-trifluoromethyl-phenyl)-ethyl7-N-/5-(4-methoxy-phenyl)-butyl7methylamine Prepared analogously to Example 9 from 1-ethoxycarbonyloxy-1 - (4-amino-3-chloro-5-trif luoromethyl-phenyl)-2-/N-/£- (4-meth oxy-phenyl)-butyl7methylamino7ethane and sodium borohydride in isopropanol. och3 nch3 6.85 ppm (q, 4H) 3.8 ppm (s, 3H) 2.25 ppm (s, 3H) aliphat. H 1.5 - 2.7 ppm *(m,'12H) M.p.: 29°C 499215 Example 160 N-/3s?-(4-Amino-3-chloro-5-trifluoromethyl-phenyl)-ethyl7-N-/2-(4-methoxy-phenyl)-ethvl7methvlamine Prepared analogously to Example 9 from 1-ethoxycarbonyloxy-1- (4-amino-3-chloro-5-trif luoromethyl-phenyl )-2-/!I-/2r- (4-meth-oxy-phenyl)-ethyl7n»ethylamino7ethane and sodium borohydride in isopropanol. Resin. — 1 IR spectrum (methylene chloride): NH2 3400 + 3500 cm OCH, 2840 + 2960 cm"1 -1 aromat. C»C 1610 cm UV spectrum (ethanol): A max. 228 nm (shoulder; 0.10) 244 nm (0.10) 310 nm (0.03) Example 161 N-/21- (4-Ami'no-3,5-dichloro-phenyl )-ethyl7-N-/5- (4-f luoro-phenyl )-propyl7methvlamine Prepared analogously to Example 9 from 1-ethoxycarbonyloxy-1 - (4-amino-3 > 5-dichloro-phenyl) -2- /3- (4-f luoro-phenyl) -propyl7-methylamino7ethane and sodium borohydride in isopropanol. Oil. IR spectrum (methylene chloride): NH2 3390 + 3490 cm" UV spectrum (ethanol): A max. 243 nm (0.13) 300 nm (0.03) Example 162 1-(4-Amino-3-trifluoromethyl-phenyl)-2-/N-/5-(4-methoxy-phenyl)-propyl7methylamino7ethanol Prepared analogously to Example 11 from 1-(4-amino-3-bromo-5-tri-fluoromethylphenyl)-2-/N-/3-(4-methoxy-phenyl)-propyl/methyl-amino/ethanol and hydrogen in the presence of palladium oxide J 9 92 1 5 on barium sulfate in methanol. Oil. NMR spectrum (CDCl^/^O): aromat. H 6.6 - 7.3 ppm (m, 7H) ch-oh och3 nch3 4.5 ppm (t, 1H) 3.7 ppm (s, 3H) 2.3 ppm (s, 3H) aliphat. h -ch2- 2.2 - 2.7 ppm (m, 6H) 1.8 ppm (q, 2H) Example 163 N-/3-(4-Acetamino-3,5-dichloro-phenyl)-propyl7-N-/2-(3»4-di-10 methoxv-phenyl)-ethyl7methylamine Prepared analogously to Example 12 from N-/3-(4-amino-3,5-dichloro phenyl)-propyl7-N-/2-(3»4-dimethoxy-phenyl)-ethyl7methylamine, acetyl chloride and trie thy lairrine in toluene. Oil. — 1 IR spectrum (methylene chloride): NH 3405 cm Example 164 2 0 1-(4-Amino-3,5-dichloro-phenyl)-2-/H-/5-(4-hydroxy-phenyl)-1 -methvl-propyl7allvlamino7 ethanol .

Prepared analogously to Example 13 from 1-(4-amino-3»5-di-chloro-phenyl)-2-/N-/3-(4-hydroxy-phenyl)-1-methyl-propyl/-amino7ethanol with allyl bromide/sodium carbonate in absolute 25 ethanol. Oil. — 1 IR spectrum (methylene chloride): OH 3580 cm 0ch3 co 2830 + 2940 cm"1 1700 cm"1 UV spectrum (ethanol: A max. 228 nm (shoulder; 0.17) 280 nm (0.04) nh2 aliphat. CH2 C=C 3390 + 3480 cm"1 1850 ♦. 2930 cm"1 1615 cm"1 101 + ,199215 UV spectrum (ethanol): /I max. 243 nm (0.26) 282 nm (0.08) 300 nm (0.08) (Ethanol + KOH): A max. 242 nm (0.47) 298 nm (0.19) Example 165 1-(4-Amino-3,5-dichloro-phenyl)-2-(4-hydroxy-phenyl)-propyl7i sopropy!amlno7ethano1 hydrochloride Prepared analogously to Example 16 from 1-(4-amino-3»5-di- chloro-phenyl)-2-/lJ-/5-(4-benzyloxy-phenyl)-propyl7isopropyl- amino/ethanol and hydrogen in the presence of palladium on charcoal. m.p. of the hydrochloride: 90 - 110°C.

Example 166 1 - (4-Amino-3-chloro-phenyl )-2-/H-/3- (4-hydroxy-phenyl)—propyl/ -ethYlamlno7ethanol Prepared analogously to Example 16 from 1-(4-amino-3,5-dichloro-phenyl ) -2-/N-/3- (4-benzyloxy-phenyl) -propyl7ethylamino7 ethanol and hydrogen in the presence of palladium on charcoal. Resin. 20 IR spectrum (methylene chloride): OH 3595 cm nh2 aliphat. CH2 C=C 3400 + 3490 cm-1 2840 + 2940 cm"1 1625 cm"1 UV spectrum (ethanol): A max. 227 nm (0.19) 244 nm (0.17) 290 nm (0.04) (Ethanol + KOH): A max. 243 nm (0.32) 297 nm (0.08) _ , 1fi7 4992 1 5 Example 167 1-(4-Amino-3»5-dichloro-phenyl) -2-/N-(4-hydroxy-phenyl)-propvl7ethylamino7ftthannl Prepared analogously to Example 16 from 1-(4-amino-3,5-dichloro- phenyl)-2-/5T-/3-(4-benzyloxy-phenyl)-propyl/ethylamino/ethanol and hydrogen in the presence of palladium on charcoal. Resin.

IR spectrum (methylene chloride): OH 3590, 3620 + 3680 cm"1 NH0 3390 + 3480 cm"1 — 1 aromat. C=C 1615 cm 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) 15 298 nm (0.08) Example 168 N-/3-(4-Dimethylamino-3,5-dichloro-phenyl)-propyl7-N-/3- (4-methoxy-phenyl)-propyl7methylamine Prepared analogously to Example 101 from N-/3-(4-amino-3,5-di-20 chloro-phenyl)-propyl7-N-/3-(4-methoxy-phenyl)-propyl/amine, paraformaldehyde and sodium cyanoborohydride in ethanol. Oil. IR spectrum (methylene chloride): OCH^ 2830 + 2940 cm NCH, 2790 cm"1 nh2 aromat. C=C 1610 cm"1 NMR spectrum (CDCl^/DgO): aromat. H 7.0 ppm (q, 4H) 7.1 ppm (s, 2H) 0CH3 3.75 ppm (s, 3H) N(CH3)2 2.85 ppm (s, 6H) aliphat. H 2.2 - 2.8 ppm (m,8H) N-CH3 2.2 ppm (s, 3H) -CH2- 1.6 - 1.8 ppm (q,4H) Example 169 - 1Q3 - 199215 N-/J- (4-Amino-3,5-dichloro-phenyl) -propyl/-N-/5- (4-methoxy-phenvl)-propvl/methvlamine Prepared analogously to Example 101 from N-/5-(4-amino-3,5-di- chloro-phenyl)-propyl/-N-/J- (4-methoxy-phenyl) -propyl/amine, paraformaldehyde and sodium cyanoborohydride in ethanol. Oil.

IR spectrum (methylene chloride): NH2 3390 + 3490 cm" OCH, 2830 + 2940 cm"1 A aromat. C=C 1610 cm UV spectrum (ethanol): \ max. 230 nm (shoulder; 0.21) 242 nm (0.10) 278 + 285 (broad; 0.03) 302 nm (broad; 0.03) Example 170 N- /2-(4-Dimethylamino-3,5-dichloro-phenyl)-ethyl/-N-/3-(4-chloro-phenvl)-propyl7methvlamine Prepared analogously to Example 101 from N-/^-(4-amino-3,5-di-chloro-phenyl)-ethyl/-N-/3-(4-chloro-phenyl)-propyl/amine, paraformaldehyde and sodium cyanoborohydride in ethanol. Oil. _ A IR spectrum (methylene chloride): NCH^ 2790 cm nh2 nh UV spectrum (ethanol): \ max. 273 nm (broad; 0.04) 199215 Example 171 N-/2-(4-Amino-3»5-dichloro-phenyl)-ethyl7-N-/5-(4-chloro-phenyl )-propyl7-2-phenvlethylamine hydrochloride Prepared analogously to Example 101 from N-/2-(4-amino-3 > 5-di-5 chloro-phenyl)-ethy 17-N-/5- (4-chloro-phenyl)-propyl/amine, phenylacetaldehyde and sodium cyanoborohydride in ethanol.

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

Example 172 N-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl7-N-/Zf-(4-methoxy-10 phenyl)-butvl7ethylamine Prepared analogously to Example 101 from N-/2-(4-amino-3»5-di-chloro-phenyl)-ethyl7-N-/5-(4-methoxy-phenyl)-butyl7amine, acetaldehyde and sodium cyanoborohydride in ethanol. Oil. IR spectrum (methylene chloride): OCH^ 2860 + 2930 cm" aromat. C«C 1610 cm~1 UV spectrum (ethanol): A max. 245 nm (0.09) 278 nm (0.02) 282 nm (0.02) 300 nm (0.01) Example 173 N-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl/-N-/3-(4-chloro-phenyl)-propylTbenzylamlne hydrochloride Prepared analogously to Example 101 from N-/2-(4-amino-3,5-dichloro-phenyl )-ethyl7-N-/3-(4-chloro-phenyl)-propylamine, benz-25 aldehyde and sodium cyanoborohydride in ethanol.

M.p. of the hydrochloride: 164 - 168°C. 199215 Example 174 N-/2-(4-Amino-3 >5-dichloro-phenyl)-ethyl7-N-/5-(4-chloro-phenvl )-propyl7isopropylamine ■ Prepared analogously to Example 101 from N-/2-(4-amino-3,5-dichloro-phenyl)-ethyl7-N-/3-(4-chloro-phenyl)-propylamine, acetone and sodium cyanoborohydride in absolute methanol.

Oil.

IR spectrum (methylene chloride): NH0 3390 + 3480 cm <- A aromat. C»C 1615 cm UV spectrum (ethanol): A 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)-propylamine hydrochloride Prepared analogously to Example 101 from 1-(4'-amino-3'»5*-di-chloro-phenyl)-aoetone, 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)-ethyl7-N-/5-(4-chloro-phenyl)-propyl7-n-propylamine Prepared analogously to Example 101 from N-/2-(4-amino-3,5-di- chloro-phenyl)-ethyl7-N-/3-(4-chloro-phenyl)-propyl7amine, propionaldehyde and sodium cyanoborohydride in ethanol. Oil. — 1 IR spectrum (methylene chloride): NH 3380 + 3480 cm 2 aromat. C=C 1610 cm UV spectrum (ethanol): A max. 242 nm (0;13) 301 nm (0.05) - 106 - ^ ^ ^ — J 99215 Example 177 N-/2-(4-Amino-3»5-dichloro-phenyl)-ethyl7-N-/3-(4-chloro-phenyl)-propyl7ethvlamine Prepared analogously to Example 101 from N-/2-(4-amino-3,5-dichloro-phenyl )-ethyl7-N-/3-(4-chloro-phenyl)-propyl/amine, acetaldehyde and sodium cyanoborohydride in ethanol at pH 6 - 6.5.

Oil.

* IR spectrum (methylene chloride): NH0 3390 + 3480 cm _-i aromat. C=C 1615 cm UV spectrum (ethanol): A max. 242 nm (0.14) 305 nm (0.04) Example 178 N-/?-(4-Amino-3,5-dichloro-phenyl)-ethyl7-N-/2-(4-methoxy- phenyl)-ethYl7ethYlamine • * Prepared analogously to Example 101 from N-/?-(4-amino-3»5-dichloro-phenyl )-ethyl7-N-/2-(4-methoxy-phenyl)-ethyl/amine, acetaldehyde and sodium cyanoborohydride in ethanol. Oil. — 1 IR spectrum (methylene chloride): NHg 3890 + 3480 cm OCH, 2830 + 2940 cm"1 3 A aromat. C=C 1620 cm UV spectrum (ethanol): A max. 244 nm (0.16) 284 nm (shoulder; 0.04) 300 nm (0.04) Example 179 N-/T-Methyl-2-(4-amino-3,5-dichloro-phenyl)-ethyl7-N-/5-(4-meth-oxv-phenvl )-propyl7methylamine Prepared analogously to Example 101 from 1-(4'-amino-3',5'-dichloro-phenyl)-acetone, 3-(4-methoxy-phenyl)-N-methyl-propylamine and 1992 1 5 sodium cyanoborohydride in ethanol. Oil.

IR spectrum (methylene chloride): NHg 3390 + 3480 cm OCH, 2840 + 2940 cm"1 -1 aromat. C=C 1615 cm UV spectrum (ethanol): A max. 242 nm (0.14) 280 nm (shoulder; 0.04) 302 nm (0.05) Example 180 N-/2- (4- Amino-3 > 5-dichloro-phenyl)-ethyl7-N-(3-phenylpropyl)-isopropylamine hydrochloride Prepared analogously to Example 101 from N-/2-(4-amino-3,5-di-chloro-phenyl)-ethyl7-3-phenyl-propylamine, acetone, molecular sieve 3 & and sodium cyanoborohydride in absolute methanol. Foam. IR spectrum (methylene chloride): NH~ 3390 + 3490 cm NH^ 2300 - 2400 cm"1 UV spectrum (ethanol): A max. 245 nm (0.12) 302 nm (0.04) Example 181 1-(4-Amino-3,5-dichloro-phenyl)-2-/N-(1-methyl-3-phenyl-propyl) -methvlamino7ethanol hydrochloride Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro-phenyl )-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 cm"1 UV spectrum (ethanol): A max. 245 nm (0.12) 302 nm (0.03) J 9 92 1 5 Example 182 1-(4-Amino-3,5-dichloro-phenyl)-2-/N-(1-methyl-3-phenyl-propvl)-methvlamino7ethanol hydrochloride Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro-phenyl )-2-/I- (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-/N-(1-methyl-3-phenyl-propyl)-propylamlno/ethanol hydrochloride Prepared analogously to Example 101 from 1-(4-amino-3,5-di-chloro-phenyl)-2- /N-(1-methyl-3-phenyl-propyl)-amino/ethanol, propionaldehyde and sodium cyanoborohydride. Oily hydro-, chloride. _ A IR spectrum (methylene chloride): NHg 3390 + 3490 cm NH + 2300 - 2400 cm"1 OH 3590 + 3680 cm"1 UV spectrum (ethanol): A max. 245 nm (0.12) 302 nm (0.03) Example 184 N-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl/-N-(3-phenyl-propyl)-n-propylamine hydrochloride Prepared analogously to Example 101 from N-/2-(4-amino-3,5-di-chloro-phenyl)-ethyl/-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"1 OH 3600 + 3650 cm"1 109 1 992 1 5 UV spectrum (ethanol): A max. 245 nm (0.17) 302 nm (0.05) Example 185 N-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl/-N-(3-phenyl)-propyl)-ethyl amine hydrochloride Prepared analogously to Example 101 from N-/2-(4-amino-3,5-dichloro-phenyl )-ethyl/-3-phenyl-propylamine, acetaldehyde and sodium cyanoborohydride in absolute ethanol. Oily hydrochloride. _ A IR spectrum (methylene chloride): NH« 3390 + 3490 cm" NH^ 2300 - 2400 cm"1 UV spectrum (ethanol): "X max. 245 nm (0.12) 302 nm (0.04) Example 186 N-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl/-N-(1-methyl-3-phenyl-propyl)-ethylamine hydrochloride Prepared analogously to Example 101 from N-/2-(4-amino-3»5-di-chloro-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 UV spectrum (ethanol): ^ max. 243 nm (0.11) 300 nm (0.04) Example 187 1-(4-Amino-3,5-dichloro-phenyl)-2-/N-(1-methyl-2-phenoxy-ethyl)-ethylamino/ethanol hydrochloride Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro-phenyl )-2-/N-(1-methyl-2-phenoxy-ethyl)-amino/ethanol, acetalde- 11992 1 5 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): A max. 248 nm (0.12) 300 nm (0.03) Example 188 1-(4-Amino-3-cyano-5-fluoro-phenyl)-2-/N-/2-(3,4-dimethoxy- phenyl) -ethyl7ethvlamlno7ethanol Prepared analogously to Example 101 from 1-(4-amino-3-cyano-5-f luoro-phenyl) -2-/N-/2- (3,4-dimethoxy-phenyl) -ethyl7amino7-ethanol, acetaldehyde and sodium cyanoborohydride in ethanol. Oil.

IR spectrum (methylene chloride): NHg 3390 + 3490 cm ' CN 2205cm"1 UV spectrum (ethanol): /I max. 240 nm (shoulder; 0.16) 280 nm (0.04) 325 nm (0.06) 2 0 Example 189 1-(4-Amino-3-chloro-5-fluoro-phenyl)-2-/firJ2~(3,4-methylene-dioxy-phenoxv)-1-methyl-ethyl7ethylamino7ethanol hydrochloride Prepared analogously to Example 101 from 1-(4-amino-3-chloro-5-fluoro-phenyl)-2-/FT-/2-(3,4-methylenedioxy-phenoxy)-1-methyl-25 ethyl/affiino/^thanol, acetaldehyde and sodium cyanoborohydride in absolute ethanol. Oily hydrochloride.

- Ill - 499215 OH UV spectrum (ethanol): A max. 243 nm (0.17) 287 nm (0.07) IR spectrum (methylene chloride): NH 3390 + 3490 cm"1 2300 - 2450 cm"1 3600 + 3680 cm"1 Example 190 1-(4-Amino-3-bromo-5-fluoro-phenyl)-2-/H-(1-methyl-2-phenoxy-ethvl)-ethvlamino7ethanol Prepared analogously to Example 101 from 1-(4-amino-3-bromo-5-fluoro-phenyl)-2-/N-(1-methyl-2-phenoxy-ethyl)-amino7ethanol, acetaldehyde and sodium cyanoborohydride in absolute ethanol. Oil. — 1 IR spectrum (methylene chloride): NH2 3390 + 3490 cm" UV spectrum (ethanol): 3 max. 240 nm (0.14) 280 - 290 nm (0.03) Example 191 1-(4-Amino-3-cyano-5-fluoro-phenyl)-2-/N-(4-methoxy-phenyl)-propyl7ethvlamino7ethanol hydrochloride Prepared analogously to Example 101 from 1-(4-amino-3-cyano-5-f luoro-phenyl) -2-/N- Jj>- (4-methoxy-phenyl) -propyl/amino~J ethanol, acetaldehyde and sodium cyanoborohydride in absolute ethanol.

Oily hydrochloride. — 1 IR spectrum (methylene chloride)* w" 3390 + 3490 cm" 2300 - 2500 cm"1 2205 cm"1 3590 + 3680 cm"1 CN OH UV spectrum (ethanol): \ max. 248 nm (0.11) 280 nm (0.03) 320 nm (0.06) 199215 Example 192 N-/2- (4- Amino-3»5-dichloro-phenyl)-ethyl7-N-/5- (4-f luoro-phenvl)-propyl7benzylamlne hydrochloride Prepared analogously to Example 101 from N-/2-(4-amino-3,5-di-chloro-phenyl)-ethyl7-N-/5- (4-f luoro-phenyl) -propyl/amine, benzaldehyde and sodium cyanoborohydride in absolute ethanol.

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

Example 193 N-/2-(4-Amino-3,5-dichloro-phenyl )-ethyl7-N-/5-(4-f luoro-^.0 phenyl)-propvl7-n-propylamine hydrochloride Prepared analogously to Example 101 from N-/2-(4-amino-3,5-dichloro-phenyl )-ethyl7-N-/3- (4-f luoro-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-di-0 chloro-phenyl)-ethyl7-N-/3- (4-fluoro-phenyl)-propyl7amine, acetaldehyde, molecular sieve 3 & and sodium cyanoborohydride in absolute methanol.

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

Example 195 199215 N-/2-(4-Amino-3»5-dichloro-phenyl)-ethyl7-N-/3-(4-fluoro-phenvl)-propyl7isopropvl-eLmine hydrochloride Prepared analogously to Example 101 from N-/2-(4-amino-5 3,5-dichloro-phenyl) -ethyl7-N-/3- (4-f luoro-phenyl) -propylamine, acetone, molecular sieve 3 ft and sodium cyanoborohydride in absolute methanol.

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

! Example 196 1-(4-Amino-3,5-dichloro-phenyl)-2-/N-/5-(4-fluoro-phenyl)-propyl7-2-phenvlethvlamino7ethanol hydrochloride Prepared analogously to Example 101 from 1-(4-amino-3,5-di-chloro-phenyl)-2-/FT-/J-(4-fluoro-phenyl)-propyl/amino/ ethanol, phenylacetaldehyde and sodium cyanoborohydride in absolute 15 ethanol. Amorphous hydrochloride.

IR spectrum (methylene chloride): NH« 3390 + 3490 cm NH^ 2300 - 2500 cm"1 OH 3590 + 3680 cm"1 UV spectrum (ethanol): X max. 243 nm (0.11) 300 nm (0.04) Example 197 1-(4-Amino-3,5-dichloro-phenyl)-2-/N-/3-(4-fluoro-phenyl)-propyl7benzylamino7ethanol hydrochloride Prepared analogously to Example 101 from 1-(4-amino-3,5-di-25 chloro-phenyl)-2-/!T-/5-(4-fluoro-phenyl)-propyl7amino7ethanol, benzaldehyde and sodium cyanoborohydride in absolute ethanol. M.p. of the hydrochloride: 132 - 134°C (decomp.). it 992 1 5 Example 198 1-(4-Amino-3,5-dichloro-phenyl)-2-/N-/3-(4-fluoro-phenyl)-propvl7-n-propvlamino7ethanol hydrochloride Prepared analogously to Example 101 from 1-(4-amino-3»5-dichloro-phenyl ) -2-/N-/5- (4-f luoro-phenyl) -propyl/amino/ethanol, 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-/!T-/5- (4-fluoro-phenyl)-propyl7ethylamino7ethanol hydrochloride Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro-phenyl )-2-/ft-/3-(4-fluoro-phenyl)-propyl/amino/ethanol, 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-/!T- (3-phenyl-propyl )-2-phenyl-ethylamino7ethano1 hydrochloride Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro-phenyl )-2-/N-(3-phenyl-propyl)-amino/ethanol, phenylacetaldehyde and sodium cyanoborohydride in absolute ethanol. Amorphous hydrochloride.

IR spectrum (methylene chloride): NH« 3390 + 3490 cm NH 2300 - 2500 cm"1 OH 3590 + 3690 cm"1 UV spectrum (ethanol): max. 243 nm (0.12) 300 nm (0.04) Example 201 4992 1 1-(4-Amino-3>5-dichloro-phenyl)-2-/fT-/5- (4-fluoro-phenyl)-Propvl7isopropvlamlno7ethanol hydrochloride Prepared analogously to Example 101 from 1-(4-amino-3»5-di-chloro-phenyl) -2- /?- (4-f luoro-phenyl) -propyl/amino/ ethanol, acetone, molecular sieve 3 ft 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-phenyl-propyl)-ethvlamino7ethanol Prepared analogously to Example 101 from 1-(4-a»ino-3,5-di-chloro-phenyl)-2-/N-(1-methyl-3-phenyl-propyl)-amino/ethanol, acetaldehyde, molecular sieve 3 ft and sodium cyanoborohydride in absolute ethanol. Oil. i A IR spectrum (methylene chloride): NHg 3390 + 3490 cm UV spectrum (ethanol): ^ max. 245 nm (0.13) 300 nm (0.03) Example 203 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-di-chloro-phenyl)-2-/N-(3-phenyl-1-methyl-propyl)-amino/ethanol, formaldehyde and sodium cyanoborohydride in absolute ethanol. Oil.

^ A IR spectrum (methylene chloride): OH 3600 + 3680 cm" N-alkyl 2800 cm'1 UV spectrum (ethanol): \ max. 275 nm (0.03) u« * - 116 - J 992 1 5 Example 204 1 1-(4-Amino-3,5-dichloro-phenyl)-2-/fJ- (3-phenyl-propyl)-benzyl flmjno7ethanol Prepared analogously to Example 101 from 1-(4-amino-3,5-di-chloro-phenyl)-2-JJH-(3-phenyl-propyl)-amino7ethanol, benzaldehyde and sodium cyanoborohydride in absolute ethanol. Oil. _ A IR spectrum (methylene chloride): NH2 3390 + 3490 cm OH 3600 + 3680 cm"1 UV spectrum (ethanol): max. 245 nm (0.12) 300 nm (0.03) Example 205 1-(4-Amino-3,5-dichloro-phenyl)-2-/N-/5-(4-methylsulfinyl-phenyl)-propyl7amino7ethanol 1.5 g (0.0039 mol) of 1-(4-amino-3»5-dichloro-phenyl)-2-/^-/5-15 (4-methylsulfenylphenyl)-propyl/amino/ethanol and 639 mg (0.0078 mol) of anhydrous sodium acetate were dissolved in 60 ml of 50 % acetic acid. A solution of 622 mg (0.0039 mol) of bromine in 3 ml of 50 % acetic acid was dropped slowly into this solution whilst stirring at room temperature. When the addition was finished 2 0 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 sul-25 fate and in vacuo evaporated to dryness. The residue was recrystallized from methanol/ether. Colourless crystals.

M.p.: 127 - 129°C. 499215 Example 206 ^ 1 - (4-Amino-3,5-dichloro-phenyl )-2-/FT-/5- (4-methylsulfenyl-phenvl)-propyl7amino7ethanol Prepared analogously to Example 5 from 4'-amino-31,5'-dichloro-acetophenone, selenium dioxide, 3-(4-methylsulfenylphenyl)-propylamine and sodium borohydride.

M.p.: 128 - 130°C.

Example 207 1-(4-Amino-3,5-dichloro-phenyl)-2-/IT ~J3~(4-methylsulfinyl-phenyl)-propyl7methvlamino7ethanol Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro-phenyl ) -2-/N-/5- ( 4-methylsulf inyl-phenyl) -propyl/amino/-ethanol, paraformaldehyde and sodium cyanoborohydride in methanol. Foam.

IR spectrum (methylene chloride): OH 3660 + 3600 cm" NH2 3490 + 3390 cm"1 SO 1050 cm"1 UV spectrum (ethanol): % max. 242 nm (0.16) 300 nm (0.03) Example 208 1-(4-Amino-3,5-dichloro-phenyl)-2-/N-/5-(4-methylsulfenyl-phenyl)-propyl7methylamino7ethanol Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro-phenyl )-2-/N-/5- (4-methylsulf enyl-phenyl) -propyl/amino/ ethanol, paraformaldehyde and sodium cyanoborohydride in methanol. Colourless oil.

IR spectrum (methylene chloride): OH 3690 + 3590 cm" NH2 3490 + 3390 cm"1 1.99215 UV spectrum (ethanol): X max. 245 nm (0.23) 295 - 300 nm (0.04) Example 209 1-(4-Amino-3,5-dichloro-phenyl)-2-/N-/3-(4-chloro-phenyl)-propyl7-n-propylamlno7ethanol Prepared analogously to Example 101 from 1-(4-amino-3,5-di- chloro-phenyl) -2-/TT-/5- (4-chloro-phenyl) -propyl/amino/ethanol, propionaldehyde and sodium cyanoborohydride in ethanol. Oil.

IR spectrum (methylene chloride): NH« 3390, 3490 cm-1 —1 aromat. C=C 1620 cm UV spectrum (ethanol): 3 max. 243 nm (0.13) 300 nm (0.04) Example 210 1 - (4-Dimethylamino-3,5-dichloro-phenyl)-2-methyl-2-/!?-/^-(4-methoxy-phenyl)-propvl7methylamlno7ethanol Prepared analogously to Example 101 from 1-(4-amino-3>5-dichloro-phenyl )-2-methyl-2-(4-methoxy-phenyl)-propyl/amino/ethanol, paraformaldehyde and sodium cyanoborohydride in ethanol at pH 3 to 7.5. Oil.

IR spectrum (methylene chloride): OH 3590 cm no NH, NH2 aromat. C-C 1610 cm"1 UV spectrum (ethanol): X max. 243 nm (0.20) 278 nm (0.06) Example 211 199215 1 -(4-Benzylamino-3,5-dichloro-phenyl) -2-/fT- 0- (4-chloro-phenvl) -propyl7amino7ethanol - Prepared analogously to Example 101 from 1-(4-amino-3,5-di-5 chloro-phenyl)-2-/N-/3-(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-/IT-/5-(4-chloro-phenyl)-10 propyl7b enzyl amino7ethanol hvdro chl ori de Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro-phenyl ) -2-/ST-/3- (4-chloro-phenyl )-propyl7amino7ethanol, benzaldehyde and sodium cyanoborohydride in ethanol.

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

Example 213 1-(4-Amino-3,5-dichloro-phenyl)-2-/N- jj>-(4-chloro-phenyl)-propyl7ethylamino7e thano 1 Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro-phenyl) -2-/N-/3- (4-chloro-phenyl )propyl7amino7ethanol, acet-2 0 aldehyde and sodium cyanoborohydride in ethanol. Oil. < IR spectrum (methylene chloride): NHg aromat. C=C UV spectrum (ethanol): \ max. 244 nm (0.13) 300 nm (0.04) -1 ► 10 499215 Example 214 ~ N-/2- (4-Amino-3,5-dichloro-phenyl )-ethyl7-N-/3- (4-chloro-phenyl) -propyl7methvlamlne ■■ Prepared analogously to Example 101 from N-/2-(4-amino-3,5-di-chloro-phenyl)-3-(4-chloro-phenyl)-propylamine, paraformaldehyde and sodium cyanoborohydride in methanol. Oil.

IR spectrum (methylene chloride): NH« 3390, 3490 cm"1 -1 aromat. C=C 1615 cm UV spectrum (ethanol): ^ max. 241 nm (0.10) 300 nm (0.04) Example 215 1-(4-Amino-3,5-dichloro-phenyl)-2-/N- jj>-(4-chloro-phenyl)-propyl7-2-phenylethylamino7ethanol hydrochloride Prepared analogously to Example 101 from 1-.(4-amino-3»5-di-chloro-phenyl)-2-/N-/5-(4-chloro-phenyl)-propyl7amino7ethanol, 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-/fT-/5-(4-chloro-phenyl)-propyl7 methylamino7ethanol hydrochloride Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro-phenyl )-2-/FT-/5-(4-chloro-phenyl)-propyl/amino/ethanol, paraformaldehyde and sodium cyanoborohydride in ethanol.

M.p. of the hydrochloride: 85 - 100°C (decomp.). 199215 - 121 Example ^*7 1 - (3-Chloro-4-pi£^ridino-phenyl) -2-/N-/J- (4-meJ propyl7methvlamlno7^,tbanol hydrochloride roxy-phenyl) - Prepared analogously to Ex 2-ZH-Z5- (4-methoxy-phenyl)-pro sodium borohydride in methan IR spectrum (methylene 3'-chloro-4'-piperidino-thylamino7acetophenone and hydrochloride. 3600 cm" 2840 cm 2300 - 2700 cm -1 UV spectrum ( 2il Example 2AQ 1-(4-Amino-3,5-dichloro-phenyl)-2-/N-/5-(3-methoxy-phenyl)-propyl7amlno7e thano 1 Prepared analogously to Example 5 from 41-amino-3',5'-dichloro-acetophenone, selenium dioxide, 3-(3-methoxy-phenyl)-propylamine and sodium borohydride.

M.p.: 124°C. 21s Example 2^9 1-(4-Amino-3,5-dichloro-phenyl)-2-J3~J3~(3-methoxy-phenyl)-propyl7ethylamino7ethanol Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro-phenyl )-2-/N-f_3- (3-methoxy-phenyl) -propyl/amino/ethanol, acet-aldehyde and sodium cyanoborohydride in methanol. Oil. — 1 IR spectrum (methylene chloride): OH 3580 cm" NH2 3490 + 3390 cm"1 0CH3 2830 cm"1 J* I ?92l 5 UV spectrum (ethanol): /\ max. 247 nm (0.06) 300 nm (0.04) ai °\ Example 220 1-(4-Amino-3,5-dichloro-phenyl)-2-/N-/3-(3-methoxy-phenyl)-propyl7methylamlno7ethanol Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro-phenyl )-2-/N-/3-(3-methoxy-phenyl)-propyl/amino/ethanol, paraformaldehyde and sodium cyanoborohydride in methanol. Oil. — 1 IR spectrum (methylene chloride): OH 3680 + 3620 cm NH2 3490 + 3390 cm"1 OCH, 2840 cm"1 - 3 UV spectrum (ethanol): A max. 246 nm (0.15) 300 nm (0.04) TJlO Example ^2-g-f 1-(3,5-Dichloro-4-isopropylamino-phenyl)-2-/N-/3-(3-methoxy-phenyl) -propyl7isopropylamino7ethanol Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro-phenyl )-2-/N-/3-(3-methoxy-phenyl)-propyl7amino7ethanol, acetone and sodium cyanoborohydride in methanol. Oil.

IR spectrum (methylene chloride): OH 3600 cm" NH 3350 cm"1 0CH3 2840 cm"1 UV spectrum (ethanol): X max. 250 nm (0.12) 278 - 280 nm (0.03) 1992.15 123 - -a* Example 222" 1 - (4-Amino-3,5-dichloro-phenyl) -2-/N-0- ( 4-chlorophenyl) -propyl7isopropvlamlno7ethanol Prepared analogously to Example 101 from 1-(4-amino-3,5-dichloro-phenyl )-2-/N-/3-(4-chloro-phenyl)-propyl7amino7ethanol, acetone and sodium cyanoborohydride in ethanol. Oil. IR spectrum (methylene chloride): IfflL, aromat. C=C aromat. H 3380 + 3480 cm 1615 cm"1 -1 NMR spectrum (CDCI2/D2O): >ch-oh 7.0 - 7.4 ppm (m,6H) 4.4 ppm (dd;1H) 3.0 ppm (dd;1H) CH2 2.3 - 2.7 ppm (m;6H) 1.6 - 2.0 ppm (m;2H) isopropyl-CH^ 0.8 - 1.2 ppm (dd;6H) -CH<. aliphat.

-XXX Example 225 1-(4-Amino-3,5-dichloro-phenyl)-2-/N-/3-(4-chlorophenyl)-propyl/- allylamino7ethanol Prepared analogously to Example 13 from 1-(4-amino-3,5-dichloro-phenyl )-2-/N-0-(4-chloro-phenyl)-propyl7amino7ethanol, allyl bromide and triethylamine. Oil.

IR spectrum (methylene chloride): NMR spectrum (CDC13/D20) nh2 aromat. C=C aromat. h olefinic h -1 \ CH-OH ^ n-ch2- aliphat. ch, 3380 + 3480 cm 1610 cm"1 7.0 - 7.4 ppm (m;6H) 5.5 - 6.1 ppm (m;1H) 5.0 - 5.3 ppm (m; 2H) 4.3 - 4.7 ppm (dd;1H) 2.8 - 3.5 ppm (m; 2H) 2.2 -'2.7 ppm (m; 6H) 1.5 - 2.0 ppm (m; 2H) * --v - l- ' i i . k'.Tr '/.IWK * 0 JAN 1985 1992.15 Example 224 *23 N-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl7-N-/5-(4-chloro-phenvl)-propyl7allylamine Prepared analogously to Example 13 from N-/2-(4-amino-3,5-dichloro-phenyl )-ethyl7-3-(4-chlorophenyl)-propylamine, allyl bromide and triethylamine. Oil.

IR spectrum (methylene chloride) nmr spectrum (CDCl^/D^) : nh2 aromat. c=*c aromat. h olefinic h > n-ch2- aliphat. CH2 + 3480 -1 cm -1 3380 1610 cm 6.9- 7.4 ppm (m; 6H) .6 - 6.1 ppm (m;1H) 5.0 - 5.3 ppm (m;2H) 3.0 - 3.3 ppm (d; 2H) 2.7 - 3.3 ppm (m; 8H) 1.3 - 1.9 ppm (m; 2H) 22. if Example N-/2-(4-Amino-3,5-dichloro-phenyl)-1-methyl-ethyl7-N-/5-(4-methoxy-phenyl)-butyl7methylamine Prepared analogously to Example 101 from 4'-amino-3',5'-dichloro-propiophenone, N-/£-(4-methoxy-phenyl)-butyl7methylamine and sodium cyanoborohydride. Oil.

IR spectrum (methylene chloride): nh, UV spectrum (ethanol): max. 3380 + 3480 cm -1 -1 aromat c=c 1610 cm 245 nm (0.13) 280 nm (broad; 0.04) 300 nm (broad; 0.04) ^QJAr ■' 1992.15 N-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl7-N-/3-(4-methoxy-phenyl)-1-methyl-propyl7ethylamlne Prepared analogously to Example 13 from N-/2-(4-amino-3,5-di- chloro-phenyl)-ethyl7-N-/3-(4-hydroxy-phenyl)-1-methyl-propyl7-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 CI 17.94 N 7.09 Found: 63.17 7.09 17.90 7.15 7,2- £ 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-dichloro-phenyl ) -2-/N-/T,1-dimethyl-3-(4-hydroxy-phenyl)-propyl/methyl-amino/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 mag- •v nesium sulfate, and in vacuo in a rotation evaporator evaporated to dryness. The evaporation residue was first purified over silica gel 60 (Macherey and Nagel ~Q JANlSS-5 - X2!> Example c, 1992-15 70 - 230 mesh, ASTM), eluent: 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 residue crystallized.

M.p. : 122 - 124°C.

XLl Example N-/2-(4-Amino-3,5-dichloro-phenyl)-ethyl7-N-/3-(4-hydroxy-phenvl)-1-methyl-propyl7ethylamine Prepared analogously to Example 227 from 4'-amino-2-bromo-3',5'-dichloro-acetophenone, N-/3-(4-hydroxy-phenyl)-1-methyl-propyl/ethylamine, sodium carbonate in aqueous tetrahydrofuran and subsequent reaction of the obtained reaction product with pyridine-borane in trifluoroacetic acid. The 15 purification was carried out over aluminium oxide (neutral, activity step III). Eluent: ether/petroleum ether =2:1. . Oil. — 1 IR spectrum (methylene chloride): OH 3590 cm NH2 3480 + 3390 cm ch0, ch, 2960 + 2930 2 3 _1 + 2860 cm N-alkyl 2810 cm"1 C=C 1585 + 1510 + 1485 cm"1 UV spectrum (ethanol): \ max. 241 nm (0.28 shoulder) 280 - 302 nm (0.08) (Ethanol + KOH): ^ max. 241 nm (0.56) ... . -1 298 nm (0.17) X2.8 Example 2gff "J 3 0 1-(4-Amino-3,5-dichloro-phenyl)-2-/N-/T,1-dimethyl-3-(4-hydroxy-phenyl)-propyl7methylamino7ethanol Prepared analogously to Example 3 from 4 '-amino-2-bromo-3'. 199215 ' -dichloro-acetophenone, N-/T,1-dimethyl-3-(4-hydroxy-phenyl)-propyl/methylamine, sodium carbonate and subsequent reduction with sodium borohydride in aqueous tetrahydrofuran. The two purification stages were carried out using silica gel 60 (Macherey and Nagel, 70 - 230 mesh, ASTM). Eluei£s ether/ tetrahydrofuran = 3 J 1 then methylene chloride/ methanol / conc. ammonia = 30 : 1 : 0.3.

M.p.: 155 - 158°C. 221 Example 250 1-(4-Amino-3,5-dichloro-phenyl1-dimethyl-3-(4-hydroxy-phenyl)-propyl7amino7ethano1 Prepared analogously to Example 3 from 4,-amino-2-bromo-3'. 5'-dichloro-acetophenone, 1,1-dimethyl-3-(4-hydroxy-phenyl)-propylamine, sodium carbonate and reduction with sodium boro-15 hydride in aqueous tetrahydrofuran. The purification was carried out using sLUca gel 60 (Macherey aiid- Nagel, 70 - 230 mesh, ASTM). Eluent: a mixture of methylene chloride/methanol/conc. ammonia - 25 : 1 : 0.2.

M.p.: 142 - 144°C.

A30 on Example -251 N-/3-(4-Chlorophenyl)-propyl7-N-/5-(3»5-dichloro-4-isopropyl-amlno-phenvl)-ethyl7isopropylamlne Prepared analogously to Example 101 from N-/?-(4-amino-3,5-di-chlorophenyl)-ethyl7-/3-(4-chloro-phenyl)-propyl/amine, acetone 25and sodium cyanoborohydride. Oil.

NMR spectrum (CDCl^): aromat. H 7 - 7.3 ppm (m; 6H) >CH- 3.5 - 4.1 ppm (m; 1H) >CH- approx. 3 ppm (m; 1H) aliphat. H 2.3-2.7 ppm (m; 8H) 30 1.5-2.0 ppm (m; 2H) 0.9 - 1.3 pp* (ids 12H) I 30 JAN 5983 199215" 23) Example 232 N-/2- (.4-Amino-3, 5-dichloro-phenyl )-ethyl7-N-( 1-methyl-3-phenvl-propylj-methylamine Prepared analogously to Example 101 from N-/2-(4-amino-3,5-dichloro-phenyl)-ethyl7~M-(1-methyl-3-phenyl-propyl)-amine, paraformaldehyde and sodium cyanoborohydride. Oily hydrochloride.

IR-spectrum (methylene chloride,): nh2 3390 + 3^90 cm CH2 2930 cm"1 UV-spectrum (ethanol): ^ max. 243 nm (0.12) 300 nm (0.04) 132 Example N-/2-(4-Amino-3,5-dichloro-phenyl}-ethyl7-W-(1-methyl-3-phenvl-propyl)-n-propvlamlne Prepared analogously to Example 101 from W-/2-(4-amino-3i5-dichloro-phenyl)-ethyl/-N-(1-methyl-3-phenyl-propyl)-amine, propionaldehyde and sodium cyanoborohydride. Oily hydrochloride. _ -1 IR-spectrum (methylene chloride): NH2 3390 + 3490 cm 20 CH2 2930 cm"1 UV-spectrum (ethanol):^ max. 245 nm (0.11) 300 nm (0.04) 199215 Example A Tablets containing 25 mg of 1-(4-amino-3,5-dichloro-phenyl)-2-/N-(^phenyl-propyl)-2-propylamlno7ethanol hydrochloride Composition: 1 tablet contains: Active ingredient Corn starch Lactose Gelatine 10 Magnesium stearate Method of preparation: The active ingredient, corn starch and lactose were mixed, homogeneously moistened with an aqueous gelatine solution 15 and granulated. After drying in a circulating drier and screening (1.5 mm mesh size) the lubricant was mixed thereto. The mixture thus obtained was pressed into tablets.

Form: biplanar with a dividing slot on one side and a facet on both sides 2 0 Diameter: 7 mm Weight: 120 mg.

Example B Coated tablets containing 10 mg of 1-(4-amino-3»5-dichloro-phenyl)-2-/FT-(3-phenyl-propyl)-2-propylamino7ethanol hydrochloride 2 5 1 coated tablet core contains: Active ingredient Corn starch Lactose Gelatine 30 Magnesium stearate .0 mg 30.0 mg 61.5 mg 3.0 mg 0.5 mg 120.0 mg .0 mg 35.0 mg 71.5 mg 3.0 mg 0.5 mg 120.0 mg r^rarrc^ 0 JANI9S o3 » 499215 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 sub-5 sequently coated with pure sugar syrup up to a weight of 165 mg and polished.

Example C Capsules containing 20 mg of 1-(4-amino-3>5-dichloro-phenyl)-2-m-(3-phenvl-propyl)-2-propylamlno7ethanol hydrochloride 1 Capsule contains: Active ingredient 20.0 mg Lactose pulverized 114.0 mg Corn starch 60.0 mg Soluble starch 5.0 mg Magnesium stearate 1.0 mg 200.0 mg Method or preparation: The active ingredient was homogeneously mixed with the other auxiliary products and the mixture obtained was filled into 2 0 gelatine capsules by means of a capsule filling machine. Capsule shot weight: 200 mg. 49921 5 Example D Drops containing 20 mg/5 ml of 1-(4-amino-3,5-dichloro-phenyl)-2-/N-(5-phenvl-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 g 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 15 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 2 0 under stirring.

Example E Suppositories containing 50 mg of 1-(4-amino-3»5-dichloro-phenyl)' 2-/N-(5-phenvl-propvl)-2-propylamlno7ethanol hydrochloride 1 Suppository contains: 2 5 Active ingredient 0.05 g Hard fat (e.g. Witepsol W 45) 1.65 g 1.70 g

Claims (74)

• 1992 1 5 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 suppo-5 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-propylanHno7ethanol hydrochloride Ampoule contains: Active ingredient 20. 0 mg Citric acid 12. 5 mg Sodium monohydrogen phosphate 37. 5 mg Sorbite 36. 5 mg Water for injection ad 5. 0 ml Method of preparation: The active ingredient, citric acid and sodium monohydrogen phosphate and sorbite were successively dissolved in the water for injection at room temperature. 2 0 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. - 133 - 499215

1. fWHAT -f/WE CLAIM ISr Compounds of general formula I R4 I / *5 R1 A — CH — N B ,(I) [wherein 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 groups R2 and , which may be the same or different, each represents a halogen atom or a trifluoromethyl, cyano or nitro group, or one of the radicals R2 or R^ represents a hydrogen atom*, R^ represents a hydrogen atom or an alkyl group containing 1 to 3 carbon atoms; R^ 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 8 l -CH-(CHa)n-D 199215 134 or R 6 - E R 7 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 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; Rg 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 represents a trifluoromethyl, cyano or nitro group, and/or R^ represents a fluorine atom, and/or R^ represents an alkyl group containing 1 to 3 carbon atoms, and/or R,. 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 Rg 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 |9 -CH — CH 2 199215 - 135 - wherein Rg represents an alkyl group containing 1 to 3 carbon atoms] 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 hydrochloric, hydrobromic, sulfuric, phosphoric^ furmaric, succinic, lactic, citric, tartaric or maleic acid.

4. Compounds as claimed in any one of the preceding claims, wherein represents an amino group (optionally substituted by a benzyl group or an alkoxycarbonyl group containing 2 to 4 carbon atoms) or an alkylamino or dialkylamino group in which each alkyl part may contain from 1 to 3 carbon atoms; R2 represents a hydrogen, chlorine, bromine, or iodine atom or a trif luoromethyl, cyano or nitro group; R-. represents a chlorine* J fluorine^or bromine atom or a cyano group; R^ represents a hydrogen atom or a methyl group; R^ represents a hydrogen atom, an alkyl group containing 1 to 3 carbon atoms (optionally substituted by a phenyl group) or an allyl or cyclo-propyl group ; A represents a methylene, ethylene or hydroxy-methylene group; and B represents a group of formula : LATENT CmGH '-mmi 30 JAN 1935 wherein Rg, D and n are as defined in claim 1; R^ 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 R^ and R^ together represent a methylenedj.oxy group; and E represents an n-propylene, 1-methyl-n-propylene, 1,1-dimethyl-n- 7 136 J 99215 propylene or n-butylene group or (when A represents a methylene or ethylene group, and/or represents an amino group optionally substituted by a benzyl group or an alkoxycarbonyl group containing 2 to 4 carbon atoms or an alkylamino or dialkylamino group, wherein each alkyl part may contain from 1 to 3 carbon atoms, and/or R2 represents a tri-fluoromethyl, cyano or nitro group, and/or R^ represents a fluorine atom, and/or R^ 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^ re presents 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; R^ represents a fluorine or chlorine atom or a cyano group; R^ represents a hydrogen atom or a methyl group; R^ represents a hydrogen atom, an alkyl group containing 1 to 3 carbon atoms (optionally substituted by a phenyl group) or an allyl or cyclopropyl group; A represents a methylene or hydroxymethylene group; and B represents a group of formula wherein E represents an n-propylene, 1-methyl-n-propylene, 1,1-aimethyl-n-propylene or n-butylene group, or (when R^ represents an ethoxycarbonylamino group, and/or R2 represents a cyano group, and/or R^ represents a fluorine atom, and/or R[- 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, 7 195215 - 137 - and R7 represents a hydrogen atom or a methoxy group.

6. Compounds as clairaed in claim 4 wherein R1 represents an amino, dimethylamino or alkylamino group containing 1 to 3 carbon atoms in the alkyl part; represents a chlorine or bromine atom; represents a fluorine or chlorine atom, or one of the radicals or R^ further represents a cyano group; R^ represents a hydrogen atom or a methyl group; R^ 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-chloro-phenyl group or a 4-(4-methoxyphenyl)-butyl group or (when R^ represents an alkyl group containing 1 to 3 Carbon atoms or an allyl group and/or R2 represents a cyano group) B may further represent a 2-(3,4-dimethoxyphenyl)-ethyl group.

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

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

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

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

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

12. Compounds as claimed in claim 1 wherein represents a hydroxy group, or an amino group optionally substituted by an alkanoyl group containing 1 to 3 carbon atoms or by an alkoxycarbonyl group containing 2 to 4 carbon atoms; Rg represents a hydrogen atom, a straight-chained or branched 199215 - 138 - alkyl group containing 1 to 4 carbon atoms, a cycloalkyl group containing 3 to 6 carbon atoms or an aralkyl group containing 7 to 10 carbon atoms; and Rg represents a hydrogen or halogen atom, a hydroxy group, or an alkoxy group containing 1 to 3 carbon atoms optionally substituted by a phenyl group and 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; and E represents a straight-chained alkylene group containing 3 to 5 carbon atoms optionally substituted by an alkyl group containing 1 to 3 carbon atoms or (when A represents a methylene or ethylene group, and/or R^ represents an amino group substituted by an alkanoyl group containing 1 to 3 carbon atoms or an alkoxycarbonyl group containing 2 to 4 carbon atoms in tots.1, and/or R2 represents a trif luoromethyl, cyano or nitro group, and/or R^ represents a fluorine atom, and/or R^ represents an alkyl group containing 1 to 3 carbon atoms, and/or R^ represents an alkyl group containing 1 to 4 carbon atoms, a cycloalkyl group containing 3 to 6 carbon atoms or an aralkyl group containing 7 to 10 carbon atoms and/or Rg represents a fluorine or a chlorine atom) E may further represent an ethylene group, or (when A represents a methylene group) E may further represent a group of formula T9 -CH CH2- wherein Rg represents an alkyl group containing 1 to 3 carbon atoms.

13. Compounds as claimed in claim 1 as herein described fjccunp'es 1 — 3.33 in any one of jbho okamplart.

14. Compounds as claimed in claim 1 as herein described in any one of Examples 1 to 20 and 23 to 10 4.

15. A process for the preparation of compounds as claimed in claim 1, which comprises reducing a compound.

16. A process as claimed in claim 15 wherein Z represents a bromine or iodine atom or a carbonic ester radical.

17. A process as claimed in claim 15 or claim 16 wherein the reaction is carried out in a solvent at temperatures between -20°C and the boiling point of the reaction 199215 - 14 C - mixture.

18. A process as claimed in any one of claims 15 to 17 wherein the reduction is carried out using a hydride, aluminium isopropylate in the presence of a primary or secondary alcohol, catalytically activated hydrogen, or nascent hydrogen.

19. A process as claimed in claim 18 for the preparation of compounds as claimed in claim 1 wherein A represents a hydroxymethylene group,wherein the reduction is effected using a complex metal hydride, aluminium isopropylate, catalytically activated hydrogen, or nascent hydrogen.

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

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

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

23. A process for the preparation of compounds, as an ofpfopruxte, claimed in claim 1 which comprises reacting ft 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,. or represents a group of formula 2 2 APR ,r;. J 19921S - 141 - R / - CH - A1 wherein R^, R2, R^ and R^ are as defined in claim 1, and A' represents a carbonyl, methylene or ethylene group) or an aldehyde hydrate thereof with an appropriate amine of general formula IV H - N / M , (IV) (wherein M and Q, which are different, represent B and as defined in claim 1, or one of the radicals M or Q represents a group of formula R/. - CH - A wherein R, , R^ and A are as defined in claim 1) 1' R2' R3' and with a reducing agent.

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

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

26. A process as claimed in claim 23 or claim 24 wherein an amine centre is methylated using formic acid and formaldehyde. If 22 APR 1986; P i xl - 142 - 992 1

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

28. A process for the preparation of compounds as claimed in claim 1, which comprises removing one or more protecting groups from a compound of general formula V R, A" - CH - N V B1 ,(v; wherein R2, Rj anc* R4 are as' defined in claim 1; R^' represents R^ 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; R,.1 represents R^ 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 8 I -CH-(CH2)n-D or - E V R ' 7 wherein R_, D, E and n are as defined in claim 1; and R_' o 6 and R71, which may be the same or different, represent Rg and R^ respectively as defined in claim 1 or each represents a hydroxy group protected by a protective radical, wherein 199215 - 143 - at least one of the radicals R,', A", R ' and/or B1 repre- l D sents or must contain one of the above-mentioned protective radicals. r

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

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

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

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

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

34. A process for the preparation of compounds as claimed in claim 1 wherein represents a hydrogen atcm, which comprises dehalogenating a compound of general formula VI wherein Rp R^, R^, A and B are as defined in claim I/R3 represents a halogen atcm or a trif luramethy1, cyano or nitro group and Hal represents a chlorine, bromine or iodine atom.

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

36. A process as claimed in claim 34 or 35 wherein the dehalogenation is effected using triphenylphosphine, using hydrogen in the presence of a hydrogenation catalyst or using a complex metal hydride. if- v' . \ 1^ 2 2 APR 1986 d v ./ - 144 - 199215

37. A process as claimed in any one of claims 34 to 36 wherein the reaction is carried out at temperatures between 0 and 15 0 °C.

38. A process for the preparation of compounds as claimed in claim 1, which comprises reacting a compound of general formula VII R. I A - CH.- N V B" ,(VII) wherein R2, R3? R4 and A are as defined in claim 1; Rj." represents R^ as defined in claim 1 and B" represents B as defined in claim 1 whereby, if R^" does not represent a hydrogen atom, at least one of the radicals Rg or R^ must repre sent 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) with an appropriate alkylating agent whereby the desired compound is obtained.

39. A process as claimed in claim 38 wherein the reaction is carried out in a solvent at temperatures between -10 and 50°C.

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

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

42. A process for the preparation of compounds as claimed in claim 1 wherein R^ represents an amino group substituted by an alkanoyl group containing 1 to 3 carbon atoms or an alkoxycarbonyl group containing 2 to 4 carboh atoms, 199215 - 145 - and Rj. does not represent a hydrogen atom, which comprises acylating a compound of general formula VIII R, h2N R. r A - CH - N B ,(VIII) (wherein R2/ t r^ t a and B are as defined in claim 1 and ' 1 is as defined for Rr in claim 1 other than a hydrogen atcm) with a compound b of formula IX - CO - R 10 (IX) (wherein R^q represents a hydrogen atom, a methyl or ethyl group or an alkoxy group containing 1 to 3 carbon atoms; and Y represents a nucleophilically exchangeable group).

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

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

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

46. A process as claimed in any one of claims 38 to 45 wherein the reaction is carried out in1 the presence of a base.

47. A process for the preparation of compounds as claimed in claim 1 wherein D represents a sulfinyl or sulfonyl group, which comprises oxidizing a compound of general formula X // v 2 2 APR 1986: - 146 - A - CH. - N R 199215" CH - (CH2)n - SOm 8 . w wherein R.. , R„, R_, R. , R.., R,, R_,, RQ, A and n are as de- / o fined in claim 1; and m is 0 or 1.

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

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

50. A process as claimed in claim 49 wherein the reaction is carried out at temperatures between -20 and 60°C.

51. A process as claimed in claim 47 or claim 48 for the preparation of compounds as claimed in claim 1 wherein D represents a sulfonyl group, wherein the oxidation is carried out with one mole of oxidising agent per mole of the compound of formula X where m is 0 and with two or more moles of oxidising agent per mole of the compound of formula X where m is 1.

52. A process for the preparation of compounds as claimed in claim 1 wherein D represents an oxygen or sulfur atom and R,. is as defined in claim 1, with the exception of a hydrogen atom, which comprises reacting a compound of general formula XI, Am - CH - N CH - (CH ) - V ! 2 n ,(XI) 8 v 2 2 APR 1986 199215 - 147 - (wherein R2, R^, R^, r^, r^ and n are as defined in claim 1, V represents a nucleophilically exchangeable group and A"' represents a methylene or ethylene group) with a compound of general formula XII h - d1 ,(xii ; (wherein R, and R_ are as defined in claim 1 and D' repre-o / sents an oxygen or sulfur atom) or an alkali metal salt or alkaline earth metal salt thereof.

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

54. A process as claimed in claim 53 wherein the reaction is carried out at temperatures between -10°C and the boiling point of the solvent used.

55. A process as claimed in claim 54 wherein the reaction is carried out at temperatures between -10 and 50°C.

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

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

58. A process as claimed in any one of claims 15 to 57 for the preparation of compounds as claimed in claim 12.

59. A process for the preparation of compounds as claimed in claim 1 substantially as herein described in any . , ,1-333 one of fth9 Example sjL

60. A process for the preparation of compounds b N ? ^ ([n 2 2 APR 1986 O Jft/I .. t - 148 - 11992)5 claimed in claim 12 substantially as herein described in any one of Examples 1 to 20 and 23 to 104.

61. Compounds as claimed in claim 1 when prepared by a process as claimed in any one of claims 15 to 60.

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

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

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

65. Compositions as claimed in claim 63 or claim 6 4 in ptacsi the form of^tablets, coated tablets, capsules, drops, suppositories or ampoules.

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

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

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

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

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

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

72. Compounds of general formula I as claimed in claim 1 and physiologically compatible acid addition salts thereof use in a method of treatment of patients suffering from cardiovascular diseases. (other th** kcunans}

73. A method of treating patients^suffering from, or susceptible to, cardiovascular diseases which comprises ad-ministering to the said patient an effective amount of a compound of formula I as defined in claim 1 or a physiologically - 149 - compatible acid addition salt thereof.

74. 74-r Eaoh and every novel mothod, process,—compound or composition herein disclosed. BALDWIN, SON & CAREY ATTORNEYS FOR THE APPLICANTS 0 ^ > AN 1985