CH651541A5 - PHENYLALKYLAMINE AND MEDICINAL PRODUCTS CONTAINING THEM. - Google Patents

Description

The present invention relates to new phenylalkylamines of the formula I.

a - ch r n their optically active antipodes, their diastereomeric racemates 65 and their optical antipodes, and their acid addition salts, in particular their physiologically tolerable acid addition salts with inorganic or organic acids and medicaments containing them.

651 541

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The new compounds have valuable pharmacological properties, in particular an effect on the heart and circulation.

In the above formula I mean

Ri is a hydroxyl group, an amino group optionally substituted by an al-kanoyl group having 1 to 3 carbon atoms or an alkoxycarbonyl group having a total of 2 to 4 carbon atoms, an alkylamino or dialkylamino group, each alkyl part containing 1 to 3 carbon atoms and each being substituted by a phenyl group ,

R2 and r3, which can be the same or different, halogen atoms, trifluoromethyl, cyano or nitro groups or one of the radicals R2 or R3 also a hydrogen atom,

R4 represents a hydrogen atom or an alkyl group with 1 to 3 carbon atoms,

Rs is a hydrogen atom, a straight-chain or branched alkyl group with 1 to 4 carbon atoms, a cycloalkyl group with 3 to 6 carbon atoms, an alkenyl group with 2 to 5 carbon atoms or an araikyl group with 7 to 10 carbon atoms,

A is the methylene, ethylene or hydroxymethylene group and

B is a group of the formulas r

e where

Rö is a hydrogen or halogen atom, a hydroxyl group, an alkoxy group with 1 to 3 carbon atoms optionally substituted by a phenyl group, an alkylsulfonyl or alkylsulfinyl group each with 1 to 3 carbon atoms,

R7 is a hydrogen atom, a hydroxyl group or an alkoxy group with 1 to 3 carbon atoms or Re and R7 together is the methylenedioxy group,

Rs is a hydrogen atom or an alkyl group having 1 to 3 carbon atoms,

D is an oxygen or sulfur atom, a sulfinyl or sulfonyl group,

n is the number 1 or 2 and

E is a straight-chain alkylene group with 3 to 5 carbon atoms which is optionally substituted by one or two alkyl groups each having 1 to 3 carbon atoms or, if A is a methylene or ethylene group and / or R 1 is replaced by an alkanoyl group with 1 to 3 carbon atoms or an alkoxycarbonyl group with a total of 2 up to 4 carbon atoms substituted amino group, a hydroxyl, alkylamino or dialkylamino group, each alkyl part containing 1 to 3 carbon atoms and each can be substituted by a phenyl group, and / or R2 a trifluoromethyl, cyano or nitro group and / or R3 a fluorine atom and or

R4 is an alkyl group with 1 to 3 carbon atoms and / or

Rs is an alkyl group with 1 to 4 carbon atoms, a cycloalkyl group with 3 to 6 carbon atoms, an alkenyl group with 2 to 5 carbon atoms or an araikyl group with 7 to 10 carbon atoms and / or

R6 represents a fluorine or chlorine atom, an alkylsulfenyl or alkylsulfinyl group each having 1 to 3 carbon atoms, an ethylene group or, if A represents the methylene group,

a group of the formula Rs I

- CH - CH2 -, in which R9 represents an alkyl group with 1 to 3 carbon atoms.

For the meanings previously mentioned in the definition of the radicals R 1 to R 9 and E, R 1 is, for example, the hydroxyl, amino, methylamino, ethylamino, propylamino, isopropylamino, benzylamino, 1-phenylethylamino , 2-Phenylethylamino-, 3-Phenylpropylamino-, Dimethylamino-, Diethylamino-, Dipropylamino-, Diisopropyl-amino-, Dibenzylamino-, Di- (2-Phenyläthyl) -amino-, Di- (3-Phenylpropyl) -amino- , Methyl-ethylamino-, methyl-propyl-amino-, methyl-isopropylamino-, ethyl-isopropylamino-, methyl-benzylamino-, ethyl-benzylamino-, propyl-benzyl-amino-, pyrrolidino-, piperidino-, hexamethyleneimino-, For -mylamino, acetylamino, propionylamino, methoxycarbonylamino, ethoxycarbonylamino, propoxycarbonylamino or isopropoxycarbonylamino group,

for R2 and R3, which can be the same or different, in each case that of the fluorine, chlorine, bromine or iodine atom, the trifluoromethyl, cyano or nitro group or for R2 or R3 also that of the hydrogen atom,

for R4 and Rs, which may be the same or different, in each case those of the hydrogen atom, the methyl, ethyl, propyl or isopropyl group,

for R5 that of the hydrogen atom, the methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, allyl,

Crotyl, pentenyl, benzyl, 1-phenylethyl, 2-phenylethyl, 3-phenylpropyl or 4-phenylbutyl group,

for R6 that of hydrogen, fluorine, chlorine or bromine atom, hydroxyl, methoxy, ethoxy, propoxy, iso-propoxy, methylsulfenyl, ethylsulfenyl, methylsulfinyl, propylsulfinyl, benzyloxy, 2- Phenylethoxy or 3-phenylpropoxy group,

for R7 that of the hydrogen atom, the hydroxyl, methoxy, ethoxy, propoxy or isopropoxy group or for R6 and R7 together that of the methylenedioxy group,

for R9 that of the methyl, ethyl, propyl or isopropyl group and for E that of the ethylene, n-propylene, n-butylene, n-pentylene, 1-methyl-n-propylene, 1- Ethyl-n-propylene-, 1-propyl-n-propylene-, 1,1-dimethyl-n-propylene-, 1,1-diethyl-n-propylene-, 1,1-dipropy 1-n-propylene- , 1-methyl-1-ethyl-n-propylene, 1-methyl-1-propyl-n-propylene, 1-ethyl-1-propyl-n-propylene, 1-methyl-n-butylene or 1-methyl-n-pentylene group into consideration.

The compounds of the formula I in which R 1 has an amino group optionally substituted by a benzyl group or an alkoxycarbonyl group with a total of 2 to 4 carbon atoms, an alkylamino or dialkylamino group, where each alkyl part can contain 1 to 3 carbon atoms,

R2 is a hydrogen, chlorine, bromine or iodine atom, a trifluoromethyl, cyan or nitro group,

R3 is a fluorine, chlorine or bromine atom or a cyano group,

R4 is a hydrogen atom or a methyl group,

Rj is a hydrogen atom, one optionally through a

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Phenyl group-substituted alkyl group having 1 to 3 carbon atoms, an allyl or cyclopropyl group,

A is the methylene, ethylene or hydroxymethylene group and

B is a group of formulas

8th

-ch- (ch2) n-d

E the n-propylene, 1-methyl-n-propylene, 1,1-dimethyl-n-propylene, n-butylene group or, if Ri the ethoxycarbonylamino group and / or R.2 the cyano group and / or R. 3 a fluorine atom and / or

Rs is an alkyl group with 1 to 3 carbon atoms which is optionally substituted by a phenyl group and which represents allyl or cyclopropyl group, also the ethylene group,

Rs is a hydrogen atom, a hydroxy or methoxy group and

R7 represents a hydrogen atom or a methoxy group.

The phenylalkylamines of the formula I can be prepared by the following processes:

a) Reduction of a compound of formula II

mean where

Rg, D and n are defined as mentioned at the beginning,

Rö is a hydrogen, fluorine or chlorine atom, a hydroxyl, methoxy, ethoxy, benzyloxy, methylsulfenyl or methylsulfinyl group,

R7 is a hydrogen atom or a methoxy group or Rs and R7 together are a methylenedioxy group and

E is the n-propylene, 1-methyl-n-propylene, 1,1-dimethyl-n-propylene or n-butylene group or, if A is the methylene or ethylene group and / or Ri is optionally a benzyl group or amino group substituted by an alkoxycarbonyl group with a total of 2 to 4 carbon atoms, an alkylamino or dialkylamino group, where each alkyl part can contain 1 to 3 carbon atoms, and / or

R2 is a trifluoromethyl, cyan or nitro group and / or R3 is a fluorine atom and / or

R5 has an alkyl group which may be substituted by a phenyl group and has 1 to 3 carbon atoms, which represent allyl or cyclopropyl group and is the ethylene group, and has particularly favorable properties.

However, particularly preferred compounds of the aforementioned formula I are those in which

Ri is an amino group which is optionally substituted by an ethoxycarbonyl group, an alkylamino or dialkylamino group, where each alkyl part can contain 1 to 3 carbon atoms,

R2 is a hydrogen, chlorine or bromine atom or the cyano group,

R3 is a fluorine or chlorine atom or the cyano group,

R4 is a hydrogen atom or the methyl group,

Rs is a hydrogen atom, an alkyl group with 1 to 3 carbon atoms optionally substituted by a phenyl group, the allyl or cyclopropyl group,

A is the methylene or hydroxymethylene group and B is a group of the formula

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x - n

20th

b

(Ii),

in the

Ri to R3, R5 and B are as defined above and X is a group of the formulas

R4

- CO - CH

OH

I.

CH O-acyl

R4

CH

I.

- CH - CO -,

- CH2 - CO -,

z r4

CH - CH

or

R4 I

CH2 represents - CH -, where R4 means as, where

Z I

- CH gear is defined,

55 acyl an organic acyl group such as the acetyl, propionyl or benzoyl group and

Z is a reductively removable group such as a bromine or iodine atom or a carbonic acid ester residue such as the methoxycarbonyloxy or ethoxycarbonyloxy group. 60 Depending on the importance of the radical X, the reduction is carried out in a suitable solvent such as methanol, methanol / water, ethanol, ethanol / water, isopropanol, trifluoroacetic acid, butanol, diethyl ether, tetrahydrofuran, tetrahydrofuran / water, dioxane or hexamethyl-phosphoric acid triamide , 65 expediently with a hydride, with aluminum isopropylate in the presence of a primary or secondary alcohol, with catalytically excited hydrogen or with nascent hydrogen at temperatures between −20 ° C. and the boiling point

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temperature of the reaction mixture, e.g. Performed at temperatures between -20 ° C and 100 ° C.

To prepare a compound of the formula I in which A represents the hydroxymethylene group, the reduction is expediently carried out, for example, with a complex metal hydride such as sodium borohydride or lithium aluminum hydride in a suitable solvent such as methanol, methanol / water, diethyl ether or tetrahydrofuran at temperatures between −20 ° and 50 ° C, the reduction with aluminum isopropylate in isopropanol at boiling temperature and while distilling off the acetone formed, the reduction with catalytically excited hydrogen with hydrogen in the presence of a catalyst such as platinum, palladium, Raney nickel or Raney cobalt at room temperature and at a hydrogen pressure from 1-5 bar, and the reduction with nascent hydrogen, e.g. with activated metallic aluminum and water or with zinc and hydrochloric acid, at temperatures up to the boiling point of the solvent used.

If X in a compound of the formula II denotes the -CO-chr4 group, the reaction is conveniently carried out at temperatures between 0 and 50 ° C, preferably at room temperature, e.g. with sodium borohydride in methanol / water, ethanol / water or isopropanol or with lithium aluminum hydride in diethyl ether or tetrahydrofuran as

O-acyl I

Solvent, or X the - CH - CO group, the reaction is preferably carried out with a hydride in a suitable solvent such as ether, tetrahydrofuran or dioxane, e.g. with diborane or lithium aluminum hydride in tetrahydrofuran at low to slightly elevated temperatures, e.g. at temperatures between 0 and 100 ° C, but expediently carried out at the boiling point of the reaction mixture.

To prepare a compound of formula I in which A represents the methylene or ethylene group, the reduction with a hydride such as sodium borohydride, lithium aluminum hydride, sodium cyanoborohydride or pyridine-borane in a suitable solvent such as ethanol, isopropanol, tetrahydrofuran, dioxane, trifluoroacetic acid is expedient or hexa-methyl-phosphoric acid triamide at temperatures between 0 and 100 ° C.

If X in a compound of the formula II denotes the -CH2-CO group, the reaction is preferably carried out at elevated temperatures, e.g. with lithium aluminum hydride in tetrahydrofuran at the boiling point of the reaction mixture, or X is the hydroxyethylene group, the reaction is preferably carried out with pyridine-borane in trifluoroacetic acid at temperatures between 25 and 100 ° C, the reaction components expediently proving to be at low temperatures, e.g. at -10 ° C, or X is a Z R4 Z R4

i I I I

- CH - CH or - CH - CH2 - CH group, the reaction is preferably carried out with sodium borohydride, sodium cyanoborohydride or lithium aluminum hydride in a suitable solvent such as isopropanol, hexamethyl-phosphoric acid triamide, tetrahydrofuran or dioxane at temperatures between 20 and 100 ° C. carried out.

b) reaction of a carbonyl compound of the formula III which may be formed in the reaction mixture

for R5 meanings mentioned above or a group of the formula

K - L

(III),

in the

K is an oxygen atom which replaces two adjacent hydrogen atoms in the alkyl part of the radical L,

L is for B or, with the exception of the hydrogen atom, is r4

I.

ch - a, where

Ri to R4 are as defined in the introduction and A 'represents the carbonyl, methylene or ethylene group, or their aldehyde hydrate with a 20 amine of the formula IV

M

H - N:

(IV),

in the

M and Q, which are different, have the meanings mentioned for B and R5 or one of the radicals M or Q is the group of the formula r;

- ch - a,

40

represents, where

45 Ri to R4 and A are as defined in the introduction, and a reducing agent.

The reaction is preferably carried out in a suitable solvent such as methanol, methanol / water, ethanol, ethanol / water, butanol, diethyl ether, tetrahydrofuran or 50 dioxane in the presence of a reducing agent at temperatures between -20 and 50 ° C., but preferably at temperatures between 0 and 25 ° C. A complex metal hydride or catalytically excited hydrogen can be used as the reducing agent.

55 If the reaction is carried out with a secondary amine of the formula IV, this is preferably carried out in tetrahydrofuran as the solvent and with sodium cyanoborohydride at pH <7, e.g. at pH 6-6.5 and then carried out with sodium borohydride at room temperature. If the reaction is carried out with a primary amine of the formula IV, the Schiff base formed in the reaction mixture is preferably reacted with a complex metal hydride such as sodium borohydride or lithium aluminum hydride in a suitable solvent such as methanol, methanol / water 65ser, diethyl ether or tetrahydrofuran at temperatures between -20 ° C and the boiling point of the solvent used, e.g. at temperatures between 0 and 80 ° C, or with catalytically excited hydrogen, e.g. with hydrogen

7

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in the presence of a catalyst such as platinum, palladium, Raney nickel or Raney cobalt, at temperatures between 0 and 100 ° C, but preferably at room temperature, and at a hydrogen pressure of 1-5 bar.

Methylation can also be carried out with formaldehyde and formic acid as reducing agents at elevated temperatures, e.g. at the boiling point of the reaction mixture.

If the reaction with a compound of formula IV, in which Ri represents an amino or alkylamino group having 1 to 3 carbon atoms, and a carbonyl compound of formula III, in which L has the meaning for Rs, this can be carried out in particular when using a corresponding excess are alkylated.

c) splitting off one or more protective residues from a compound of formula V.

Aw - CH - N '

(V),

-CH- (CH2) n-D

or

Examples of protective residues are acyl residues such as the ethoxycarbonyl, acetyl, propionyl or benzoyl group or the benzyl group and for A "the acetyl, methoxycarbonyl or ethoxycarbonyl group.

One of the abovementioned acyl and / or alkoxycarbonyl radicals is preferably cleaved hydrolytically in an aqueous solvent, e.g. in water, isopropanol / water, tetrahydrofuran / water or dioxane / water, in the presence of an acid such as hydrochloric acid or sulfuric acid or in the presence of an alkali base such as sodium hydroxide or potassium hydroxide at temperatures between 0 and 100 ° C., preferably at the boiling point of the reaction mixture. A benzyl radical is preferably split off hydrogenolytically, e.g. with hydrogen in the presence of a catalyst such as palladium / carbon, in a solvent such as methanol, ethanol, ethyl acetate or glacial acetic acid, optionally with the addition of an acid such as hydrochloric acid at temperatures between 0 and 50 ° C, but preferably at room temperature-2o temperature, and a hydrogen pressure of 1 to 7 bar, but preferably from 3 to 5 bar.

d) For the preparation of a compound of the formula I in which one of the radicals R2 or R3 represents a hydrogen atom: enthalogenation of a compound of the formula VI

25th

Shark in the

R2, R3 and R4 are as defined at the beginning,

Ri 'has the meanings mentioned for Ri or represents a hydroxyl or amino group protected by a protective radical,

A "has the meanings mentioned for A at the outset or represents a hydroxymethylene group protected by a protective radical,

Rs' has the meanings mentioned for R5 or represents a protective radical for an amino group and

B 'has the meanings mentioned at the beginning for B or a group of the formulas

8th

%

A - CH - N

B

(VI),

in the

40 Ri, R3 to R5, A and B are as defined at the beginning and shark represents a chlorine, bromine or iodine atom.

The dehalogenation is preferably carried out in a solvent, advantageously with triphenylphosphine in benzene or toluene, with hydrogen in methanol, ethanol, 45 vinegar or tetrahydrofuran and in the presence of a hydrogenation catalyst or with a complex metal hydride such as lithium aluminum hydride or sodium diethoxy aluminum hydride Tetrahydrofuran, dioxane or toluene. Depending on the method used, the reaction is carried out at room temperature 50 or elevated temperature, for example at temperatures between 60 ° and 150 ° C, and at normal pressure or moderate excess pressure; when using Raney nickel or palladium / carbon, for example, the dehalogenation takes place at room temperature and normal pressure. 55 e) alkylation of a compound of formula VII

A - CH - N

represents, where

Rs, D, E and n are as defined in the introduction and Ré 'and R7', which may be the same or different, have the meanings mentioned for Rö and R7 or represent hydroxyl groups protected by protective radicals, at least one of the radicals Ri ', A ", R5 'and / or B' must represent or contain one of the protective residues mentioned above.

V

B "

(VII),

in the

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Ri to R4 and A are defined as at the beginning,

R5 "has the meanings mentioned for R5 or a hydrogen atom and

B "has the meanings mentioned for B at the beginning, where if R5" is not a hydrogen atom, at least one of the radicals Rö or R7 is a hydroxyl group or Ri is an amino group which is optionally substituted by an alkyl group having 1 to 3 carbon atoms, the alkyl group additionally being substituted by a phenyl radical can be, must represent.

The reaction is carried out in a solvent such as water / methanol, ethanol / water, tetrahydrofuran, dioxane, acetone or dimethyl sulfoxide with an alkylating agent such as methyl iodide, dimethyl sulfate, ethyl bromide, diethyl sulfate, benzyl bromide, 2-phenylethyl bromide or methyl p-toluenesulfonate, optionally in the presence of a base such as sodium hydroxide solution or potassium carbonate, conveniently at temperatures between -10 and 50 ° C, but preferably at temperatures between 0 and 30 ° C. However, the reaction can also be carried out without a solvent.

The alkylation of the nitrogen atom can also be carried out using formaldehyde / formic acid at elevated temperatures, e.g. at the boiling temperature of the reaction mixture, or with an appropriate carbonyl compound and a complex metal hydride, preferably with sodium cyanoborohydride at pH <7, e.g. at pH 6-6.5, in a solvent such as water / methanol, ethanol, ethanol / water or tetrahydrofuran at temperatures between 0 and 50 ° C, but preferably at room temperature.

Furthermore, the alkylation of a phenolic hydroxyl group with a corresponding diazoalkane in a solvent such as diethyl ether or tetrahydrofuran can be carried out at temperatures between 0 and 50 ° C., but preferably at room temperature.

f) For the preparation of a compound of the formula I in which Ri is an amino group substituted by an alkanoyl group having 1 to 3 carbon atoms or alkoxycarbonyl group having a total of 2 to 4 carbon atoms and R5 is not a hydrogen atom:

Acylation of a compound of formula VIII

a - ch - n h2n in the

R2 to r5, A and B are as defined in the introduction, with a compound of the formula IX

Y-CO

Rh

(IX),

in the

Rio represents a hydrogen atom, a methyl or ethyl group or an alkoxy group with 1 to 3 carbon atoms and

Y represents a nucleophilically exchangeable group such as a halogen atom, a nitrophenyl radical, an imidazolyl group or a radical of the formula -O-cor10.

The reaction is carried out, for example, with acetyl chloride, acetic anhydride, propionic anhydride or a corresponding chloroformate, e.g. Ethyl chloroformate, which can simultaneously serve as a solvent, optionally in a solvent such as water / tetrahydrofuran, diethyl ether, tetrahydrofuran or methylene chloride, optionally in the presence of a base such as triethylamine or pyridine, where a tertiary organic base can also serve as a solvent at temperatures between 0 and 100 ° C, preferably, however, carried out at room temperature. The reaction can also be carried out without a solvent.

g) To prepare a compound of formula I in which D represents a sulfinyl or sulfonyl group:

Oxidation of a compound of formula X

A - CH - H

• CH - ICH2) n - SO ".

/

(X),

in the

Ri to Rs, A and n are as defined above and m represents the number 0 or 1.

The oxidation is preferably carried out in a solvent, e.g. in water, water / pyridih, ethanol, methanol, acetone, glacial acetic acid, formic acid, dilute sulfuric acid or trifluoroacetic acid, depending on the oxidizing agent used, conveniently carried out at temperatures between -80 ° and 100 ° C.

35 To prepare a sulfinyl compound of formula I, the oxidation is conveniently carried out with one equivalent of the oxidizing agent used, e.g. with hydrogen peroxide in glacial acetic acid, trifluoroacetic acid or formic acid at 0 to 20 ° C or in acetone at 0 to 60 ° C, with a per-40 acid such as performic acid in glacial acetic acid or trifluoroacetic acid at 0 to 50 ° C or with m-chloroperbenzoic acid in methylene chloride or Chloroform at -20 to 60 ° C, with sodium meta-periodate in aqueous methanol or ethanol at 15 to 25 ° C. To prepare a sulfonyl compound of the formula I, the oxidation is expediently carried out with one or with two or more equivalents of the oxidizing agent used , e.g. with hydrogen peroxide in glacial acetic acid, trifluoroacetic acid or in formic acid at 20 to 100 ° C or in acetone at 0 to 60 ° C, with a peracid such as performic acid 50 or m-chloro-perbenzoic acid in glacial acetic acid, trifluoroacetic acid, methylene chloride or chloroform at temperatures between 0 and 60 ° C or potassium permanganate in glacial acetic acid, water / sulfuric acid or in acetone at 0 to 20 ° C.

h) For the preparation of a compound of the formula I in which D 55 represents an oxygen or sulfur atom and R5 does not represent a hydrogen atom:

Implementation of a compound of formula XI

A1 "- CH - N

CH - - V (xa in the

Ri to R5, Rs and n are as defined in the introduction,

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V is a nucleophilically exchangeable group such as a halogen atom or a sulfonic acid ester residue, e.g. a chlorine, bromine or iodine atom, a p-toluenesulfonyloxy or methanesulfonyloxy group, and

A '"denote the methylene or ethylene group, with a compound of formula XII

D '

7

in the

Rö and R7 are as defined in the beginning and

D 'represents an oxygen or sulfur atom, or their alkali or alkaline earth metal salt.

The reaction is conveniently carried out in a solvent such as chloroform, tetrahydrofuran, dioxane or toluene, but preferably in an anhydrous aprotic solvent such as acetone, dimethylformamide or dimethyl sulfoxide, optionally in the presence of an alkali base such as sodium carbonate, potassium carbonate, sodium hydroxide, sodium hydride or potassium. tert.butylate at temperatures between -10 ° C and the boiling point of the solvent used, eg at temperatures between -10 and 100 ° C, but preferably at temperatures between 0 and 50 ° C. However, the reaction can also be carried out without a solvent.

A compound of the formula I which contains one, two or three optically active carbon atoms can then be separated into its optically active antipodes, its diastereomeric racemates and the optical antipodes thereof by conventional methods.

A racemate of a compound of formula I above is preferably cleaved via a fractional crystallization of a mixture of its diastereomeric salts with an optically active acid, e.g. di (-) - tartaric acid, L (+) -tartaric acid, dibenzoyl-D-tartaric acid, dibenzoyl-L-tartaric acid, (+) - camphor-10-sulfonic acid, L (-) - malic acid, L (+ ) -Mandelic acid, da-Bromkampfer-7r-sulfonic acid or 1-quinic acid and subsequent release of the respective optically active base. However, the resolution can also be resolved by column chromatography on an optically active carrier material, e.g. on acetyl cellulose.

The purification of the diastereomeric racemates is carried out, for example, by fractional crystallization and / or column chromatography on an inert support.

Furthermore, if desired, a compound of the formula I can subsequently be converted into its physiologically tolerable salts with inorganic or organic acids. Examples of suitable acids for this purpose are hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, fumaric acid, succinic acid, lactic acid, citric acid, tartaric acid or maleic acid.

Some of the compounds of the formulas II to XII used as starting materials are new. They can be obtained by methods known per se.

For example, a compound of formula II in which X represents a -CO-CHR4 group is obtained by reacting a corresponding a-halogeno-ketone with a corresponding amine and a compound of formula II in which X is -CH2-CO Represents group, by reacting a corresponding phenylacetic acid derivative with a corresponding amine.

A compound of the formula used as a starting material

III, in which A 'represents the carbonyl group and R4 represents a hydrogen atom, is obtained, for example, by selenium dioxide oxidation of a corresponding acetophenone or a compound of the formula III, in which A' represents a methylene or ethylene group, by converting a corresponding hydroxy compound in a corresponding halogen compound or by acylation of a corresponding hydroxy compound with a corresponding chloroformate.

A compound of formula V used as a starting material is obtained, for example, by reacting an appropriate w-phenylalkyl halide with an appropriate amine.

A compound of the formulas VI, VII and VIII used as the starting material is obtained, for example, by reducing an appropriate carboxamide or aminoaceto-phenone.

A compound of the formula used as a starting material

X is obtained, for example, by alkylation of an appropriate mercapto compound and, if appropriate, subsequent oxidation.

A compound of the formula used as a starting material

XI is obtained, for example, by alkylating a corresponding phenylalkylamine.

As already mentioned at the beginning, the new compounds have valuable pharmacological properties with a low acute toxicity and with few side effects, namely an effect on the heart and circulation, in particular an effect on blood pressure, an antiarrhythmic and / or cardiotonic effect.

For example, the compounds A = 1- (4-amino-3,5-dichlorophenyl) -2- [N- [3- (4-methoxyphenyl) propyl] amino] ethanol,

B = 1- (4-amino-3-cyano-5-fluorophenyl) -2- [N- [3- (4-methoxyphenyl) propyl] methylamino] ethanol,

C = 1- (4-amino-3,5-dichlorophenyl) -2- [N- (3-phenylpropyl) -2-propylamino] ethanol hydrochloride,

D = 1- (4-amino-3,5-dichlorophenyl) -2- [N- [3- (4-hydroxyphenyl) -1-methylpropyl] methylamino] ethanol,

E = N- [l-methyl-2- (4-amino-3,5-dichlorophenyl) ethyl] -N - [3- (4-methoxyphenyl) propyl] amine hydrochloride,

F = N- [2- (4-amino-3,5-dichlorophenyl) ethyl] -N- [3- (4-chlorophenyl) propyl] isopropylamine,

G = N- [3- (4-chlorophenyl) propyl] -N- [2- (3,5-dichloro-4-iso-propylamino-phenyl) ethyl] isopropylamine and

H = N- [2- (4-amino-3-bromo-5-cyanophenyl) ethyl] -N- [4- (4-methoxyphenyl) butyl] methylamine on their biological effects as follows examined:

1. Measurement of the contractility parameter dp / dtmax or the heart rate in anesthetized cats. Male and female cats weighing approx. 2-4 kg were anesthetized with pentobarbital sodium (40 mg / kg intraperitoneally) and pentobarbital was used to maintain the anesthetic - Infused sodium (8 mg / kg / h) continuously.

The animals breathed spontaneously.

Body temperature was maintained at 38 ° C with a heating pad and thermostat.

The pressure in the left ventricle of the heart was recorded using a pressure transducer (Miliar PC 350) advanced into the left ventricle of the right aorta and the pressure rise rate dp / dt was continuously determined from the pressure signal using a differentiator.

Heart rate was measured continuously with a Grass tachograph (model 7P4). Either an EKG or the left ventricular pressure curve was used as the trigger signal. The parameters were registered on a Grass polygraph.

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All substances were injected as a solution (water or polyethylene glycol 200) into a V. saphena. The dose was 0.3 mg / kg i.v.

The maximum effect and the time after the application up to which the effect decreased to half the maximum effect were specified.

The following tables contain the values found:

Table I:

substance

<7o increase from

Half-life

dp / dtmax in minutes

A

+ 93

38

B

+ 124

> 140

C.

+ 83

112

D

+ 105

> 100

Table II:

Substance% reduction in half-life

Heart rate in minutes

E - 27 39

F - 17 150

G - 13> 90

H - 14> 52

2. Acute toxicity

Male and female mice with a weight of approx. 20 g received the respective test substance in a V. saphena (0.1 or 0.2 ml / 10 g body weight) or in the stomach. After an observation period of 14 days, the LD50 was determined using the Lichtfield and Wilcoxon method:

substance

LD50 mg / kg

i.v.

p.o.

A

19th

> 100

C.

32

250

Because of their pharmacological properties, the compounds produced according to the invention are suitable for the treatment of cardiovascular diseases. Thus, the compounds which have a positive inotropic action, in particular for the treatment of heart failure, and the compounds which lower the heart rate, are particularly suitable for the treatment of cardiac arrhythmias and coronary heart diseases.

For this purpose, the new compounds, if appropriate in combination with other active substances, can be incorporated into the usual galenical preparations such as dragées, tablets, powders, suppositories, suspensions, ampoules or drops. The single dose for adults is 1 to 4 times a day, 5 to 75 mg, but preferably 10 to 50 mg.

The following examples are intended to explain the invention in more detail:

example 1

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (4-methoxyphenyl) propylj-methylaminoj-ethanol

To a solution of 3.45 g (9 mmol) of 4'-amino-3'.5'-di-

chloro-2- [N- [3- (4-methoxy-phenyl) -propyl] -me £ hy] amino] -aceto-phenone in 40 ml of methanol and 15 ml of water are 0.5 g (13.5 mmol) Sodium borohydride added in portions. The pH is kept between 3 and 6 with 2N hydrochloric acid. After the addition, stirring is continued for 30 minutes and the solution is concentrated on a rotary evaporator. The residue obtained is distributed between 100 ml of ether and 100 ml of 2N ammonia solution. The ethereal phase is washed with water, dried with sodium sulfate and concentrated. The remaining oil is chromatographed with methylene chloride: methanol = 19: 1 as eluent over silica gel (Macherey and Nagel 70-230 mesh ASTM). The fractions containing the desired compound are combined, evaporated and the oil obtained is freed from solvent residues in vacuo at 40 ° C.

IR spectrum (methylene chloride):

Oh

3610 cm "1

nh2

3400 + 3490

ch2

2850 + 2940

och3

2830 cm "1

N-alkyl

2800 cm "1

c = c

1610 cm1

UV spectrum (ethanol): X max.

243 nm (0.23)

280 nm (0.08)

300 nm (0.08)

Example 2

1- (4-Amino-3,5-dichlorophenyl) -2- [N- (3-phenyl-propyl) methylaminoj-ethanol hydrochloride

10 g (0.035 mol) of 4'-amino-2-bromo-3 ', 5'-dichloro-aceto-phenone, 6.7 g (0.036 mol) of N- (3-phenyl-propyl) methylamine hydrochloride and 10.5 ml (0.075 mol) of triethylamine are added to 250 ml of methylene chloride. This mixture is heated to reflux temperature for 6 hours and then left to stand at room temperature overnight, washed with water, dried over sodium sulfate and concentrated on a rotary evaporator under vacuum. The oily residue, consisting of crude 4'-amino-3 *, 5'-dichloro-2- [N- (3-phenylpropyl) methylamino] acetophenone, is dissolved in 100 ml of 90% ethanol. While stirring and cooling with water, 5 g of sodium borohydride are added in portions. The mixture is left to stand at room temperature for one hour and excess sodium borohydride is destroyed with acetone. After dilution with water, the mixture is extracted with methylene chloride. The methylene chloride phase is separated off, washed with water, dried over sodium sulfate and concentrated on a rotary evaporator under vacuum. The yellowish oily residue is chromatographed on silica gel using methylene chloride: ethyl acetate = 4: 1 as the eluent. The fractions containing the desired compound are evaporated. The remaining oily residue is dissolved in isopropanol, acidified with ethereal hydrochloric acid and mixed with ether until crystallization occurs. A colorless crystalline product is obtained.

Melting point: from 85 ° C (with sintering).

Example 3

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (4-hydroxyphenyl) -1-methylpropyl] methylamino] ethanol

To an ice-water-cooled solution of 0.1 mol of 4'-amino-3 ', 5'-dichloro-2- [N- [3- (4-hydroxyphenyl) -l-methyl-propyl] methylaminoj-acetophenone in 300 ml of tetrahydrofuran and 50 ml of water, 0.2 mol of sodium borohydride are added in portions with stirring. The reaction solution is stirred for 60 minutes at room temperature and after acidification

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distill the tetrahydrofuran on a rotary evaporator with 2 N hydrochloric acid. The aqueous hydrochloric acid residue obtained is extracted twice with 250 ml ether after addition of 8.5 N ammonia until basic reaction, then the ether extracts are washed twice with 75 ml water and dried with magnesium sulfate. The filtrate is concentrated on a rotary evaporator and the evaporation residue obtained is purified on silica gel 60 (Macherey and Nagel, 70-230 mesh, ASTM). A mixture of methylene chloride: methanol = 30: 1 is used as the eluent. The evaporation residue obtained after fractionation and concentration on a rotary evaporator crystallizes after inoculation. The crude crystals are recrystallized from methylene chloride and are present as a 1: 1 mixture of the diastereomeric racemates.

Melting point: 112-115 ° C.

Example 4

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (4-methoxyphenyl) -1-methylpropyl] methylamino] ethanol

0.02 mol of 1- (4-amino-3,5-dichlorophenyl) -2- [N- [3- (4-methoxyphenyl) -1-methylpropyl] methylamino] ethanol dissolved in 22 ml of 1 N sodium hydroxide solution and 10 ml of water. 0.022 mol of dimethyl sulfate is added dropwise to this solution with stirring and ice-water cooling, and the reaction solution is stirred at room temperature for 20 hours after the addition of 50 ml of tetrahydrofuran. Then 100 ml of ether are added, the organic phase is separated off, washed with 50 ml of 0.5 N sodium hydroxide solution, 3 times with 75 ml of water each time and dried over magnesium sulfate. The organic phase is concentrated on a rotary evaporator and the evaporation residue obtained is purified on silica gel 60 (Macherey and Nagel, 70-230 mesh, ASTM) using methylene chloride: methanol = 30: 1 as the eluent. The oily evaporation residue obtained is freed from solvent residues in vacuo over sulfuric acid. The oil obtained is in the form of a 1: 1 mixture of the diastereomeric racemates.

IR spectrum (methylene chloride):

OH 3200 - 3500 cnr1 wide

(below NH2) NH2 3480 + 3390 cm "1

CH2 2930, 2850 cm "1

OCH3 2830 cm1

N-alkyl 2800 cm-1

C = C 1580.1510.1485 cm "1

C = C + NH2 deformation 1620 cm "1

UV spectrum (ethanol): X max.

244 nm (0.27)

280 nm (0.08)

300 nm (0.08)

Example 5

1- (4-Ethoxycarbonylamino-3-cyano-5-fluorophenyl) -2- [N- [3 - (4-methoxyphenyl) propylJ-aminoJ-ethanol

0.5 g Celite and then 2.5 g (0.01 mol) 4 are placed in a solution of 1.16 g (0.01 mol) selenium dioxide in 12 ml dioxane and 0.7 ml water at 60 ° C with stirring '-Athoxycarbonyl-amino-3'-cyan-5'-fluoro-acetophenone entered in portions. The mixture is then heated to reflux temperature for 4 hours and then filtered off from the undissolved. In the solution of 4'-ethoxy-carbonylamino-3'-cyan-5'-fluorophenyl-glyoxal thus represented, 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, are added dropwise. The solution containing the crude 4'-ethoxycarbonylamino-3 'cyan - 5'-fluorophenylglyoxylidene-3- (4-methoxyphenyl) propylamine is added in portions with 1.5 g of sodium borohydride while stirring and cooling with ice added and left overnight at room temperature. Excess sodium borohydride is then destroyed with acetone, concentrated to a small volume in vacuo, mixed with water and extracted with methylene chloride. The methylene chloride solution is washed with water, dried with sodium sulfate and evaporated to dryness in vacuo. The remaining oily residue is chromatographed over 200 g of silica gel with methylene chloride: methanol = 20: 1 as the eluent. The fractions containing the desired compound are evaporated. A colorless crystalline product is obtained.

Melting point: 111-112 ° C.

Example 6

1- (4-ethoxycarbonylamino-3-cyano-5-fluorophenyl) -2- [N- [3 - (4-methoxyphenyl) propyl] methylamino] ethanol

15 g (0.06 mol) of 4'-ethoxycarbonylamino-3'-cyan-5 'are placed in a solution of 6.6 g (0.06 mol) of selenium dioxide in 60 ml of dioxane and 2 ml of water at 60 ° C. with stirring. -fluoro-aceto-phenone entered in portions. The mixture is then heated to the reflux temperature for 4 hours, then diluted with 100 ml of tetrahydrofuran and the undissolved material is filtered off. 10.7 g (0.06 mol) of N- [3- (4-methoxy-phenyl) are added to the solution of 4'-ethoxycarbonylamino-3 '- cyan-5'-fluorophenylglyoxal thus prepared after cooling at room temperature. -propyl] - methylamine, dissolved in 100 ml of tetrahydrofuran. 8 g (0.13 mol) of sodium cyanoborohydride are added in portions to this solution, the solution being kept at pH 6 by dropwise addition of 2N hydrochloric acid. The mixture is left to stand at room temperature overnight, 5 g of sodium borohydride are added and the mixture is left to stand at room temperature for 5 hours again. Excess sodium borohydride is then destroyed with acetone, diluted with water and extracted with methylene chloride. The methylene chloride solution is washed with water, dried over sodium sulfate and evaporated to dryness in vacuo. The remaining oily residue is chromatographed over 700 g of silica gel with ethyl acetate as the eluent. The fractions containing the desired compound are combined, evaporated and the oil obtained is freed from solvent residues in vacuo at 40 ° C.

IR spectrum (methylene chloride):

Oh

3600 cm "1

nh

3400 cm "1

ch2

2930 cnr1

OCH3

2830 cm "1

N-alkyl

2800 cm "1

cn

2220 cm "1

nhcooc2h5

1735 cm "1

UV spectrum (ethanol): X max.

228 nm (shoulder; 0.19)

240 nm (shoulder; 0.12)

285 nm (0.06)

UV spectrum (ethanol + KOH): X max.

223 nm (shoulder; 0.39)

253 - 265 nm (shoulder, 0.1)

318 nm (0.06)

Example 7

N- [2- (4-Amino-3-bromophenyl) ethyl] -N- [3- (4-methoxy-phenyl) propyl] methylamine dihydrochloride

2.9 g (0.077 mol) of lithium aluminum hydride are suspended in 100 ml of absolute tetrahydrofuran in a nitrogen atmosphere. For this purpose, a solution of 14.4 g (0.031 mol) of 4-amino-3,5-dibromo-N- [3- (4-methoxy-phenyl) -propyl] -N-methyl-phenylacetic acid amide in 100 ml of absolute tetrahydrofuran added dropwise at room temperature with stirring. Connecting

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send is heated to reflux for one hour. The excess lithium aluminum hydride is decomposed with ethyl acetate and water and 10N sodium hydroxide solution is added dropwise until the inorganic material precipitates as granules. The supernatant tetrahydrofuran phase is decanted off, dried over sodium sulfate and concentrated on a rotary evaporator. With methylene chloride: methanol = 19: 1 as the eluent, the mixture is chromatographed on silica gel (Macherey and Nagel, 70-230 mesh ASTM). The fractions with the desired product are combined and concentrated. The oil obtained is dissolved in a little absolute ethanol and the crystalline dihydrochloride is prepared with ethanolic hydrochloric acid with the addition of ether.

Melting point: 168-171 ° C (dec.).

Example 8

N- [2- (4-Amino-3,5-dibromo-phenyl) ethyl] -N- [4- (4-methoxy-phenyl) butyl] methylamine

2.9 g (0.077 mol) of lithium aluminum hydride are suspended in 100 ml of absolute tetrahydrofuran in a nitrogen atmosphere. For this purpose, a solution of 15.0 g (0.031 mol) of 4-amino-3,5-dibromo-N- [4- (4-methoxyphenyl) butyl] -N-methylphenylacetic acid amide in 100 ml of absolute tetrahydrofuran added dropwise at room temperature with stirring. The mixture is then heated to reflux for one hour. The excess lithium aluminum hydride is decomposed with ethyl acetate and water, and 10N sodium hydroxide solution is added dropwise until the inorganic material precipitates as a pellet. The supernatant tetrahydrofuran phase is decanted off, dried over sodium sulfate and concentrated on a rotary evaporator. With methylene chloride: methanol = 19: 1 as the eluent, the mixture is chromatographed on silica gel (Macherey and Nagel, 70-230 mesh ASTM). The fractions with the desired product are combined and concentrated. The oil obtained is freed from solvent residues in vacuo at 40 ° C.

IR spectrum (methylene chloride):

NH2

3380 + 3470

N-alkyl

2790 cm "1

OCHj

2830 cm "1

aliphatic. CH2

2850 + 2930

C = C

1610 cm-1

UV spectrum (ethanol): X max. 246 nm (0.24) 281 nm (0.08) 305 nm (0.09)

Example 9

N- [2- (4-Amino-3-chloro-5-cyanophenyl) ethylJ-N- [3- (4-methoxyphenyl) propyl] methylamine

6.6 g (0.014 mol) of l- (ethoxycarbonyloxy) -l- (4-amino-3-chloro-5-cyano-phenyl) -2- [N- [3- (4-methoxy-phenyl) propyl ] - methylamino] -ethane are dissolved in 70 ml of isopropanol and stirred with 5.5 g (0.14 mol) of sodium borohydride at room temperature overnight. The solution obtained is evaporated to dryness and taken up in 100 ml of water. The excess sodium borohydride is destroyed with 50 ml of 2N hydrochloric acid. The mixture is then made basic again with 100 ml of 2N ammonia and extracted twice with 150 ml of ethyl acetate. The organic phase is dried with magnesium sulfate and concentrated. The oil obtained is chromatographed on silica gel (Macherey and Nagel, 70-230 mesh ASTM) using methylene chloride: methanol = 19: 1 as the eluent. The fractions containing the desired compound are combined and evaporated, and the oil obtained is freed from solvent residues in vacuo at 40 ° C.

IR spectrum (methylene chloride):

NH2 3400 + 3500 cm "1

N-alkyl 2800 cm-1

aliphatic. CH2 2860 + 2940 cm "1

aromatic. C = C 1600 cm-1

NH2 deformation 1625 cm "1 UV spectrum (ethanol): X max.

244 nm (0.23)

278 nm (0.06)

330 nm (0.13)

Example 10

N- [2- (4-Amino-3-chloro-5-cyanophenyl) ethyl] -N- [3- (4 - methoxyphenyl) propyl] methylamine

1.3 g (0.0027 mol) of l- (4-amino-3-chloro-5-cyanophenyl) -2- [N - [3- (4-methoxyphenyl) propyl] methylamino] ethyl iodide are dissolved in 30 ml of hexamethylphosphoric triamide. 0.25 g (0.004 mol) of sodium cyanoborohydride are added to this solution and the mixture is then heated at 70 ° C. for 3 hours. After cooling, the mixture is diluted with 100 ml of water and extracted with ether. The ethereal solution is washed with water, dried over sodium sulfate and evaporated to dryness in vacuo. The remaining oily residue is chromatographed on silica gel with methylene chloride: methanol = 20: 1 as the eluent. The oily residue obtained is freed from solvent residues in vacuo.

Mass spectrum: found M + 357/59

Molecular weight: 357.8.

Example 11

1- (4-Amino-3-fluorophenyl) -2- [N- [3- (4-methoxyphenyl) propylj-methylaminoj-ethanol

A solution of 3.9 g (0.0095 mol) of l- (4-amino-3-bromo-5-fluorophenyl) -2- [N- [3- (4-methoxyphenyl) propyl] -methylamino] ethanol in 50 ml of methanol is mixed with 2 g of 10% palladium / carbon and hydrogenated in an autoclave at room temperature and a pressure of 3.5 bar. After the theoretically calculated amount of hydrogen has been taken up, the mixture is filtered off and the filtrate is concentrated on a rotary evaporator. The 4 g of oil obtained in this way are chromatographed on silica gel (Macherey and Nagel, 70-230 mesh ASTM) using chloroform: methanol = 19: 1 as the eluent. The fractions containing the desired substance are pooled and concentrated. The oil obtained is dissolved in isopropanol and the hydrochloride is precipitated with isopropanolic hydrochloric acid and ethyl acetate. The crystals are filtered off, washed with a little cold isopropanol and dried in vacuo.

Melting point: 110 ° C (decomp.).

Example 12

l- (4-Àthoxycarbonylamino-3-bromophenyl) -2- [N- [4- (4 - methoxyphenyl) butyl] methylamino] ethanol

To a solution of 5.1 g (0.0125 mol) of 1- (4-amino-3-bromophenyl) -2- [N- [4- (4-methoxyphenyl) butyl] methylamino ] ethanol in 40 ml of absolute pyridine, 1.5 ml (0.015 mol) of ethyl chloroformate are added with ice cooling at 0 ° C. The solution obtained is stored in the refrigerator at + 4 ° C. overnight. The pyridine is then distilled off on a rotary evaporator at 50 ° C. The oil obtained is dissolved in 100 ml of methylene chloride and washed twice with 100 ml of water. The organic phase is dried over sodium sulfate, filtered and evaporated on a rotary evaporator. The oil obtained is chromatographed on silica gel (Macherey and Nagel, 70-230 mesh ASTM) using methylene chloride: methanol = 9: 1 as the eluent. The Fractio5

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nen, which contain the desired substance, are combined and concentrated. The oil obtained is freed from solvent residues in vacuo at 40 ° C.

IR spectrum (methylene chloride):

3610 cm "1 3400 cm1 2830 cm" 1 2800 cm "1 2860 + 2940 cm" 1 1735 cm "1 1610 cm-1

OH NH OCH3 N-alkyl aliphatic. CH2

c = o aromat. C = C UV spectrum (ethanol): X max. 224 nm (0.42) 240 am (0.29) 280 nm (0.04)

Example 13

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [3- (4-hydroxyphenyl) -1-methyl-propyl] methylamine

0.012 mol of N- [2- (4-amino-3,5-dichlorophenyl) ethyl] -N- [3 - (4-hydroxy-phenyl) -l-methyl-propyl] -amine are in 13 ml 1 N sodium hydroxide solution dissolved. 0.014 mol of dimethyl sulfate is added dropwise to the solution while cooling with ice water. After a short time, the reaction product is greasy and is dissolved by adding 150 ml of tetrahydrofuran. The reaction solution is stirred for 24 hours at room temperature and then extracted twice with 150 ml of ether each time. The organic extracts are washed with water, dried over magnesium sulfate and concentrated in vacuo. The evaporation residue obtained was purified on silica gel (Polygosil 60-1525; Macherey and Nagel) with methylene chloride: methanol / conc. Ammonia = 19: 1: 0.1. The oily evaporation residue is freed of adhering solvents in vacuo over potassium hydroxide.

IR spectrum (methylene chloride):

OH 3580 cm "1

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

UV spectrum (ethanol): X max.

240 nm (0.26; shoulder)

288 nm (0.08)

301 nm (0.08)

UV spectrum (ethanol + KOH): X max.

241 nm (0.56)

299 nm (0.17)

Example 14

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [2- (4-methoxyphenylsulfinyl) ethyl] methylamino] ethanol

7.0 g of l- (4-amino-3,5-dichlorophenyl) -2- [N- [2- (4-methoxy-phenylsulfenyl) ethyl] methylamino] ethanol are dissolved in 100 ml of glacial acetic acid and 2.0 g of 30% hydrogen peroxide are added dropwise with stirring at room temperature. The mixture is stirred overnight at the same temperature and then the solution is evaporated in vacuo. The residue is taken up in water and potassium carbonate is added until the reaction is basic. It is extracted with dichloromethane, the organic phase is washed with water, dried with magnesium sulfate and evaporated in vacuo. The residue is purified by chromatography (column: 40 × 200 mm; silica gel 60, from E. Merck, particle size: 0.06-0.2 mm, methylene chloride: methanol = 50: 1). After evaporating the desired one

35

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Oil.

IR spectrum (methylene chloride):

NH2 3390 + 3480 cm'1

CH2 2940 cm "1

OCH3 2840 cm "1

N-alkyl 2800 cm "1

C = C 1590, 1510 + 1480 cm "1

S = 0 1040 cm "1 (shoulder)

UV spectrum (ethanol): X max.

244 nm (0.54)

300 nm (0.07; shoulder)

Example 15

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [2- (4-methoxyphenylsulfonyl) ethyl] methylamino] ethanol

7.0 g of l- (4-amino-3,5-dichlorophenyl) -2- [N- [2- (4-methoxy - phenylsulfenyl) ethyl] methylamino] ethanol, as in Example 14 described, converted into the sulfinyl derivative. The residue obtained after evaporation of the dichloromethane extract (4.7 g) is dissolved in 100 ml of dioxane and 30 ml of water, and 4.0 g of magnesium sulfate are added. While stirring, 2.5 g of powdered potassium permanganate are added in portions. When the addition is complete, stirring is continued for two hours and then the undissolved material is filtered off over Celite. The dioxane is removed in vacuo and partitioned between dichloromethane and water. The evaporation residue of the dried organic phase is purified by chromatography twice (1st column: 60 x 300 mm, Al 2 O 3 II neutral, methylene chloride: tetrahydrofuran = 5: 1; 2nd column: 35 x 300 mm, silica gel 60, from E. Merck, Grain size: 0.015 - 0.025 mm, dichloromethane, 8.5 bar). After evaporating the desired fractions in vacuo, the substance mentioned remains as an oil.

IR spectrum (methylene chloride):

NH2 3395 + 3480 cm "1

CH2 2940 cm "1

OCH3 2840 cm "1

N-alkyl 2800 cm -1

C = C 1595, 1520 + 1495 cm "1

S02 1150 + 1315 cm "1

UV spectrum (ethanol): X max.

241 nm (0.59)

300 nm (0.09)

Example 16

50 liters of (4-amino-3,5-dichlorophenyl) -2- [N- [3- (4-hydroxyphenyl) propyl] methylamino] ethanol

9.2 g of l- (4-amino-3,5-dichlorophenyl) -2- [N- [3- (4-benzyloxyphenyl) propyl] methylamino] ethanol are dissolved in 150 ml of Me- 55 ethanol dissolved. The solution is mixed with 1 g of 5% palladium / carbon and hydrogenated at room temperature under a pressure of 5 bar hydrogen. After the calculated amount of hydrogen has been taken up, the catalyst is filtered off, the solution is evaporated to dryness on a rotary evaporator and the 60% oily residue is chromatographed on silica gel using methylene chloride / methanol = 20: 1 as the eluent. The fractions containing the desired compound are combined, evaporated and the oil obtained is freed from solvent residues in vacuo at 40 ° C.

65 IR spectrum (methylene chloride):

OH 3580 cm "1

NH2 3395 + 3495 cm "1

N-alkyl 2800 cm "1

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Example 17

1- (4-Amino-3-bromophenyl) -2- [N- [4- (4-methoxyphenyl) butylj-methylaminoj-ethanol

3 g of l- (4-acetamino-3-bromophenyl) -2- [N- [4- (4-methoxyphenyl) butyl] methylamino] ethanol are dissolved in 100 ml of semi-concentrated hydrochloric acid for one hour Reflux temperature heated. After cooling, the mixture is made alkaline with 10N sodium hydroxide solution, extracted with methylene chloride, the methylene chloride solution is washed with water, dried over sodium sulfate and concentrated to dryness in a rotary evaporator. The remaining oil is chromatographed on silica gel using methylene chloride / methanol = 20: 1 as the eluent. The fractions containing the desired compound are obtained as an oil by evaporation in vacuo at 40 ° C. IR spectrum (methylene chloride):

OH 3590 cnr1

NH2 3380 + 3470 cm "1

N-alkyl 2800 cm -1

OCH3 2830 cm "1

aliph. CH2 2850 + 2930 cm "1

aroma. C = C 1620 cm-1

UV spectrum (ethanol): X max.

224 nm (0.20)

243 nm (0.14)

280 nm (0.04)

300 nm (0.04)

Example 18

1- (4-Amino-3-cyano-5-fluorophenyl) -2- [N- [3- (4-methoxyphenyl) propyl] methylamino] ethanol

Prepared from 4'-amino-3'-cyan-5'-fluoro-2- [N- [3- (4-meth-oxy-phenyl) propyl] methylamino] acetophenone and sodium borohydride in 90% methanol as in Example 1 IR spectrum (methylene chloride):

Oh

3590 cm'1

NH2

3400 + 3490

ch2

2850 + 2940

och3

2830 cm'1

N-alkyl

2800 cm "1

c = N

2210 cm'1

NH2 deformation

1635 cm "1

aromatic. c = c 1

1610 cm "1

UV spectrum (ethanol): X max. 242 nm (0.3) 325 nm (0.14)

Example 19

I- (4-Amino-3-bromo-5-cyanophenyl) -2- [N- [3- (4-methoxyphenyl) propyl] methylamino] ethanol

Prepared from 4'-amino-3'-bromo-5'-cyan-2- [N- [3- (4-meth-oxy-phenyl) propyl] methylaminol acetophenone and sodium borohydride in 80% methanol according to the example 1. IR spectrum (methylene chloride):

OH 3590 cm "1 weak

NH2 3400 + 3480 cm "1

CH2 2850 + 2930 cm "1

C s N 2200 cm "1

C = C 1640 cm- '

UV spectrum (ethanol): X max. 243 nm (0.20) 280 nm (0.04) 334 nm (0.12)

Example 20

1- (4-Amino-3,5-dibromophenyl) -2- [N- [3- (4-methoxyphenyl) propyl] methylamino] ethanol

Prepared from 4, -amino-3 ', 5'-dibromo-2- [N - [- 3- (4-methoxy-phenyl) propyl] methylamino] acetophenone and sodium borohydride in 80% methanol as in Example 1 .

IR spectrum (methylene chloride):

OH 3590 cm "1

NH2 3380 + 3460 cm "1

N-alkyl 2800 cm -1

OCH3 2830 cm'1

aliphatic. CH2 2850 + 2940 cm "1

C = C 1610 cm "1

UV spectrum (ethanol): X max.

244 nm (0.16)

303 nm (0.06)

Example 21

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [1,1-dimethyl-3 - (4-methoxyphenyl) propyl] 'amino] ethanol

Made from l- (4-amino-3,5-dichlorophenyl) -2- [N- [l, l - dimethyl-3- (4-hydroxyphenyl) propyl] amino] ethanol, tetrahydrofuran , Sodium hydroxide solution and dimethyl sulfate analogous to Example 13. Oil.

IR spectrum (methylene chloride):

OH 3600 cm "1

NH2 3390 + 3490 cm "1

CH2 2860 + 2960 cm "1

OCH3 2830 cm "1

C = C 1580 + 1620 cm "1

UV spectrum (ethanol): X max. 243 nm (0.23) 280 nm (0.08) 300 nm (0.08)

Example 22

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [1,1-dimethyl-3 - (4-methoxyphenyl) propyl] methylamino] ethanol

Made from l- (4-amino-3,5-dichlorophenyl) -2- [N- [l, l - dimethyl-3- (4-hydroxyphenyl) propyl] amino] ethanol, tetra -hydrofuran, sodium hydroxide solution and dimethyl sulfate analogously to Example 13. Oil.

Calculated: C 61.31 H 6.86 Cl 17.24 N 6.81

Found: C 61.13 H 6.99 Cl 17.25 N 6.75

Example 23

1- (4-Amino-3-chloro-5-trifluoromethylphenyl) -2- [N- [3 - (4-methoxyphenyl) propyl] methylamino] ethanol

Made from 4'-amino-3'-chloro-5'-trifluoromethyl-2- [N - [3- (4-methoxyphenyl) propyl] methylamino] acetophenone and sodium borohydride in 80% methanol as in Example 1. IR spectrum (methylene chloride):

OH 3590 cm'1

NH2 3410 + 3510 cm'1

N-alkyl 2800 cm -1

OCH3 2830 cm'1

aliphatic. CH2 2850 + 2940 cm'1

C = C 1630 cm'1

UV spectrum (ethanol): X max.

225 nm (0.36)

245 nm (0.31)

280 nm (0.05)

310 nm (0.1)

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Example 24

1- (3,5-dichloro-4-hydroxyphenyl) -2- [N- [3- (4-methoxyphenyl) propylJ-methylamino] ethanol

Prepared from 3 ', 5'-dichloro-4'-hydroxy-2- [N- [3- (4-methoxyphenyl) propyl] methylamino] acetophenone and sodium borohydride in 80% methanol as in Example 1 Melting point: 156-157 ° C.

Example 25

1- (3,5-dibromo-4-hydroxy-phenyl) -2- [N- [3- (4-methoxy-phenylj-propylj-methylaminoj-ethanol

Prepared from 3 ', 5'-dibromo-4'-hydroxy-2- [N- [3- (4-methoxyphenyl) propyl] methylamino] acetophenone and sodium borohydride in 80% methanol as in Example 1 Hydrochloride melting point: 159-162 ° C.

Example 26

1- (4-Amino-3-bromo-5-fluoro-phenyl) -2- [N- [3- (4-methoxy-phenylj-propylj-methylaminoj-ethanol

Prepared analogously from 4'-amino-3'-bromo-5'-fluoro-2- [N- [3- (4-methoxyphenyl) propyl] methylamino] acetophenone and sodium borohydride in 80% methanol Example 1. Melting point of the hydrochloride (amorphous): from 60 ° C.

Example 27

1- (4-Amino-3-chloro-5-fluorophenyl) -2- [N- [3- (4-methoxyphenyl) propyl] methylamino] ethanol

Prepared analogously from 4'-amino-3'-chloro-5'-fluoro-2- [N- [3- (4-meth-oxy-phenyl) propyl] methylamino] acetophenone and sodium borohydride in 80% methanol Example 1. Melting point of the hydrochloride: 103-108 ° C (dec.).

Example 28

1- (4-Amino-3-chloro-5-cyanophenyl) -2- [N- [3- (4-methoxyphenyl) propyl] methylamino] ethanol

Prepared analogously from 4'-amino-3'-chloro-5'-cyan-2- [N- [3- (4-methoxyphenyl) propyl] methylamino] acetophenone and sodium borohydride in 80% methanol Example 1. IR spectrum (methylene chloride):

OH 3590 cm "1

NH2 3400 + 3500 cm "1

N-alkyl 2800 cm "1

OCHa 2830 cm "1

aliphatic. CH2 2850 + 2940 cm'1

C s N 2210 cm "1

C = C 1625 cm "1

UV spectrum (ethanol): X max.

245 nm (0.26)

278 nm (0.06)

332 nm (0.16)

Example 29

1- (4-Amino-3-chloro-5-nitro-phenyl) -2- [N- [3- (4-methoxy-phenyl) propyl] methylamino] ethanol

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

IR spectrum (methylene chloride):

OH 3590 cm "1

NH2 3390 + 3500 cm "1

N-alkyl 2800 cm "1

OCH3 2830 cm "1

aliphatic. CH2 2850 + 2940 cm "1

C = C 1630 cm "1

NOZ 1330 + 1515 cm "1

UV spectrum (ethanol): X max.

227 nm (0.64)

280 nm (0.16)

400 nm (0.12)

Example 30

1- (4-Amino-3-chlorophenyl) -2- [N- [3- (4-methoxyphenyl) propyl] methylamino] ethanol

Prepared from 4'-amino-3'-chloro-2- [N- [3- (4-methoxyphenyl) propyl] methylamino] acetophenone and sodium borohydride in 80% methanol as in Example 1.

IR spectrum (methylene chloride):

OH 3600 cm "1

NH2 3380 + 3470 cm "1

N-alkyl 2800 cm "1

OCH3 2830 cm "1

aliphatic. CH2 2850 + 2940 cm "1

C = C 1620 cm "1

UV spectrum (ethanol): X max.

225 nm (0.44)

243 nm (0.36)

280 nm (0.09)

295 nm (0.08)

Example 31

1- (4-Amino-3-bromophenyl) -2- [N- [3- (4-methoxyphenyl) propyl] methylamino] ethanol

Prepared from 4'-amino-3'-bromo-2- [N- [3- (4-methoxyphenyl) propyl] methylamino] acetophenone and sodium borohydride in 80% methanol as in Example 1.

Melting point of the dihydrochloride: 137 ° C (dec.).

Example 32

1- (4-Amino-3,5-dicyanophenyl) -2- [N- [3- (4-methoxyphenyl) propylj-methylaminoj-ethanol

Prepared from 4'-amino-3 ', 5'-dicyan-2- [N- [3- (4-methoxyphenyl) propyl] methylamino] acetophenone and sodium borohydride in 80% methanol as in Example 1.

Melting point of the hydrochloride: 167-170 ° C.

Example 33

1- (4-Amino-3-bromophenyl) -2- [N- [4- (4-methoxyphenyl) butyl] methylamino] ethanol

Prepared from 4'-amino-3'-bromo-2- [N- [4- (4-methoxyphenyl) butyl] methylamino] acetophenone and sodium borohydride in 80% methanol as in Example 1.

IR spectrum (methylene chloride):

OH 3590 cm "1

NH2 3380 + 3470 cm "1

N-alkyl 2800 cm "1

OCH3 2830 cm "1

aliphatic. CH2 2850 + 2930 cm'1

C = C 1620 cm'1

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UV spectrum (ethanol): X max. 224 nm (0.44) 243 nm (0.28) 280 nm (0.08) 300 nm (0.06)

Example 34

1- (4-Amino-3-bromo-phenyl) -2- [N- [2- (4-methoxy-phenyl) - ethylj-methylaminoj-ethanol

Made from 4'-amino-3'-bromo-2- [N- [2- (4-methoxyphenyl) ethyl] methylamino] acetophenone and sodium borohydride in 80% methanol analogous to Example 1. IR spectrum (Methylene chloride):

Oh

3590 cm "1

NH2

3380 + 3470 cm "1

N-alkyl

2800 cm "1

och3

2830 cm "1

aliphatic. ch2

2840 + 2940 cm "1

c = c

1620 cm "1

UV spectrum (ethanol): X max. 225 nm (0.43) 243 nm (0.36) 280 nm (0.08) 296 nm (0.08)

Example 35

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [4- (4-methoxyphenyl) butyl] methylamino] ethanol

Prepared from 4'-amino-3 ', 5'-dichloro-2- [N- [4- (4-methoxyphenyl) butyl] methylamino] acetophenone and sodium borohydride in 80% methanol as in Example 1.

IR spectrum (methylene chloride):

OH 3590 cm "1

NH2 3390 + 3490 cm "1

N-alkyl 2800 cm "1

OCHj 2830 cm "1

aliphatic. CH2 2850 + 2930 cm "1

C = C 1610 cm1

UV spectrum (ethanol): X max.

245 nm (0.25)

320 nm (0.48)

Example 36

1- (4-Amino-3-bromo-5-cyanophenyl) -2- [N- [4- (4-methoxyphenyl) butyl] methylamino] ethanol

Made from 4'-amino-3'-bromo-5'-cyan-2- [N- [4- (4-methoxyphenyl) butyl] methylamino] acetophenone and sodium borohydride in 80% Methanol analogous to example 1. IR spectrum (methylene chloride):

OH 3590 cm "1

NH2 3390 + 3490 cm "1

N-alkyl 2800 cm "1

OCH3 2830 cm "1

aliphatic. CH2 2850 + 2930 cm "1

C = N 2210 cm -1

C = C 1620 cm'1

UV spectrum (ethanol): X max.

245 nm (0.27)

278 nm (0.08)

330 nm (0.15)

Example 37

1- (4-Amino-3-bromo-5-cyanophenyl) -2- [N- [2- (4-methoxyphenyl) ethyl] methylamino] ethanol

Manufactured analogously from 4'-amino-3'-bromo-5'-cyan-2- [N- [2- (4-meth-oxy-phenyl) ethyl] methylamino] acetophenone and sodium borohydride in 80% methanol Example 1. IR spectrum (methylene chloride):

OH 3590 cm1

NH2 3390 + 3490 cm'1

N-alkyl 2800 cm -1

OCH3 2830 cm'1

aliphatic. CH2 2850 + 2950 cm "1

C = N 2210 cm "1

C = C 1620 cm "1

UV spectrum (ethanol): X max.

245 nm (0.25)

277 nm (0.09)

331 nm (0.10)

Example 38

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [2- (4-methoxyphenyl) ethylj-methylaminoj-ethanol

Prepared from 4'-amino-3 ', 5'-dichloro-2- [N- [2- (4-methoxyphenyl) ethyl] methylamino] acetophenone and sodium borohydride in 80% methanol as in Example 1.

IR spectrum (methylene chloride):

OH 3590 cm "1

NH2 3390 + 3490 cm "1

N-alkyl 2800 cm -1

OCH3 2830 cm'1

aliphatic. CH2 2850 + 2930 cm "1

C = C 1610 cm "1

Example 39

1- (4-Amino-3-chloro-5-cyanophenyl) -2- [N- [4- (4-methoxyphenyl) butyl] methylamino] ethanol

Prepared from 4'-amino-3'-chloro-5'-cyan-2- [N- [4- (4-meth-oxy-phenyl) butyl] methylamino] acetophenone and sodium borohydride in methanol as described in Example 1 IR spectrum (methylene chloride):

OH 3590 cm "1

NH2 3400 + 3500 cm "1

N-alkyl 2800 cm "1

OCHj 2830 cm "1

aliphatic. CH2 2850 + 2930 cm "1

C = N 2210 cm "1

C = C 1625 cm "1

UV spectrum (ethanol): X max.

245 nm (0.23)

280 nm (0.05)

332 nm (0.13)

Example 40

1- (4-Amino-3-chloro-5-cyanophenyl) -2- [N- [2- (4-methoxyphenyl) ethyl] methylamino] ethanol

Prepared analogously from 4'-amino-3'-chloro-5'-cyan-2- [N- [2- (4-meth-oxy-phenyl) ethyl] methylamino] acetophenone and sodium borohydride in 80% methanol Example 1.

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IR spectrum (methylene chloride):

OH 3590 cm "1

NH2 3390 + 3490 cm "1

N-alkyl 2800 cm "1

OCH3 2830 cm1

CH2 2850 + 2940 cm "1

C = N 2210 cm "1

C = C 1620 cm "1

UV spectrum (ethanol): X max.

245 nm (0.24)

280 nm (0.04)

332 nm (0.13)

Example 41 *

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [2- (4-methoxyphenylsulfenyl) ethyl] methylamino] ethanol

Made from 4'-amino-3 ', 5'-dichloro-2- [N- [2- (4-methoxy-phenylsulfenyl) ethyl] methylamino] acetophenone and sodium borohydride in tetrahydrofuran: water: methanol = 25: 5:10 as in Example 1. Oil.

IR spectrum (methylene chloride):

OH 3200-2500 cm "1 (under NH2)

NH2 3480 + 3390 cm "1

CH2 2940 cm "1

N-alkyl 2800 cm "1

OCH3 2830 cm "1

C = C 1580 + 1490 cm "1

UV spectrum (ethanol): X max.

230 nm (0.58; shoulder)

245 nm (0.54)

298 nm (0.14)

Example 42

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [2- (4-methoxyphenoxy) ethyl] methylamino] ethanol

Made from 4'-amino-3 ', 5'-dichloro-2- [N- [2- (4-methoxyphenoxy) ethyl] methylamino] acetophenone and sodium borohydride in tetrahydrofuran: water: methanol = 15: 5: 3 analogous to example 1. Oil.

IR spectrum (methylene chloride):

OH 3200-3500 cm "1 (under NH2)

NH2 3480 + 3390 cm "1

CH2 2940 cm "1

N-alkyl 2790 cnr1

OCH3 2830 cm1

C = C 1580, 1505 + 1485 cm "1

C-O-aryl 1250 cm "'

UV spectrum (ethanol): X max.

230 nm (0.32; shoulder)

244 nm (0.26; shoulder)

294 nm (0.12)

Example 43

l- (4-amino-3,5-dichlorophenyl) -2- [N- [3- (4-methoxyphenyl) propylj-aminoj-propanol- (l)

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

Melting point of the hydrochloride: 201-202 ° C (dec.).

Example 44

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (4-methoxyphetiyl) propylJ-2-propylaminoJ-ethanol

Made from 4'-amino-3 ', 5'-dichloro-2- [N- [3- (4-methoxy-

-phenyl) -propyl] -2-propylamino] -acetophenone and sodium borohydride analogously to Example 1. Oil.

IR spectrum (methylene chloride):

OH 3600 cm "1

NH2 3400 + 3490 cm "'

OCH3 2830 cm "'

UV spectrum (ethanol): X max.

243 nm (0.13)

280 nm (0.03)

300 nm (0.03)

Example 45

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (4-methoxyphenyl) propylj-ethylaminoj-ethanol

Prepared from 4'-amino-3 ', 5'-dichloro-2- [N- [3- (4-methoxyphenyl) propyl] ethylamino] acetophenone and sodium borohydride analogously to Example 1.

IR spectrum (methylene chloride):

OH 3600 cm "'

NH2 3395 + 3490 cm "1

OCH3 2830 cm "'

UV spectrum (ethanol): X max.

243 nm (0.13)

280 nm (0.04)

300 nm (0.04)

Example 46

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (4-methoxyphenyl) propyl] propylamino] ethanol

Made from 4'-amino-3 ', 5'-dichloro-2- [N- [3- (4-methoxyphenyl) propyl] propylamino] acetophenone and sodium borohydride analogously to Example 1. Oil.

IR spectrum (methylene chloride):

OH 3600 cm "1

NH2 3395 + 3495 cm "1

OCH3 2850 cm "1

UV spectrum (ethanol): X max.

245 nm (0.10)

280 nm (0.03)

300 nm (0.03)

Example 47

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (4-methoxyphenyl) propylj-cyclopropylam inoj-ethanol

Prepared from 4'-amino-3 ', 5'-dichloro-2- [N- [3- (4-methoxyphenyl) propyl] cyclopropylamino] acetophenone and sodium borohydride analogously to Example 1. Oil.

IR spectrum (methylene chloride):

OH 3590 cm "1

NH2 3395 + 3495 cm "1

OCH3 2850 cm "1

UV spectrum (ethanol): X max.

245 nm (0.12)

280 nm (0.04)

300 nm (0.04)

Example 48

1- (4-amino-3,5-dichlorophenyl) -2- [N- [3- (4-methoxyphenyl) propyl] methylamino] propanol (l), isomer B

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

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IR spectrum (methylene chloride):

OH 3600 + 3680 cm "1

NH2 3390 + 3490 cm "1

OCH3 2835 + 2940 cm "1

Aromat 1510, 1585 + 1610 cnrJ

UV spectrum (ethanol): X max.

246 nm (0.14)

278 nm (0.08)

285 nm (0.08)

300 nm (0.08)

NMR spectrum (CDCI3 / D2O): signal of the proton at carbon atom 1 of the propanol part: doublet at 4.1 ppm (J = 10 Hz).

Example 49

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (4-methoxyphenyl) propyl] methylamino] propanol (l), isomer A

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

Melting point of the hydrochloride: 178-181 ° C. NRM spectrum of the base (CDCI3 / D2O): signal of the proton at carbon atom 1 of the propanol part: doublet at 4.6 ppm (J = 4.5 Hz).

Example 50

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (4-ethoxyphenyl) propyl] methylaminoJ-ethanol

Made from 4'-amino-3 ', 5'-dichloro-2-bromo-acetophenone, l- (4-ethoxy-phenyl) -3-methylamino-propane hydrochloride, triethylamine and sodium borohydride analogously to Example 2. Oil. IR spectrum (methylene chloride):

OH 3590 cm "1

NH2 3395 + 3495 cm "1

N-alkyl 2800 cm "1

UV spectrum (ethanol): X max.

245 nm (0.13)

280 nm (0.04)

300 nm (0.04)

Example 51

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (4-benzyloxyphenyl) propyl] methylaminoJ-ethanol

Made from 4'-amino-3 ', 5'-dichloro-2-bromo-acetophenone, 1- (4-benzyloxy-phenyl) -3-methylamino-propane hydrochloride, triethylamine and sodium borohydride analogously to Example 2. Oil. IR spectrum (methylene chloride):

OH 3590 cm "1

NH2 3395 + 3495 cm "1

N-alkyl 2800 cm "1

Example 52

1- (4-Amino-3-iodo-5-fluorophenyl) -2- [N- [3- (4-methoxyphenyl) propyl] methylamino] ethanol

Made from 4'-amino-3'-iodo-5'-fluoro-2-bromo-aceto-phenone, l- (4-methoxy-phenyl) -3-methylamino-propane-hydrochloride, triethylamine and sodium borohydride analogously to the example 2nd

Oil.

IR spectrum (methylene chloride):

OH 3590 cm "1

NH2 3395 + 3495 cm "1

N-alkyl 2800 cm "1 2800 cm" 1

Example 53

1- (4-Amino-3-cyan-5-fluorophenyl) -2- [N- [3- (4-methoxyphenyl) propyl] -2-propylamino] ethanol

Made from 4'-amino-3 '-cyan-5' -fluoro-2-bromo-aceto-phenone, 1 - (4-methoxyphenyl) -3- (2-propylamino) propane - hydrochloride and sodium borohydride analogously Example 2. Oil. IR spectrum (methylene chloride):

OH 3600 cm "1

NH2 3395 + 3495 cm "1

OCH3 2830 cm "1

N-alkyl 2800 cm "1

C = N 2220 cm "1

Example 54

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (2-methoxyphenyl) propylj-methylaminoj-ethanol hydrochloride

Made from 4'-amino-3'55'-dichlororr2-bromo-acetophenone, l- (2-methoxy-phenyl) -3-methylamino-propane hydrochloride, triethylamine and sodium borohydride analogously to Example 2. Melting point: from 75 ° C under sintering).

Example 55

1- (4-A mino-3,5-dichlorophenyl) -2- [N- [3- (3,4-dimethoxyphenyl) propyl] methylamino] ethanol

Made from 4'-amino-3 ', 5'-dichloro-2-bromo-acetophenone, l- (3,4-dimethoxy-phenyl) -3-methylamino-propane hydrochloride, triethylamine and sodium borohydride analogously to Example 2. IR- Spectrum (methylene chloride):

OH 3600 cm "1

NH2 3390 + 3485 cm "1

OCH3 2830 cm1

N-alkyl 2800 cm "1

Example 56

1- (4-Amino-3-chloro-5-trifluoromethylphenyl) -2- [N- [2- (4 - methoxyphenyl) ethyl] methylamino] ethanol

Made from 4'-amino-3'-chloro-5'-trifluoromethyl-2- [N- [2 - (4-methoxyphenyl) ethyl] methylamino] acetophenone, and sodium borohydride in 80% methanol analog Example 1. IR spectrum (methylene chloride):

OH 3600 cm "1

NH2 3410 + 3510 cm "1

N-alkyl 2800 cm "1

O-CH3 2830 cm "1

aliphatic. CH2 2850 + 2940 cm "1

C = C 1630 cm "1

UV spectrum (ethanol): X max.

225 nm (0.38)

244 nm (0.34)

280 nm (0.07)

307 nm (0.10)

Example 57

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (4-methoxyphenyl) propylj-aminoj-ethanol hydrochloride

Prepared from 4'-amino-3 ', 5'-dichloro-2- [N- [3- (4-methoxyphenyl) propyl] amino] acetophenone and sodium borohydride in 90% ethanol as in Example 1.

Melting point of the hydrochloride: 185-186 ° C (ethanol / ether).

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Example 58

1- (4-Amino-3,5-dichlorophenyl) -2- [N- (3-phenyl-propyl) -2-propylaminoJ-ethanol hydrochloride

Made from 4'-amino-3 ', 5'-dichloro-2-bromo-acetophenone, l-phenyl-3- (2-propylamino) propane hydrochloride, triethylamine and sodium borohydride analogously to Example 2.

Melting point: 124-128 ° C.

Example 59

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (4-fluorophenyl) propyl] methylamino] ethanol hydrochloride

Prepared from 4'-amino-3 ', 5'-dichloro-2-bromo-acetophenone, l- (4-fluorophenyl) -3-methylamino-propane hydrochloride, triethylamine and sodium borohydride analogously to Example 2.

Melting point: 185-188 ° C (dec.).

Example 60

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (4-hydroxyphenyl) -1-methyl-propylJ-aminoJ-ethanol

Prepared from 4'-amino-3 ', 5'-dichloro-2- [N- [3- (4-hydroxy-phenyl) -l-methyl-propyl] -amino] -acetophenone and sodium borohydride in aqueous tetrahydrofuran as in Example 4. A mixture of dichloromethane / methanol / conc. Ammonia = 19: 1: 0.05 used.

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

IR spectrum (KBr):

OH 2300-3500 cm-1 (wide, associated)

NH2 3460 + 3370 cm "1

CH2 2920 + 2960 cm "1

C = C 1580, 1510 + 1480 cm "1

UV spectrum (ethanol): X max.

244 nm (0.28)

280 nm (0.08)

300 nm (0.08)

UV spectrum (ethanol + KOH): X max.

243 nm (0.54)

299 nm (0.15)

Example 61

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (4-methoxyphenyl) -1-methylpropylJ-aminoJ-ethanol

Prepared from 4'-amino-3 ', 5'-dichloro-2- [N- [3- (4-methoxy-phenyl) -l-methyl-propyl] -amino] -acetophenone and sodium borohydride in aqueous tetrahydrofuran as in Example 4. Oil.

The compound is present as a 1: 1 mixture of the diastereomeric racemates.

IR spectrum (methylene chloride): -

OH 3600 cm "1

NH2 3480 + 3390 cm "1

CH2 2930 cm "'

OCH3 2830 cm'1

C = C 1580, 1510 + 1485 cm "1

UV spectrum (ethanol): X max.

244 nm (0.28)

280 nm (0.08)

300 nm (0.09)

Example 62

1- (4-Amino-3-cyan-5-fluorophenyl) -2- [N- [2- (3,4-dimethoxyphenyl) ethyl] amino] ethanol hydrochloride

Made from 4'-amino-3'-fluoro-5'-cyan-acetophenone,

Selenium dioxide, 2- (3,4-dimethoxy-phenyl) ethylamine and sodium borohydride as in Example 5.

Melting point: 196-197 ° C (dec.).

Example 63

1- (4-Amino-3-fluoro-5-iodophenyl) -2- [N- [2- (3,4-dimethoxyphenyl) ethyl] amino] ethanol hydrochloride

Prepared from 4'-amino-3'-fluoro-5'-iodo-acetophenone, selenium dioxide, 2- (3,4-dimethoxy-phenyl) -ethylamine and sodium borohydride analogously to Example 5.

Melting point: 192-193 ° C (dec.).

Example 64

1- (4-Amino-3-chloro-5-fluorophenyl) -2- [N- [2- (3,4-dimethoxy - phenylj-ethylj-aminoj-ethanol hydrochloride

Prepared from 4'-amino-3'-chloro-5'-fluoro-acetophenone, selenium dioxide, 2- (3,4-dimethoxy-phenyl) -ethylamine and sodium borohydride as in Example 5.

Melting point: 184-186 ° C (dec.).

Example 65

1- (4-Amino-3-bromo-5-fluorophenyl) -2- [N- [2- (3,4-dimethoxyphenyl) ethyl] amino] ethanol hydrochloride

Prepared from 4'-amino-3'-bromo-5'-fluoro-acetophenone, selenium dioxide, 2- (3,4-dimethoxy-phenyl) -ethylamine and sodium borohydride as in Example 5.

Melting point: 194-195 ° C (dec.).

Example 66

1- (4-Amino-3-fluoro-5-cyanophenyl) -2- [N- [3- (4-methoxyphenyl) propyl] amino] ethanol

Prepared from 4'-amino-3'-fluoro-5'-cyano-acetophenone, selenium dioxide, 3- (4-methoxyphenyl) propylamine and sodium borohydride as in Example 5.

Melting point: 119-121 ° C.

Example 67

1- (4-Amino-3,5-dichlorophenyl) -2- [N- (3-phenylpropyl) aminoamethanol hydrochloride

Prepared from 4'-amino-3 ', 5'-dichloroacetophenone, selenium dioxide, 3-phenyl-propylamine and sodium borohydride analogously to Example 5.

Melting point: 180-181 ° C (dec.).

Example 68

1- (4-Amino-3-chloro-5-fluorophenyl) -2- [N- (1- methyl-2-phenoxyethyl) amino] ethanol hydrochloride

Prepared from 4'-amino-3'-chloro-5'-fluoro-acetophenone, selenium dioxide, l-methyl-2-phenoxy-ethylamine and sodium borohydride as in Example 5.

Melting point: 158-160 ° C (dec.).

Example 69

1- (4-A mino-3-cyano-5-fluorophenyl) -2- [N- (1- methyl-2-phenoxy-ethyl) amino] ethanol hydrochloride

Prepared from 4'-amino-3'-cyan-5'-fluoro-acetophenone, selenium dioxide, l-methyl-2-phenoxy-ethylamine and sodium borohydride analogously to Example 5.

Melting point: 178-184 ° C (dec.).

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Example 70

1- (4-Amino-3-bromo-5-fluorophenyl) -2- [N- (1- methyl-2-phenoxy-ethyl) -amino] ethanol-hydrochloride

Prepared from 4'-amino-3'-bromo-5'-fluoro-acetophenone, selenium dioxide, l-methyl-2-phenoxy-ethylamine and sodium borohydride as in Example 5.

Melting point: 156-158 ° C (dec.).

Example 71

N- [2- (4-Amino-3,5-dibromo-phenyl) ethyl] -N- [3- (4-methoxy-phenyl) propyl] methylamine

Prepared from 4-amino-3,5-dibromo-N- [3- (4-methoxyphenyl) propyl] N-methylphenylacetic acid amide and lithium aluminum hydride analogously to Example 7.

Melting point of the hydrochloride: 149-153 ° C.

Example 72

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [3- (4-methoxyphenyl) propyl] methylamine

Prepared from 4-amino-3,5-dichloro-N- [3- (4-methoxyphenyl) propyl] N-methylphenylacetic acid amide and lithium aluminum hydride analogously to Example 7.

Melting point of the hydrochloride: 90-94 ° C.

Example 73

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [2- (4-methoxyphenyl) ethyl] methylamine

Prepared from 4-amino-3,5-dichloro-N- [2- (4-methoxyphenyl) ethyl] -N-methylphenylacetic acid amide and lithium aluminum hydride analogously to Example 8.

IR spectrum (methylene chloride):

NH2 3380 + 3470 cm "1

N-alkyl 2780 cm "1

OCH3 2830 cm "1

aliphatic. CH2 2850 + 2930 cm "1

C = C 1610 cm "1

UV spectrum (ethanol): X max.

245 nm (0.24)

281 nm (0.08)

305 nm (0.07)

Example 74

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [4- (4-methoxyphenyl) butyl] methylamine

Prepared from 4-amino-3,5-dichloro-N- [4- (4-methoxyphenyl) butyl] N-methylphenylacetic acid amide and lithium aluminum hydride analogously to Example 8.

IR spectrum (methylene chloride):

NHZ 3380 + 3480 cm "1

OCH3 2830 cm "1

aliphatic. CH2 2850 + 2930 cm "1

NH + 2100-2500 cm "1

C = C 1630 cm1

UV spectrum (ethanol): X max.

245 nm (0.22)

280 nm (0.07)

304 nm (0.08)

Example 75

N- [3- (4-Amino-3,5-dichlorophenyl) propyl] -2- (3,4-dimethoxyphenyl) ethylamine hydrochloride

Made from 3- (4-amino-3,5-dichlorophenyI) -N- [2- (3,4-di-

methoxy-phenyl) -ethyl] -propionic acid amide and lithium aluminum hydride analogously to Example 7.

Melting point: 142-145 ° C.

Example 76

N- [3- (4-Amino-3,5-dichlorophenyl) propyl] -N- [2- (3,4-di-methoxyphenyl) ethyl] methylamine

Prepared from 3- (4-amino-3,5-dichlorophenyl) -N- [2- (3,4-dimethoxyphenyl) ethyl] -N-methyl-propionic acid amide and lithium aluminum hydride analogously to Example 8. Oil .

IR spectrum (methylene chloride):

NH2 3400 + 3500 cm "1

OCH3 2835 + 2960 cm'1

NCH3 2800 cm "1

Aromat 1510 + 1590/1615 cm-1

UV spectrum (ethanol): X max.

239 nm (shoulder)

281 nm (0.11)

300 nm (0.08)

Example 77

N- [3- (4-Amino-3-bromophenyl) propyl] -2- (3,4-dimethoxyphenyl) ethylamine hydrochloride

Prepared from 3- (4-amino-3,5-dibromophenyl) -N ~ [2- (3,4-dimethoxyphenyl) ethyl] propionic acid amide and lithium aluminum hydride analogously to Example 7.

Melting point: 131-134 ° C.

Example 78

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [3- (4-hydroxyphenyl) -1-methyl-propyl] amine

Prepared from 4-amino-3,5-dichloro-N- [3- (4-hydroxy-phenyl) -l-methyl-propyl] -phenylacetic acid amide and lithium aluminum hydride in tetrahydrofuran analogously to Example 8. The chromatographic purification is carried out by means of medium pressure Chromatography on silica gel (grain size: 0.015 - 0.025 mm) with methylene chloride: methanol: conc. Ammonia = 19: 1: 0.1 as Ehlens. Foam.

IR spectrum (methylene chloride):

OH 3580 cm'1

NH2 3480 + 3385 cm "1

CH2 2920 cm "1

C = C 1580, 1510 + 1480 cm "1

UV spectrum (ethanol): X max.

242 nm (0.24; shoulder)

280 nm (0.07)

303 nm (0.08)

UV spectrum (ethanol + KOH): X max.

242 nm (0.53)

300 nm (0.16)

Example 79

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [3- (4-methoxy-phenyl) -] - methyl-propylj-amine

Prepared from 4-amino-3,5-dichloro-N- [3- (4-methoxy-phenyl) -l-methyl-propyl] -pheny! Acetic acid amide and lithium aluminum hydride in tetrahydrofuran analogously to Example 8. Oil. IR spectrum (methylene chloride):

NH2 3480 + 3385 cm "1

CH2 2930 cm "1

OCH3 2830 cm "1

C = C 1580, 1510 + 1485 cm "1

5

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35

40

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50

55

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65

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651 541

UV spectrum (ethanol): X max.

242 nm (0.25; shoulder)

280 nm (0.07)

302 nm (0.08)

Example 80

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [3- (4-benzyloxyphenyl) propyl] methylamine

Prepared from 4-amino-3,5-dichloro-N- [3- (4-benzyloxyphenyl) propyl] N-methylphenylacetic acid amide and lithium aluminum hydride analogously to Example 8. Oil.

IR spectrum (methylene chloride):

NH2 3390 + 3490 cnr1

N-alkyl 2800 cm "1

UV spectrum (ethanol): X max.

245 nm (0.10)

280 nm (0.04)

300 nm (0.04)

Example 81

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [3- (3,4-dimethoxyphenyl) propyl] methylamine

Prepared from 4-amino-3,5-dichloro-N- [3- (3,4-dimethoxyphenyl) propyl] N-methylphenylacetic acid amide and lithium aluminum hydride analogously to Example 8. Oil.

IR spectrum (methylene chloride):

NH2 3395 + 3495 cm "1

OCH3 2830 cm "1

N-alkyl 2800 cm "1

UV spectrum (ethanol): X max.

230 nm (shoulder; 0.18)

245 nm (shoulder; 0.12)

282 nm (0.04)

302 nm (0.03)

Example 82

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [3- (2-methoxyphenyl) propyl] methylamine hydrochloride

Prepared from 4-amino-3,5-dichloro-N- [3- (2-methoxy-phenyl) propyl] -N-methylphenylacetic acid amide and lithium aluminum hydride analogously to Example 7.

Melting point: 160-164 ° C.

Example 83

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl J-N- (3-phenyl-propyl) methylamine

Made from 4-amino-3,5-dichloro-N- (3-phenyl-propyl) -N-methyl-phenylacetic acid amide and lithium aluminum hydride analogously to Example 8. Oil.

IR spectrum (methylene chloride):

NH2 3390 + 3490 cm "1

N-alkyl 2800 cm "1

UV spectrum (ethanol): X max.

245 nm (0.12)

300 nm (0.03)

Example 84

N- [2- (4-A mino-3,5-dichlorophenyl) ethyl] -N- [3- (4-methoxy - phenylj-propylj-amine hydrochloride

Prepared from 4-amino-3,5-dichloro-N- [3- (4-methoxy-phenyl) propyl] phenylacetic acid amide and lithium aluminum hydride analogously to Example 7.

Melting point: 203-205 ° C.

Example 85

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [3- (4-methoxyphenyl) propyl] cyclopropylamine

Prepared from 4-amino-3,5-dichloro-N- [3- (4-methoxy-phenyl) -propyl] -N-cyclopropyI-phenylacetic acid amide and lithium aluminum hydride analogously to Example 8. Oil.

IR spectrum (methylene chloride):

NH2 3390 + 3490 cm "1

OCH3 2830 cm "1

UV spectrum (ethanol): X max.

245 nm (0.15)

280 nm (0.04)

300 nm (0.05)

Example 86

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [3- (4-methoxyphenyl) propyl] propylamine

Made from 4-amino-3,5-dichloro-N- [3- (4-methoxy-phenyl) -propyl] -N-propyl-phenylacetic acid amide and lithium aluminum hydride analogously to Example 8. Oil.

IR spectrum (methylene chloride):

NH2 3390 + 3490 cm "1

OCH3 2830 cm'1

N-alkyl 2800 cm "1

UV spectrum (ethanol): X max.

243 nm (0.13)

280 nm (0.04)

300 nm (0.04)

Example 87

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [3- (4-methoxy-phenylj-propylj-ethylamine

Made from 4-amino-3,5-dichloro-N- [3- (4-methoxy-phenyl) propyl] -N-ethyl-phenylacetic acid amide and lithium aluminum hydride analogously to Example 8. Oil.

IR spectrum (methylene chloride):

NH2 3390 + 3490 cm "1

OCH3 2830 cm "1

N-alkyl 2800 cm "1

UV spectrum (ethanol): X max.

243 nm (0.13)

280 nm (0.04)

300 nm (0.04)

Example 88

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [3- (4-methoxyphenyl) propyl] -2-propylamine

Prepared from 4-amino-3,5-dichloro-N- [3- (4-methoxy-phenyl) -propyl] -N- (2-propyl) -phenylacetic acid amide and lithium aluminum hydride analogously to Example 8. Oil.

IR spectrum (methylene chloride):

NH2 3390 + 3490 cm "1

OCH3. 2830 cm "1

UV spectrum (ethanol): X max.

243 nm (0.13)

280 nm (0.04)

300 nm (0.04)

Example 89

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [3- (4-ethoxyphenyl) propyl] methylamine

Made from 4-amino-3,5-dichloro-N- [3- (4-ethoxy-phenyl) propyl] -N-methyl-phenylacetic acid amide and lithium aluminum hydride analogously to Example 8. Oil.

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55

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65

651 541

22

IR spectrum (methylene chloride):

NH2 3390 + 3490 cm "1

OCH3 2830 cm * 1

N-alkyl 2800 cm "1

UV spectrum (ethanol) X max.

245 nm (0.12)

280 nm (0.03)

300 nm (0.04)

Example 90

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [3- (4-methoxy-phenyl) -1-methyl-propyl] methylamine

Made from l-ethoxycarbonyloxy-l- (4-amino-3,5-di-chlorophenyl) -2- [N- [3- (4-methoxy-phenyl) -l-methyl-propyl] methylamino] -ethane and sodium borohydride in isopropanol analogous to Example 9. Oil.

IR spectrum (methylene chloride):

NH2 3480 + 3380 cm "1

CH2 2930 cm "1

N-alkyl 2790 cm "1

OCH3 2840 cm'1

C = C 1580, 1510 + 1480 cm'1

Example 91

N- [2- (4-Amino-3-bromo-5-cyanophenyl) ethyl] -N- [4- (4-methoxyphenyl) butyl] methylamine

Made from l-ethoxycarbonyloxy-l- (4-amino-3-bromo-5-cyanophenyl) -2- [N- [4- (4-methoxyphenyl) butyl] methylamino] ethane and sodium borohydride analogous to Example 9. Analysis:

Calculated: C 60.6 H 6.3 Br 19.2 N 10.1

Found: C 60.5 H 6.1 Br 19.2 N 10.1

Example 92

N- [2- (4-Amino-3-chloro-5-cyanophenyl) ethyl] -N- [2- (4-meth-oxyphenyl) ethyl] methylamine

Made from l-ethoxycarbonyloxy-l- (4-amino-3-chloro-5-cyanophenyl) -2- [N- [2- (4-methoxyphenyl) ethyl] methyl amino] ethane and sodium borohydride analogous to Example 9, IR spectrum (methylene chloride):

NH2 3400 + 3490 cm "1

N-alkyl 3790 cm "1

OCH3 2830 cm "1

aliphatic. CH2 2850 + 2940 cm "1

C = N 2210 cm "1

C = C 1620 cm "1

UV spectrum (ethanol): X max.

244 nm (0.26)

280 nm (0.04)

335 nm (0.15)

Example 93

N- [2- (4-Amino-3-bromo-5-cyanophenyl) ethyl] -N- [3- (4-methoxyphenyl) propyl] methylamine

Made from l-ethoxycarbonyloxy-l- (4-aminoc-3-bromo-5-cyanophenyl) -2- [N- [3- (4-methoxyphenyl) propyl] methylamino] ethane and sodium borohydride analogous to Example 9. IR spectrum (methylene chloride):

NH2 3390 + 3490 cm "1

N-alkyl 3790 cm "1

OCH3 3830 cm "1

aliphatic. CH2 2850 + 2940 cnr1

C = N 2210 cm "1

C = C 1620 cm "1

UV spectrum (ethanol): X max. .

244 nm (0.2)

280 nm (0.04)

334 nm (0.13)

Example 94

N- [2- (4-Amino-3-chloro-5-cyanophenyl) ethyl] -N- [4- (4-methoxyphenyl) butyl] methylamine

Made from l-ethoxycarbonyloxy-l- (4-amino-3-chloro-5-cyanophenyl) -2- [N- [4- (4-methoxyphenyl) butyl] methylamino] ethanol and sodium borohydride analogous to Example 9. Analysis:

Calc .: C 67.5 H 7.3 Cl 9.53 N 11.25

Found: C 67.5 H 7.14 Cl 9.65 N 11.34

Example 95

I- (4-Amino-3-chloro-5-trifluoromethylphenyl) -2- [N- [4- (4 - methoxyphenyl) butyl] methylamino] ethanol

Made from 4'-amino-3'-chloro-5'-trifluoromethyl-2- [N - [4- (4-methoxyphenyl) butyl] methylamino] acetophenone and sodium borohydride in 80% methanol as in Example 1. IR spectrum (methylene chloride):

Oh

3590 cm'1

nh2

3410 + 3510

N-alkyl

2800 cm "1

och3

2830 cm "1

aliphatic. ch2

2850 + 2930

aromatic. c = c

1630 cm "1

UV spectrum (ethanol): X max. 225 nm (0.32) 245 nm (0.31) 280 nm (0.06) 308 nm (0.10)

Example 96

l '(4-amino-3-cyanophenyl) -2- [N- [3- (4-methoxyphenyl) propylj-methylaminoj-ethanol

Made from l- (4-amino-3-bromo-5-cyanophenyl) -2- [N - [3- (4-methoxyphenyl) propyl] methylamino] ethanol in the presence of palladium / carbon and hydrogen as in Example 11.

IR spectrum (methylene chloride):

OH 3610 cnr1

NH2 3400 + 3490 cm "1

N-alkyl 2800 cnr "

OCH3 2830 cm "1

aliphatic. CH2 2850 + 2940 cm "1

C = N 2210 cm "1

C = C 1630 cm "1

UV spectrum (ethanol): X max.

251 nm (0.31)

280 nm (0.6)

328 nm (0.12)

Example 97

N- [2- (4-Amino-3-chlorophenyl) ethyl] -N- [3- (4-benzyloxy-phenyl) propyl] methylamine

Made from N- [2- (4-amino-3,5-dichlorophenyl) ethyl] - N- [3- (4-benzyloxy-phenyl) propyl] methylamine and hydrogen analogously to Example 11. Oil IR Spectrum (methylene chloride):

NH2 3390 + 3490 cm'1

N-alkyl 2790 cm "1

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Example 98

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [3 - (4-hydroxy-phenyl) propyl] methylamine

Prepared from N- [2- (4-amino-3,5-dichlorophenyl) ethyl] - N- [3- (4-benzyloxyphenyl) propyl] methylamine and hydrogen analogously to Example 16. Oil.

IR spectrum (methylene chloride):

OH 3580 cm "1

NH2 3390 + 3490 cm "1

N-alkyl 2800 cm "1

Then, until the reaction is clearly alkaline, 2N sodium hydroxide solution is added, the mixture is extracted twice with methylene chloride, the combined methylene chloride phases are washed with water, dried over sodium sulfate and evaporated to dryness in vacuo. An almost colorless oil remains, which is dissolved in ethanol. This ethanolic solution is acidified to pH 5 with ethereal hydrochloric acid. The solvents are then removed in vacuo on a rotary evaporator. The remaining oily residue is brought to crystallization in ethyl acetate. Colorless crystals of melting point 102-105 ° C. are obtained.

Example 99

1- (4-Amino-3-fluorophenyl) -2- [N- (1- methyl-2-phenoxy - ethyl) amino] ethanol tosylate

Prepared from l- (4-acetamino-3-fluorophenyl) -2- [N- (l-methyl-2-phenoxy) ethyl] aminoethanol and sodium hydroxide analogously to Example 17.

Melting point: 124-128 ° C.

Example 100

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [3- (4-methoxyphenyl) propyl] methylamine

1.74 g (0.014 mol) of 4-methoxyphenol are dissolved in 60 ml of dry tetrahydrofuran, the solution is cooled to -5 ° C. and 0.67 g (0.014 mol) of a 50% dispersion of sodium hydride is added with stirring Add oil. The mixture is stirred for a further 2 hours at 0 ° C. and then a solution of 4.2 g of N- [2- (4-amino-3,5-di-chlorophenyl) ethyl] -N- is added dropwise at the same temperature. (3-chloropropyl) methylamine in 50 ml dry tetrahydrofuran. The mixture is stirred at about 20 ° C. for 18 hours. The reaction mixture is then concentrated in vacuo and the evaporation residue is distributed between ether and water. The phases are separated and the aqueous layer is extracted three more times with ether. The combined ether extracts washed with water are dried and evaporated in vacuo. The oily evaporation residue is purified chromatographically on a silica gel column (eluent: ether). After evaporating the desired fractions, the above-mentioned compound is obtained as an oil.

IR spectrum (methylene chloride):

NH2 3390 + 3480 cm "1

CH2 2950 cm "1

N-alkyl 2800 cm-1

C = C 1585 + 1560 + 1505 cm "1

UV spectrum (ethanol): X max.

230 nm (0.18; shoulder)

246 nm (0.085; shoulder)

295 nm (0.05)

Example 101

1- (4-Amino-3, S-dichlorophenyl) -2- [N- (3-phenylpropyl ') - ethylaminoj-ethanol hydrochloride

Example 102

15

1- (4-Ethoxycarbonylamino-3-cyano-5-fluorophenyl) -2- [N- [2 - (3,4-dimethoxyphenyl) ethyl] amino] ethanol hydrochloride

Prepared from 4'-ethoxycarbonylamino-3'-cyan-5'-fluoro-20-acetophenone, selenium dioxide, 2- (3,4-dimethoxy-phenyl) -ethylamine and sodium borohydride as in Example 4.

Melting point: 190-191 ° C (dec.).

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Example 103

1- (4-Amino-3-cyano-5-fluorophenyl) -2- [N- [4- (4-methoxyphenyl) butyl] methylamino] ethanol

Prepared analogously from 4'-amino-3'-cyan-5'-fluoro-2- [N- [4- (4-methoxyphenyl) butyl] methylamino] acetophenone and sodium borohydride in 80% methanol Example 1. IR spectrum (methylene chloride):

Oh

3590 cm'1

nh2

3400 + 3490

N-alkyl

2800 cm "1

och3

2830 cm'1

aliphatic. ch2

2850 + 2930

c = N

2210 cm'1

c = c

1635 cm "1

UV spectrum (ethanol): X max.

241 nm (0.27)

40 280 nm (0.07)

322 nm (0.14)

Example 104

45 liters of (4-acetamino-3-bromophenyl) -2- [N- [4- (4-methoxyphenyl) butylJ-methylamino] ethanol

Prepared from 4'-acetamino-3'-bromo-2- [N- [4- (4-methoxyphenyl) butyl] methylamino] acetophenone and sodium borohydride in 80% methanol as in Example 1. 50 IR Spectrum (methylene chloride):

OH NH

N-alkyl OCH3

aliphatic. CH2 aromat. C = C

c = o

Amide II

3590 cm-1 3410 cm-1 2800 cm-1 2830 cm "1 2850 + 2930 cm" 1 1610 cm-1 1700 cm "! 1510 cm" 1

2 g of l- (4-amino-3,5-dichlorophenyl) -2- [N- (3-phenyl-propylene) - aminoj-ethanol hydrochloride are dissolved in 50 ml of ethanol. 0.4 ml of acetaldehyde is added to this solution and then 1.2 g of sodium cyanoborohydride are added with stirring at room temperature, care being taken to add and maintain a pH of 6-6.5 by adding 2N hydrochloric acid becomes. At this pH, stirring is continued for 2 hours. The solution is poured into water and acidified with 2N hydrochloric acid to destroy excess sodium cyanoborohydride.

60 Example 105

Racemates A and B of I- (4-amino-3,5-dichlorophenyl) -2- [N - [3- (4-hydroxyphenyl) -1-methyl-propyl] methylamino] ethanol

36 g of l- (4-amino-3,5-dichlorophenyl) -2- [N- [3- (4-hydroxy-65-phenyl) -l-methylpropyl] methylamino] ethanol (1: 1 mixture of the diastereomeric racemates A and B) are dissolved in ether and mixed with 0.5 equivalents of 3N hydrogen chloride in ether. The crude crystals of hydrochloride of Ra-

651 541

24th

cemats A is first recrystallized from isopropanol and then twice by dissolving in a lot of methanol and then evaporating until crystallization begins. Melting point of the hydrochloride: 248-249 ° C (dec.). 13C-NMR spectrum of the base (CDCI3 / CD3OD):

NH2

OCH3

CN

aroma. C = C

3390 + 3490 cm'1 2830 + 2940 cm "1 2210 cm'1 1610 cm" 1

ch3

I.

- ch2 - ÇH2 - ch -

ch3

I.

- ch2 - ch2 - ch -

> ch - ch3

> n - ch3

) n - ch2 -

Oh

I.

- ch-

37.50 ppm

58.36 ppm 13.91 ppm 36.33 ppm 61.03 ppm

68.89 ppm

5 UV spectrum (ethanol): X max. 223 nm (0.43)

244 nm (shoulder, wide; 0.07) 330 nm (wide; 0.05)

Example 108

The isopropanolic mother liquor is evaporated and distributed between ether and 2N ammonia. The evaporation residue of the dried organic phase is separated from adhering racemate A by HPLC to isolate the racemate B (SiO 2 60; Merck; 0.015-0.025 mm; ether: methanol = 10: 1). The crystalline evaporation residue is recrystallized from a lot of ether by concentrating at the boiling point.

Melting point: 128-131 ° C.

13C-NMR spectrum (CDCI3 / CD3OD):

1- (4-Amino-3-bromo-5-cyanophenyl) -2- [N- [4- (4-methoxyphenyl) butyl] isopropylamino] ethanol hydrochloride

15 Prepared with 4'-amino-3'-bromo-5'-cyan-2- [N- [4- (4-methoxyphenyl) butyl] isopropylamino] acetophenone and sodium borohydride in 90% methanol analogous to example 1.

Melting point of the hydrochloride: sintering from 40 ° C. Calculated: C 55.6 H 6.29 Br 16.2 Cl 2.14 N 8.46

20 Found: C 55.3 H 6.37 Br 15.4 Cl 6.84 N 8.83

Example 109

1- (4-Amino-3-bromo-5-cyano-phenyl) -2- [N- [4- (4-methoxy- ~ phenyl) -butyl] -n-propylaminoJ-ethanol hydrochloride

Made from 4'-amino-3'-bromo-5'-cyan-2- [N- [4- (4-methoxyphenyl) butyl] n-propylamino] acetophenone and sodium borohydride in 90% Methanol analogous to example 1.

Melting point of the hydrochloride: sintering from 40 ° C.

30 calc .: C 55.60 H 6.29 N 8.46

Found: C 55.52 H 6.32 N 8.39

ch3

I.

- ch2 - ch2 - ch -

chj

I.

- ch2 - ch2 - ch -) ch - ch3

; n-> N '

ch3 ch2

Oh

- CH

35.61 ppm

59.21 ppm 14.56 ppm 35.03 ppm 63.11 ppm

69.08 ppm

Example 106

1- (4-Amino-3-bromo-5-cyanophenyl) -2- [N- [4- (4-methoxyphenyl) butyl] benzylamino] ethanol hydrochloride

Prepared analogously from 4'-amino-3'-bromo-5'-cyan-2- [N- [4- (4-methoxyphenyl) butyl] benzylamino] acetophenone and sodium borohydride in 90% methanol Example 1.

Melting point of the hydrochloride: 122-126 ° C.

Example 107

1- (4-Amino-3 ~ bromo-5-cyanophenyl) -2- [N- [4- (4-methoxyphenyl) butyl] allylamino] ethanol

Manufactured analogously from 4'-amino-3'-bromo-5'-cyan-2- [N- [4- (4-methoxyphenyl) butyl] allylamino] acetophenone and sodium borohydride in 90% methanol Example 1. Resin. IR spectrum (methylene chloride):

Example 110

35 l- (4-Amino-3-bromo-5-cyanophenyl) -2- [N- [4- (4-methoxy-phenyl) butyl] ethylamino] ethanol hydrochloride

Made from 4'-amino-3'-bromo-5'-cyan-2- [N- [4- (4-meth-oxyphenyl) butyl] ethylamino] acetophenone and sodium boron 40 hydride in 90% methanol similar to Example 1.

Melting point of the hydrochloride: 139-142 ° C.

Example 111

45 l- (4-A mino-3-bromo-5-trifluoromethylphenyl) -2- [N- [3- (4 - methoxyphenyl) propyl] methylamino] ethanol

Made from 4'-amino-3'-bromo-5'-trifluoromethyl-2- [N- [3 - (4-methoxyphenylene) propyl] methylamino] acetophenone and

50 sodium borohydride in 90% methanol analogous to Example 1. Oil. IR spectrum (methylene chloride):

NH2 3400 + 3490 cm "1

OCH3 2840 + 2940 cm "1

aroma. C = C 1610 cm "1

55 UV spectrum (ethanol): X max.

223 nm (0.26)

244 nm (0.1)

310 nm (very wide; 0.04)

60

Example 112

1- (4-Amino-3-bromo-5-cyanophenyl) -2- [N- (4-phenylbutyl) methylaminoj ethanol hydrochloride

65 Made from 4'-amino-3'-bromo-5'-cyan-2- [N- (4-phenylbutyl) methylamino] acetophenone and sodium borohydride in 90% methanol as in Example 1.

Melting point of the hydrochloride: 153-155 ° C.

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651 541

Example 113

1- (4-Amino-3-cyan-5-fluorophenyl) -2- [N- [2- (4-methoxyphenyl) ethyl] methylamino] ethanol hydrochloride

Made from 4'-amino-3'-cyan-5'-fluoro-2- [N- [2- (4-meth-oxyphenyl) ethyl] methylamino] acetophenone and sodium borohydride in 90% methanol analogous to example 1.

Melting point of the hydrochloride: sintering from 68 ° C. Calc .: C 60.1 H 6.12 Cl 9.35 N 11.05

Found: C 59.91 H 6.07 Cl 9.40 N 10.69

Example 114

1- (4-Amino-3,5-dichlorophenyl) -2- [N- (3-phenylsulfenylpropyl) methylamino] ethanol

Made from 4'-amino-2-bromo-3 ', 5'-dichloroacetophenone, N- [3- (4-methoxy-phenylsulfenyl) propyl] methylamine and sodium borohydride in 80% methanol as in Example 2. Oil . IR spectrum (methylene chloride):

NH2 3390 + 3490 cm "1

OH 3600 + 3680 cnr1

UV spectrum (ethanol): X max.

246 nm (0.18)

300 nm (0.05)

Example IIS

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (4-hydroxyphenyl) propyl] amino] ethanol

Made from 4'-amino-3 ', 5'-dichloro-2- [N- [3- (4-hydroxyphenyl) propyl] amino] acetophenone and sodium borohydride in aqueous tetrahydrofuran analogously to Example 3. Oil.

IR spectrum (KBr):

OH, NH2 3300-3600 cm "1

aroma. C = C 1615 cm "1

UV spectrum (ethanol + KOH): X max.

244 nm (0.26)

299 nm (0.08)

Example 116

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (4-chlorophenyl) propylj-aminoj-ethanol

Prepared from 4'-amino-3 ', 5'-dichloro-2- [N- [3- (4-chloro-phenyl) propyl] amino] acetophenone and sodium borohydride in aqueous tetrahydrofuran as in Example 3.

Melting point: 103-106 ° C.

Example 117

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (4-hydroxyphenyl) -1-methylpropyl] isopropylamino] ethanol

Prepared from 4'-amino-3 ', 5'-dichloro-2- [N- [3- (4-hydroxyphenyl) -1-methylpropyl] isopropylamino] acetophenone and sodium borohydride analogously to Example 3. Oil .

Calculated: C 61.31 H 6.86 Cl 17.24 N 6.81

Found: C 61.07 H 6.86 Cl 16.67 N 6.53

Example 118

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (4-hydroxypheny / J - 1-methylpropyl] ethylamino] ethanol

Prepared from 4'-amino-3 ', 5'-dichloro-2- [N- [3- (4-hydroxyphenyl) -1-methyl-propyl] ethylamino] acetophenone and sodium borohydride analogously to Example 3. Oil .

Calc .: "C 60.45 H 6.60 Cl 17.85 N 7.05 Found: C 60.45 H 6.76 Cl 17.70 N 6.86

Example 119

1- (4-Methylamino-3,5-dichlorophenyl) -2- [N- [3- (4-hydroxyphenyl) -1-methylpropyl] methylamino] ethanol

Prepared from 4'-methylamino-3 ', 5'-dichloro-2- [N- [3- (4-hydroxy-phenyl) -l-methylpropyl] methylamino] acetophenone and sodium borohydride analogously to Example 3. Oil .

Calculated: C 60.45 H 6.60 Cl 17.85 N 7.05

Found: C 60.68 H 6.73 Cl 17.50 N 6.71

Example 120

1- (4-Dimethylamino-3,5-dichlorophenylJ-2- [N- [3- (4-hydroxyphenyl) -1-methylpropyl] methylamino] ethanol

Prepared from 4'-dimethylamino-3 ', 5'-dichloro-2- [N- [3- (4-hydroxyphenyl) -1-methyl-propyl] -methylamino] -acetophenone and sodium borohydride analogously to Example 3. Oil.

Calculated: C 61.31 H 6.86 Cl 17.24 N 6.81

Found: C 61.28 H 6.57 CI 16.80 N 6.42

Example 121

1- (4-Acetylamino-3,5-dichlorophenyl) -2- [N- [3- (4-hydroxyphenyl) -1-methylpropyl] methylamino] ethanol

Made from 4'-acetylamino-3 ', 5'-dichloro-2- [N- [3- (4-hydroxy-phenyl) -l-methylpropyl] methylamino] acetophenone and sodium borohydride analogously to Example 3. Foam . IR spectrum (methylene chloride):

OH 3580 cm "1

NH 3410 cm "1

N-alkyl 2800 cm "1

C = 0 1700 cm "1

C = C 1610.1595 cm "1

Amide II 1515 cm "1

UV spectrum (ethanol): X max.

230 nm (0.3; shoulder)

280 nm (0.04)

UV spectrum (ethanol + KOH): X max.

243 nm (0.46)

294 nm (0.08)

Example 122

1- (4-Ethoxycarbonylamino-3,5-dichlorophenyl) -2- [N- [3 - (4-hydroxy-phenylj-l-methyl-propylJ-methylaminoJ-ethanol

Made from 4'-ethoxycarbonylamino-3 ', 5'-dichloro-2- [N-- [3- (4-hydroxyphenyl) -1-methyl 1-propyl] methylamino] acetophenone and sodium borohydride analogously to Example 3. Oil. Calculated: C 58.02 H 6.20 Cl 15.57 N 6.15

Found: C 58.20 H 6.32 Cl 15.32 N 6.03

Example 123

Racemates A and B of 1- (4-amino-3-cyano-5-fluorophenyl) -2- [N - [1- methyl-3- (4-hydroxyphenyl) propyl] methylamino] - ethanol

Prepared from 4'-amino-3'-cyan-5'-fluoro-2- [N- [l-methyl-3 - (4-hydroxyphenyl) propyl] methylamino] acetophenone and sodium borohydride analogously to Example 3 The mixture of the diastereomeric racemates obtained is separated by means of column chromatography (SiO 2; methylene chloride: methanol: concentrated ammonia = 50: 1: 0.1).

Racemate A:

Melting point: 161-163 ° C.

, 3C NMR spectrum (dö-dimethyl sulfoxide):

5

10th

15

20th

25th

30th

35

40

45

50

55

60

65

651 541

26

CH3 I

- CH2 - CH2 - CH -

CH3

I.

- CH2 - CH2 - CH -) CH - CH3

) N - CH3> N - CH2 -

OH

I.

- CH -

37.17 ppm

57.91 ppm 13.26 ppm 35.74 ppm 60.90 ppm

69.21 ppm

NH2

o-ch3

N-alkyl c = N 5 c = c c = c + NH2 Deformation UV spectrum (ethanol): X max. 242 nm (0.27)

278 nm (0.05) io 286 nm (0.05)

324 nm (0.12)

Example 127

3400 + 3500 cm'1 2830 cm "1 2800 cm" 1 2210 cm "1 1580, 1510 cm" 1 1620 cm "1

Racemat B:

Melting point: 92-98 ° C.

13C-NMR spectrum (dg-dimethyl sulfoxide):

CH3

!

- CH2 - CHj - CH - 36.52 ppm

CH3

I.

- CH2 - CH2 - CH - 57.78 ppm) CH - CHj 13.19 ppm> N - ÇH3 35.74 ppm} N - CH2 - 61.48 ppm

OH

I.

- CH - 69.02 ppm

Example 124

1- (4-A mino-3-cyano-5-fluorophenyl) -2- [N- [1- methyl-3 - (4-methoxyphenyl) propyl] amino] ethanol

Prepared from 4'-amino-3'-cyan-5'-fluoro-2- [N- [l-methyl-3 - (4-methoxyphenyl) propyl] amino] acetophenone and sodium borohydride analogously to Example 3 .

Melting point: 108-110 ° C.

Example 125

1- (4-Amino-3-cyano-5-fluorophenyl) -2- [N- [1- methyl-3 - (4-hydroxyphenyl) propyl] amino] ethanol

Prepared from 4'-amino-3'-cyan-5'-fluoro-2- [N- [l-methyl-3 - (4-hydroxyphenyl) propyl] amino] acetophenone and sodium borohydride analogously to Example 3 .

Melting point: 162-164 ° C.

Example 126

1- (4-Amino-3-cyan-5-fluorophenyl) -2- [N- [1- methyl-3 - (4-methoxyphenyl) propyl] methylamino] ethanol

Made from l- (4-amino-3-cyan-5-fluorophenyl) -2- [N- [l - methyl-3- (4-hydroxyphenyI) propyl] methylamino] ethanol and dimethyl sulfate / 1 N sodium hydroxide in tetrahydrofuran analogous to Example 4. Oil.

IR spectrum (methylene chloride):

1- (4-Amino-3,5-dichlorophenyl) -2- [N- (1-methyl-2-phenoxy - ethyl) amino] ethanol hydrochloride

Made from 4'-amino-3 \ 5'-dichloro-acetophenone, selenium dioxide, l-methyl-2-phenoxy-ethylamine and sodium borohydride analogously to Example 5. Amorphous hydrochloride.

20 IR spectrum (methylene chloride):

NH2 3390 + 3490 cm "1

UV spectrum (ethanol): X max.

245 nm (0.15)

300 nm (0.04)

25th

Example 128

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (4-fluoro-phenyl) propylj-aminoj-ethanol hydrochloride

30 Made from 4'-amino-3 ', 5'-dichloroacetophenone, selenium dioxide, 3- (4-fluorophenyl) propylamine and sodium borohydride analogously to Example 5.

Melting point of the hydrochloride: 185-187 ° C (dec.).

Example 129

1- (4-Amino-3,5-dichlorophenyl) -2- [N- (3-phenyl-1-methylpropyl) methylamino] ethanol

»Made from 4'-amino-3 ', 5'-dichloroacetophenone, selenium dioxide, 3-phenyl-l-methyl-propylamine and sodium borohydride analogously to Example 5. Oil.

IR spectrum (methylene chloride):

_ NH2 3390 + 3490 cm'1

45 OH 3600 + 3680 cm "1

UV spectrum (ethanol): X max.

245 nm (0.18)

300 nm (0.06)

50 Example 130

1- (4-Amino-3,5-dichlorophenyl) -2- [N- (1-methyl-2-phenoxy - ethyl) amino] ethanol hydrochloride

Prepared from 4'-amino-3 ', 5'-dichloroacetophenone, selenium 55 dioxide, l-methyl-2-phenoxyethylamine and sodium borohydride analogously to Example 5.

Melting point of the hydrochloride: 122-125 ° C.

60

Example 131

N- [3- (4-A mino-3-bromophenyl) propyl I-N- [2- (3,4-dimethoxyphenyl) ethyl] methylamine hydrochloride

Made from N-methyl-N- [2- (3,4-dimethoxy-phenyl) - ethyl] -3- (4-amino-3,5-dibromophenyl) propionic acid amide and 65 lithium aluminum hydride in absolute tetrahydrofuran as in Example 7.

Melting point of the hydrochloride: 70-120 ° C (sintering). IR spectrum (KBr):

27th

651 541

NH © 2500-2650 cm "1

Alkyl 2800-3000 cm "1

UV spectrum (ethanol): X max.

234 nm (0.17)

280 nm (0.04)

300 nm (shoulder; 0.03)

Example 132

N- [2- (4-Amino-3-chlorophenyl) ethyl] -N- (l-methyl-3-phenylpropyl) isopropylamine

Made from 4-amino-3,5-dichloro-N-isopropyl-N- (1-methyl-3-phenyl-propyl) -phenylacetic acid amide and lithium aluminum hydride in tetrahydrofuran analogously to Example 7. Oil. IR spectrum (methylene chloride):

NH2 3390 + 3490 cm "1

UV spectrum (ethanol): X max.

241 nm (0.15)

300 nm (0.03)

Example 133

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- (l-methyl-3-phenylpropyl) isopropylamine

Prepared from 4-amino-3,5-dichloro-N-isopropylamine-N- (1-methyl-3-phenyl-propyl) -phenyle "sigsigsäüreamid and lithium aluminum hydride in tetrahydrofuran analogously to Example 7. Oil. IR spectrum (methylene chloride) :

NH2 3390 + 3490 cm "1

UV spectrum (ethanol): X max.

245 nm (0.15)

302 nm (0.04)

Example 134

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -3- (4-fluoro-phenyl) propylamine hydrochloride

Prepared from 4-amino-3,5-dichloro-N- [3- (4-fluorophenyl) propy 1] phenylacetic acid amide and lithium aluminum hydride in tetrahydrofuran as in Example 7.

Melting point of the hydrochloride: 205-206 ° C.

Example 135

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- (l-methyl-3-phenyl-propyl) methylamine

Made from 4-amino-3,5-dichloro-N- (l-methyl-3-phenyl) propyty-phenylacetic acid amide and lithium aluminum hydride in tetrahydrofuran analogously to Example 7. Oil.

IR spectrum (methylene chloride):

NH2 3390 + 3490 cm "1

UV spectrum (ethanol): X max.

243 nm (0.14)

300 nm (0.05)

Example 136

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [3- (4-methoxy-phenyl-sulfenyl) propyl] methylamine

Made from 4-amino-3,5-dichloro-N- [3- (4-methoxy-phenylsulfenyl) propyl] -N-methylphenylacetic acid amide and lithium aluminum hydride in tetrahydrofuran as in Example 7. Oil.

IR spectrum (methylene chloride):

NH2 3390 + 3490 cm "'

UV spectrum (ethanol): X max.

245 nm (0.16)

300 nm (0.04)

Example 137

N- [2- (4-Amino-3-bromophenyl) ethyl] -N- [4- (4-methoxyphenyl) butyl] methylamine

Prepared from 4-amino-3-bromo-N- [2- (4-methoxy-phenyl) butyl] -N-methylphenylacetic acid amide and lithium aluminum hydride in absolute tetrahydrofuran analogously to Example 8. IR spectrum (methylene chloride):

NH2 3380 + 3470 cm "1

OCHs 2830 + 2930 cm "1

aroma. C = C 1620 cm "1

NMR spectrum (CDC13 / D20):

aroma H 6.4-7.3 ppm (m, 7H)

OCH3 3.7 ppm (s, 3H)

NCH3 2.2 ppm (s, 3H)

aliphatic. H 1.3-2.8 ppm (m, 8H)

Example 138

N- [2- (4-Amino-3-bromo-phenyl) ethyl] -N- [2- (4-methoxy-phenyl) ethyl] methylamine

Prepared from 4-amino-3-bromo-N- [2- (4-methoxy-phenyl) - ethyl] -N-methyl-phenylacetic acid amide and lithium aluminum hydride in absolute tetrahydrofuran analogously to Example 8. IR spectrum (methylene chloride):

NH2 3380 + 3480 cm "1

OCH3 2840 + 2940 cm "1

aroma. C = C 1620 cm "1

UV spectrum (ethanol): X max.

224 nm (0.24)

242 nm (0.15)

280 nm (wide; 0.03)

300 nm (wide; 0.03)

Example 139

N- [2- (4-Amino-3-fluorophenyl) ethyl] -N- [3- (4-methoxyphenyl) propyl] methylamine

Prepared from 4-amino-3-fluoro-N- [3- (4-methoxyphenyl) propyl] N-methylphenylacetic acid amide and lithium aluminum hydride in absolute tetrahydrofuran as in Example 8.

Oil.

IR spectrum (methylene chloride):

NH2 3390 + 3460 cm "1

OCH3 2840 + 2940 cm "1

aroma. C = C 1610 cm "1

UV spectrum (ethanol): X max.

227 nm (0.3)

279 nm (0.06)

285 nm (0.06)

Example 140

N- [2- (4-Amino-3-chlorophenyl) ethyl] -N- [3- (4-methoxyphenyl) propyl] methylamine

Prepared from 4-amino-3-chloro-N-methyl-N- [3- (4-methoxyphenyl) propyl] phenylacetic acid amide and lithium aluminum hydride in absolute tetrahydrofuran as in Example 8. Resin. IR spectrum (methylene chloride):

NH2 3390 + 3470 cm'1

OCH3 2840 + 2940 cm "1

aroma. C = C 1610 cm "1

UV spectrum (ethanol): X max.

224 nm (0.25)

240 nm (0.18)

280 nm (0.04)

300 nm (0.03)

s io

15

20th

25th

30th

35

40

45

50

55

60

65

651 541

28

Example 141

N- [3- (4-Amino-3,5-dichlorophenyl) propyl] -N- [3- (4-methoxyphenyl) propyl] amine hydrochloride

Prepared from 3- (4-amino-3,5-dichlorophenyl) -N- [3- (4-raethoxy-phenyl) propyl] -N-propionic acid amide and lithium aluminum hydride in absolute tetrahydrofuran as in Example 8.

Melting point of the hydrochloride: 138-142 ° C.

Example 142

N- [3- (4-Amino-3,5-dichlorophenyl) propyl] -N- [2- (4-methoxyphenyl) ethyl] methylamine dihydrochloride

Prepared from 3- (4-amino-3,5-dichlorophenyl) -N-methyl-N - [2- (4-methoxyphenyl) ethyl] propionic acid amide and lithium aluminum hydride in absolute tetrahydrofuran as in Example 8.

Melting point of the dihydrochloride: 147-157 ° C.

Example 143

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [4- (4-methoxyphenyl) butyl] amine hydrochloride

Prepared from N- [2- (4-amino-3,5-dichlorophenyl) ethyl] -4 - (4-methoxyphenyl) butyric acid amide and lithium aluminum hydride in absolute tetrahydrofuran analogously to Example 8.

Melting point of the hydrochloride: 186-189 ° C.

Example 144

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [3- (4-chlorophenyl) propyl] amine hydrochloride

Prepared from 4-amino-3,5-dichloro-N- [3- (4-chlorophenyl) propyl] phenylacetic acid amide and lithium aluminum hydride in absolute tetrahydrofuran as in Example 8.

Melting point of the hydrochloride: 186-190 ° C.

Example 145

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [4- (4-methoxyphenyl) butyl] isopropylamine

Made from N- [2- (4-amino-3,5-dichlorophenyl) ethyl] -N-isopropyl-4- (4-methoxy-phenyl) butyric acid amide and lithium aluminum hydride in absolute tetrahydrofuran analogously to Example 8. Oil .

IR spectrum (methylene chloride):

NH2 3390 + 3490 cm1

OCH3 2850 + 2930 cm "1

aroma. C = C 1610 cm "1

UV spectrum (ethanol): X max.

242 nm (0.12)

280 nm (shoulder, 0.04)

301 nm (0.04)

Example 146

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [2- (4-methoxy-phenylj-ethylj-isopropylamine

Made from N- [2- (4-amino-3,5-dichlorophenyl) ethyl] -N-isopropyl-4-methoxy-phenylacetic acid amide and lithium aluminum hydride in absolute tetrahydrofuran analogously to Example 8. Oil.

IR spectrum (methylene chloride):

NH2 3390 + 3490 cm "1

OCH3 2830 + 2960 cm "1

aroma. C = C 1610 cm "1

UV spectrum (ethanol): X max.

244 nm (shoulder, 0.12)

280 nm (shoulder; 0.05)

301 nm (0.05)

Example 147

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [2- (4-methoxy-phenyl) ethylJ-amine hydrochloride

Prepared from 4-amino-3,5-dichloro-N- [2- (4-methoxy-phenyl) ethyl] phenylacetic acid amide and lithium aluminum hydride in absolute tetrahydrofuran as in Example 8.

Melting point of the hydrochloride: 206-208 ° C.

Example 148

N- [3- (4-Amino-3,5-dibromophenyl) propyl] -N- [2- (3,4-di-methoxyphenyl) ethyl] methylamine

Prepared from N-methyl-N- [2- (3,4-dimethoxy-phenyl) - ethyl] -3- (4-amino-3,5-dibromophenyl) propionic acid amide and lithium aluminum hydride in absolute tetrahydrofuran analogously to Example 8 OIL

IR spectrum (methylene chloride):

NH2 3480 + 3380 cm "1

OCH3 2840 + 2940 cm "1

NMR spectrum (CDC13 / D20):

0-CH3 4.85 ppm (s, 6H)

N-CH3 2.25 ppm (s, 3H)

aroma H 6.75 ppm (d, 3H)

7.2 ppm (s, 2H)

aliph. H 1.5-2.9 ppm (m, 12H)

Example 149

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -3-phenylpropylamine hydrochloride

Prepared from 4-amino-3,5-dichloro-N- (3-phenyl-propyl) -phenylacetic acid amide and lithium aluminum hydride in tetrahydrofuran analogously to Example 8.

Melting point of the hydrochloride: 197-199 ° C.

Example 150

N- [2- (4-Amino-3-bromo-5-cyanophenyl) ethyl] -N- [4- (4-methoxyphenyl) butyl] benzylamine

Made from l-ethoxycarbonyloxy-l- (4-amino-3-bromo-5-cyanophenyl) -2- [N- [4- (4-methoxyphenyl) butyl] benzylamino] - ethane and Sodium borohydride in isopropanol as in Example 9.

Oil.

IR spectrum (methylene chloride):

NH2 3390 + 3490 cm "1

OCH3 2830 + 2930 cm "1

CN 2210 cm "1

aroma. C = C 1620 cm "1

UV spectrum (ethanol): X max.

222 nm (0.42)

244 nm (shoulder, 0.09)

335 nm (broad; 0.05)

Example 151

N- [2- (4-Amino-3-bromo-5-cyanophenyl) ethyl] -N- [4- (4-methoxyphenyl) butyl] allylamine

Made from l-ethoxycarbonyloxy-l- (4-amino-3-bromo-5-cyanophenyl) -2- [N- [4- (4-methoxyphenyl) butyl] allylamino] - ethane and Sodium borohydride in isopropanol analogous to Example 9. Oil.

5

10th

15

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40

45

50

55

60

65

29

651 541

IR spectrum (methylene chloride):

nh2 och3

CN

aroma. C =

3390 + 3490 cm "1 2830 + 2930 cm" 1 2210 cm "1 1620 cm" 1

UV spectrum (ethanol): X max. 222 nm (0.49) 244 nm (shoulder; 0.1) 335 nm (broad; 0.06)

Example 152

N- [2- (4-Amino-3-bromo-5-cyanophenyl) ethyl] -N- [4- (4-methoxyphenyl) butyl] ethylamine

Made from l-ethoxycarbonyloxy-l- (4-amino-3-bromo-5-cyanophenyl) -2- [N- [4- (4-methoxyphenyl) butyl] ethylamino] - ethane and Sodium borohydride in isopropanol as in Example 9.

Oil.

IR spectrum (methylene chloride):

NH2 3390 + 3490 cm "1

OCH3 2830 + 2960 cm1

CN 2210 cm "1

aroma. C = C 1620 cm "1

UV spectrum (ethanol): X max.

222 nm (0.49)

244 nm (shoulder, 0.08)

333 nm (broad; 0.06)

Example 153

N- [2- (4-Amino-3-bromo-5-cyanophenyl) ethyl] -N- [4- (4-methoxyphenyl) butyl] isopropylamine

Made from l-ethoxycarbonyloxy-1- (4-amino-3-bromo-5-cyanophenyl) -2- [N- [4- (4-methoxyphenyl) butyl] isopropylamino] ethane and sodium borohydride in isopropanol as in Example 9. Resin.

IR spectrum (methylene chloride):

NH2 3390 + 3490 cm1

OCH3 2830 + 2960 cm "1

CN 2210 cm "1

aroma. C = C 1620 cm "1

UV spectrum (ethanol): X max.

221 nm (0.53)

244 nm (shoulder, 0.1)

330 nm (wide; 0.07)

Example 154

N- [2- (4-Amino-3-bromo-5-cyanophenyl) ethyl] -N- [4- (4-methoxyphenyl) butyl] n-propylamine

Made from l-ethoxycarbonyloxy-l- (4-amino-3-bromo-5 - cyanophenyl) -2- [N- [4- (4-methoxyphenyl) butyl] -n-propylaminoj- ethane and sodium borohydride in isopropanol as in Example 9. Oil.

IR spectrum (methylene chloride):

NH2 3390 + 3490 cm "1

CN 2210 cm "1

OCH3 2830 + 2950 cm "1

aroma. C = C 1620 cm "1

UV spectrum (ethanol): X max.

222 nm (0.46)

244 nm (shoulder, 0.08)

330 nm (wide; 0.05)

Example 155

N- [2- (4-Amino-3-bromo-5-cyanophenyl) ethyl] -N- (4-phenylbutyl) methylamine s Made from l-ethoxycarbonyloxy-l- (4-amino- 3-bromo-5-cyanophenyl) -2- [N- (4-phenylbutyl) methylamino] ethane and sodium borohydride in isopropanol as in Example 9. Oil. NMR spectrum (CDC13):

aroma H 7.0-7.4 ppm (m, 7H)

io NCH3 2.2 ppm (s, 3H)

aliph. H 1.3-2.7 ppm (m, 12H)

Example 156

15 N- [2- (4-Amino-3-cyan-5-fluorophenyl) ethyl] -N- [2- (4-methoxyphenyl) ethyl] methylamine

Made from l-ethoxycarbonyloxy-l- (4-amino-3-cyan-5-fluorophenyl) -2- [N- [2- (4-methoxyphenyl) ethyl] methyamino] -20 -ethane and sodium borohydride in isopropanol as in Example 9. Oil.

NMR spectrum (CDCl3 / CH3OD):

aroma H 6.7-7.2 ppm (m, 6H)

OCH3 3.75 ppm (s, 3H)

25 NCH3 2.3 ppm (s, 3H)

aliph. H 2.4-2.7 ppm (m, 8H)

Example 157

30 N- [2- (4-A mino-3-cyano-5-fluorophenyl) ethyl] -N- [3- (4-methoxyphenyl) propyl] methylamine hydrochloride

Made from l-ethoxycarbonyloxy-l- (4-amino-3-cyan-5 - fluorophenyl) -2- [N- [3- (4-methoxyphenyl) propyl] methyl-35 amino] - ethane and sodium borohydride in isopropanol analogous to Example 9. hydrochloride as resin.

NMR spectrum (CDC13):

40

aroma. h och3 © nch3

aliph. H

6.7-7.2 ppm (m, 6H) 3.75 ppm (s; 3H) 2.8 ppm (s; 3H) 1.5-3.5 ppm (m; 10H)

Example 158

45 N- [2- (4-Amino-3-cyan-5-fluorophenyl) ethyl] -N- [4- (4-methoxyphenyl) butyl] methylamine

Made from l-ethoxycarbonyloxy-l- (4-amino-3-cyan-5 - fluorophenyl) -2- [N- [4- (4-methoxyphenyI) butyl] methylami-50 no] - ethane and sodium borohydride in isopropanol analogous to Example 9. resin.

NMR spectrum (CDC13 / D20):

aroma H 7.2 ppm (s; 2H)

6.85 ppm (q; 4H) 55 OCH3 3.8 ppm (s; 3H)

NCH3 2.25 ppm (s; 3H)

aliph. H 1.5-2.7 ppm (m; 12H)

Example 159

N- [2- (4-Amino-3-chloro-5-trifluoromethylphenyl) ethyl] -N - [4- (4-methoxyphenyl) butyl] methylamine

Made from l-ethoxycarbonyloxy-l- (4-amino-3-chloro-5 - trifluoromethylphenyl) -2- [N- [4- (4-methoxyphenyl) butyl] methylamino] ethane and Sodium borohydride in isopropanol as in Example 9.

Melting point: 29 ° C.

651 541

30th

Example 160

N- [2- (4-Amino-3-chloro-5-trifluoromethylphenyl) ethyl J-N - [2- (4-methoxyphenyl) ethyl] methylamine

Made from l-ethoxycarbonyloxy-l- (4-amino-3-chloro-5-trifluoromethyl-phenyl) -2- [N- [2- (4-methoxy-phenyl) -ethyl] - methylamino] -ethane and Sodium borohydride in isopropanol analogous to Example 9. Resin.

IR spectrum (methylene chloride):

NH2 3400 + 3500 cm "1

OCH3 2840 + 2960 cm "1

aroma. C = C 1610 cm "1

UV spectrum (ethanol): X max.

228 nm (shoulder, 0.10)

244 nm (0.10)

310 nm (0.03)

Example 161

N- [2- (4-A mino-3,5-dichlorophenyl) ethyl] -N - [3- (4-fluorophenyl) propylJ-methylamine

Made from l-ethoxycarbonyloxy-l- (4-amino-3,5-di-chlorophenyl) -2- [N- [3- (4-fluorophenyl) propyl] methylamino] ethane and sodium borohydride in isopropanol as in Example 9. Oil.

IR spectrum (methylene chloride):

NH2 3390 + 3490 cm "1

UV spectrum (ethanol): X max.

243 nm (0.13)

300 nm (0.03)

Example 162

1 - (4-A mino-3-trifluoromethylphenyl) -2- [N- [3- (4-methoxyphenyl) propyl] methylamino] ethanol

Made from l- (4-amino-3-bromo-trifluoromethyl-phenyl) - 2- [N- [3- (4-methoxy-phenyl) -propyl] methylamino] ethanol and hydrogen in the presence of palladium oxide on barium sulfate in methanol as in Example 11. Oil.

NMR spectrum (CDC13 / D20):

aroma H 6.6-7.3 ppm (m; 7H)

) CH - OH 4.5 ppm (t; 1H)

OCH3 3.7 ppm (s; 3H)

NCH3 2.3 ppm (s; 3H)

aliph. H 2.2-2.7 ppm (m; 6H)

- CH2-1.8ppm (q; 2H)

Example 163

N- [3- (4-Acetamino-3,5-dichlorophenyl) propyl] -N- {2 - (3,4-dimethoxyphenyl) ethyl] methylamine

Made from N- [3- (4-amino-3,5-dichlorophenyl) propyl] - N- [2- (3,4-dimethoxyphenyl) ethyl] methylamine, acetyl chloride and triethylamine in toluene analogous to Example 12. Oil.

IR spectrum (methylene chloride):

NH 3405 cm "1

OCH3 2830 + 2940 cm "1

CO 1700 cm "1

UV spectrum (ethanol): X max.

228 nm (shoulder; 0.17)

280 nm (0.04)

Example 164

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (4-hydroxyphenyl) -1-methytopropyl] allylamino] ethanol

Made from l- (4-amino-3,5-dichlorophenyl) -2- [N- [3- (4 - hydroxyphenyl) -1-methylpropyl] amino] ethanol with allyl-

bromide / sodium carbonate in absolute ethanol analogous to example 13. Oil.

IR spectrum (methylene chloride):

OH 3580 cm "1

s NH2 3390 + 3480 cm "1

aliph. CH2 1850 + 2930 cm "1

C = C 1615 cm "1

UV spectrum (ethanol): X max.

243 nm (0.26)

io 282 nm (0.08)

300 nm (0.08)

UV spectrum (ethanol 4- KOH): X max.

242 nm (0.47)

298 nm (0.19)

15

Example 165

1- (4-amino-3,5-dichlorophenyl) -2- [N- [3- (4-hydroxy-

20th

-phenyl) -propyl] -isopropylamino] -ethanol hydrochloride

Made from l- (4-amino-3,5-dichlorophenyl) -2- [N- [3- (4 - benzyloxyphenyl) propyl] isopropylamino] ethanol and hydrogen in the presence of palladium on carbon analogous to example 16.

Melting point of the hydrochloride: 90-110 ° C.

Example 166

30 liters of (4-amino-3-chlorophenyl) -2- [N- [3- (4-hydroxyphenyl) propylj-ethylaminoj-ethanol

Made from l- (4-amino-3,5-dichlorophenyl) -2- [N- [3- (4 - benzyloxyphenyl) propyl] ethylamino] ethanol and hydrogen in the presence of palladium on carbon analogous to example 35. 16. Harz.

IR spectrum (methylene chloride):

OH 3595 cm "1

NH2 3400 + 3490 cm "1

aliphatic. CH2 2840 + 2940 cm "1

40 C = C 1625 cm "1

UV spectrum (ethanol): X max.

227 nm (0.19)

244 nm (0.17)

290 nm (0.04)

45 UV spectrum (ethanol + KOH): X max.

243 nm (0.32)

297 nm (0.08)

50 Example 167

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (4-hydroxyphenyl) propyl] ethylamino] ethanol

Made from l- (4-amino-3,5-dichlorophenyl) -2- [N- [3- (4-55 -benzyloxyphenyl) propyl] ethylamino] ethanol and water in the presence of Palladium on carbon analogous to Example 16. Resin.

IR spectrum (methylene chloride):

OH 3590, 3620 + 3680 cm "1

60 NH2 3390 + 3480 cm "1

aroma. C = C 1615 cm'1

UV spectrum (ethanol): X max.

244 nm (0.17)

284 nm (0.06)

65 200 nm (0.05)

UV spectrum (ethanol + KOH): X max.

243 nm (0.31)

298 nm (0.08)

31

651 541

Example 168

N- [3- (4-Dimethylamino-3,5-dichlorophenyl) propyl] -N - [3- (4-methoxyphenyl) propyl] methylamine

Made from N- [3- (4-amino-3,5-dichlorophenyl) propyl] - N- [3- (4-methoxyphenyl) propyl] amine, paraformaldehyde and sodium cyanoborohydride in ethanol as in Example 101. Oil. IR spectrum (methylene chloride):

OCH3 2830 + 2940 cm "1

NCHj 2790 cm "1

NH2

aroma. C = C 1610 cm "1

NMR spectrum (CDCI3 / D2O):

aroma H 7.0 ppm (q; 4H)

7.1 ppm (s; 2H) OCH3 3.75 ppm (s; 3H)

N (CH3) 2 2.85 ppm (s; 6H)

aliph. H 2.2-2.8 ppm (m; 8H)

N - CH3 2.2 ppm (s; 3H)

- CH2 - 1.6-1.8 ppm (q; 4H)

Example 169

N- [3- (4-Amino-3,5-dichlorophenyl) propyl] -N- [3- (4-methoxyphenyl) propyl] methylamine

Made from N- [3- (4-amino-3,5-dichlorophenyl) propyl] - N- [3- (4-methoxyphenyl) propyl] amine, paraformaldehyde and sodium cyanoborohydride in ethanol as in Example 101. Oil. IR spectrum (methylene chloride):

NH2 3390 + 3490 cm "1

OCH3 2830 + 2940 cm "1

aroma. C = C 1610 cm "1

UV spectrum (ethanol): X max.

230 nm (shoulder; 0.21)

242 nm (0.1)

278 + 285 nm (wide; 0.03)

302 nm (wide; 0.03)

Example 170

N- [2- (4-Dimethylamino-3,5-dichlorophenyl) ethyl] -N - [3- (4-chlorophenyl) propyl] methylamine

Made from N- [2- (4-amino-3,5-dichlorophenyl) ethyl] - N- [3- (4-chlorophenyl) propyl] amine, paraformaldehyde and sodium cyanoborohydride in ethanol as in Example 101. Oil. IR spectrum (methylene chloride):

NCHj 2790 cm "1

NH2 -

NH -

UV spectrum (ethanol): X max.

273 nm (broad; 0.04)

Example 171

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [3- (4-chlorophenyl) propyl] -2-phenylethylamine hydrochloride

Made from N- [2- (4- (amino-3,5-dichlorophenyl) ethyl) - N- [3- (4-chlorophenyl) propyl] amine, phenylacetaldehyde and sodium cyanoborohydride in ethanol analogously Example 101.

Melting point of the hydrochloride; 158-161 ° C.

Example 172

N- [2- (4-A mitio-3,5-dichlorophenyl) ethyl] -N- [4- (4-methoxyphenyl) butyl] ethylamine

Made from N- [2- (4-amino-3,5-dichlorophenyl) ethyl] - N- [4- (4-methoxyphenyl) butyI] amine, acetaldehyde and sodium cyanoborohydride in ethanol as in Example 101. Oil.

IR spectrum (methylene chloride):

OCH3 2860 + 2930 cm "1

aroma. C = 0610 cm "1

UV spectrum (ethanol): X 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-dichlorophenyl) ethyl] -N- [3- (4-chlorophenyl) propyl] benzylamine hydrochloride

Made from N- [2- (4-amino-3,5-dichlorophenyl) ethyl] - N- [3- (4-chlorophenyl) propyl] amine, benzaldehyde and sodium cyanoborohydride in ethanol analogously to the example 101.

Melting point of the hydrochloride: 164-168 ° C.

Example 174

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [3- (4-chlorophenyl) propyl] isopropylamine

Made from N- [2- (4-amino-3,5-dichlorophenyl) ethyl] - N- [3- (4-chlorophenyl) propyl] amine, acetone and sodium cyanoborohydride in absolute methanol analog Example 101. Oil. IR spectrum (methylene chloride):

NH2 3390 + 3480 cm "1

aroma. C = C 1615 cm "1

UV spectrum (ethanol): X max.

241 nm (0.13)

300 nm (0.05)

Example 175

N- [l-Methyl-2- (4-amino-3,5-dichlorophenyl) ethyl J-N - [3- (4-methoxyphenyl) propyl] amine hydrochloride

Prepared from l- (4'-amino-3 ', 5'-dichlorophenyl) acetone, 3- (4-methoxyphenyl) propylamine and sodium cyanoborohydride in ethanol analogously to Example 101.

Melting point of the hydrochloride: 193-195 ° C.

Example 176

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [3- (4-chlorophenyl) propyl] n-propylamine

Made from N- [2- (4-amino-3,5-dichlorophenyl) ethyl] - N- [3- (4-chlorophenyl) propyl] amine, propionaldehyde and sodium cyanoborohydride in ethanol as in Example 101. Oil. IR spectrum (methylene chloride):

NH2 3380 + 3480 cm "1

aroma. C = C 1610 cm "1

UV spectrum (ethanol): X max.

242 nm (0.13)

301 nm (0.05)

Example 177

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [3- (4-chloro-phenyl) propylJ-ethylamine

Made from N- [2- (4-amino-3,5-dichlorophenyl) ethyl] - N- [3- (4-chlorophenyl) propyl] amine, acetaldehyde and sodium cyanoborohydride in ethanol at pH 6-6.5 analogous to Example 101. Oil.

IR spectrum (methylene chloride):

NH2 3390 + 3480 cm "1

aroma. C = C 1615 cm "1

UV spectrum (ethanol): X max.

242 nm (0.14)

305 nm (0.04)

5

10th

15

20th

25th

30th

35

40

45

50

55

60

65

651 541

32

Example 178

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [2- (4-methoxyphenyl) ethyl] ethylamine

Made from N- [2- (4-amino-3,5-dichlorophenyl) ethyl] - N- [2- (4-methoxy-phenyl) ethyl] amine, acetaldehyde and sodium cyanoborohydride in ethanol as in Example 101. Oil. IR spectrum (methylene chloride):

nh2 3890 + 3480 cm "1

och3 2830 + 2940 cm "1

aroma. c = c 1620 cnr1

UV spectrum (ethanol): X max.

244 nm (0.16)

284 nm (shoulder, 0.04)

300 nm (0.04)

Example 179

N- [l-Methyl-2- (4-amino-3,5-dichlorophenyl) ethyl] -N - [3- (4-methoxyphenyl) propyl] methylamine

Prepared from l- (4'-amino-3 ', 5'-dichlorophenyl) acetone, 3- (4-methoxyphenyl) -N-methyl-propylamine and sodium cyanoborohydride in ethanol as in Example 101. Oil.

IR spectrum (methylene chloride):

NH2 3390 + 3480 cm "1

OCH3 2840 + 2940 cm "1

aroma. C = C 1615 cm "1

UV spectrum (ethanol): X max.

242 nm (0.14)

280 nm (shoulder, 0.04)

302 nm (0.05)

Example 180

N- [2- (4-A mino-3,5-dichlorophenyl) ethyl] -N- (3-phenyl-propyl) isopropylamine hydrochloride

Made from N- [2- (4-amino-3,5-dichlorophenyl) ethyl] - 3-phenyl-propylamine, acetone, molecular sieve 3 Â and sodium cyanoborohydride in absolute methanol as in Example 101. Foam. IR spectrum (methylene chloride):

NH2 3390 + 3490 cm "1

NH © 2300-2400 cm "1

UV spectrum (ethanol): X max.

245 nm (0.12)

302 nm (0.04)

Example 181

1- (4-Amino-3,5-dichlorophenyl) -2- [N- (1- methyl-3-phenylpropyl) methylamino] ethanol hydrochloride

Prepared from l- (4-amino-3,5-dichlorophenyl) -2- [N- (l-methyl-3-phenyl-propyl) -amino] ethanol, paraformaldehyde and sodium cyanoborohydride in ethanol analogously to Example 101. Oily hydrochloride.

IR spectrum (methylene chloride):

NH2 3390 + 3490 cm "1

NH © 2300-2400 cm "1

OH 3580 cm "1

UV spectrum (ethanol): X max.

245 nm (0.12)

302 nm (0.03)

Example 182

1- (4-Amino-3,5-dichlorophenyl) -2- [N- (1- methyl-3-phenylpropyl) methylamino] ethanol hydrochloride

Prepared from l- (4-amino-3,5-dichlorophenyl) -2- [N- (l - methyl-3-phenyl-propyl) -amino] ethanol, paraformaldehyde and sodium cyanoborohydride in absolute ethanol as in Example 101 .

Melting point of the hydrochloride: 170-173 ° C.

Example 183

l- (4-Amino-3,5-dichlorophenyl) -2- [N- (l-methyl-3-phenyl-propylj-propylaminoj-ethanol hydrochloride io Made from l- (4-amino-3, 5-dichlorophenyl) -2- [N- (1-methyl-3-phenylpropyl) amino] ethanol, propionaldehyde and sodium cyanoborohydride analogously to Example 101. Oily hydrochloride.

IR spectrum (methylene chloride): 15 NH2 3390 + 3490 cm "1

NH © 2300-2400 cm "1

OH 3590 + 3680 cnr1

UV spectrum (ethanol): X max.

245 nm (0.12)

20 302 nm (0.03)

Example 184

N- [2- (4-Amiho-3,5-dichlorophenyl) ethyl] -N- (3-phenyl-25-propyl) -n-propylamine hydrochloride

Manufactured from N- [2- (4-amino-3,5-dichlorophenyl) ethyl] - 3-phenyl-propylamine, propionaldehyde and sodium cyanoborohydride in absolute ethanol analogously to Example 101. Oily Hy-3o hydrochloride.

IR spectrum (methylene chloride):

NH2 3390 + 3490 cm "1

NH © 2300-2400 cm "1

OH 3600 + 3650 cm "1

35 UV spectrum (ethanol): X max.

245 nm (0.17)

302 nm (0.05)

40 Example 185

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- (3-phenylpropyl) ethylamine hydrochloride

Prepared from N- [2- (4-amino-3,5-dichlorophenyl) ethyl] -45 -3-phenyl-propylamine, acetaldehyde and sodium cyanoborohydride in absolute ethanol analogously to Example 101. Oily hydrochloride.

IR spectrum (methylene chloride):

NH2 3390 + 3490 cm "1

so 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-dichlorophenyl) ethyl] -N- (l-methyl-3-phenyl-propyl) ethylamine hydrochloride

60 Made from N- [2- (4-amino-3,5-dichlorophenyl) ethyl] - N- (l-methylphenyl propyl) amine, acetaldehyde and sodium cyanoborohydride in absolute ethanol analogous to Example 101. ^ Oily hydrochloride.

IR spectrum (methylene chloride):

NH2

3390 + 3490 cm '

-l

UV spectrum (ethanol): X max. 243 nm (0.11) 300 nm (0.04)

33

651 541

Example 187

1- (4-Amino-3,5-dichlorophenyl) -2- [N- (1-methyl-2-phenoxy-ethyl) ethylamino] ethanol hydrochloride

Prepared from l- (4-amino-3,5-dichlorophenyl) -2- [N- (l-methyl-2-phenoxyethyl) amino] ethanol, acetaldehyde and sodium cyanoborohydride in absolute ethanol analogous to Example 101 Oily hydrochloride.

IR spectrum (methylene chloride):

NH2 3390 + 3490 cm "1

NH © 2320-2460 cm "1

OH 3600 + 3680 cm "'

UV spectrum (ethanol): X max.

248 nm (0.12)

300 nm (0.03)

Example 188

1- (4-Amino-3-cyano-5-fluoro-phenyl) -2- [N- [2- (3,4-di-methoxy-phenylj-ethylj-ethylaminoj-ethanol

Made from l- (4-amino-3-cyan-5-fluorophenyl) -2- [N- [2 - (3,4-dimethoxyphenyl) ethyl] amino] ethanol, acetaldehyde and sodium cyanoborohydride in ethanol analogously to Example 101. Oil. IR spectrum (methylene chloride):

NH2 3390 + 3490 cm "1

CN 2205 cm "1

UV spectrum (ethanol): X max.

240 nm (shoulder; 0.16)

280 nm (0.04)

325 nm (0.06)

Sodium cyanoborohydride in absolute ethanol analogous to Example 101. Oily hydrochloride.

IR spectrum (methylene chloride):

NH2 3390 + 3490 cm "1

s NH © 2300-2500 cm "'

CN 2205 cm "1

OH 3590 + 3680 cm "1

UV spectrum (ethanol): X max.

248 nm (0.11)

io 280 nm (0.03)

320 nm (0.06)

Example 192

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [3- (4-fluoro-15-phenyl) propyl] benzylamine hydrochloride

Made from N- [2- (4-amino-3,5-dichlorophenyl) ethyl] - N- [3- (4-fluoro-phenyl) propyl] amine, benzaldehyde and sodium cyanoborohydride in absolute ethanol analog Example 101. 20 ° melting point of the hydrochloride: 118-120 ° C.

Example 193

N- [2- (4-Amitio-3,5-dichlorophenyl) ethyl] -N- [3- (4-fluoro-phenyl) propyl] n-propylamine hydrochloride

25th

Made from N- [2- (4-amino-3,5-dichlorophenyl) ethyl] - N- [3- (4-fluorophenyI) propyI] amine, propionaldehyde and sodium cyanoborohydride in absolute ethanol analogously Example 101.

Melting point of the hydrochloride: 130-133 ° C.

30th

Example 189

1- (4-Amino-3-chloro-5-fluorophenyl) -2- [N- [2- (3,4-methylenedioxy-phenoxy) -l-methyl-ethyl] ethylamino] ethanol hydrochloride

Made from l- (4-amino-3-chloro ~ 5-fluoro-phenyl) -2- [N- [2 - (3,4-methylenedioxy-phenoxy) -1-methyl-ethyl] -amino] ethanol , Acetaldehyde and sodium cyanoborohydride in absolute ethanol analogous to Example 101. Oily hydrochloride.

IR spectrum (methylene chloride):

NH2 3390 + 3490 cm "1

NH © 2300-2450 cm "1

OH 3600 + 3680 cm1

UV spectrum (ethanol): X max.

243 nm (0.17)

287 nm (0.07)

Example 190

1- (4-Amino-3-bromo-5-fluoro-phenyl) -2- [N- (1- methyl-2-phenoxyethyl] ethylamino] ethanol

Made from l- (4-amino-3-bromo-5-fluorophenyl) -2- [N- (l - methyl-2-phenoxy-ethyl] -amino] ethanol, acetaldehyde and sodium cyanoborohydride in absolute ethanol analogously Example 101. Oil.

IR spectrum (methylene chloride):

NH2 3390 + 3490 cm "1

UV spectrum (ethanol): X max.

240 nm (0.14)

280-290 nm (0.03)

Example 191

1- (4-Amino-3-cyan-5-fluorophenyl) -2- [N- [3- (4-methoxyphenyl) propylI-ethylaminoI-ethanol hydrochloride

Made from l- (4-amino-3-cyan-5-fluorophenyl) -2 ~ [N- [3 - (4-methoxyphenyl) propyl] amino] ethanol, acetaldehyde and

Example 194

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [3- (4-fluoro-phenyl) propylJ-ethylamine hydrochloride

Made from N- [2- (4-amino-3,5-dichlorophenyl) ethyl] - N- [3- (4-fluoro-phenyl) propyl] amine, acetaldehyde, molecular sieve 3 Â and sodium cyanoborohydride in absolute methanol as in Example 101.

4o melting point of the hydrochloride: 182-184 ° C (dec.).

Example 195

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [3- (4-fluoro-phenyl) propylJ-isopropylamine hydrochloride

Made from N- [2- (4-amino-3,5-dichlorophenyl) ethyl] - N- [3- (4-fluoro-phenyl) propyl] amine, acetone, molecular sieve 3 Â and sodium cyanoborohydride in absolute methanol as in example 50 game 101.

Melting point of the hydrochloride: 182-184 ° C (dec.).

Example 196

55 l- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (4-fluorophenyl) propyl] -2-phenylethylamino] ethanol hydrochloride

Made from l- (4-amino-3,5-dichlorophenyl) -2- [N- [3- (4 - fluorophenyl) propyl] amino] ethanol, phenylacetaldehyde and 6o sodium cyanoborohydride in absolute ethanol analogous to Example 101. Amorphous hydrochloride.

IR spectrum (methylene chloride):

NH2 3390 + 3490 cm "1

NH © 2300-2500 cm "1

65 OH 3590 + 3680 cm "1

UV spectrum (ethanol): X max.

243 nm (0.11)

300 nm (0.04)

651 541

34

Example 197

I- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (4-fluorophenyl) propylj-benzylaminoj-ethanol hydrochloride

Manufactured analogously from l- (4-amino-3,5-dichlorophenyl) -2- [N- [3- (4-fluorophenyl) propyl] amino] ethanol, benzaldehyde and sodium cyanoborohydride in absolute ethanol Example 101 Melting point of the hydrochloride: 132-134 ° C (dec.).

Example 198

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (4-fluorophenyl) propylj-n-propylamino] ethanol hydrochloride

Made from l- (4-amino-3,5-dichlorophenyl) -2- [N- [3- (4 - fluorophenyl) propyl] amino] ethanol, propionaldehyde and sodium cyanoborohydride in absolute ethanol analogously Example 101.

Melting point of the hydrochloride: 136-138 ° C (dec.).

Example 199

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (4 ~ fluorophenyl) propylj-ethylaminoj-ethanol hydrochloride

Made from l- (4-amino-3,5-dichlorophenyl) -2- [N- [3- (4 - fluorophenyl) propyl] amino] ethanol, acetaldehyde and sodium cyanoborohydride in absolute ethanol analogously Example 101.

Melting point of the hydrochloride: 130-134 ° C.

Example 200

1- (4-Amino-3,5-dichlorophenyl) -2- [N- (3-phenyl-propyl) -2-phenylethylaminoJ-ethanol hydrochloride

Prepared from l- (4-amino-3,5-dichlorophenyl) -2- [N- (3-phenylpropyl) amino] ethanol, phenylacetaldehyde and sodium cyanoborohydride in absolute ethanol analogous to Example 101. Amorphous hydrochloride.

IR spectrum (methylene chloride):

NH2 3390 + 3490 cm "1

NH © 2300-2500 cm "1

OH 3590 + 3690 cm "1

UV spectrum (ethanol): X max.

243 nm (0.12)

300 nm (0.04)

Example 201

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (4-fluorophenyl) propyl] isopropylamino] ethanol hydrochloride

Made from l- (4-amino-3,5-dichlorophenyl) -2- [N- [3- (4 - fluorophenyl) propyl] amino] ethanol, acetone, molecular sieve 3 Â and sodium cyanoborohydride in absolute methanol as in Example 101.

Melting point of the hydrochloride: 80-85 ° C (decomp.).

Example 202

1- (4-Amino-3,5-dichlorophenyl) -2- [N- (1- methyl-3-phenylpropyl) ethylamino] ethanol

Made from l- (4-amino-3,5-dichlorophenyl) -2- [N- (l - methyI-3 - phenylpropyl) amino] ethanol, acetaldehyde, molecular sieve 3 Â and sodium cyanoborohydride in absolute ethanol analogous to Example 101. oil.

IR spectrum (methylene chloride):

NH2 3390 + 3490 cm "1

UV spectrum (ethanol): X max.

245 nm (0.13)

300 nm (0.13)

Example 203

1- (4-Dimethylamino-3,5-dichlorophenyl) -2- [N- (3-phenyl-l-methylpropyl) methylamino] ethanol

Prepared from l- (4-amino-3,5-dichlorophenyl) -2- [N- (3-phenyl-l-methylpropyl) amino] ethanol, formaldehyde and sodium cyanoborohydride in absolute ethanol as in Example 101 Oil.

IR spectrum (methylene chloride):

OH 3600 + 3680 cm "1

N-alkyl 2800 cm-1

UV spectrum (ethanol): X max.

275 nm (0.03)

Example 204

1- (4-Amino-3,5-dichlorophenyl) -2- [N- (3-phenyl-propyl) benzylaminoj-ethanol

Prepared from l- (4-amino-3,5-dichlorophenyl) -2- [N- (3-phenyl-propyl) amino] ethanol, benzaldehyde and sodium cyanoborohydride in absolute ethanol analogous to Example 101. Oil. IR spectrum (methylene chloride):

NH2 3390 + 3490 cm "1

OH 3600 + 3680 cm1

UV spectrum (ethanol): X max.

245 nm (0.12)

300 nm (0.03)

Example 205

1- (4-A mino-3,5-dichlorophenyl) -2- [N- [3- (4-methylsulfinyl - phenyl) propylJ-aminoJ-ethanol

1.5 g (0.0039 mol) of l- (4-amino-3,5-dichlorophenyl) -2- [N- [3 - (4-methylsulfenylphenyl) propyl] amino] ethanol and 639 mg (0.0078 mol) of anhydrous sodium acetate are 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 is slowly added dropwise to this solution while stirring at room temperature. When the addition is complete, the light brown solution is left to stand at room temperature for one hour and then poured into water. While cooling with ice, conc. Ammonia made alkaline to pH 8.5 and extracted exhaustively with methylene chloride. The combined methylene chloride extracts are dried over sodium sulfate and evaporated to dryness in vacuo. The residue is crystallized from methanol / ether. Colorless crystals.

Melting point: 127-129 ° C.

Example 206

1- (4 ~ Amino-3,5-dichlorophenyl) -2- [N- [3- (4-methylsulfenylphenyl) propyl] amino] ethanol

Prepared from 4'-amino-3 ', 5'-dichloroacetophenone, selenium dioxide, 3- (4-methylsulfenylphenyl) propylamine and sodium borohydride as in Example 5.

Melting point: 128-130 ° C.

Example 207

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (4-methylsulfinylphenyl) propyl] methylamino] ethanol

Made from l- (4-amino-3,5-dichlorophenyl) -2- [N- [3- (4-methylsulfinylphenyl) propyl] amino] ethanol, paraformaldehyde and sodium cyanoborohydride in methanol analogous to Example 101. foam.

IR spectrum (methylene chloride):

OH 3660 + 3600 cm "1

NH2 3490 + 3390 cm "1

SO 1050 cm "1

5

10th

15

20th

25th

30th

35

40

45

50

55

60

65

35

651 541

UV spectrum (ethanol): X max.

242 nm (0.16)

300 nm (0.03)

Example 208

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (4-methylsulfenylphenyl) propyl] methylamino] ethanol

Made from l- (4-amino-3,5-dichlorophenyl) -2- [N- [3- (4 - methylsulfylphenyl) propyl] amino] ethanol, paraformaldehyde and sodium cyanoborohydride in methanol analogous to Example 101. Colorless oil.

IR spectrum (methylene chloride):

OH 3690 + 3590 cm1

NH2 3490 + 3390 cm "1

UV spectrum (ethanol): X max.

245 nm (0.23)

295-300 nm (0.04)

Example 209

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (4-chlorophenyl) propyl] n-propylamino] ethanol

Made from l- (4-amino-3,5-dichlorophenyl) -2- [N- [3- (4-chlorophenyl) propyl] amino] ethanol, propionaldehyde and sodium cyanoborohydride in ethanol as in Example 101. Oil. IR spectrum (methylene chloride):

NH2 3390, 3490 cm "1

aroma. C = C 1620 cm-1

UV spectrum (ethanol): X max.

243 nm (0.13)

300 nm (0.04)

Example 210

1- (4-dimethylamino-3,5-dichlorophenyl) -2-methyl-2- [N-

- [3- (4-methoxyphenyl) propyl] methylamino] ethanol

Made from l- (4-amino-3,5-dichlorophenyl) -2-methyl-2 - [N- [3- (4-methoxyphenyl) propyl] amino] ethanol, paraformaldehyde and sodium cyanoborohydride in ethanol at pH 3-7.5 as in Example 101. Oil.

IR spectrum (methylene chloride):

OH 3590 cm "1

no NH, NH2

aroma. C = C 1610 cm-1

UV spectrum (ethanol): X max.

243 nm (0.20)

278 nm (0.06)

Example 211

1- (4-Benzylamino-3,5-dichlorophenyl) -2- [N- [3- (4-chlorophenyl) propyl] amino] ethanol

Made from l- (4-amino-3,5-dichlorophenyl) -2- [N- [3- (4-chlorophenyl) propyl] amino] ethanol, benzaldehyde and sodium cyanoborohydride in ethanol as in Example 101.

Base melting point: 85-95 ° C.

Example 212

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (4-chlorophenyl) propylj-benzylaminoj-ethanol hydrochloride

Made from l- (4-amino-3,5-dichlorophenyl) -2- [N- [3- (4-chlorophenyl) propyl] amino] ethanol, benzaldehyde and sodium cyanoborohydride in ethanol as in Example 101.

Melting point of the hydrochloride: 110-114 ° C.

Example 213

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (4-chlorophenyl) propyl] ethylaminoI-ethanol

Made from l- (4-amino-3,5-dichlorophenyl) -2- [N- [3- (4-chlorophenyl) propyl] amino] ethanol, acetaldehyde and sodium cyanoborohydride in ethanol as in Example 101. Oil. IR spectrum (methylene chloride):

NH2 3390, 3490 cm "1

aroma. C = C 1620 cm "1

UV spectrum (ethanol): X max.

244 nm (0.13)

300 nm (0.04)

Example 214

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [3- (4-chlorophenyl) propyl] methylamine

Prepared from N- [2- (4-amino-3,5-dichlorophenyl) ethyl] -3- (4-chlorophenyl) propylamine, paraformaldehyde and sodium cyanoborohydride in methanol as in Example 101. Oil. IR spectrum (methylene chloride):

NH2 3390, 3490 cnr1

aroma. C = C 1615 cm "1

UV spectrum (ethanol): X max.

241 nm (0.10)

300 nm (0.04)

Example 215

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (4-chlorophenyl) propyl] -2-phenylethylamino] ethanol hydrochloride

Made from l- (4-amino-3,5-dichlorophenyl) -2- [N- [3- (4-chlorophenyl) propyl] amino] ethanol, phenylacetaldehyde and sodium cyanoborohydride in ethanol as in Example 101.

Melting point of the hydrochloride: 103-109 ° C (dec.).

Example 216

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (4-chlorophenyl) propyl] methylamino] ethanol hydrochloride

Made from l- (4-amino-3,5-dichlorophenyl) -2- [N- [3- (4-chlorophenyl) propyl] amino] ethanol, paraformaldehyde and sodium cyanoborohydride in ethanol as in Example 101.

Melting point of the hydrochloride: 85-100 ° C (decomp.).

Example 217

1- (3-Chloro-4-piperidino-phenyl) -2- [N- [3- (4-methoxy-phenyl) propylj-methylaminoj-ethanol hydrochloride

Prepared from 3'-chloro-4'-piperidino-2- [N- [3- (4-methoxyphenyl) propyl] methylamino] acetophenone and sodium borohydride in methanol / water analogously to Example 1. Oily hydrochloride.

IR spectrum (methylene chloride):

OH 3600 cnr1

OCH3 2840 cm "1

NH © 2300-2700 cm "1

UV spectrum (ethanol): X max.

258 nm (0.12)

283 nm (shoulder, 0.05)

Example 218

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (3-methoxyphenyl) propyl] amino] ethanol

Made from 4'-amino-3 ', 5'-dichloro-acetophenone, selenium5

10th

15

20th

25th

30th

35

40

45

50

55

60

65

651 541

36

Dioxide, 3- (3-methoxyphenyl) propylamine and sodium borohydride as in Example 5.

Melting point: 124 ° C.

Example 219

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (3-methoxyphenyl) propyl] ethylamino] ethanol

Made from l- (4-amino-3,5-dichlorophenyl) -2- [N- [3- (3-methoxyphenyl) propyl] amino] ethanol, acetaldehyde and sodium cyanoborohydride in.Methanol analog Example 101. Oil. IR spectrum (methylene chloride):

OH 3580 cm "1

NH2 3490 + 3390 cm "1

OCH3 2830 cm "1

UV spectrum (ethanol): X max.

247 nm (0.06)

300 nm (0.04)

Example 220

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (3-methoxyphenyl) propyl] methylamino] ethanol

Made from l- (4-amino-3,5-dichlorophenyl) -2- [N- [3- (3-methoxyphenyl) propyl] amino] ethanol, paraformaldehyde and sodium cyanoborohydride in methanol as in Example 101.

Oil.

IR spectrum (methylene chloride):

OH 3680 + 3620 cm "1

NH2 3490 + 3390 cm "1

OCH3 2840 cm "1

UV spectrum (ethanol): X max.

246 nm (0.15)

300 nm (0.04)

Example 221

1- (3,5-dichloro-4-isopropylaminophenyl) -2- [N- [3- (3-methoxyphenyl) propyl] isopropylamino] ethanol

Prepared from l- (4-amino-3,5-dichlorophenyl) -2- [N- [3- (3 - methoxyphenyl) propyl] amino] ethanol, acetone and sodium cyanoborohydride in methanol as in Example 101. Oil. IR spectrum (methylene chloride):

OH 3600 cm "1

NH 3350 cm "1

OCH3 2840 cm "1

UV spectrum (ethanol): X max.

250 nm (0.12)

278-280 nm (0.03)

Example 222

1- (4-Amino-3,5-dichlorophenyl) -2-fN- [3- (4-chlorophenyl) propylj-isopropylamino-ethanol

Made from l- (4-amino-3,5-dichlorophenyl) -2- [N- [3- (4-chlorophenyl) propyl] amino] ethanol, acetone and sodium cyanoborohydride in ethanol as in Example 101. Oil. IR spectrum (methylene chlorine):

NH2 3380 + 3480 cm "1

aroma. C = C 1615 cm "1

NMR spectrum (CDC13 / D20):

aroma H 7.0-7.4 ppm (m; 6H)

) CH - OH 4.4 ppm (dd; 1H)

- CH (3.0 ppm (dd; 1H)

aliph. CH2 2.3-2.7 ppm (m; 6H)

1.6-2.0 ppm (m; 2H) isopropyl-CH3 0.8-1.2 ppm (dd; 6H)

Example 223

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [3- (4-chlorophenyl) propyl] allylamino] ethanol

5 Made from l- (4-amino-3,5-dichlorophenyl) -2- [N- [3- (4-chlorophenyl) propyl] amino] ethanol, allyl bromide and triethylamine analogously to example 13 Oil.

IR spectrum (methylene chloride):

NH2 3380 + 3480 cm "1

io aroma. C = C 1610 cm "1

NMR spectrum (CDC13 / D20):

aroma H 7.0-7.4 ppm (m; 6H)

olef. H 5.5-6.1 ppm (m; 1H)

5.0-5.3 ppm (m; 2H) 15> CH - OH 4.3-4.7 ppm (dd; 1H)

> N - CH2 2.8-3.5 ppm (m; 2H)

aliph. - CH2 - 2.2-2.7 ppm (m; 6H) 1.5-2.0 ppm (m; 2H)

Example 224

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [3- (4-chlorophenyl) propyl] allylamine

25 Made from N- [2- (4-amino-3,5-dichlorophenyl) ethyl] -3 - (4-chlorophenyl) propylamine, allyl bromide and triethylamine analogously to Example 13. Oil.

IR spectrum (methylene chloride):

NH2 3380 + 3480 cm "1

30 aroma. C = C 1610 cm-1

NMR spectrum (CDC13 / D20):

aroma H 6.9-7.4 ppm (m; 6H)

olef. H 5.6-6.1 ppm (m; 1H)

5.0-5.3 ppm (m; 2H) 35> N - CH2 - 3.0-3.3 ppm (d; 2H)

aliph. - CH2 - 2.7-3.3 ppm (m; 8H) 1.3-1.9 ppm (m; 2H)

4o Example 225

N- [2- (4-Amino-3,5-dichlorophenyl) -1-methyl-ethyl] -N- [4 - (4-methoxy-phenyl) butyl] methylamine

Prepared from 4'-amino-3 ', 5'-dichloropropiophenone, N- [4-45 (4-methoxyphenyl) butyl] methylamine and sodium cyanoborohydride analogously to Example 101. Oil.

IR spectrum (methylene chloride):

NH2 3380 + 3480 cm "1

aroma. C = C 1610 cm "1

see UV spectrum (ethanol): X max.

245 nm (0.13)

280 nm (wide; 0.04)

300 nm (wide; 0.04)

Example 226

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [3- (4-methoxyphenyl) -1-methyl-propyl] ethylamine

6o Made from N- [2- (4-amino-3,5-dichlorophenyl) ethyl] -N - [3- (4-hydroxy-phenyl) -l-methyl-propyl] ethylamine in tetrahydrofuran with Sodium hydroxide solution and dimethyl sulfate as in Example 13.

The cleaning is carried out using aluminum oxide (neutral, activity level I) and the eluent mixture ether: petroleum ether = 1: 1.5. Oil.

Calculated: C 63.79 H 7.14 Cl 17.94 N 7.09

Found: C 63.17 H 7.09 Cl 17.90 N 7.15

37

651 541

Example 227

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [l, l-dimethyl - 3- (4-hydroxyphenyl) propyl] methylamine

To a solution of 3 g (0.0075 mol) of l- (4-amino-3,5-di-chlorophenyl) -2- [N- [1,1-dimethyl-3- (4-hydroxy-phenyl ) -propyl] --methylamino] ethanol in 12 ml of trifluoroacetic acid, 1.8 ml (0.018 mol) of pyridine-borane is added dropwise with stirring at −10 ° C. After removal of the cooling, the reaction solution warms up to room temperature within 30 minutes and is then heated on the steam bath for 60 minutes with stirring. After evaporation of the trifluoroacetic acid on a rotary evaporator at 50 ° C in a vacuum, the evaporation residue is mixed with 40 ml of 2N sodium hydroxide solution and heated at 120 ° C with stirring for 30 minutes. After cooling, the reaction mixture is carefully acidified with concentrated hydrochloric acid and mixed with concentrated ammonia until a basic reaction is carried out and then extracted twice with 75 ml of ether each time. The ether extracts obtained are washed with 2 x 50 ml of water, dried after combining with magnesium sulfate and concentrated to dryness in vacuo on a rotary evaporator. The evaporation residue is pre-cleaned over silica gel 60 (Macherey and Nagel 70-230 mesh, ASTM) and the eluent methylene chloride / methanol = 2: 1. Post-cleaning is carried out using aluminum oxide (neutral, activity level III). Ether / n-hexane = 2: 1 is used as the eluent. The oily evaporation residue obtained crystallizes after a short time.

Melting point: 122-124 ° C.

Example 230

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [1,1-dimethyl-3- (4-hydroxyphenyl) propyl] amino] ethanol

5 Made from 4'-amino-2-bromo-3 ', 5'-dichloro-acetophenone, 1,1-dimethyl-3-hydroxy-phenyl) -propylamine, sodium carbonate and reduction with sodium borohydride in aqueous tetrahydrofuran analogously to Example 3. Die Cleaning takes place over silica gel 60 (Macherey and Nagel, 70-230 mesh, ASTM). A mixture of methylene chloride / methanol / conc. Ammonia = 25: 1: 0.2 used.

Melting point: 142-144 ° C.

Example 231

15 N- [3- (4-chlorophenyl) propyl] -N- [2- (3,5-dichloro-4-isopropylamino-phenyl) ethyl] isopropylamine

Manufactured from N- [2- (4-amino-3,5-dichlorophenyl) ethyl] - [3- (4-chloro-phenyl) propyl] amine, acetone and sodium cyanide-20 borohydride analogously to Example 101. Oil .

NMR spectrum (CDC13):

aroma H 7-7.3 ppm (m; 6H)

> CH - 3.5-4.1 ppm (m; 1H)

) CH - approx. 3 ppm (m; 1H)

25 aliph. H 2.3-2.7 ppm (m; 8H)

1.5-2.0 ppm (m; 2H)

0.9-1.3 ppm (dd; 12H)

30th

Example 228

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- [3- (4-hydroxy-phenyl) -1-methyl-propyl] ethylamine

Made from 4'-amino-2-bromo-3 ', 5'-dichloroacetophenone, N- [3- (4-hydroxy-phenyl) -l-methyl-propyl] ethylamine, sodium carbonate in aqueous tetrahydrofuran and subsequent reaction of the reaction product obtained with pyridine-borane in trifluoroacetic acid analogously to Example 227. The purification is carried out using aluminum oxide (neutral, activity level III). Ether / petroleum ether = 2: 1 is used as eluent. Oil.

IR spectrum (methylene chloride):

OH 3590 cm1

NH2 3480 + 3390 cm "1

CH2, CH3 2960 + 2930 + 2860 cnr1

N-alkyl 2810 cm "1

C = C 1585 + 1510 + 1485 cm "1

UV spectrum (ethanol): X max.

241 nm (shoulder, 0.28)

280-302 nm (0.08)

UV spectrum (ethanol + KOH): X max.

241 nm (0.56)

298 nm (0.17)

Example 229

1- (4-Amino-3,5-dichlorophenyl) -2- [N- [1,1-dimethyl-3- (4-hydroxyphenyl) propyl] methylamino] ethanol

Example 232

N- [2- (4-amino-3,5-dichlorophenyl) ethyl] -N- (3-phenyl-1-methyl-propyl) methylam iti

Prepared from N- [2- (4-amino-3,5-dichlorophenyl) ethyl] -N - (3-phenyl-1-methylpropyl) amine, paraformaldehyde and Na-35 triumcyanborohydride analogously to Example 101. Oily hydrochloride. IR spectrum (methylene chloride):

NH2 3390 + 3490 cm "1

CH2 2930 cnr1

UV spectrum (ethanol): X max.

40 243 nm (0.12)

300 nm (0.04)

Example 233

N- [2- (4-Amino-3,5-dichlorophenyl) ethyl] -N- (3-phenyl-45-l-methyl-propyl) -n-propylamine

Prepared from N- [2- (4-amino-3,5-dichlorophenyl) ethyl] -N - (3-phenyl-l-methyl-propyl) amine, propionaldehyde and sodium cyanoborohydride analogously to Example 101. Oily hydrochloride . 50 IR spectrum (methylene chloride):

NH2 3390 + 3490 cnr1

CH2 2930 cm "1

UV spectrum (ethanol): X max.

245 nm (0.11)

300 nm (0.04)

Example A

Tablets of 25 mg l- (4-amino-3,5-dichlorophenyl) -2- [N- (3-phenyl-propyl) -2-propylamino] ethanol hydrochloride

Made from 4'-amino-2-bromo-3 ', 5'-dichloroacetophenone, 60

Composition:

N- [l, l-dimethyl-3- (4-hydroxyphenyl) propyl] methylamine, Na

1 tablet contains:

trium carbonate and subsequent reduction with sodium boron

Active substance

25.0

mg hydride in aqueous tetrahydrofuran analogously to Example 3. Die

Cornstarch

30.0

mg

Pre- and post-cleaning is carried out using silica gel 60 (Macherey u.

Milk sugar

61.5

mg

Nagel, 70-230 mesh, ASTM). Ether / 65

gelatin

3.0

mg

Tetrahydrofuran = 3: 1 and methylene chloride / methanol /

Magnesium stearate

0.5

mg conc. Ammonia = 30: 1: 0.3 used.

Melting point: 155-158 ° C.

120.0 mg

38

651 541

Manufacturing:

The active ingredient, corn starch and milk sugar are mixed, moistened evenly with the aqueous gelatin solution and granulated. After drying in a circulating air drying cabinet and sieving (1.5 mm clear sieve width), the lubricant is added. The ready-to-press mixture thus obtained is pressed into tablets.

Shape: biplane with one-sided partial notch and double-sided

facet

Diameter: 7 mm Weight: 120 mg.

Example B

Dragées to 10 mg of l- (4-amino-3,5-dichlorophenyl) -2- [N - (3-phenyl-propyl) -2-propylamino] ethanol hydrachloride

1 tablet core contains:

Active substance 10.0 mg

Corn starch 35.0 mg

Milk sugar 71.5 mg

Gelatin 3.0 mg

Magnesium stearate 0.5 mg

Example D

Drops of 20 mg I- (4-amino-3,5-dichlorophenyl) -2- [N- (3-phenyl-propyl) -2-propylamino] ethanol hydrochloride contain 100 ml drip solution per 5 ml s :

Active substance 0.4 g

Hydroxyethyl cellulose 0.15 g

Tartaric acid 0.1 g

Sorbitol solution 70% dry matter 30.0 g io glycerin 10.0 g

Benzoic acid 0.15 g

Distilled water to 100.0 ml

Manufacturing:

15 Dest. Water is heated to 70 ° C. The hydroxyethyl cellulose, benzoic acid and tartaric acid are dissolved therein with stirring. It is cooled to room temperature and the glycerin and the sorbitol solution are added with stirring. The active ingredient is added at room temperature and stirred until completely dissolved. Subsequently, the juice is evacuated with stirring.

120.0 mg

Manufacturing:

Analogous to example A.

Pressing into cores with a diameter of 7 mm and a radius of 6 mm.

The cores thus produced are coated in a coating pan with a sugar coating paste up to a weight of 160 mg. The mixture is then further coated with pure sugar syrup up to 165 mg and the coatings thus obtained are polished.

Example C

Capsules of 20 mg l- (4-amino-3, S-dichlorophenyl) -2- [N - (, 3-phenyl-propyl) -2-propylamino] ethanol hydrochloride

1 capsule contains: active ingredient milk sugar powdered corn starch soluble starch magnesium stearate

20.0 mg 114.0 mg 60.0 mg 5.0 mg 1.0 mg

200.0 mg

Manufacturing:

The active ingredient is mixed homogeneously with the other excipients and filled into size 2 gelatin capsules in a capsule filling machine.

Capsule filling weight: 200 mg.

Example E

Suppositories of 50 mg l- (4-amino-3,5-dichlorophenyl) -2 - [N- (3-phenyl-propyl) -2-propylamino] ethanol hydrochloride

1 suppository contains: active substance 30 hard fat (e.g. Witepsol W 45)

0.05 g 1.65 g

1.70 g

Manufacturing:

35 The hard fat is melted. The ground active substance is dispersed in the melt at 38 ° C. It is cooled to 35 ° C and poured into weakly pre-cooled suppository molds.

Suppository weight: 1.7 g.

Example F

Ampoules of 20 mg l- (4-amino-3,5-dichlorophenyl) -2- [N - (3-phenyl-propyl) -2-propylamino] ethanol hydrochloride

1 ampoule contains:

Active substance

citric acid

Sodium monohydrogen phosphate 50 sorbitol water for injections ad

20.0 mg 12.5 mg 37.5 mg 36.5 mg 5.0 ml

Manufacturing:

55 Water for injection is placed in a calibrated preparation vessel and the active ingredient, citric acid, sodium monohydrogen phosphate and sorbitol are dissolved in succession at room temperature while stirring.

After filling up to the calibration mark, it is filtered through a 6o membrane filter and filled into cleaned and sterilized ampoules under inert gassing.

Sterilization: 20 minutes at 121 ° C.

v

Claims (8)

651 541 2nd PATENT CLAIMS 1. Phenylalkylamines of formula I r, r, a - ch - n R1 r in the Ri is a hydroxy group, an amino group optionally substituted by an al-kanoyl group with 1 to 3 carbon atoms or an alkoxy-carbonyl group with a total of 2 to 4 carbon atoms, an alkylamino or dialkylamino group, each alkyl part containing 1 to 3 carbon atoms and in each case by one Phenyl group, where the two alkyl groups of the dialkylamino group together with the nitrogen atom to which they are attached can form a saturated heterocyclic ring with up to 7 ring members, R2 and R3, which can be the same or different, halogen atoms, trifluoromethyl, cyano or nitro groups or one of the radicals R2 or R3 also a hydrogen atom, R4 represents a hydrogen atom or an alkyl group with 1 to 3 carbon atoms, Rs is a hydrogen atom, a straight-chain or branched alkyl group with 1 to 4 carbon atoms, a cycloalkyl group with 3 to 6 carbon atoms, an alkenyl group with 2 to 5 carbon atoms or an araikyl group with 7 to 10 carbon atoms, A is the methylene, ethylene or hydroxymethylene group and B is a group of the formula 8th -ch- (ch2) or e oxy group with 1 to 3 carbon atoms or Re and R7 together represent the methylenedioxy group, Rs is a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, 5 D is an oxygen or sulfur atom, a sulfinyl or sulfonyl group, n is the number 1 or 2 and E is a straight-chain 10 alkylene group with 3 to 5 carbon atoms which is optionally substituted by one or two alkyl groups each with 1 to 3 carbon atoms or, if A is a methylene or ethylene group and / or R 1 is replaced by an alkanoyl group with 1 to 3 carbon atoms or an alkoxycarbonyl group with a total of 2 to 4 carbon atoms substituted amino group, a hydroxyl, 15 alkylamino or dialkylamino group, each alkyl part containing 1 to 3 carbon atoms and each can be substituted by a phenyl group, and / or R2 a trifluoromethyl, cyano or nitro group and / or R3 a fluorine atom and / or 20 R4 an alkyl group with 1 to 3 carbon atoms and / or Rs an alkyl group with 1 to 4 carbon atoms, a cycloalkyl group with 3 to 6 carbon atoms, an alkenyl group with 2 to 5 carbon atoms or an araikyl group with 7 to 10 Carbon atoms and / or 25 Rö a fluorine or chlorine atom, an alkylsulfenyl or alkyl sulfi represent nyl groups each having 1 to 3 carbon atoms, an ethylene group or, if A represents the methylene group, a group of formula 30 R9 I. --CH - CH2 - in which R9 represents an alkyl group with 1 to 3 carbon atoms, their optically active antipodes, their diastereomeric racemates 35 and their optical antipodes and their acid addition salts. 2, phenylalkylamines of the formula I according to claim 1, in which Ri is an amino group optionally substituted by a benzyl group or an alkoxycarbonyl group with a total of 2 to 4 carbon atoms, an alkylamino or dialkylamino group, where each alkyl part can contain 1 to 3 carbon atoms, R2 is a hydrogen, chlorine, bromine or iodine atom, a trifluoromethyl, cyan or nitro group, 45 R3 is a fluorine, chlorine or bromine atom or a cyan group, R4 is a hydrogen atom or a methyl group, Rs is a hydrogen atom, an alkyl group with 1 to 3 carbon atoms optionally substituted by a phenyl group, an allyl or cyclopropyl group, A is the methylene, ethylene or hydroxymethylene group and B is a group of formulas 55 60 8th -ch- (ch2) n-d where Ré is a hydrogen or halogen atom, a hydroxyl group, an alkoxy group with 1 to 3 carbon atoms optionally substituted by a phenyl group, an alkylsulfonyl or alkylsulfinyl group each with 1 to 3 carbon atoms, R7 represents a hydrogen atom, a hydroxy group or an alkoder - e 3rd 651 541 mean where Rs, D and n are defined as mentioned at the beginning, Rö is a hydrogen, fluorine or chlorine atom, a hydroxyl, methoxy, ethoxy, benzyloxy, methylsulfenyl or methylsulfinyl group, 5 R7 represents a hydrogen atom or a methoxy group or R6 and R7 together represent the methylenedioxy group and E is the n-propylene, 1-methyl-n-propylene, 1,1-dimethyl-n-propylene or n-butylene group or, if A is the methylene or ethylene group and / or 10 Ri is an amino group which is optionally substituted by a benzyl group or by an alkoxycarbonyl group having a total of 2 to 4 carbon atoms, an alkylamino or dialkylamino group, where each alkyl part can contain 1 to 3 carbon atoms, and / or 15 R2 a trifluoromethyl, cyano or nitro group and / or r3 is a fluorine atom and / or Rs is an alkyl group with 1 to 3 carbon atoms, which is optionally substituted by a phenyl group, which represents allyl or cyclopropyl group, 20 also mean an ethylene group, their optically active antipodes, their diastereomeric racemates and their optical antipodes and their physiologically tolerated acid addition salts with inorganic or organic acids. 3. phenylalkylamines according to claim 1, in the 25th Ri is an amino group which is optionally substituted by an ethoxycarbonyl group, an alkylamino or dialkylamino group, where each alkyl part can contain 1 to 3 carbon atoms, R2 is a hydrogen, chlorine or bromine atom or the cyan group, R3 is a fluorine or chlorine atom or the cyano group, R4 is a hydrogen atom or the methyl group, R5 is a hydrogen atom, an alkyl group with 1 to 3 carbon atoms, optionally substituted by a phenyl group, the allyl or cyclopropyl group, A is the methylene or hydroxymethylene group and B is a group of the formula where E is the n-propylene, 1-methyl-n-propylene, 1,1-dimethyl-n-propylene, n-butylene group or if Ri is the ethoxycarbonylamino group and / or R2 is the cyano group and / or R3 is a fluorine atom and /or R5 is an alkyl group with 1 to 3 carbon atoms, which is allyl or cyclopropyl group, which is optionally substituted by a phenyl group, also an ethylene group, R.6 is a hydrogen atom, a hydroxy or methoxy group and R7 represents a hydrogen atom or a methoxy group, their optically active antipodes, their diastereomeric racemates and their optical antipodes and their physiologically tolerated acid addition salts with inorganic or organic acids. 4. phenylalkylamines of the formula I according to claim 1, in which Ri is an amino, dimethylamino or alkylamino group with 1 to 3 carbon atoms in the alkyl part, R2 is a chlorine or bromine atom, R3 is a fluorine or chlorine atom or one of the radicals R2 or R3 is also a cyano group, Rt is a hydrogen atom or the methyl group, Rs is a hydrogen atom, an alkyl group having 1 to 3 carbon atoms or the allyl group, A is the methylene or hydroxymethylene group and B is a n-propyl-, 1-methyl-n-propyl- or 1,1-dimethyl-n-propyl- substituted in the 3-position by a phenyl, 4-hydroxyphenyl, 4-methoxyphenyl or 4-chlorophenyl group group, a 4- (4-methoxyphenyl) -butyl group or also a 2- (3,4-dimethoxy-phenyl) -ethyl group if R5 is an alkyl group having 1 to 3 carbon atoms, the allyl group and / or R2 is the cyano group , their optically active antipodes, their diastereomeric racemates and their optical antipodes and their physiologically tolerated acid addition salts with inorganic or organic acids. 5. phenylalkylamines of the formula I according to claim 1, in which Ri to R5 and A are as defined in claim 4 and B is a n-propyl, 1-methyl-n-propyl or 1,1-dimethyl-n-propyl group or substituted in the 3-position by a phenyl, 4-hydroxyphenyl, 4-methoxyphenyl or 4-chlorophenyl group are a 4- (4-methoxyphenyl) -butyl group, their optically active antipodes, their diastereomeric racemates and their optical antipodes and their physiologically tolerable acid addition salts with inorganic or organic acids. 6. l- (4-Amino-3,5-dichlorophenyl) -2- [N- (3-phenyl-propyl) -2-propylamino] aethol, its optically active antipodes and their acid addition salts as compounds according to claim 1. 7. 1 - (4-amino-3,5-dichlorophenyl) -2- [N- [1,1-dimethyl-3 - (4-hydroxyphenyl) propyl] amino] ethanol, its optically active antipodes and their acid addition salts as compounds according to claim 1. 8. Medicament containing a compound of formula I according to claim 1 in addition to one or more inert carriers and / or diluents. 9. Use of a compound of formula 1 according to claim 1 for the production of a medicament intended for combating heart and circulatory diseases in a non-chemical way. 45