NO137782B - ANALOGICAL PROCEDURE FOR THE PREPARATION OF NEW PHARMACOLOGICALLY ACTIVE AMINO-PHENYL-ETHANOLAMINES - Google Patents

Description

The subject of the present application is an analogue process for the production of new, therapeutically active aminophenyl-ethanolamines with the general formula I:

their optically active antipodes,

and the physiologically compatible acid addition salts of the compounds of the above general formula I with inorganic and organic acids.

In the above general formula I means

R-^ a hydrogen, fluorine, chlorine, bromine or iodine atom or a cyano group,

1*2 a fluorine atom, a linear or branched alkyl group, a hydroxyalkyl-, aminoalkyl-, dialkylaminoalkyl-, trifluoromethyl-, alkoxy-, nitro-, cyano-, carboxy-, caralkyloxy- or carbamoyl group, where the alkyl groups contain up to 5 carbon atoms ome r ,

R., and R^ , so*, may be the same or different, are hydrogen atoms, linear or branched alkyl, hydroxyalkyl, alkenyl or alkynyl groups with up to 6 carbon atoms, cycloalkyl or cycloalkylalkyl groups with 3-8 carbon atoms, or a phenylalkyl group optionally substituted with a methylenedioxy group, and A means a hydrogen atom or together with R^ the group ^CH-R,-

where Rg means a hydrogen atom or a linear or branched alkyl group.

The compounds of the above general formula I have valuable pharmacological properties, in addition to an analgesic, uterine spasmolytic and an antispastic effect on the striated muscles, in particular 0>2-mimetog/or 3-^-blocking action, whereby depending on the substitution, one or other effects prevail. The D(+) compounds in particular exhibit a selective effect on the (^-receptors 09 the 1(-) compounds a preferred effect on the 32-resPtors•

The analogy method for producing the new compounds is distinctive in that

a) an acetophenone of the general formula II:

where R 1 to R 4 are as indicated above, is reduced.

The reduction is preferably carried out in a solvent such as methanol, methanol/water, ethanol, isopropanol, ether, tetrahydrofuran or dioxane, suitably with a complex metal hydride such as lithium aluminum hydride or sodium borohydride, with aluminum isopropylate in the presence of a primary or secondary alcohol or with catalytic generated hydrogen and at temperatures between -2 0°C and the boiling temperature of the solvent used.

The reduction with complex metal hydrides is carried out

however preferably with sodium hydride and at room temperature. By using a more reactive complex metal hydride such as lithium aluminum hydride and possibly at elevated temperatures, the cyano, carboxy, carbalkoxy or carbamoyl groups mentioned in the definition of the residue R2 can be co-reduced.

If the reduction is carried out with hydrogen in the presence of a catalyst such as Raney nickel, platinum or palladium/charcoal, the alkenyl or alkynyl residues mentioned in the definition of the residues R^ and/or R^ can be transferred to the corresponding alkyl residues, and or any existing benzyl residues are split off hydrogenolytically.

b) For preparing a<y> compounds of the general formula I,

where R 1 and R 4 are as indicated at the outset with the exception of alkenyl and alkynyl residues, and R 1 means a chlorine, bromine or iodine atom, a compound with the general formula III is halogenated:

where R 2 to R 4 are as stated at the outset with the exception of alkenyl and alkynyl residues.

The reaction is carried out with a halogenating agent, for example with chlorine, bromine, iodine, tribromophenol bromine, or phenyliodine dichloride, preferably in a solvent, for example in 50 to 100% acetic acid or in tetrahydrofuran in the presence of a tertiary organic base, optionally in presence of a heavy metal salt such as mercuric (IT) oxide and suitably at temperatures between 0 and 50°C. Per mol of a compound of the general formula III/ which can be used as a base or also as a salt, for example as mono-, di- or trihydrochloride, 1 mol of halogenating agent or a small excess is suitably used. If a halohydrogen acid salt is formed during the reaction, this can be isolated directly as such or it can, if desired, be further purified over the base.

c) From a compound of the general formula IV:

where R^, R2 and R^ are as indicated at the outset, X is a protective residue for a hydroxyl group or a hydrogen atom, is a protective residue for an amino group or a hydrogen atom, and Y2

is a protective residue for an anino group or has the meanings given at the outset for R^, with however at least one of the residues X, Y^ and/or Y.> representing one of the above-mentioned protective residues, one or more protective residues are cleaved off.

For Y^ and/or comes into consideration in particular the meaning of an acyl residue, for example the meaning of an acetyl-, benzoyl- or p-toluenesulfonyl residue, or the meaning of a benzyl radical, and for X the meaning of an acyl residue, for example an acetyl-, benzoyl- or p-toluenesulfonyl -residue, or the meaning of trimethylsilyl, benzyl or tetrahydro-pyranyl-(2)-residue.

If Y-j^ and/or Y« is, for example, a random acetyl residue, the cleavage of this residue takes place hydrolytically, for example with ethanolic hydrochloric acid or with caustic soda at temperatures up to the boiling point of the solvent used. In a compound with the general formula IV, R2 means a cyano group, then this can simultaneously be saponified into a carbamoyl or carboxyl group, R2 means a carbalkoxy or carbamoyl group, then these can simultaneously be saponified into carboxyl groups.

If X, Y1 and/or Y2 in a compound of the general formula IV, where R2 does not mean the nitro group, for example a benzyl residue, then the cleavage of this residue takes place hydrogenolytically, for example with hydrogen in the presence of a catalyst such as palladium on charcoal or palladium oxide hydrate on barium sulphate, platinum or Raney nickel, preferably in a solvent such as methanol, methanol/hydrochloric acid or ethanol, at room temperature or slightly elevated temperature and at normal pressure or slightly overpressure. During the reaction, the alkynyl or alkenyl residue mentioned in the definition of the residue R^ and/or R^ can be simultaneously transferred to the corresponding alkyl residues.

If X represents, for example, a freely chosen acyl residue, trimethylsilyl or tetrahydropyranyl-(2) group, then the cleavage of this residue takes place hydrolytically, preferably in the presence of an acid, and at temperatures up to the boiling point of the solvent used,

d) For the preparation of compounds of the general formula I where R^ means a hydrogen atom, a compound is dehalogenated with the

general formula V:

where R 2 to R 4 are as indicated at the outset, and Hal is a chlorine, bromine or iodine atom.

The dehalogenation preferably takes place in a solvent and suitably either with triphenylphosphine in benzene or toluene or with hydrogen in methanol, ethanol, acetic acid ethyl ester or tetrahydrofuran and in the presence of a hydrogenation catalyst. Depending on the method used, the reaction is carried out at room temperature or elevated temperature, for example at temperatures between 100 and 150°C, and at normal pressure or moderate overpressure, when using Raney nickel or palladium/coal, for example, the dehalogenation takes place at room temperature and

normal pressure. Herein, in a compound with the general formula V and R and/or R. means an alkenyl or alkynyl residue, then this can be hydrogenated by the 3-hydrogenolytic dehalogenation. to the corresponding alkyl residue, and/or a benzyl residue, this can simultaneously be split off hydrogenolytically.

If R 2 in a compound of the general formula V means a nitro group, the dehalogenation is preferably carried out with triphenylphosphine.

e) For the preparation of compounds of the general formula I where R 2 means an aminomethyl group, a compound is subjected to

the general formula VI:

where R^, R^ and R^ are, as stated at the outset, reduction and then hydrolysis.

The reaction is carried out in a solvent, preferably by reduction with sodium in pentyl alcohol at temperatures between 0 and 50°C, and the subsequent hydrolysis of the thus formed 1,2,3,4-tetrahydro-quinazoline, which does not need to be isolated, takes place preferably by using hydrochloric acid - at an elevated temperature, for example at the boiling temperature of the hydrochloric acid used,

f) A compound of the general formula VII:

where and R,, are as indicated at the outset, and Z means a chlorine, bromine or iodine atom or a p-toluenesulfonyloxy group, is reacted with an amine of the general formula VIII:

where R^ and R^ are as indicated at the outset.

The reaction is conveniently carried out in a solvent such as methanol, ethanol, chloroform, carbon tetrachloride, dioxane or in an excess of the amine used with the general formula VIII and preferably at temperatures between 0 and 100°C. However, the turnover can also be carried out without solvent.

g) For the preparation of compounds of the general formula I where R 2 does not mean a nitro group, a compound is reduced

with the general formula IX:

where R^, R^ and R^ are as indicated at the beginning, and R2' has the meanings indicated at the beginning for R2 with the exception of a nitro group.

The reduction is conveniently carried out in a solvent such as water, methanol, ethanol, water/methanol or ethyl acetic acid, preferably with nascent hydrogen, for example with zinc/glacial acetic acid or iron/hydrochloric acid, with hydrogen in the presence of a catalyst such as Raney nickel, platinum or palladium/charcoal, with a complex metal hydride such as lithium aluminum hydride or with stannous chloride/hydrochloric acid, suitably at temperatures between 0 and 100°C.

h) For the preparation of compounds of the general formula I where R 1 does not mean a cyano group and R 2 does not mean one

nitro, cyano, carboxy, carbaloxy or carbamoyl group, a compound of the general formula X is reduced:

where R^ and R^ are as indicated at the beginning, R^' has the meanings indicated for R^ at the beginning with the exception of a cyan-

group, R2" has the meanings given for R2 at the outset with the exception of a nitro, cyano, carboxy, caralkyloxy or carbamoyl group, and A means a carbonyl or hydroxymethylene group.

The reaction is carried out in a solvent such as ether, tetrahydrofuran, dioxane or tetrahydrofuran/

benzene, preferably with a reducing agent such as a complex metal hydride, for example with lithium aluminum hydride, with sodium borohydride in the presence of a Lewis acid or with sodium borohydride in pyridine, for example at temperatures between 0 and 120°C, suitably at the boiling temperature of the used solvent.

i) For the preparation of compounds of the general formula I where R^ means a hydrogen atom, an oxazolidone is hydrolyzed with

the general formula XI:

where R^, R2 and R^ are as indicated at the outset.

The hydrolysis is suitably carried out in a solvent such as water, methanol, ethanol, stanol/water or glacial acetic acid in the presence of an acid such as hydrochloric acid, hydrobromic acid or sulfuric acid or in the presence of a base such as sodium hydroxide or potassium hydroxide and suitably by temperatures between 0 and 110°C and depending on the nature of the hydrolysing agent used, preferably at room temperature or at the boiling temperature of the solvent used,

j) For the preparation of compounds of the general formula I where R^ denotes a hydrogen atom, an aldehyde of the general formula XII is reduced:

where R and R2 are as initially indicated, or the hydrate thereof in the presence of an amine of the general formula Villa:

where R^ is as indicated at the outset.

The reduction is conveniently carried out in a solvent such as methanol, ethanol, ether or tetrahydrofuran, preferably with a complex metal hydride such as sodium hydride or lithium aluminum hydride, with nascent hydrogen or with hydrogen in the presence of a catalyst such as Raney nickel, palladium/coal or platinum, suitably at temperatures between -20 and 100°C, preferably, however, at temperatures up to the boiling point of the solvent used.

However, the conversion can also be carried out in such a way that the reduction takes place on an in situ obtained compound with the general formula Xlla:

where R^, and R2 and R^ are as indicated at the outset,

k) For the preparation of compounds of the general formula I where R2 is a nitro group, a compound of the general formula XIII is nitrated:

where R^, R^ and R^ are as indicated at the outset.

The reaction is carried out with a nitrating agent, preferably with nitric acid or a mixture of concentrated nitric acid and concentrated sulfuric acid, suitably at temperatures between -20 and 100°C.

According to methods a) to k), the conditions obtained

compounds of the general formula I can then, if desired, be cleaved into their optically active antipodes by means of racemate resolution or by splitting a mixture of the diastereomeric compounds of the general formula XIV:

where R^, R2, R3 and R^ are as indicated at the outset, Rg is a hydrogen atom or an acyl residue and R^ is a chiral acyl residue,

and subsequent cleavage of the residues R^, Rg Qg R if Rg means an acyl residue and R^ an optionally substituted ^benzyl residue.

As chiral acyl residues, optically active α-aminoacyl residues protected by the nitrogen atom, for example the N-benzyloxycarbonyl-L-alanyl residue, or optically active terpenyloxycarbonyl residues, for example the (-)-menthyloxycarbonyl residue, come into consideration here.

Separation of a mixture of diastereomeric compounds, with the above general formula XIV into the pure diastereomeric compounds conveniently takes place by fractional crystallization and/or by column chromatography on an inert support material.

The subsequent splitting off of the residues Rg and R^ conveniently takes place by means of hydrolysis or solvolysis in the presence of water or a suitable alcohol such as methanol, optionally in the presence of an acid or base and at temperatures between 0 and 100°C.

The cleavage of the residue R^ can also be carried out using a complex metal hydride such as lithium aluminum hydride in a suitable solvent, for example in ether, tetrahydrofuran or dioxane and suitably at temperatures between -20 and 20°C. If R2 hereby means the cyano group in a compound with the general formula XIV, this can be reduced at the same time. Depending on the substituents Rg and R^, their cleavage can take place step by step or in one step.

If R4 means an optionally substituted benzyl residue, its cleavage takes place in compounds in which R2 does not mean a nitro group, by means of hydrogenolysis in the presence of a suitable catalyst such as palladium on charcoal or barium sulphate, in a suitable solvent, for example in an alcohol which for example methanol, ethanol or in acetic acid, optionally with the addition of a mineral acid such as hydrochloric acid and optionally at elevated hydrogen pressure and preferably at temperatures between 20 and 50°C. If R2 hereby means a cyano group in a compound with the general formula XIV, then this can be reduced at the same time. The cleavage of R4 can take place before or after the cleavage of the residues Rc and R.

b /

The racemate cleavage of the d,l form of a compound of the general formula I takes place preferably by fractional crystallization of a mixture of their diastereomeric salts with an optically active acid, for example d(-)-tartaric acid, 1(+)-tartaric acid, dibenzoyl -1-tartaric acid, (+)-camphor-10-sulfonic acid, 1(-)-malic acid, 1(+)-mandelic acid, d-a-bromo-camphor-ir-sulfonic acid or 1-quinic acid, the Racemate cleavage however, can also take place by column chromatography on an optically active support material, for example on acetyl cellulose.

If a compound of the general formula I is obtained according to the methods a) to k) where R2 means a cyano group, this can be transferred to the corresponding carbamoyl compound, and/or a carbamoyl or carbolicoxy compound, these can be transferred to the corresponding carboxyl compound of the general formula I

by means of hydrolysis, and/or a compound of the general formula I is obtained where R4 means a hydrogen atom, this can, if desired, by reaction with an aldehyde of the general formula XV:

where R,, is as indicated at the outset, is transferred to a compound of formula I where A together with R^ means ^CH-R,..

The reaction with an aldehyde of the general formula XV conveniently takes place in a solvent such as ethanol, benzene, toluene or dioxane under water-splitting conditions,

for example in the presence of anhydrous copper (II) sulphate, at temperatures up to the boiling temperature of the solvent used, for example at temperatures between 20 and 100°C, but can however also be carried out without solvent. Particularly advantageously, however, the reaction is carried out using a water separator in the presence of a solvent such as benzene or toluene.

They obtained compounds of the general formula I

can, if desired, be converted into their physiologically compatible acid addition salts with 1, 2 or 3 equivalents of an organic or inorganic acid. As acids, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, lactic acid, citric acid, tartaric acid, maleic acid and fumaric acid have proven suitable.

The compounds with the general formulas II to XIV used as starting materials are obtained according to methods known from the literature.

Thus, for example, the compounds with the general formula II used as starting materials are obtained by reacting the corresponding 2-halo-acetophenones with the corresponding amines.

The compounds with the general formulas III, IV and V are obtained by reaction of the corresponding 2-halo-avetophenones with the corresponding amines and subsequent reduction of the

kept ketones, for example with sodium borohydride, a starting compound with the general formula IV is also obtained by halogenation of a corresponding compound or by catalytic reduction of a corresponding 4-nitro-phenyl compound.

The compounds with the general formula VI are obtained, for example, by reduction of the corresponding aminoavethylquinazolines with sodium borohydride.

For example, an output connection is obtained with it

general formula VII by reaction of a corresponding phenylethylene glycol with p-toluenesulfonic acid chloride in the presence of pyridine or by reduction of a corresponding amino-phenacyl halide by means of sodium borohydride.

A starting compound of the general formula IX is-

is kept, for example, by reduction of a corresponding ketone with sodium borohydride. °

A starting compound of the general formula X is-

is kept, for example, by reacting a corresponding acid with a corresponding amine in the presence of a condensing agent such as N,N'-dicyclohexylcarbodiimide or N,N'-carbonyldiimidazole or

by activation over an acid chloride or a mixed anhydride and subsequent reaction with a corresponding amine, respectively by reduction of a corresponding ketocarboxylic acid amide.

A starting compound with the general formula XI is obtained, for example, by halogenation of a corresponding oxazolidone where means a hydrogen atom, or by alkylation of an

corresponding oxazolidone where R 1 means a hydrogen atom.

A starting compound of the general formula XII

is obtained, for example, by oxidation of a corresponding acetophenone with selenium dioxide or by oxidation of a corresponding phenacyl bromide with dimethylsulfoxide.

A starting compound of the general formula XIII is conveniently obtained by a method according to the accompanying application.

The starting materials with formulas II-XIII used in the methods a)-k) do not in all cases need to be purified, they can also be suitably used as a raw product.

As already mentioned at the outset, the new compounds of formula I exhibit valuable pharmacological properties, in particular a 32-mimetic and/or 3^-blocking effect, whereby depending on the substitution one or the other effect is strongest. The D ( + ) compounds in particular exhibit a selective effect on the 3j_ receptors and the 1(-) compounds a preferred effect on the receptors.

For example, the following substances were examined for their effect on the 3-receptors: A = 1-(4-amino-3-bromo-5-fluoro-phenyl)-2-tert-butylamino-ethanol- hydrochloride.

B = 5-(4-amino-3-bromo-5-fluoro-phenyl)-3-tert-butyl-oxazolidine dihydrochloride.

C = 1-(4-amino-3-chloro-5-fluoro-phenyl)-2-cyclopropylamino-ethanol hydrochloride,

D = 1-(4-amino-3-chloro-5-fluoro-phenyl)-2-tert-butylamino-ethanol hydrochloride, 0

E = 1-(4-amino-3-fluoro-phenyl)-2-tert-butylamino-ethanol hydrochloride,

F = 1-(4-amino-3-trifluoromethyl-phenyl)-2-tert-phenylamino-ethanol hydrobromide,

G = 1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert-butylamino-ethanol hydrochloride,

H = 1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-cyclobutylamino-ethanol hydrochloride.

I = 1-(4-amino-3-chloro-5-cyano-phenyl)-2-tert-butylamino-ethanol,

j = 1-(4-amino-3-bromo-5-cyano-phenyl)-2-tert-butylamino-ethanol hydrochloride.

K = 1-(4-amino-3-bromo-5-fluoro-phenyl)-2-cyclobutylamino-ethanol hydrochloride,

L = 1-(4-amino-3-fluoro-5-iodo-phenyl)-2-cyclopropylamino-ethanol hydrochloride,

M = 1-(4-amino-3-fluoro-5-cyano-phenyl)-2-isopropylamino-ethanol hydrochloride,

N = 1-(4-amino-3-fluoro-5-cyano-phenyl)-2-tert-butylamino-ethanol hydrochloride,

0 = 1-(4-amino-3-cyano-phenyl)-2-cyclobutylamino-ethanol hydrobromide,

P = i-(4-amino-3-cyano-phenyl)-2-tert-pentylamino-ethanol,

Q = 1-(4-amino-3-chloro-5-cyano-phenyl)-2-propylamino-ethanol hydrochloride,

R = 1-(4-amino-3-chloro-5-cyano-phenyl)-2-sec-butylamino-ethanol hydrochloride,

S = 1-(4-amino-3-chloro-5-cyano-phenyl)-2-(hydroxy-tert-butylamino)-ethanol hydrochloride,

T = 1-(4-amino-3-chloro-5-cyano-phenyl)-2-tert-pentylamino-ethanol hydrochloride,

U = 1-(4-amino-3-chloro-5-cyano-phenyl)-2-cyclophentylamino-ethanol hydrochloride,

V = 1-(4-amino-3-chloro-5-cyano-phenyl)-2-[1-(3,4-methylenedioxy-phenyl)-2-propylamino]-ethanol hydrochloride,

W = 1-(4-amino-3-bromo-5-cyano-phenyl)-2-cyclobutylamino-ethanol hydrochloride,

X = 1-(4-amino-3,5-dicyano-phenyl)-2-tert-butylamino-ethanol hydrochloride,

Y = 1-(4-amino-3-bromo-5-nitro-phenyl)-2-tert-butylamino-ethanol

and

Z = 1-(4-amino-3-chloro-5-nitro-phenyl)-2-tert-butylamino-ethanol

The (^-blocking effect was examined as antagonism to that at a standard dose of 1.0^/kg i.v. N-isopropyl-norepinephrine sulfate triggered tachycardia in anesthetized cats. From that with the different doses obtained mean percentage attenuation of that at the N-isopropyl-norepinephrine sulfate-induced heart rate increase was ED^Q determined by graphical extrapolation (see

tables II and III).

The denf^^imetic effect was investigated as antagonism to that of i.v. given 20vVkg of acetylcholine triggered bronchospasm in anesthetized guinea pigs in the experimental device according to Konzett-Røssler after i.v. application. From the percentage attenuation of the bronchospasm achieved with the different doses, ED^ was calculated by graphical extrapolation (see Table I).

The 82" blocking effect was investigated as antagonism to the broncholytic effect, which was observed with 5^/kg i.v. of N-isopropyl-noradrenaline sulfate in the Konzett-Rössler experimental device on anesthetized guinea pigs, when the bronchospasm in these was triggered with a standard amount of 20^kg i.v. acetylcholine (see table III) .

The acute toxicity of the substances was determined on groups of 10 mice each. Hereby, the LD5Q, the dose at which 50% of the animals died within 14 days after intravenous dosing, was calculated according to the method of Litchfield and Wilcoxon (see Tables II and III).

The new compounds of the general formula I

can possibly be incorporated in combination with other active substances in the usual pharmaceutical preparation forms. Hereby, the single dose amounts to 1 to 1°0^*, preferably, however, 5 to 50tø<h>

The following examples will explain the invention.

Example- 1.

1-(4-amino-3-bromo-5-fluorophenyl)-2-diethylaminoethanol

3.4 g of 4'-amino-3<1->bromo-2-diethylamino-5<1->fluoro-acetophenone hydrochloride are dissolved in 20 ml of methanol. While stirring, a solution of 570 mg of sodium borohydride is slowly added at room temperature in 5

ml of water. By simultaneous addition of 3n hydrochloric acid, the pH value is set to between pH 3 and pH 6. After finishing the addition of the sodium borohydride solution, stir for a further 30 minutes at room temperature. Then add 3n hydrochloric acid until pH 1 is reached.

The hydrochloric acid solution is extracted twice with chloroform, and the chloroform extracts are discarded. The aqueous solution is made alkaline with ammonia and extracted exhaustively with chloroform. The chloroform extracts are combined, dried over sodium sulfate and evaporated to dryness. A colorless oil remains which is dissolved in acetic acid^ ethyl ester. After the addition of ethereal hydrochloric acid, a colored

loose sediment, which is suctioned off and dissolved in water. The aqueous solution is made alkaline with caustic soda and extracted with chloroform. The chloroform extract is washed with water, dried over sodium sulphate and evaporated in vacuo. A colorless oil remains.

Evidence of structure by NMR spectrum (CDCT^ : 0.85 - 1.2 ppm triplet

[6 protons, N (CH2-CH_3) 2 ] , 2.4 - 2.9 ppm multiplet [6 protons, N(CH2~)3], 4.15 ppm singlet (2 protons, NH2), 4.4 - 4.7 ppm multiplet (1 proton, CH), 4.85 ppm singlet (1 proton, OH),

6.9 - 7.4 ppm multiplet (2 aromatic protons.)

Example 2.

1-(amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert-butylaminoethanol hydrochloride 80 g 4<1->amino-2-tert-butylamino-3'-chloro-5'-trifluoromethyl- Acetophenone hydrochloride (decomposition between 223 and 231°C) is dissolved in 500 ml. methanol and cool to -15°C. While stirring, 9.5 g of sodium borohydride are added in portions over the course of an hour, whereby the temperature is kept between -5 and -15°C. After a further hour at -15°C, acidify with 2N hydrochloric acid and the methanol is removed in vacuo. The remaining aqueous solution is made alkaline with 2N ammonia and extracted with ethyl acetate. The organic phase is washed with water, dried and 50 ml of 4.5N hydrochloric acid in isopropanol is added. The precipitated hydrochloride of the above-mentioned substance is filtered off with suction and watered with acetic acid ethyl ester and ether.

Melting point: 205-207°C (dec.)

By concentrating the mother liquor, more substance can be extracted.

Example 3.

1-( 4- amino- 3- bromo- 5- cyano- phenyl)- 2- dimethylaminoethanol hydrochloride.

15.2 g of 4'-amino-3'-bromo-5'-cyano-2-dimethylamino-acetophenone are dissolved in 300 ml of methanol and a solution of 10 g of sodium borohydride in 100 ml of water is added dropwise at room temperature with stirring. The mixture is allowed to stand overnight, sodium boron h-rcl-xd still present is destroyed by acidification with hydrochloric acid, the methanol is evaporated in vacuo, the residue is taken up in water, made alkaline with ammonia, extracted three times with each time approx. 150 ml chloroform, the chloroform solution is washed twice with a little water, dried over sodium sulphate and evaporated to dryness in vacuo. The residue is taken up in ethanol and slightly acidified with alcoholic hydrochloric acid, whereupon 1-(4-amino-3-bromo-5-cyano-phenyl)-2-dimethylaminoethanol hydrochloride crystallizes out. It is recrystallized from ethanol.

Melting point: 187-190°C.

Example 4.

1-(4-Amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert-pentylaminoethanol hydrochloride.

0.37 g of 1-(4-amino-3-trifluoromethyl-phenyl)-2-tert.-pentyl-aminoethanol hydrobromide and 0.2 ml of pyridine are dissolved in 30 ml of tetrahydrofuran and cooled to 0°C. Then 0.3 g of phenyliodine dichloride is added, kept for 2 hours at this temperature and a further 0.1 g of phenyliodine dichloride is added. After 20 hours at approx. At 4°C the solution is evaporated, it is distributed between ethyl acetate and water, the aqueous extract is made alkaline with 2N ammonia and extracted again with ethyl acetate. The organic phase is washed with water, dried and a few drops of 4N hydrochloric acid in isopropanol are added. The precipitated hydrochloride of the above compound is filtered off with suction and washed with ether.

Melting point: 176-178°C (dec.).

Example 5.

1-(4-amino-3-bromo-5-methylphenyl)-2-tert-butylaminoethanol dihydrochloride..

Dissolve 2.6 g of 1-(4-amino-3-methylphenyl)-2-tert-butylaminoethanol hydrochloride in 90 ml of 50% acetic acid and add at 0-5°C

1.6 g of bromine dissolved in 5 ml of glacial acetic acid and 1 ml of water. After 15 minutes, consumed bromine is not destroyed with sodium hydrogen sulphite. It is diluted with water and insoluble by-products are removed by filtration over charcoal. The filtrate is made alkaline with caustic soda under cooling and extracted with chloroform. After drying over sodium sulfate, the chloroform solution is filtered over charcoal and evaporated to dryness in vacuo. The oil base thus obtained is dissolved in isopropanol and clearly acidified with isopropanolic hydrochloric acid. It is evaporated in vacuo, cooled, 1-(4-amino-3-bromo-5-methylphenyl)-2-tert-butylaminoethanol dihydrochloride is filtered off with suction and recrystallized from isopropanol/ether.

Melting point: from 148°C decomposition.

Example 6.

1- ( 4- amino- 5- bromo- 3- hydroxymethylphenyl) ;-- 2- tert.- butylaminoethanol.

Dissolve 2.0 g of 1-(4-amino-3-hydroxymethyl-phenyl)-2-tert-butylaminoethanol in 18 ml of glacial acetic acid and 2 ml of water and add dropwise

show 1.3 g of bromine. The reaction mixture is then evaporated, the residue is dissolved in water, made alkaline with 2N ammonia and shaken for four

times with chloroform. The organic phase is evaporated after drying with sodium sulphate and the residue is purified over a silica gel column with

ethanol as eluent. The fractions containing substance are combined and evaporated in a vacuum. The evaporation residue crystallizes after longer standing under ether.

Melting point: 121-124°C.

Example 7.

1-(4-amino-3-trifluoromethyl-phenyl)-2-tert.-butylamino-ethanol.

5.05 g of 1-(4-acetylamino-3-trifluoromethyl-phenyl)-2-tert. - butylamino-ethanol hydrochloride is boiled in a mixture of 50 ml of ethanol and 50 nil of 4n caustic soda for 3 hours at reflux. The ethanol is expelled in a vacuum and the precipitated crystals are suctioned off. After recrystallization from ethanol/water, the melting point is 145-147°C.

For transfer into the monohydrochloride, the product is dissolved in

the calculated amount of hydrochloric acid is brought to dryness in a vacuum and the solid residue is recrystallized from isopropanol/ether.

Melting point of the hydrochloride: 172-174°C (dec.).

Example 8"

1-(4-amino-3-trifluoromethyl-phenyl)-2-(N-benzyl-N-tert-butyl)-amino-ethanol.

0.5 g of 1-(4-acetylamino-3-trifluoromethyl-phenyl)-2-(N-benzyl-N-tert.-butyl)-aminoethanol (melting point: 98-100°C) is boiled in a mixture of 10 ml . ethanol and 10 ml of 4N caustic soda for 1/ hour at reflux. The ethanol is distilled off in a vacuum and the aqueous phase is extracted with acetic acid ethyl ester. The organic extract is washed with water, dried and evaporated in vacuo. The oil residue is homogeneous by thin-layer chromatography (silica gel; chloroform::methanol = 19:1, Rf-verui: ^ 0.5).

Example 9.

1- ( 4- amino- 3- carboxy- phenyl)- 2- tert.- butylamino- ethanol.

Dissolve 0.3 g of 1-(4-acetylamino-3-carboxy-phenyl)-2-tert-butylamino-ethanol in 6 ml of ethanol and add 4 ml of conc. hydrochloric acid. It is heated for 40 minutes to 70°C, evaporated in vacuo to dryness and the product is purified by chromatography on silica gel with chloroform:methanol = 3:2 as eluent. 1-(4-amino-3-carboxy-phenyl)-2-tert-butylamino-ethanol is obtained, the structure of which was determined by nuclear resonance spectrum (CD^OD): 1.4 ppm singlet

[9 protons, C(CH3)3], 3.3 ppm multiplet (2 protons, CH2), 4.5

ppm multiplet (1 proton, CH), 6.8 - 7.8 ppm multiplet (3

aromatic protons).

Example 10.

1-(4-amino-3-trifluoromethyl-phenyl)-2-tert.-butylamino-ethanol.

0.45 g of 1-(4-amino-3-trifluoromethyl-phenyl)-2-(N-benzyl-N-tert.-butyl)-amino-ethanol is dissolved in a hydration flask in 10 ml of methanol and 1.4 ml of ln hydrochloric acid and hydrogenated in the presence of 50 mg of palladium/charcoal catalyst (10%) to absorb 1 mol of hydrogen. The catalyst is separated by filtration, the solution is evaporated in

vacuum and the residue is distributed between acetic acid ethyl ester and 2n ammonia. The water-washed organic phase is dried and re-evaporated in a vacuum. The residue crystallizes from ethanol/water.

Melting point: 145-147°C.

Example 11.

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert-butylamino-ethanol hydrochloride.

0.76 g of 1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-(N-benzyl-N-tert-butylamino-ethanol) is dissolved in a hydration flask for 20

ml of methanol and 1.95 ml of ln hydrochloric acid and hydrated in the presence of 80 mg of palladium/charcoal catalyst (10%). until absorption of 1 mole of hydrogen. The hydrogenation is interrupted, the catalyst is removed by filtration and the filtrate is brought to dryness by evaporation in a vacuum. The oily evaporation residue is purified over a silica gel column using chloroform:methanol:conc. ammonia = 80:20:1 as eluent. The fractions containing substance are combined and freed from solvent in a vacuum. The remaining, crystallized base of the desired compound is transferred into the hydrochloride with

the calculated amount of 1.07n hydrochloric acid in isopropanol and recrystallized from acetic acid ethyl ester/ether.

Melting point: 205-207°C (dec.).

Example 12.

1-(4-amino-3-chloro-5-methyl-phenyl)-2-tert-butylamino-ethanol dihydrochloride."

0.7 g of 1-(4-amino-3-chloro-5-methyl-phenyl)-2-(N-benzyl-N-tert.-butyl)-amino-ethanol hydrochloride is dissolved in 50 ml of methanol and 0, 92 ml of 2N hydrochloric acid and hydrated in the presence of 50 mg of palladium on

charcoal (10%). The hydrogenation is interrupted after absorption of 41 Nml of hydrogen. The catalyst is filtered off and the filtrate is evaporated to dryness in a vacuum. The residue is dissolved in ethanol and the dihydrochloride is precipitated by the addition of ether.

Melting point: from 95°C (decomposition).

Example 13.

1-(4- amino- 3- methoxy- phenyl)- 2- tert.- butylamino- ethanol.

8.5 g of 1-(4-amino-3-methoxy-phenyl)-2-(N-benzyl-N-tert.-butyl)-amino-ethanol are dissolved in 150 ml of methanol and acidified with ethanolic hydrochloric acid to pH 6. 1 g of palladium on charcoal (10%) is added to this solution and hydrogenated in a shaker at room temperature and atmospheric pressure until the calculated amount of hydrogen has been taken up. After aspiration of the catalyst, it is evaporated to a small volume.

The separated crystals are suctioned off and recrystallized from ethanol.

The colorless crystals of the obtained hydrochloride of the desired substance melt at 174-176°C (dec.).

Example 14.

1-(4-amino-3-trifluoromethyl-phenyl)-2-cyclopropylamino-ethanol-dihydro-chloride.

4.1 g of 1-(4-amino-3-bromo-5-trifluoromethyl-phenyl)-2-cyclopropylamino-ethanol are dissolved in a hydration flask in 200 ml of methanol and 2 g of palladium oxide/barium sulfate catalyst (5%) are added. It is hydrogenated until 1 mol of hydrogen has been taken up, the catalyst is filtered off and the filtrate is brought to dryness in a vacuum. The rest up-

taken in water, made alkaline with 2N ammonia and the aqueous phase extracted with ethyl acetate. The organic extracts are washed with water, dried and evaporated again. The solid residue is dissolved in isopropanol and 2 equivalents of 4n hydrochloric acid in isopropanol are added to the solution. The crystallized dihydrochloride of the aforementioned compound of-

suction and wash with isopropanol and ether.

Melting point: 141.5-142°C (dec.).

Example 15.

1-(4-Amino-3-trifluoromethyl-phenyl)-2-tert-pentylamino-ethanol hydrobromide. 5 . g 1-(4-amino-3-bromo-5-trifluoromethyl-phenyl)-2-tert. - pentylamino ethanol hydrochloride is distributed between acetic acid ethyl ester and 2n ammonia. The organic phase is dried and evaporated in vacuo.

The remaining base is dissolved in 100 ml of methanol in a hydration flask, 2.5 g of palladium oxide/barium sulphate catalyst (5%) are added and hydrated until 1 mol of hydrogen is taken up. After the catalyst

has been removed by filtration, the filtrate is evaporated in vacuo and the solid residue is recrystallized from isopropanol. The obtained hydrobromide of the aforementioned compound melts at 174-175°C (dec.).

Example 16.

1-(4-amino-3-methyl-phenyl)-2-(N-benzyl-N-tert.-butyl)-amino-ethanol.

4.5 g of 1-(4-amino-3-bromo-5-methyl-phenyl)-2-(N-benzyl-N-tert.-butyl)-amino-ethanol are dissolved in 100 ml of methanol and 11.6 ml 2n hydrochloric acid and is hydrated in the presence of 250 mg of palladium on charcoal (5%). After absorption of 315 ml of hydrogen, the hydration is interrupted, aspirated

from the catalyst, the solvent is distilled off in a vacuum, the residue is taken up in water and the base is set free with ammonia, this is extracted with chloroform and chromatographed over a silica gel column.

The base is obtained with a melting point of 96-98°C and hence the hydrochloride,

which decomposes from 145°C.

Example 17.

1- ( 4- amino- 3- aminomethyl- phenyl)- 2- tert.- butylamino- ethanol.

Dissolve 2.0 g of 6-(2-tert.-butylamino-1-hydroxy-ethyl)-3,4-dihydro-2-methyl-quinazoline in 80 ml of pentyl alcohol, add 7.5 g of sodium portionwise over the course of an hour and after a further half hour is slowly heated to boiling. After five hours of boiling, the solution is cooled and 100 ml of water is added. 60 ml of concentrated hydrochloric acid are then added dropwise, the reaction mixture is stirred for 2 hours and then shaken twice with ether. The acid phase is made alkaline with 10N caustic soda, the base is extracted with ether, the ether phase is dried with sodium sulphate and evaporated. The crude product is purified by column chromatography over silica gel with methanol:chloroform (2:1). After evaporation of the corresponding fractions, 1-(4-amino-3-aminomethyl-phenyl)-2-tert-butylamino-ethanol is obtained as an amorphous substance.

Elemental analysis:

<C>13<H>23N3° (237.34)

Example 18.

1-(4- amino- 3- bromo- 5- carbamoyl- phenyl)- 2- dimethylamino- ethanol.

2 g of 1-(4-amino-3-bromo-5-cyano-phenyl)-2-dimethylaminoethanol is boiled for 4 hours with a solution of 5 g of sodium hydroxide in 120 ml of 50% ethanol. The ethanol is distilled off, the remaining aqueous solution is diluted with 100 ml of water and extracted 3 times with chloroform. The chloroform solution is dried over sodium sulfate and evaporated in vacuo. The residue becomes solid and is then recrystallized from chloroform.

Melting point: from 9 3°C (splitting).

Example 19.

1-(4- amino- 3- bromo- 5- carboxy- phenyl)- 2- dimethylamino- ethanol.

2 g of 1-(4-amino-3-bromo-5-cyano-phenyl)-2-dimethylaminoethanol is boiled for 4 hours with a solution of 5 g of sodium hydroxide in 120 ml of 50% ethanol. The ethanol is distilled off, the remaining aqueous solution is diluted with 100 ml of water and extracted three times with chloroform. The aqueous phase is neutralized, evaporated to dryness, the residue is treated with ethanol, filtered off, the filtrate is evaporated, the residue is treated again with ethanol and filtered off. When the last filtrate is evaporated, a residue of 1-(4-amino-3-bromo-5-carboxy-phenyl)-2-dimethylamino-ethanol remains, which melts at 240-250°C (dec.) and if structure was established by IR and UV spectrum: IR (KBr):COO<_> at 1620 cm<-1>, NH+ at 2000-3500 cm"<1>. UV (ethanol): maxima at 220 and 330- 340 nm,

shoulder at 250 nm.

Example 20.

5-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-3-tert-butyl-1,3-oxazolidine.

1.35 g of 1-(3-amino-chloro-5-trifluoromethyl-phenyl)-2-tert-butylamino-ethanol is dissolved in 30 ml of benzene and 1.2 ml of a 40% aqueous formaldehyde solution is added. It is evaporated at normal pressure to half the volume, approx. 35 ml of benzene and boil for 5 hours at reflux. A further 5 ml of formaldehyde solution is then added and the described procedure is repeated three times. It is evaporated to dryness in a vacuum, dissolved in ether and some insoluble particles are filtered off. The filtrate is made slightly acidic with ethereal hydrochloric acid and the precipitated product crystallizes by trituration. It is filtered off and recrystallized from acetone/ether. Hydrochloride was obtained from it

the above compound melts at 163-165°C (dec.).

Example 21.

1-(4-amino-3-fluoro-phenyl)-2-tert.-butylamino-ethanol.

Melting point of the hydrochloride: 196-197°C (dec.). Prepared according to method a) from 4'-amino-2-tert-butylamino-3'-fluoro-acetophenone hydrochloride and sodium hydride analogously to example 1.

Example 22.

1-(4- amino- 3- bromo- 5- fluoro- phenyl)- 2- tert.- butylamino- ethanol.

Melting point of the hydrochloride: 207-208°C (dec.).

Prepared according to method a) fra-4'-amino-3'-bromo-tert-butylamino-5'-fluoro-acetophenone hydrochloride and sodium hydride analogously to example 1.

Example 23.

1- (4- amino- 3- chloro- 5.- trifluoromethyl- phenyl) - 2- cyclobutylamino- ethanol. Melting point of the hydrochloride: 177-178°C.

Prepared according to method a) from 4<1->amino-3'-chloro-2-cyclobutylamino-5'-trifluoromethyl-acetophenone hydrochloride and sodium borohydride analogously to example 2.

Example 24.

1-(4-amino-3-fluoro-phenyl)-2-cyclopropylamino-ethanol.

Melting point of the hydrochloride: 157-158°C (dec.). Prepared according to method c) from 1-(4-acetylamino-3-fluoro-phenyl)-2-cyclopropylamino-ethanol and caustic soda analogous to example 7.

Example 25.

1- ( 4- amino- 3- fluoro- phenyl)- 2- tert.- butylamino- ethanol.

Melting point of the hydrochloride: 196-197°C (dec.). Prepared according to method c) from 1-(4-amino-3-fluoro-phenyl)-2-(N-benzyl-N-tert-butyl)-amino-ethanol hydrochloride and catalytically activated hydrogen analogous to example 13.

Example 26.

2-ethylamino-1-(4-amino-3-chloro-5-fluoro-phenyl)-ethanol.

Melting point of the hydrochloride: 186-188°C (dec.). <1> prepared according to method a) from 2-ethylamino-4'-amino-3<1->chloro-5<1->fluoro-acetophenone and sodium borohydride analogously to example 1.

Example 27.

1-( 4- amino- 3- chloro- 5- fluoro- phenyl)- 2- isopropylamino- ethanol.

The hydrochloride's melting point: 152-154°C (dec.). Prepared according to method a) from 4'-amino-3<1->chloro-5<1->fluoro-2-isopropylamino-acetophenone hydrochloride and sodium borohydride analogously to example 1.

Example 28.

1- (4- amino- 3- chloro- 5- fluoro- phenyl)- 2- cyclopropylamino- ethanol.

Melting point of the hydrochloride: 175-177°C (dec.).

Prepared according to method a) from 4'-amino-3'-chloro-cyclopropylamino-5<1->fluoro-acetophenone hydrochloride and sodium hydride analogously to example 1.

Example 29.

1- ( 4- amino- 3- chloro- 5- fluoro- phenyl)- 2- tert.- butylamino- ethanol.

Melting point of the hydrochloride: 206-208°C (dec.). Prepared according to method a) from 4<1->amino-2-tert-butylamino-3<1->chloro-5<1->fluoro-acetophenone hydrochloride and sodium borohydride analogously to example 1.

Example 30.

1-(4- amino- 3- chloro- 5- fluoro- phenyl)- 2- tert.- pentylamino- ethanol.

Melting point of the hydrochloride: 187-188°C (dec.).

■ Prepared according to method a) from 4'-amino-3'-chloro-5<1->fluoro-2-tert.-pentylamino-acetophenone hydrochloride and sodium borohydride analogously to example 1.

Example 31.

1-(4-amino-3-chloro-5-fluoro-phenyl)2-[1-(3,4-methylenedioxy-phenyl)-2-propylamino]-ethanol.

Melting point of the hydrochloride: 119-121°C (dec.). Prepared according to method a) from 4'-amino-3<1->chloro-5'-fluoro-2-[1-(3,4-methylenedioxy-phenyl)-2-propylamino]-acetophenone and sodium borohydride analogously to example 1 .

Example 32.

1-(4- amino- 3- chloro- 5- fluoro- phenyl)- 2- dimethylamino- ethanol.

Melting point of the hydrochloride: 208-210°C (dec.).

Prepared according to method a) from 4'-amino-3'-chloro-2-dimethylamino-5'-fluoro-acetophenone hydrochloride and sodium borohydride analogously to example 1.

Example 33.

1-( 4- amino- 3- chloro- 5- fluoro- phenyl)- 2- diethylamino- ethanol.

Melting point: 39-41°C.

Prepared according to method a) from 4<1->amino-3<1->chloro-2-diethyl-amino-5'-fluoro-acetophenone hydrochloride and sodium borohydride analogously to example 1.

Example 34.

2-ethylamino-1-(4-amino-3-bromo-5-fluoro-phenyl)-ethanol.

Melting point of the hydrochloride: 167-169°C (dec.).

. Prepared according to method a) from 2-ethylamino-4'-amino-3'-bromo-5'-fluoro-acetophenone hydrochloride and sodium borohydride analogously to example 1.

Example 35.

1-(4- amino- 3- bromo- 5- fluoro- phenyl)- 2- isopropylamino- ethanol.

Melting point of the hydrochloride: 171-173°C (dec.).

Prepared according to method a) from 4'-amino-3<1->bromo-5'-fluoro-2-isopropylamino-acetophenone hydrochloride and sodium borohydride analogously to example 1.

Example 36.

1-(4-amino-3-bromo-"5-fluoro-phenyl)-2-cyclopropylamino-ethanol.

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

: Prepared according to method a) from 4'-amino-3"-bromo-2-cyclopropylamino-5<1->fluoro-acetophenone and sodium borohydride analogously to example 1.

Example 37.

1-(4-amino-3-bromo-5-fluoro-phenyl)-2-(hydroxy-tert-butylamino)-ethanol..._

Melting point: 122-125°C.

Prepared according to method a) from 4'-amino-3<1->bromo-51-fluoro-2-(hydroxy-tert-butylamino)-acetophenone hydrochloride and sodium borohydride analogously to example 1.

Example 38.

1-(4- amino- 3- bromo- 5- fluoro- phenyl)- 2- tert.-pentylamino- ethanol.

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

Prepared according to method a) from 4'-amino-3'-bromo-5'-fluoro-2-tert.-pentylamino-acetophenone hydrochloride and sodium borohydride analogously to example 1.

Example 39.

1-(4-amino-3-bromo-5-fluoro-phenyl)-2-[1-(3,4-methylenedioxy-phenyl)-2-propylamino]-ethanol.

Melting point: 126-128°C.

: Prepared according to method a) from 4'-amino-3<1->bromo-5'-fluoro-2-[1-(3,4-methylenedioxy-phenyl)-2-propylamino]-acetophenone and sodium borohydride analogous example 1.

Example 40.

1-( 4- amino- 3- chloro- 5- trifluoromethyl- phenyl)- 2- isopropylamino- ethanol.

Melting point: 104-106°C.

Prepared according to method a) from 4'-amino-31-chloro-2-isopropylamino-5'-trifluoromethyl-acetophenone hydrochloride and sodium borohydride analogously to example 2.

Example 41.

1-(4- amino- 3- chloro- 5- trifluoromethyl- phenyl)- 2- cyclopropylamino- ethanol.

Melting point: 138-139°C.

Prepared according to method a) from 4'-amino-3'-chloro-2-cyclopropylamino-5'-trifluoromethyl-acetophenone and sodium borohydride analogously to example 2.

Example 42.

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-(hydroxy-tert-butylamino)-ethanol.

Melting point of the hydrochloride: 219-220°C.

• Prepared according to method a) from 4'-amino-3'-chloro-2-(hydroxy-tert-butylamino)-5<1->trifluoromethyl-acetophenone hydrochloride and sodium borohydride analogously to example 2.

Example 43.

1-(4- amino- 3- chloro- 5- trifluoromethyl- phenyl)- 2- tert.- pentylamino- ethanol.

Melting point of the hydrochloride: 176-178°C (dec.).

Prepared according to method a) from 4'-amino-3'-chloro-2-tert-pentylamino-51-trifluoromethyl-acetophenone hydrochloride and sodium borohydride analogously to example 2.

Example 44.

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-[2-methyl-4-hydroxybutyl-(2)-amino]-ethanol.

Melting point of the hydrochloride: 148-150°C (dec.). <;> Prepared according to method a) from 4'-amino-3'-chloro-2-[2-methyl-4-hydroxy-butyl-(2)-amino]-5'-trifluoromethyl-acetophenone and sodium borohydride analogously to example 1 .

Example 45.

2-[3-ethynyl-pentyl-(3)-amino]-1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-ethanol.

Melting point of the hydrochloride: 185-187°C (dec.). '. Prepared according to method a) from 2-[3-ethynyl-pentyl-(3)-amino]-41-amino-31-chloro-51-trifluoromethyl-acetophenone hydrochloride and sodium borohydride analogously to example 2.

Example 46.

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-[1-(3,4-methylenedioxy-phenyl)-2-propylamino]-ethanol.

Melting point of the hydrochloride: 206-207°C (dec.). ) Prepared according to method a) from 4<1->amino-3'-chloro-2-[1-(3,4-methylenedioxy-phenyl)-2-propylamino]-5'-trifluoromethyl-acetophenone hydrochloride and sodium borohydride analogous to example 2.

Example 47.

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-dimethylamino-ethanol.

Melting point of the hydrochloride: 162-164°C. • Prepared according to method a) from 4'-amino-3'-chloro-2-dimethylamino-5'-trifluoromethyl-acetophenone hydrochloride and sodium borohydride analogously to example 2.

Example 48.

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-(N-methyl-ethylamino)-ethanol...

Melting point: 48-49°C.

': Prepared according to method a) from 4'-amino-3'-chloro-2-(N-methyl-ethylamino)-5'-trifluoromethyl-acetophenone hydrochloride

and sodium borohydride analogous to example 2.

Example 49.

1-( 4- amino- 3- chloro- 5- trifluoromethyl- phenyl)- 2- diethylamino- ethanol.

Melting point of the hydrochloride: 149-151°C.

Prepared according to method a) from 4'-amino-3'-chloro-2-diethylamino-51-trifluoromethyl-acetophenone hydrochloride and sodium borohydride analogously to example 2.

Example 50.

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-(N-benzyl-N-tert-butyl)-amino-ethanol.

Oil, thin-layer chromatographically uniform (SiO 2 J chloroform:methanol = 15:1; Rf value: ^0.75).

Prepared according to method a) from 2<1->amino-2-(N-benzyl-N-tert-butyl)-amino-3<1->chloro-5<1->trifluoromethyl-acetophenone hydrochloride and sodium borohydride analogously example 2.

Example 51.

1-( 4- amino- 3- bromo- 5- trifluoromethyl- phenyl)- 2- isopropylamino- ethanol.

Melting point: 102-103°C.

Melting point for the hydrochloride: 177-179°C (dec.).

'; Prepared according to method a) from 4'-amino-3'-bromo-2-isopropylamino-51-trifluoromethyl-acetophenone hydrochloride and sodium borohydride analogously to example 2.

Example 52.

1-(4- amino- 3- bromo- 5- trifluoromethyl- phenyl)- 2- cyclopropylamino- ethanol.

Melting point: 141.5-142.5°C. Melting point of the hydrochloride: 195-195.5°C (dec.).

Prepared according to method a) from 4'-amino-3'-bromo-2-cyclopropylamino-5'-trifluoromethyl-acetophenone hydrochloride and sodium borohydride analogously to example 2.

Example 53.

1-(4- amino- 3- bromo- 5- trifluoromethyl- phenyl)- 2- tert.- butylamino- ethanol.

Melting point: 85-87°C.

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

Prepared according to method a) from 4'-amino-3'-bromo-2-tert-butylamino-5'-trifluoromethyl-acetophenone hydrochloride

and sodium borohydride analogous to example 2.

Example 54.

1-(4- amino- 3- bromo- 5- trifluoromethyl- phenyl)- 2- cyclobvtylamino- ethanol.

Melting point of the hydrochloride: 189-191°C. (column.).

Prepared according to method a) from 4'-amino-3'-bromo-2-cyclobutylamino-5'-trifluoromethyl-acetophenone hydrochloride and sodium borohydride analogously to example 2.

Example 55.

1- (4- amino- 3- bromo- 5- trifluoromethyl- phenyl)- 2- tert.- pentylamino- ethanol.

Melting point of the hydrochloride: 166.5-168.5°C (dec.). ', Prepared according to method a) from 4'-amino-3'-bromo-2-tert.-pentylamino-5'-trifluoromethyl-acetophenone hydrochloride and sodium borohydride analogously to example 2.

Example 56.

2-[3-ethynyl-pentyl-(3)-amino]-1-(4-amino-3-bromo-5-trifluoromethyl-phenyl)-ethanol.

Melting point of the hydrochloride: 189-190°C (dec.). Prepared according to method a) from 2-[3-ethynyl-pentyl-(3)-amino]-4'-amino-3'-bromo-5'-trifluoromethyl-acetophenone hydrochloride and sodium borohydride analogously to example 2.

Example 57.

1-( 4- amino- 3- bromo- 5- trifluoromethyl- phenyl)- 2- dimethylamino- ethanol.

Melting point of the hydrochloride: 149-151°C.

, Prepared according to method a) from 4'-amino-3'-bromo-2-dimethylamino-5'-trifluoromethyl-acetophenone hydrochloride and sodium borohydride analogously to example 2.

Example 58.

1-(4-amino-3-bromo-5-trifluoromethyl-phenyl)-2-(N-methyl-ethylamino)-ethanol..

Melting point: 52.5-53.5°C.

Prepared according to method a) from 4 1 -amino-3 1 -bromo-2-(N-methyl-ethylamino)-51-trifluoromethyl-acetophenone hydrochloride and sodium borohydride analogously to example 2.

Example 59.

1-(4- amino- 3- bromo- 5- trifluoromethyl- phenyl)- 2- diethylamino- ethanol.

Melting point of the hydrochloride: 159-160°C.

Prepared according to method a) from 4'-amino-3'-bromo-2-diethylamino-5'-trifluoromethyl-acetophenone hydrochloride and sodium borohydride analogously to example 2.

Example 60.

1-(4- amino- 3- methyl- phenyl)- 2- tert.- butylamino- ethanol.

Melting point of the dihydrochloride: 108°C (dec.). ,• Prepared according to method a) from 4'-amino-31-methyl-2-tert-butylamino-acetophenone and sodium borohydride analogously to example 3.

Example 61.

1-( 4- amino- 3- chloro- 5- methyl- phenyl)- 2- methylamino- ethanol.

Melting point: 95-96°C.

Prepared according to method a) from 4'-amino-3'-chloro-5<1->methyl-2-methylamino-acetophenone and sodium borohydride analogously to example 3.

Example 62.

2-ethylamino-1(4-amino-3-chloro-5-methyl-phenyl)-ethanol.

Melting point: 107-108.5°C.

Prepared according to method a) from 2-ethylamino-4'-amino-3'-chloro-5'-methyl-acetophenone and sodium borohydride analogously to example 3.

Example 63.

1-( 4- amino- 3- chloro- 5- methyl- phenyl)- 2- dimethylamino- ethanol.

Melting point of the hydrochloride: 120-125°C (decomp.). Prepared according to method a) from 4'-amino-3'-chloro-2-dimethylamino-5'-methyl-acetophenone hydrochloride and sodium borohydride analogously to example 1.

Example 64.

1-( 4- amino- 3- chloro- 5- methyl- phenyl)- 2-( N- methyl- ethylamino)- ethanol.

Melting point of the hydrochloride: 93-96°C.

. Prepared according to method a) from 4'-amino-3'-chloro-5'-methyl-2-(N-methyl-ethylamino)-acetophenone hydrochloride and sodium borohydride analogously to example 1.

Example 65.

1-(4- amino- 3- chloro- 5- methyl- phenyl)- 2- diethylamino- ethanol.

Melting point of the hydrochloride: 118-122°C.

Prepared according to method a) from 4'-amino-3'-chloro-2-diethylamino-5'-methyl-acetophenone hydrochloride and sodium borohydride analogously to example 1.

Example 66.

1-(4-amino-3-chloro-5-methyl-phenyl)-2-(N-benzyl-N-tert-butyl)-amino-ethanol.

Melting point of the hydrochloride: 2 00-201°C.

Prepared according to method a) from 4 1 -amino-2-(N-benzyl-N-tert-butyl)-amino-3'-chloro-5'-methyl-acetophenone and sodium borohydride according to example 3.

Example 67.

1-( 4- amino- 3- bromo- 5- methyl- phenyl)- 2- dimethylamino- ethanol.

Melting point of the hydrochloride: 123-125°C (dec.). . Prepared according to method a) from 4'-amino-3'-bromo-2-dimethylamino-5'-methyl-acetophenone and sodium borohydride analogously to example 3.

Example 68.

1-( 4- amino- 3- bromo- 5- methyl- phenyl)- 2- diethylamino- ethanol.

Melting point: 48-50°C.

Prepared according to method a) from 4'-amino-3'-bromo-2-diethylamino-5'-methyl-acetophenone and sodium borohydride analogously to example 3.

Example 69.

1-(4-amino-3-bromo-5-methyl-phenyl)-2-(N-benzyl-N-tert-butyl)-amino-ethanol.

Prepared according to method a) from 4<1->amino-3<1->bromo-2-(N-benzyl-N-tert-butyl)-amino-5'-methyl-acetophenone and sodium borohydride analogously to example 3.

The substance is thin-layer chromatographically pure (SiO 2 ; chloroform:methanol = 9:1, Rf value: ^0.9).

Example 7. 0.

1-( 3- ethyl- 4- amino- 5- chloro- phenyl)- 2- diethylamino- ethanol.

Melting point of the hydrochloride: 121-124°C.

Prepared according to method a) from 3'-ethyl-4'-amino-5<1->chloro-2-diethylamino-acetophenone and sodium borohydride analogously to example 3.

Example 71.

1-( 3- ethyl- 4- amino- 5- bromo- phenyl)- 2- diethylamino- ethanol.

Melting point of the hydrochloride: 132-134°C.

: Prepared according to method a) from 3'-ethyl-4'-amino-5<1->bromo-2-diethylamino-acetophenone and sodium borohydride analogously to example 3.

Example 72.

1-( 4- amino- 3- tert.- butyl- 5- chloro- phenyl)- 2- tert.- butylamino- ethanol.

Melting point of the hydrochloride: from 218°C (decomposition).

Prepared according to method a) from 4<1->amino-3<1->tert-butyl-2-tert-butylamino-5<1->chloro-acetophenone and sodium borohydride analogously to example 1.

Example 73.

1-(4- amino- 3- hydroxymethyl- phenyl)- 2- dimethylamino- ethanol.

Prepared according to method a) from 4 1-amino-2-dimethylamino-3'-hydroxymethyl-acetophenone and sodium borohydride analogously to example 1.

Structural proof of. UV and IR spectra. : UV (ethanol): maximum at 250 nm (E = 0.5), shoulder at 275-305 nm (E=0.11); IR (CII2C12) : OH at 3600 cm"<1>, NH2 at 3380 and 3450 cm"<1>, N(CH3)2 at 2780 and 2830 cm"<1>.

Example 74.

1-(4- amino- 3- hydroxymethyl- phenyl)- 2- diethylamino- ethanol.

Melting point of the hydrochloride: from 125°C (decomposition). . Prepared according to method a) from 4'-amino-2-diethylamino-2'-hydroxymethyl-acetophenone and sodium borohydride analogously to example 1.

Example 75..

1-(4- amino- 3- chloro- 5- cyano- phenyl)- 2- isopropylamino- ethanol.

Melting point of the hydrochloride: 185-188°C.

Prepared according to method a) from 4'-amino-3'-chloro-5'-cyano-2-isopropylamino-acetophenone and sodium borohydride analogously to example 3.

Example 76.

1-(4- amino- 3- chloro- 5- cyano- phenyl)- 2- tert.- butylamino- ethanol.

Melting point: 125-133°C.

Prepared according to method a) from 4'-amino-3'-chloro-5'-cyano-2-tert-butylamino-acetophenone and sodium borohydride analogously to example 3.

Example 77.

1-( 4- amino- 3- chloro- 5- cyano- phenyl)- 2- dimethylamino- ethanol.

Melting point of the hydrochloride: 187-189°C.

Prepared according to method a) from 4'-amino-3'-chloro-5'-cyano-2-dimethylamino-acetophenone and sodium borohydride analogously to example 3.

Example 78.

1-( 4- amino- 3- chloro- 5- cyano- phenyl)- 2- diethylamino- ethanol.

Melting point: 69-71°C.

'. Prepared according to method a) from 4 1-amino-3'-chloro-5'-cyano-2-diethylamino-acetophenone and sodium borohydride analogously to example 3.

Example 79.

1-(4- amino- 3- bromo- 5- cyano- phenyl) 2- isopropylamino- ethanol.

Melting point of the hydrochloride: 186-189°C. 5remHt. Oxygen according to method a) from 4'-amino-3'-bromo-5'-cyano-2-isopropylamino-acetophenone and sodium borohydride analogous to example 3.

Example 80.

1- ( 4- amino- 3- bromo- 5- cyano- phenyl-)- 2- tert.- butylamino- ethanol.

Melting point of the hydrochloride: 213-215°C.

Prepared according to method a) from 4'-amino-3'-bromo-2-tert-butylamino-5'-cyano-acetophenone and sodium borohydride analogously to example 3.

Example 81.

1-(4- amino- 3- bromo- 5- cyano- phenyl)- 2- diethylamino- ethanol.

Melting point: 72-74°C.

Prepared according to method a) from 4 1-amino-31-bromo-5'-cyano-2-diethylamino-acetophenone and sodium borohydride analogously to example 3.

Example 82.

1-(4- amino- 3- bromo- 5- carboxy- phenyl)- 2- tert.- butylamino- ethanol.

Melting point: from 218°C (dec.).

'. Prepared according to method a) from 4'-amino-3'-bromo-2-tert-butylamino-5'-carboxy-acetophenone and sodium borohydride analogously to example 3.

Example 83.

1-(4- amino- 3- chloro- 5- methoxy- phenyl)- 2- tert.- butylamino- ethanol.

Melting point of the hydrochloride: 175-178°C.

Prepared according to method a) from 4'-amino-2-tert-butylamino-3'-chloro-5<1->methoxy-acetophenone hydrochloride and sodium borohydride analogously to example 1.

Example 84.

1- (4- amino- 5- br' om- 3- hydroxymethyl- phenyl) - 2- dimethylamino- ethanol.

Melting point: 87-92°C.

Prepared according to method b) by bromination of 1-(4-amino-3-hydroxymethyl-phenyl)-2-dimethylamine-ethanol analogously to example 6.

Example . 85.

1-(4-amino-5-bromo-3-dimethylaminomethyl-phenyl)-2-tert-butylamino-ethanol.

Melting point: 127-129°C.

'; Prepared according to method b) by bromination of 1-(4-amino-3-dimethylaminomethyl-phenyl)-2-tert. -butylamino-ethanol analogous to example 6.

Example 86.

1-(4- amino- 5- bromo- 3- dimethylaminomethyl- phenyl)- 2- dimethylamino- ethanol.

Prepared according to method b) by bromination of 1-(4-amino-3-dimethylaminomethyl-phenyl)-2-dimethylamino-ethanol analogously to example 6.

Structural evidence by NMR spectrum (CDC_3/CD3OD): 2.2 ppm singlet [6 protons, N(CH-).2] , 2>35 ppm singlet [6 protons, N(CH3)2] , 1.8-3 .0 ppm multiplet (2 protons, CH2), 3.45 ppm singlet (2 protons, CH2), 4.4-4.8 ppm multiplet (1 proton, CE), 6.96 ppm doublet and 7.4 ppm doublet (2 aromatic protons).

Example 87.

2-ethylamino-1-(4-amino-3-fluoro-phenyl)-ethanol.

Melting point of the hydrochloride: 187-188°C. (column.).

Prepared according to method c) from 1-(4-acetylamino-3-fluoro-phenyl)-2-ethylamino-ethanol and caustic soda analogously to example 7.

Example 88.

1-(4-amino-3-fluoro-phenyl)-2- isopropylamino-ethanol.

Melting point of the hydrochloride: 156-158°C (dec.).

Prepared according to method c) from 1-(4-acetylamino-3-fluoro-phenyl)-2-isopropylamino-ethanol and caustic soda analogously to example 7.

Example 89.

1-(4-amino-3-fluoro-phenyl)-2-tert.-pentylamino-ethanol.

Melting point of the hydrochloride: 153-155°C (dec.). ; Prepared according to method c) from 1-(4-acetylamino-3-fluoro-phenyl)-2-tert.-pentylamino-ethanol and caustic soda analogously to example 7.

Example 90.

1- 14- amino- 3- fluoro- phenyl)- 2- dimethylamino- ethanol.

Prepared according to method c) from 1-(4-acetylamino-_'-fluoro-phenyl)-2-dimethylamino-ethanol and caustic soda analog example 7.

Oil; structural evidence by IR and UV spectra. IR (CH2C12): OH free at 3550 cm"<1>, NH_ at 3370 and 3450 cm 1, OH associated at 3200-3500 cm -xi , N(CH3)2 at 2780 and 2830 cm -1, aromatic C=C at 1635 cm"1.' UV (ethanol): maxima at 238 nm (E=0.6) and 288 nm (E=0.13).

Example 91.

1-(4-amino-3-fluoro-phenyl)-2-diethylamino-ethanol.

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

Prepared according to method c) from 1-H-acetylamino-S-fluoro-phenyl)-2-diethylamino-ethanol and caustic soda analogously to example 7.

Example 92.-1-(4-amino-3-dimethylaminomethyl-phenyl)-2-tert.-butylamino-ethanol.

Melting point: 55-59°C.

: Prepared according to method c) by saponification of 1-(4-acetylamino-3-dimethylaminomethyl-phenyl)-2-tert-butylamino-ethanol with ethanolic caustic soda analogous to example 7.

Example 93.

1-( 4-amino- 3- dimethylaminomethyl, phenyl)- 2- dimethylamino- ethanol.

Prepared according to method c) by saponification of 1-(4-acetylamino-3-dimethylaminomethyl-phenyl)-2-dimethylamino-ethanol with ethanolic caustic soda analogous to example 7.

Structural evidence by NMR spectrum (CDC13) : 2.2 ppm singlet [6 protons, N(CH3)2], 2.35 ppm singlet [6 protons, N(CH3)2], 1.6-2.9 ppm multiplet (2 protons, CE^), 3.42 ppm singlet (2 protons, CH2), 4.4-4.8 ppm multiplet (1 proton, CH), 6.6-7.18 ppm multiplet (3 aromatic protons) .

Example 94.

1-(4- amino- 3- hydroxymethyl- phenyl)- 2- tert.- butylamino- ethanol»

Melting point: 123-128°C.

Prepared according to method c) fr*. 1-(4--Amino-3-hydroxymethyl-phenyl)-2-(N-benzyl-N-tert.-!vu_yl)-amino-ethanol with hydrogen in the presence of palladium activated carbon analogue _ example 13.

Example 95.

1-( 4- amino- 3- chloro- 5- hydroxymethyl- phenyl)- 2- tert.- butylamino- ethanol.

Prepared according to method c) from 1-(4-amino-3-chloro-5-hydroxymethyl-phenyl)-2-(N-benzyl-N-tert-butyl)-amino-ethanol with hydrogen in the presence of palladium activated carbon analogous to example 13.

Structural evidence by NMR spectrum (CDC13):1.1 ppm singlet [9 protons, C(CH3)3], 2.0-3.6 ppm multiplet (2 protons, CH2), 4.6 ppm singlet (2 protons, CH2), 4.2-4.6 ppm multiplet (1 proton, CH), 6.9 ppm doublet and 7.2 ppm doublet (2 aromatic protons).

Example 96.

1-(4-amino-3-trifluoromethyl-phenyl)-2- isopropylamino-ethanol.

Melting point: 136-137.5°C.

: Prepared according to method d) from 1-(4-amino-3-bromo-5-trifluoromethyl-phenyl)-2-isopropylamino-ethanol and catalytically activated hydrogen analogous to example 14..

Example 97.

1-(4-amino-3-trifluoromethyl-phenyl)-2-dimethylamino-ethanol. Melting point: 64-66.6°C.

: Prepared according to method d) from 1-(4-amino-3-bromo-5-trifluoromethyl-phenyl)-2-dimethylamino-ethanol and catalytically activated hydrogen analogously to example 14.

Example 98.

1-(4-amino-3-trifluoromethyl-phenyl)-2-(N-methyl-ethylamino)- ethanol.

Prepared according to method d) from 1-(4-amino-3-bromo-5-trifluoromethyl-phenyl)-2-(N-methyl-ethylamino)-ethanol and catalytically activated hydrogen analogously to example 14.

•Oil; thin layer chromatographic uniform (Rf value: 0.2; SiO2; chloroform:methanol:concentrated ammonia = 90:10:1). Elemental analysis: C12H17 F3N2° (262.3)

Example 99.

1 - •' - i - amino- 3- tri f fluoromethyl- phenyl) - 2- die ty 1 ap_. no- ethanol.

Prepared according to method d) from 1-(4-amino-3-bromo-5-trifluoromethyl-phenyl)-2-diethylamino-ethanol hydrochloride and catalytically activated hydrogen analogously to example 14.

Oil. Thin layer chromatographic uniform (Rf value: 0.3, SiO 2 , chloroform: methanol: conc. ammonia = 90:10:1); Evidence of structure by NMR spectrum (CDC 13 ): 1.1 ppm triplet

[6 protons, N(C<H>2_CH3)2], 2.55 ppm multiplet [6 protons, N(CH2-)3], 4.5 ppm multiplet ( 1 proton, CH), 6.7 doublet and 7 ,3 doublet (2 aromatic protons).

Example 100.

1-(4-amino-3-methyl-phenyl)-2-(N-benzyl-N-tert.-butyl)-amino-ethanol.

Melting point of the dihydrochloride: from 145°C (decomposition). ; Prepared according to method d) from 1-(4-amino-3-bromo-5-methyl-phenyl)-2-(N-benzyl-N-tert-butyl)-amino-ethanol. with catalytically activated hydrogen analogous to example 16.

Example 101.

1-(4-amino-3-cyano-phenyl)-2-isopropylamino-ethanol.

Melting point: 159-161°C.

; Prepared according to method d) from 1-(4-amino-3-bromo-j-cyano-phenyl)-2-isopropylamino-ethanol and catalytically activated hydrogen analogously to example 16.

Example 102.

1-(4-amino-3-cyano-phenyl)-2-tert.-butylamino-ethanol.

Melting point: 181-185°C.

; Prepared according to method d) from 1(4-amino-3-bromo-5-cyano-phenyl)-2-tert-butylamino-ethanol and catalytically activated hydrogen analogously to example 16.

Example 103.

1-(4-amino-3-cyanophenyl)-2-dimethylamino-ethanol.

Melting point of the dihydrochloride: 130-133°C (dec.). ; Prepared according to method d) from 1-(4-amino-3-bromo-5-cyano-phenyl)-2-dimethylamino-ethanol with catalytically activated hydrogen analogously to example 16.

Example 104.

1-(4-amino-3-cyano-phenyl)-2-diethylamino-ethanol.

; Prepared according to method d) from 1-(4-amino-3-bromo-5-cyano-phenyl)-2-diethylamino-ethanol and catalytically activated hydrogen analogously to example 16.

Oil, elemental analysis:

Example 105.

5-(4- amino^ 3- bromo- 5- fluoro- phenyl)- 3- tert.- butyl- oxazolidine..

Melting point of the dihydrochloride: 16 4-178°C (dec.). : Prepared from 1-(4-amino-3-bromo-5-fluoro-phenyl)-2-tert-butyl-amino-ethanol and 40% formaldehyde solution analogous to example 20.

Example 106.

1-(4- amino- 3- chloro- 5- trifluoromethyl- phenyl)- 2- tert.- butylamino- ethanol.

Melting point of the hydrochloride: 205-207°C (dec.).

Prepared according to method c) from 2-tert.-butylamino-1-t3-chloro-4-(p-chloro-benzoylamino)-5-trifluoromethyl-phenyl]-ethanol and caustic soda analogously to example 8.

Example 107.

1-(4-amino-3-fluoro-phenyl)-2-tert.-butylamino-ethanol.

Melting point of the hydrochloride: 196-197°C (dec.). ; Prepared according to method c) from 1-(4-benzoylamino-3-fluoro-phenyl)-2-tert-butylamino-ethanol and caustic soda analogously to example 7.

Example 108.

1-(4- amino- 3- chloro- 5- fluoro- phenyl)- 2- tert.- butylamino- ethanol.

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

r Prepared according to method c) from 2-tert.-butylamino-1-(3-chloro-5-fluoro-4-propionylamino-phenyl)-ethanol and caustic soda analogously to example 7.

Example 109.

1-( 4- amino- 3- bromo- 5- trifluoromethyl- phenyl)- 2- cyclopentylamino- ethanol.

Melting point: 100-102 .5°C (splitn =

1 Prepared according to method a) from 4'-amino-3'-bromo-2-cyclopentylamino-5<1->trifluoromethyl-acetophenone hydrochloride and sodium borohydride analogously to example 2.

Example 110. 1-(4-amino-3-bromo-5-cyano-phenyl)-2-cyclopropylamino-ethanol.

7.5 g of 4'-amino-3'-bromo-5<1->cyano-2-cyclopropylamino-

acetophenone dissolved in 200 ml of tetrahydrofuran and 100 ml of water, 3 g of sodium borohydride are added at room temperature and stirred for one hour.

shot sodium borohydride is destroyed by the addition of acetone. Insoluble substances are filtered off and the solvent is distilled off in a vacuum.

The remainder is dissolved in hot isopropanol, and by adding isopropanol

hydrochloric acid, 1-(4-amino-3-bromo-5-cyano-phenyl)-2-cyclopropylamino-ethanol is obtained, which is recrystallized from isopropanol.

Melting point: 190-193°C (dec.).

Example 111.

1-(4- amino- 3- bromo- 5- fluoro- phenyl)- 2- cyclobutylamino- ethanol.

a) 20 g of 4<1->amino-3'-bromo-5'-fluoro-acetophenone is dissolved in

300 ml of chloroform. \ed boiling heat is slowly added while stirring

a solution of 4.3 ml of bromine in 20 ml of chloroform. After the addition is finished, stir for 5 minutes at boiling temperature and

then cool to room temperature. A mixture of 15 g of cyclobutylamine and 14 ml of triethylamine is added dropwise to the crude solution of 4'-amino-3<1>,2-dibromo-5'-fluoro-acetophenone with continued stirring and under ice-cooling. After the addition is finished, heat for 2 hours at reflux temperature. After cooling, wash with water and the organic phase is evaporated to dryness in a vacuum. The residue consists of crude 4<1->amino-3<1->bromo-2-cyclobutylamino-5<1->fluoroacetophenone.

b) The crude ketone obtained under a) is dissolved in 30 ml of tetrahydrofuran. The solution is added to 5 ml of water, and then added below

stirring and cooling with ice portionwise 4.5 g of sodium borohydride. The solution is stirred while cooling for 3 hours and then allowed to stand overnight at room temperature. Excess sodium borohydride is then destroyed with acetone and the solution is evaporated to dryness in a vacuum. The residue is distributed between water and chloroform, the organic phase is extracted three times with each Tang I0n ml 2n hydrochloric acid, the combined hydrochloric acid extracts are made alkaline with sodium hydroxide and extracted with chloroform. The chloroform solution is washed with water, dried over sodium sulfate and evaporated to dryness in vacuo.

ethanol is dissolved in isopropanol and acidified with ethereal hydrochloric acid to pH 5. With the addition of ether, crystallization occurs. The separated hydrochloride of the desired compound is recrystallized from isopropanol.

Melting point: 164-166°C (dec.).

Example 112.

1-( 4- amino- 3- fluoro- 5- iodo- phenyl)- 2- isopropylamino- ethanol- hydrochloride.

5.15 g of 1-(4-amino-3-fluoro-phenyl)-2-isopropylamino-ethanol

is dissolved in 300 ml of acetic acid, 80 g of iodine and 4.0 g of mercury(II) oxide are added and stirred vigorously for 2 hours at room temperature. Solids are then filtered off, the dark brown filtrate is decolored with saturated sodium hydrogen sulphite solution and diluted with water to approx. 1 1. liider cooling is made alkaline with 10n caustic soda and extracted with chloroform. The chloroform phase is dried over sodium sulfate and evaporated to dryness in vacuo. The residue is dissolved in methanol and acidified to pH 4.5 with ethereal hydrochloric acid. The solution is evaporated to dryness in vacuo and the solid residue crystallizes from absolute ethanol.

Melting point: 203-205°C (dec.).

Example 113.

1-(4- amino- 3- diethylaminomethyl- phenyl)- 2- tert.- butylamino- ethanol. 6.0 g of 1-(4-acetylamino-3-diethylaminomethyl-phenyl)-2-tert.-butylamino-ethanol is boiled in a mixture of 50 ml of ethanol and 50 ml of 4N caustic soda for 35 hours at reflux. It is then distilled off

the ethanol, dilute with water and extract with chloroform twice. The organic phase is dried with sodium sulphate and evaporated. After column chromatographic purification (silica gel, methanol), 1-(4-amino-3-diethylaminomethyl-phenyl)-2-tert-butylamino-ethanol crystallizes from petroleum ether.

Melting point: 86-90°C.

Example 114.

1-( 4- amino- 3- cyano- phenyl)- 2- cyclopropylamino- ethanol.

4 g of 1-(4-amino-3-bform-5-cyano-phenyl)-2-cyclopropylamino-ethanol are dissolved in methanol and hydrogenated after adding 1 g of palladium on charcoal (10%) at room temperature and a hydrogen pressure of 3-5 ato. After completion of hydrogen absorption, the catalyst is filtered off, the filtrate is evaporated to dryness in a vacuum and the residue is distributed between diluted caustic soda and chloroform. By evaporation of the chloroform phase, 1-(4-amino-3-cyano-phenyl)-2-cyclopropylamino-ethanol is obtained as an oil, which is purified by chromatography on silica gel (eluent: chloroform:methanol =9:1) and upon addition of ethereal hydrochloric acid crystallizes as dihydrochloride from isopropanol.

Melting point: 148-151°C (dec.).

Example 115.

2-ethyl-5-(4-amino-3-bromo-5-fluoro-phenyl)-3-tert.-butyl-oxazolidine.

5 g of 1-(4-amino-3-bromo-5-fluoro-phenyl)-2-tert-butylamino-ethanol are dissolved in 100 ml of benzene. 5 g of propionaldehyde are added to this and heated for 6 hours with a water separator at reflux temperature. A new 5 g of propionaldehyde is then added and heated further

for 3 hours. After cooling, it is evaporated to dryness in vacuo and the residue is chromatographed over a chromatography column filled with 50 g of silica gel, whereby benzene is used as eluent. The eluates containing substance are combined and evaporated to dryness in vacuum, whereby the aforementioned compound is formed in the form of foam.

Structural evidence by NMR spectrum (CDCl^):

0.7-1.8 ppm multiplet [14 protons, -C(CH3)3 and -CH2-CH3], 2.5-2.95 and 3.1-3.7 ppm 2 multiplets [2 protons Ar-Cri -CH--N<], 4.0-4.3 ppm singlet [2 protons, NH,,], 4.4-5.2 ppm multiplet [2 protons, Ar-CH-CH2-N<<>. and

6.8-7.35 ppm multiplet [2 aromatic protons].

Example 116.

1-(4- amino- 3- bromo- 5- fluoro- phenyl)- 2- cyclopentylamino- ethanol.

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

Prepared according to method a) from 4'-amirio-3'-bromo-2-cyclopentyl-amino-5'-fluoro-acetophenone and sodium borohydride analogously to example 111. . Example 117. .V-(4-amino-3-bromo-5-fluoro-phenyl)-2-cyclohexylam. ino-ethanol» Melting point of the hydrochloride: 191-195°C (dec.).

Prepared according to method a) from 4'-amino-3'-bromo~2-cyclohexylamino-5'-fluoro-acetophenone and sodium borohydride analogously to example 111.

Example 118.

1-(4- amino- 3- bromo- 5- fluoro- phenyl)- 2- cycloheptylamino- ethanol.

Melting point of the hydrochloride: 187-189°C (dec.).

Prepared from 4<1->amino-3<1->bromo-2-cycloheptylamino-5'-fluoro-acetophenone and sodium borohydride according to method a) analogous to example 111.

Example 119.

1-(4-amino-3-fluoro-5-iodo-phenyl)-2-cyclopropylamino-ethanol.

; Prepared according to method a) from 4'-amino-2-cyclopropylamino-3'-fluoro-5'-iodo-acetophenone and sodium borohydride analogously to example 111.

Example 120.

1-(4- amino- 3- fluoro- 5- iodo- phenyl)- 2- isopropylamino- ethanol.

Melting point of the hydrochloride: 203-205°C (dec.).

; Prepared according to method a) from 4'-amino-3'-fluoro-2-isopropylamino-5<1->iodo-acetophenone and sodium borohydride analogously to example 111.

Example 121.

1-(4- amino- 3- fluoro- 5- iodo- phenyl)- 2- cyclobutylamino- ethanol.

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

Prepared according to method a) from 4'-amino-2-cyclobutylamino-3<1->fluoro-5'-iodo-acetophenone and sodium borohydride analogously to example 111.

Example 122.

1-(4- amino- 3- fluoro- 5- iodo- phenyl)- 2- tert.- butylamino- ethanol.

Melting point of the hydrochloride: 207-209°C (dec.).

Prepared according to method a) from 4'-amino-2-tert-butylamino-3<1->fluoro-5'-iodo-acetophenone and sodium borohydride analogously to example 111.

Example 123.

1-(4-amino-3-fluoro-5-iodo-phenyl)-2-(hydroxy-tert-butylamino)-ethanol.

Melting point of the hydrochloride: 200-202°C (decomp.).

; Prepared according to method a) from 4'-amino-3'-fluoro-2-(hydroxy-tert-butylamino)-51-iodo-acetophenone and sodium borohydride analogously to example 111.

Example 124.

2-ethylamino-1-(4-amino-3-cyano-5-fluoro-phenyl)-ethanol.

Melting point of the hydrochloride: 216-218°C (dec.).

: Prepared according to method a) from 2-ethylamino-4'-amino-3'-cyano-5'-fluoro-acetophenone and sodium borohydride analogously to example 111.

Example 125.

1-( 4- amino- 3- cyano- 5- fluoro- phenyl)- 2- cyclopropylamino- ethanol.

Melting point of the hydrochloride: 188-190°C (dec.).

Prepared according to method a) from 4'-amino-3'-cyano-2-cyclopropylamino-5'-fluoro-acetophenone and sodium borohydride analogously to example 111.

Example 126.

1-( 4- amino- 3- cyano- 5- fluoro- phenyl)- 2- isopropylamino- ethanol.

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

Prepared according to method a) from 4'-amino-3'-cyano-5'-fluoro-2-isopropylamino-acetoienone and sodium borohydride analogously to example 111.

Example 127.

1-( 4- amino- 3- cyano- 5- fluoro- phenyl)- 2- cyclobutylamino- ethanol.

Melting point of the hydrochloride: 222-224°C (dec.).

. Prepared according to method a) from 4'-amino-3'-cyano-2-cyclobutylamino-5<1->fluoro-acetophenone and sodium borohydride analogously to example 111.

Example 128.

1-(4-amino-3-cyano-5-fluoro-phenyl)-2- tert. -- butylamino-ethanol.

Melting point of the hydrochloride: 242-243°C (dec.).

Prepared according to method a) from 4'-amino-2 = T3.t.-butylamino-3'-cyano-5'-fluoro-acetophenone and sodium borohydride analogously to example 111.

Example 129.

1-( 4- amino- 3- cyano- 5- fluoro- phenyl)- 2- cyclopentylamino- ethanol.

Melting point of the hydrochloride: 184-186°C (dec.).

. Prepared according to method a) from 4'-amino-3'-cyano-2-cyclopentylamino-5'-fluoro-acetophenone and sodium borohydride ana-

log example 111.

Example 130.

1-(4- amino- 3- cyano- 5- fluoro- phenyl)- 2- tert.- pentylamino- ethanol.

Melting point of the hydrochloride: 172-175°C (dec.).

. Prepared according to method a) from 4'-amino-3'-cyano-5'-fluoro-2-tert.-pentylamino-acetophenone and sodium borohydride

analogous example 111.

Example 131.

1-( 4- amino- 3- cyano- 5- fluoro- phenyl)- 2- dimethylamino- ethanol.

': Prepared according to method a) from 4'-amino-3'-cyano-2-dimethylamino-5'-fluoro-acetophenone and sodium borohydride analogously to example 111.

Oil, evidence of structure by NMR spectrum (CD_OD) : 2.2-2.65

ppm multiplet, [8 protons, N-CH3 and

4.6-4.9 ppm multiplet, [4 protons, 3 yield protons and

15-7,4

ppm multiplet [2 aromatic protons].

Example 132.

1-( 4- amino- 3- cyano- 5- fluoro- phenyl)- 2- diethylamino- ethanol.

Prepared according to method a) from 4'-amino-3<1->cyan-2-diethylamino-5'-fluoro-acetophenone and sodium borohydride analogously to example 111.

Oil, evidence of structure by NMR spectrum (CD 3 OD): 0.85-1.2

ppm triplet, [6 protons, -N(CH2-CH3)2j, 2.45-2.85 ppm multiplet,

[6 protons, -N(CH - CH-.) 2 and

4.5-4.85 ppm singlet and triplet [4 protons, 3 yield protons and

7.1-7.4

<pp>m multiplet [2 aromatic protons].

Example 133.

1-(4-amino-3-trifluoromethyl-phenyl)-2-(cyclopropylmethyl-amino)-ethanol.

Melting point of the hydrochloride: 122-127°C (decomposition, - from 110°C discolouration).

Prepared according to method d) from 1~(4-amino-3-fc...'om-5-trifluoromethyl-phenyl)-2-(cyclopropylmethyl-amino)-ethanol and catalytically activated hydrogen analogously to example 114.

Example 134.

1-(4-amino-3-trifluoromethyl-phenyl)-2- cyclopentylamino-ethanol.

Melting point of the hydrochloride: 144-145°C.

, Prepared according to method d) from 1-(4-amino-3-bromo-5-trifluoromethyl-phenyl)-2-cyclopentylamino-ethanol and catalytically activated hydrogen analogously to example 114.

Example 135.

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-(cyclopropylmethylamino)-ethanol.

Melting point of the hydrochloride: 186-187°C (dec.). ; Prepared according to method a) from 4'-amino-3'-'chloro-2-(cyclopropylmethyl-amino)-5'-trifluoromethyl-acetophenone and sodium borohydride analogously to example 110.

Example 136.

1-( 4- amino- 3- chloro- 5- trifluoromethyl- phenyl)- 2- cyclopentylamino- ethanol.

Melting point of the hydrochloride: 188-190°C (dec.).

Prepared according to method a) from 4'-amino-3<1->chloro-2-cyclopentylamino-5'-trifluoromethyl-acetophenone and sodium borohydride analogously to example 110.

Example 137.

1-(4- amino- 3- chloro- 5- trifluoromethyl- phenyl)- 2- cyclohexylamino- ethanol.

Melting point of the hydrochloride: 213-214°C (dec.).

Prepared according to method a) from 4'-amino-3'-chloro-2-cyclohexylamino-5'-trifluoromethyl-acetophenone and sodium borohydride analogously to example 110.

Example 138.

1-(4- amino- 3- chloro- 5- trifluoromethyl- phenyl)- 2- cycloheptylamino- ethanol.

Melting point of the hydrochloride: 163-165°C.

Prepared according to method a) from 4'-amino-3'-

v

chloro-2-cycloheptylamino-5'-trifluoromethyl-acetophenone and sodium borohydride analogous to example 110.

Example 139.

1-(4-amino-3-bromo-5-trifluoromethyl-phenyl)-2-(cyclopropylarru.no)-ethanol.

Melting point of the hydrochloride: 1^-3-.175°C (spnltn.).

Prepared according to method a) from 4'-amino-3'-bromo-2-(cyclopropylmethyl-amino)-51-trifluoromethyl-acetophenone and sodium borohydride analogous to example 110.

Example 140.

1-(4-amino-3-cyano-phenyl)-2-cyclobutylamino-ethanol.

Melting point of the hydrobromide: from 193°C decomposition. Prepared according to method d) from 1-(4-amino-3-bromo-5-cyano-phenyl)-2-cyclobutylamino-ethanol and catalytically activated hydrogen analogous to example 114.

Example 141.

1-(4-amino-3-cyano-phenyl)-2-cyclopentylamino-ethanol.

Melting point: 158-160°C.

: Prepared according to method d) from 1-(4-amino-3-bromo-5-cyano-phenyl)-2-cyclopentylamino-ethanol and catalytically activated hydrogen analogously to example 114.

Example 142.

1-(4-amino-3-cyano-phenyl)-2-tert.-pentylamino-ethanol.

Melting point: 14 3°C.

Prepared according to method d) from 1-(4-amino-3-bromo-5-cyano-phenyl)-2-tert.-pentylamino-ethanol and catalytically activated hydrogen analogously to example 114.

Example 14 3.

1-( 4- amino- 3- chloro- 5- cyano- phenyl)- 2- cyclopropylamino- ethanol.

Melting point of the hydrochloride: 175-177°C.

Prepared according to method a) from 4'-amino-3'-chloro-5'-cyano-2-cyclopropylamino-acetophenone and sodium borohydride analogous to example 110.

Example 144.

1-( 4- amino- 3- chloro- 5- cyano- phenyl)- 2- propylamino- ethanol.

Melting point of the hydrochloride: 187-189°C.

Prepared according to method a) from 4'--amino-3'-chloro-5'-cyano-2-propylamino-acetophenone and sodium borohydride analogously to example 110.

Example 145.

1-( 4- amino- 3- chloro- 5- cyano- phenyl)- 2- cyclo^ u ^ ylamino- ethanox.

Melting point of the hydrochloride: 178-180°C (dec.).

i Eremstilt according to method a) from 4'-amino-3'-chloro-5'-cyano-2-cyclobutylamino-acetophenone and sodium borohydride analogous example"110.

Example 146.

1-( 4- amino- 3- chloro- 5- cyano- phenyl)- 2- sec.- butylamino- ethanol.

Melting point of the dihydrochloride: 190-191°C.

Prepared according to method a) from 4'-amino-2-sec.-butylamino-3'-chloro-5'-cyano-acetophenone and sodium borohydride

analogous example 110.

Example 147.

1-(4-amino-3-chloro-5-cyano-phenyl)-2-(hydroxy-tert-butylamino)-ethanol..

Melting point of the hydrochloride: 228-230°C (dec.).

Prepared according to method a) from 4'-amino-3'-chloro-5'-cyano-2-(hydroxy-tert-butylamino)-acetophenone and sodium borohydride analogously to example 110....

Example 148...

1-( 4- amino- 3- chloro- 5- cyano- phenyl)- 2- cyclopentylamino- ethanol.

Melting point of the hydrochloride: 138-144°C.

Prepared according to method a) from 4'-amino-3'-chloro-5'-cyano-2-cyclopentylamino-acetophenone and sodium borohydride analogous to example 110.

Example 149.

1-(4- amino- 3- chloro- 5- cyano-phenyl)- 2- tert.-pentylamino- ethanol.

Melting point of the hydrochloride: 218-220°C (dec.). : Prepared according to method a) from 4'-amino-3' - . chloro-5<1->cyano-2-tert.-pentylamino-acetophenone and sodium borohydride analogous to example 110.

Example 150.

1-( 4- amino- 3- chloro- 5- cyano- phenyl)- 2- cycloheptylamino- ethanol.

Melting point of the hydrochloride: 235-237°C (dec.). ; Prepared according to method a) from 4'-amino-3'-chloro-5'-cyano-2-cycloheptylamino-acetophenone and sodium borohydride analogous to example 110.

Example 151.

1-(4-amino-3-chloro-5-cyano-phenyl)-2-[1-(3,4-methylenedioxy-phenyl)-2-propylamino]-ethanol.

Melting point of the hydrochloride: 189-192°C. ; Prepared according to method a) from 4'-amino-3'-chloro-5'-cyano-2-[1-(3,4-methylenedioxy-phenyl)-2-propylamino]-acetophenone and sodium borohydride analogous to example 110.

Example 152.

1-(4-amino-3-bromo-5-cyano-phenyl)-2-cyclobutylamino-ethanol.

Melting point of the hydrochloride: 215-216°C (dec.).

Prepared according to method a) from 4'-amino-3'-bromo-5'-cyano-2-cyclobutylamino-acetophenone and sodium borohydride analogous to example 110.

Example 153.

1-(4-amino-3-bromo-5-cyano-phenyl)-2-(hydroxy-tert-butylamino)-ethanol.

Melting point of the hydrochloride: 221-222°C.

. Prepared according to method a) from 4'-amino-3'-bromo-5*-cyano-2-(hydroxy-tert-butylamino)-acetophenone and sodium borohydride analogous to example 110.

Example 154.

1-(4- amino- 3- bromo- 5- cyano- phenyl)- 2- cyclopentylamino- ethanol.

Melting point of the hydrochloride: 177°C.

Prepared according to method a) from 4"-amino-3'-bromo-5'-cyano-2-cyclopentylamino-acetophenone and sodium borohydride analogously to example 110.

Example 155.

1-(4- amino- 3- bromo- 5- cyano- phenyl)- 2- tert.- pentylamino- ethanol.

Melting point of the hydrochloride: 202-204°C (dec.).

Prepared according to method a) from 4'-amino-3'-bromo-5<1->cyano-2-tert.-pentylamino-acetophenone and sodium borohydride analogously to example 110.

Example 156.

1-(4- amino- 3- bromo- 5- cyano- phenyl)- 2- cyclohexylamino- ethanol.

Melting point of the hydrochloride: 209-210°C (dec.). Prepared according to method a) from 4'-amino-3'-bromo-5'-cyano-2-cyclohexylamino-acetophenone and sodium borohydride analogous to example 110.

Example 157.

1-(4-amino-3,5-dicyano-phenyl)-2-cyclopropylamino-ethanol.

Melting point of the hydrochloride: 222-223°C (dec.).

Prepared according to method a) from 4'-amino-2-cyclopropylamino-3<1> , 5'-dicyano-acetophenone and sodium borohydride analogously to example 110.

Example 158.

1-(4-amino-3,5-dicyano-phenyl)-2-isopropylamino-ethanol.

Melting point of the hydrochloride: 224-226°C (dec.). Prepared according to method a) from 4'-amino-3<1>,5<1->dicyan-2-isopropylamino-acetophenone and sodium borohydride analogously to example 110.

Example 159.

1-(4-amino-3,5-dicyano-phenyl)-2-cyclobutylamino-ethanol.

Melting point of the hydrochloride: 258°C (dec.). : Prepared according to method a) from 4'-amino-2-cyclobutylamino-3<1>,5'-dicyano-acetophenone and sodium borohydride analogously to example 110.

Example 160.

1-(4- amino- 3, 5- dicyan- phenyl)- 2- sec.- butylamino- ethanol.

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

i Eremstilt according to method a) from 4'-amino-2-sec.-butylamino-3<1>,5'-dicyano-acetophenone and sodium borohydride analogously to example 110.

Example 161.

1--( 4- amino- 3, 5- dicyan- phenyl)- 2- tert.- butylamino- ethanol.

Melting point of the hydrochloride: 251-253°C (dec.).

Prepared according to method a) from 4'-amino-2-tert-butylamino-3',5'-dr.cyano-acetophenone and sodium borohydride analogously to example 110.

Example 162.

1- ( 4- amino- 3, 5- dicyan- phenyl) - 2- ( hydroxy- tert.- butylamino)- ethanol.

Melting point of the hydrochloride: 240-241°C (dec.).

Prepared according to method a) from 4'-amino-3',5'-dicyan-2-(hydroxy-tert-butylamino)-acetophenone and sodium borohydride analogously to example 110.

Example 163.

1-(4-amino-3,5-dicyano-phenyl)-2-cyclopentylamino-ethanol.

Melting point of the hydrochloride: 214-216°C.

: Prepared according to method a) from 4'-amino-2-cyclopentylamino-3',5'-dicyanoacetophenone and sodium borohydride analogously to example 110.

Example 164.

1-(4- amino- 3, 5- dicyan- phenyl)- 2- tert.-pentylamino- ethanol.

Melting point of the hydrochloride: 231-233°C (dec.).

Prepared according to method a) from 4'-amino-3',5<1->dicyan-2-tert.-pentylamino-acetophenone and sodium borohydride analogously to example 110.

Example 165.

1-(4-amino-3,5-dicyano-phenyl)-2-[1-(3,4-methylenedioxy-phenyl)-2-propylamino]-ethanol.

Melting point of the hydrochloride: 219-222°C (dec.).

': Prepared according to method a) from 4'-amino-3',5'-dicyan-2-[1-(3,4-methylenehexy-phenyl)-2-propylamino]-acetophenone and sodium borohydride analogously to example 110.

Example 166.

1-( 4- amino- 3- chloro- 5- diethylaminomethyl- phenyl)- 2- tert.- butylamino- ethanol.,

Melting point: 65-69°C.

Prepared according to method a) from 4'-amino-2-tert. - butylamino-3'-chloro-5'-diethylaminomethyl-acetophenone and sodium borohydride analogous to example 110.

Example 167.

1-(4- amino- 3- bromo- 5- diethylaminomethyl- phenyl)- 2- tert.- butylamino- ethanol.

Melting point: 96-100°C.

. Prepared according to method a) from 4'-amino-3'-bromo-2-tert-butylamino-5'-diethylaminomethyl-acetophenone and sodium borohydride analogously to example 110.

Example 168.

1-(4-amino-3-chloro-5-nitro-phenyl)-2- tert. - butylamino-ethanol.

Melting point: 148-149°C.

Prepared according to method a) from 4'-amino-2-tert-butylamino-3<1->chloro-5'-nitro-acetophenone and sodium borohydride analogously to example 110.

Example 169.

1- ( 4- amino- 3- bromo- 5- nitro- phenyl)- 2- tert.- butylamino- ethanol.

Melting point: 151-152°C.

, Prepared according to method a) from 4'-amino-3'-bromo-2-tert-butylamino-51-nitro-acetophenone and sodium borohydride analogously to example 110.

Example 170.

5-(4-amino-3-bromo-5-fluoro-phenyl)-3-tert-butyl-2-isopropyl-oxazolidine.

Prepared from 1-(4-amino-3-bromo-5-fluoro-phenyl)-2-tert-butylamino-ethanol and isobutyraldehyde analogous to example 115.

Amorphous substance, evidence of structure by NMR spectrum (CDC13): 0.85-1.2 ppm multiplet [15 protons, -C(CH3)3 and ?CH-CH(CH3)2], 1.5-1.85 ppm multiplet [1 proton, ) CH-C_H(CH3) 2 ] , 2.5-2.9 and 3.2-3.7 ppm 2 multiplets [2 protons, Ar-CH-CH2"N<] , 3.9 -4.2

ppm singlet [2 protons, NH2], 4.4-4.9 ppm multiplet [2 pro-

tones, Ar-CH-CH2~N< and -0-CH-CH(CH3)2], 6.8-7.3 ppm multiplet [2 aromatic protons] . N

Example 171.

5-(4-amino-3-bromo-5-fluoro-phenyl)-3-tert.-butyl-oxazolidine.

Melting point of the dihydrochloride: 164-178°C (dec.).

Prepared from 1-(4-amino-3-bromo-5-fluoro-phenyl)-2-tert-butylamino-ethanol and formaldehyde analogously to example 115-

Example 172.

5-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-3-tert-butyl-2-methyl-oxazolidine.

Melting point of the hydrochloride: 199-202°C (dec.).

Prepared from 1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert-butylamino-ethanol and acetaldehyde analogously to example 115.

Example 173.

1-1-(4-amino-3-fluoro-phenyl)-2-tert-butylamino-ethanol and d-1(4-amino-3-fluoro-phenyl)-2- tert-butylamino-ethanol.

a) 1-1-(4-acetylamino-3-fluoro-phenyl)-2-(N-benzyl-N-tert.-butyl)-amino-O-(N-carbobenzoxy-L-alanyl)-ethanol and d -1-(4-acetylamino-3-fluoro-phenyl)-2-(N-benzyl-N-tert-butyl)-amino-

O-(N-carbobenzoxy-L-alanyl)-ethanol.

To a solution of 15 g of N-carbobenzoxy-L-alanine i

300 ml of absolute tetrahydrofuran are added to 14.5 g of N,N'-carbonyldiimidazole and stirred for three hours at room temperature. A solution of 10 g of d,1-1-(4-acetylamino-3-fluoro-phenyl)-2-(N-benzyl-N-tert-butyl)-amino-ethanol in 200 ml of absolute tetrahydrofuran and a pea-sized piece of sodium and stirred for 12 days at room temperature. After this time, it is evaporated to dryness in vacuo and the residue is distributed between chloroform and water. The chloroform phase is dried over sodium sulfate and evaporated to dryness in vacuo. The two diastereomeric esters thus obtained, present in a mixture, show different Rf values by thin-layer chromatography ("Silica gel G", Merck, chloroform:acetone = 10:1).

"The above evaporation residue is purified over a silica gel chromatography column, without separating the diastereomeric esters. (500

g silica gel, eluent: chloroform:acetone = 10:1).

The fractions containing substance are evaporated to dryness in vacuo and recrystallized from ether. Colorless crystals are obtained which consist of pure 1-1-(4-acetylamino-3-fluoro-phenyl)-2-(N-benzyl-N-tert-butyl)-amino-0-(N-carbobenzoxy-L- alanyl)-ethanol.

[α]364 = 101° (c = 2.0, methanol, Rf value = 0.27.

The mother liquor obtained above is evaporated to dryness

in vacuum. Over a chromatography column (100 g silica gel, eluent: chloroform:acetone = 20:1), the diastereomeric ester with the largest Rf value (Rf = 0.33) is isolated: I Earless oil, which consists of d-1-(4- acetylamino-3-fluoro-phenyl)-2-(N-benzyl-N-tert-butyl)-amino-O-(N-carbobenzoxy-L-alanyl)-ethanol.

[v-llcA = "65° (c = 2.0, methanol), Rf value = 0.33.

b) 1-1-(4-amino-3-fluoro-phenyl)-2-tert.-butylamino-ethanol.

2 g of 1-1-(4-acetylamino-3-fluoro-phenyl)-2-(N-benzyl-N-tert.-butyl)-amino-O-(N-carbobenzoxy-L-alanyl)-ethanol are dissolved in 60 ml of ethanol. 20 ml of 5N caustic soda is added to the solution and heated for 4 hours at reflux temperature. After cooling, it is distributed between chloroform and water and the aqueous phase is extracted four more times with chloroform. The combined chloroform solutions are dried over sodium sulfate and evaporated to dryness in vacuo. The residue, consisting of 1-1-(4-amino-3-fluoro-phenyl)-2-(N-benzyl-N-tert.-butyl)-aminoethanol, is dissolved in 50 ml of methanol and acidified with ethereal salt

acid to pH 6, 0.2 g palladium on charcoal (10%) is added and hydrogenated at room temperature and 5 atmospheres pressure in a Parr apparatus, until no more hydrogen is absorbed. After aspiration of the catalyst in vacuum, it is evaporated to dryness and the solid residue, consisting of 1-1-(4-amino-3-fluoro-phenyl)-2-tert-butylamino-ethanol hydrochloride, crystallizes from isopropanol after the addition of ether.

Melting point: 199-200°C (decomposition),

[a]^. -123.3° (c = 1.0, methanol).

c) d- 1-(4-amino-3-fluoro-phenyl)-2-tert.-butylamino-ethanol.

The above obtained oily d-1-(4-acetylamino-3-fluoro-phenyl)-2-(N-benzyl-N-tert-butyl)-amino-O-(N-carbobenzoxy-L-alanyl)-ethanol dissolve in 30 ml of ethanol. The solution is added to 10 ml

5n caustic soda and heated for 4 hours at reflux temperature.

After cooling, distribute between chloroform and water and the aqueous

phase is extracted a further 4 times with chloroform. The combined chloroform solutions are dried over sodium sulfate and evaporated to dryness in vacuo. The residue consisting of d-1-(4-amino-3-fluoro-phenyl)-2-(N-benzyl-N-tert-butyl)-amino-ethanol is dissolved in 25 ml of methanol and acidified with ethereal hydrochloric acid to pH 6, 0.1 g palladium on charcoal (10% strength) is added and hydrogenated at room temperature and 5 atmospheres pressure in a Parr apparatus until no more hydrogen is taken up. After aspiration of the catalyst, it is evaporated to dryness in vacuum and the solid residue, consisting of d-1-(4-amino-3-fluoro-phenyl)-2-tert-butylamino-ethanol hydrochloride, is brought to crystallize from isopropanol after addition of ether. Melting point: 198-200°C (decomposition).

[α]^, = +124.4° (c = 1.142, methanol).

364

Example 174. d-1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert-butylamino-ethanol and 1-1-(4-amino-3-chloro-5-trifluoromethyl-phenyl) )-2-tert-butylamino-ethanol. a) d,1-1-(4-amino-3-kbr-5-trifluoromethyl-phenyl)-2-tert-butylamino-O-[(-)-menthoxy-carbonyl]-ethanol.

To a solution of 8.8 g of d,l-l-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert-butylamino-ethanol in 50 ml of pyridine is added dropwise while stirring and at 20°C 56.6 ml of a 0.5 molar solution of chloroformate-(-)-menthyl ester in toluene. After two hours, the solution is evaporated to dryness in a vacuum. The oily residue is first triturated with water and taken up after decanting off the above solution in ether. The ethereal solution is washed in sequence with water, 2n ammonia (whereby a precipitate precipitated between the phases dissolves) and again with water. The magnesium sulfate-dried ether solution is brought to pH 6 with 4N isopropanolic hydrochloric acid. Thereby, the mixture of the hydrochlorides of the aforementioned diastereomeric compounds is crystallized. It is filtered off with suction and washed with ether.

In the thin-layer chromatogram on "Kieselgel G", Merck, with butyl acetate: cyclohexane = 9:1, the crystallisate shows two equally strong spots with the approximate Rf values of 0.45 and 0.55. b) Separation of d- and 1-1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert.-butylamino-O-[(-)-menthoxy-carbonyl]-ethanol.

3.0 g of the above mixture of hydrochlorides of d- and 1-1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert-butylamino-O-{-)-menthoxy-carbonyl ]-ethanol is suspended in a little water, covered with ether, 5.0 ml of 2N ammonia is added and shaken until everything dissolves. The ether phase is separated, washed with water, dried over magnesium sulphate and evaporated in vacuo. The oil residue is chromatographed over a silica gel column (6.5 cm diameter, 107 cm long, 2.2 kg silica gel) with a mixture of butyl acetate and cyclohexane (19:1)

(flow rate 120 ml/hour). The fractions with pure substance with an Rf value of 0.55 are combined and freed from solvent in vacuo. The residue is crystallized from petroleum ether (boiling point: 40-60°C).

d-1-(4-amino-3-chloro-5-thifluoromethyl-phenyl)-2-tert-butylamino-O-[(-)-menthoxy-carbonyl]-ethanol is obtained.

Melting point: 95.5-96.5°C.

tight],?/! = +74.1° (c = 1.0, chloroform).

After sorting out fractions containing mixtures of the diastereomeric compounds and which can be returned to a further chromatographic separation, the fractions containing the almost pure substance with an Rf value of 0.45 are combined and evaporated in vacuo. obtained residue from petroleum ether, chromatographically pure 1-1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert-butylamino-O-[(-)-menthoxy-carbonylj-ethanol is obtained.

Melting point: 102-104°C.

[ct] 364 = "273'5° <c = 1'0' chloroform).

c) d-1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert-butylamino-ethanol.

1.6 g of d-1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert-butylamino-O-[(-)-menthoxy-carbonyl]-ethanol are dissolved in 16 ml of methanol and allowed to stand for 65 hours at approx. 20°C. It is evaporated in vacuo and the residue is purified by column chromatography (silica gel, chloroform: methanol: concentrated ammonia = 90:10:1). The fractions with the desired substance are combined and evaporated in vacuo. The residue is dissolved in acetic acid ethyl ester, and the calculated amount of 4N hydrochloric acid in isopropanol is added to the solution, whereby the hydrochloride of the aforementioned compound crystallizes out.

Melting point: above 194°C slow decomposition.

tot]364 = +154'9° (c = 1'0' methanol).

d) 1-1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert-butylamino-ethanol. . Prepared from 1.58 g of 1-1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert-butylamino-O-[(-)-menthoxy-carbonyl]-ethanol by solvolysis with methanol and chromatographic purification analogously to the example for the enantiomeric compound.

Melting point of the hydrochloride: above 194°C slow decomposition.

[01]364 ~154'8° (c = 1'0' methanol).

Example 175. d-1-(4-amino-3-bromo-5-fluoro-phenyl)-2-tert-butylamino-ethanol and 1-1-(4-amino-3-bromo-5-fluoro-phenyl) )- 2-tert.-butylamino-ethanol.

205 g of d,1-1(4-amino-3-bromo-5-fluoro-phenyl)-2-tert-butylamino-ethanol and 118 g of dibenzoyl-D-tartaric acid are dissolved in 2.5 1

hot ethanol, filtered and allowed to stand for a day at room temperature for crystallization. The product obtained is recrystallized six times from methanol-ether, whereby the pure d-[1-(4-amino-3-bromo-5-fluoro-phenyl)-2-tert-butylamino-ethanol]-dibenzoyl-D -tartrate with melting point 206-208 C (decomposition).

[α]° = 332.9° (c = 2.0, methanol).

364

The salt is dissolved in methanol and concentrated ammonia under heating and the base is brought to crystallize by the addition of water. The base obtained is dissolved in absolute ethanol, neutralized with absolute ethanolic hydrochloric acid and the crystallization of the d-1-(4-amino-3-bromo-5-fluoro-phenyl)-2-tert-butylamino-ethanol hydrochloride is completed by adding of ether.

Melting point: 234-235°C (decomposition).

[α]^g4 = + 132.0° (c = 2.0, methanol).

The mother liquor from the precipitation of the d-[1-(4-amino-3-bromo-5-fluoro-phenyl-2-tert-butylamino-ethanol]-dibenzoyl-D-tartrate and that from the first recrystallization are combined, evaporated to a small volume and the base is precipitated by the addition of concentrated ammonia and water 140 g of thus obtained 1-(4-amino-3-bromo-5-fluoro-phenyl)-2-tert-butylamino-ethanol (1-form enriched)

is dissolved in 1.8 1 of absolute ethanol and a solution of 82 g of dibenzoyl-L-tartaric acid in 500 ml of absolute ethanol is added, evaporated to a volume of 1 1 and allowed to stand for three days at room temperature for crystallization. The product obtained is recrystallized six times from methanol/ether. Thereby 1-[1-(4-amino-3-bromo-5-fluoro-phenyl)-2-tert-butylamino-ethanol]-dibenzoyl-L-tartrate is obtained in pure form.

Melting point: 204-206°C. (cleavage.)

[α]^g4 = -330.2° (c = 2.0, methanol).

The salt is dissolved in methanol and concentrated ammonia during heating and the base is precipitated by the addition of water. The base obtained is dissolved in absolute ethanol, neutralized with absolute ethanolic hydrochloric acid and 1-1-(4-amino-3-bromo-5-fluoro-phenyl)-2-tert-butylamino-ethanol hydrochloride is caused to crystallize by adding of ether.

Melting point: 218-220°C (decomposition).

[α]364 = "133'9° <c 2'0' methanol).

Example 176. d-1-(4-amino-3-chloro-5-fluoro-phenyl)-2-tert-butylamino-ethanol.

Melting point of the hydrochloride: 210-211°C (decomposition).

[α]3g4 = + 139.7° (c = 2.0, methanol).

. Prepared from d,l-l-(4-amino-3-chloro-5-fluoro-phenyl)-2-tert-butylamino-ethanol by fractional crystallization of the dibenzoyl-D-tartrate analogous to example 175.

1- 1-( 4- amino- 3- chloro- 5- fluoro- phenyl)- 2- tert.- butylamino- ethanol.

Melting point of the hydrochloride: 209-210°C (decomposition).

Prepared from d,1-1-(4-amino-3-chloro-5-fluoro-phenyl)-2-tert-butylamine p-ethanol by fractional crystallization of the dibenzoyl-L-tartrate analogous to example 175.

Example 177. d-1-(4-amino-3-chloro-5-cyano-phenyl)-2-tert-butylamino-ethanol.

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

[a]364<=><+>59'9°c <c = 2'0' methanol),

Prepared from d,l-l-(4-amino-3-chloro-5-cyano-phenyl)-2-tert-butylamino-ethanol by fractional crystallization of the dibenzoyl-D-tartrate analogously to example 175.

1- 1-( 4- amino- 3- chloro- 5- cyano- phenyl)- 2- tert.- butylamino- ethanol.

Melting point of the hydrochloride: 199-202°C (decomposition). Ca"l364"59'85° (c = 2'°~ methanol). .Prepared from d,l-l-(4-amino-3-chloro-5-cyano-phenyl)-2-tert-butylamino-ethanol by fractional crystallization of the dibenzoyl-L-tartrate analogous to example 175.

Example 178.

d- 1-(4- amino- 3- chloro- 5- fluoro- phenyl)- 2- tert.- butylamino- ethanol.

0.26 g of d-1-(4-amino-3-fluoro-phenyl)-2-tert-butylamino-ethanol hydrochloride and 0.2 ml of pyridine are dissolved in 30 ml of tetrahydrofuran and cooled to 0°C. 0.3 g of phenyliodine dichloride is added. After 20 hours at approx. At 4°C, the solution is evaporated, distributed between ethyl acetate and water, the aqueous extract is made alkaline with 2N ammonia and extracted again with ethyl acetate. The organic phase is washed with water, dried and evaporated to dryness in vacuo. The residue is dissolved in absolute ethanol, neutralized with ethanolic hydrochloric acid and the hydrochloride of the said compound is caused to crystallize with the addition of ether.

Melting point: 210-211°C (decomposition).

[ct]364 = + 139'6° <c = 2'0' methanol).

Example 179.

d- 1-(4- amino- 3- bromo- 5- fluoro- phenyl)- 2- tert.- butylamino- ethanol.

0.26 g of d-1-(4-amino-3-fluoro-phenyl)-2-tert-butylamino-ethanol hydrochloride is dissolved in 30 ml of 50% acetic acid and added dropwise at 0-5°C 0, 16 g of bromine dissolved in 5 ml of glacial acetic acid and 1 ml of water. After 15 minutes, the reaction mixture is evaporated, the residue is dissolved

in water, made alkaline with 2n ammonia and extracted with chloro-

shape. The chloroform solution is dried with sodium sulfate and evaporated to dryness in vacuo. The residue is transferred into solution with ethanol, it is neutralized with ethanolic hydrochloric acid and ether is added, whereby the hydrochloride of the aforementioned compound is obtained. Melting point: 234-235°C (decomposition).

[α]3°4 = +132.0° (c = 2.0, methanol).

Example 180.

1-(4-amino-3-cyano-phenyl)-2-cyclobutylamino-ethanol.

Melting point of the hydrobromide: from 19 3°C (decomposition). Prepared from 4'-amino-3'-cyano-2-cyclobutylamino-acetophenone hydrochloride and sodium borohydride analogously to example 1.

Analogously, the following compounds were prepared: 1-(4-amino-3-cyano-phenyl)-2-tert.-pentylamino-ethanol Melting point: 14 3°C.

1-(4-amino-3-trifluoromethyl-phenyl)-2-tert-butylamino-ethanol Melting point of the hydrochloride: 172-174°C (decomposition).

1-(4-amino-9-trifluoromethyl-phenyl)-2-tert.-pentylamino-ethanol Melting point of the hydrobromide: 174-175°C (decomposition).

Example 181.

1-(4- amino- 3- chloro- 5- fluoro- phenyl)- 2- isopropylamino- ethanol.

Melting point of the hydrochloride: 152-154°C (decomposition^ Prepared from 1-(4-amino-3-fluoro-phenyl)-2-isopropylamino-ethanol hydrochloride and chlorine analogously to example 4.

Analogous to example 4, 5 or 112, the following compounds were prepared: 1-(4-amino-3-chloro-5-fluoro-phenyl)-2-cyclopropylamino-ethanol hydrochloride.

Melting point: 175-177°C (decomposition).

1-(4-amino-3-chloro-5-fluoro-phenyl)-2-tert-butylamino-ethanol hydrochloride.

Melting point: 206-208°C (decomposition).

1-(4-amino-3-chloro-5-fluoro-phenyl)-2-tert-pentylamino-ethanol hydrochloride.

Melting point: 187-188°C (melting point).

1-(4-Amino-9-bromo-5-fluoro-phenyl)-2-isopropylamino-ethanol hydrochloride.

Melting point: 171-173°C (decomposition).

1-(4-amino-3-bromo-5-fluoro-phenyl)-tert-butylamino-ethanol hydrochloride

Melting point: 207-208°C (decomposition).

1-(4-amino-3-bromo-5-fluoro-phenyl)-2-cyclobutylamino-ethanol hydrochloride

Melting point: 164-166°C (decomposition).

1-(4-amino-3-fluoro-5-iodo-phenyl)-2-cyclopropylamino-ethanol hydrochloride

Melting point: 199-201°C (decomposition).

1-(-4-amino-3-chloro-5-cyano-phenyl)-2-propylamino-ethanol hydrochloride

Melting point: 187-189°C.

1-(4-amino-3-chloro-5-cyano-phenyl)-2-sec.-butylamino-ethanol-dihydrochloride Melting point: 190-191°C.

1-(4-amino-3-chloro-5-cyano-phenyl)-2-tert-butylamino-ethanol Melting point: 125-133°C.

1-(4-amino-3-chloro-5-cyano-phenyl)-2-(hydroxy-tert-butylamino)-ethanol hydrochloride

Melting point: 228-230°C (decomposition).

1-(4-amino-3-chloro-5-cyano-phenyl)-2-tert-pentylamino-ethanol hydrochloride

Melting point: 218-220°C (decomposition).

1-(4-amino-3-chloro-5-cyano-phenyl)-2-cyclopentylamino-ethanol hydrochloride

Melting point: 138-144°C.

1-(4-amino-3-chloro-5-cyano-phenyl)-2-[1-(3,4-methylenedioxy-phenyl)-2-propylamino]-ethanol hydrochloride.

Melting point: 189-192°C.

1-(4-amino-3-bromo-5-cyano-phenyl)-2-isopropylamino-ethanol hydrochloride

Melting point: 186-189°C.

1-(4-amino-3-bromo-5-cyano-phenyl)-2-tert-butylamino-ethanol hydrochloride

Melting point: 213-215°C.

1-(4-amino-3-bromo-5-cyano-phenyl)-2-cyclobutylamino-ethanol hydrochloride

Melting point: 215-216°C (decomposition).

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-isopropylamino-ethanol

Melting point: 104-106°C.

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert-butylamino-ethanol hydrochloride

Melting point: 205-207°C (decomposition).

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-cyclobutylamino-ethanol hydrochloride

Melting point: 177-178°C.

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert-pentylamino-ethanol hydrochloride

Melting point: 176-178°C (decomposition).

1-(4-amino-3-bromo-5-trifluoromethyl-phenyl)-2-isopropylamino-ethanol hydrochloride

Melting point: 177-179°C (decomposition).

1-(4-amino-3-chloro-5-nitro-phenyl)-2-tert-butylamino-ethanol Melting point: 148-149°C.

1-(4-amino-3-bromo-5-nitro-phenyl)-2-tert-butylamino-ethanol Melting point: 151-152°C.

Example 182.

1-( 4- amino- 3- chloro- 5- fluoro- phenyl)- 2- isopropylamino- ethanol.

Melting point of the hydrochloride: 152-154°C (decomposition). : Prepared from 1-(4-acetylamino-3-chloro-5-fluoro-phenyl)-2-isopropylamino-ethanol hydrochloride analogous to example 7 or from 1-(4-amino-3-chloro-5-fluoro-phenyl) -2-(N-benzyl-N-isopropyl)-amino-ethanol analogous to example 10.

■ The following compounds were prepared analogously: 1-(-4-amino-3-chloro-5-fluoro-phenyl)-2-cyclopropylamino-ethanol hydrochloride

Melting point: 175-177°C (decomposition).

1-(4-Amino-3-chloro-5-fluoro-pheryl)-2-tert-pentylamino-ethanol hydrochloride.

Melting point: 187-188°C (decomposition).

1-(4-amino-3-bromo-5-fluoro-phenyl)-2- isopropylamino-ethanol hydrochloride

Melting point: 171-173°C (decomposition).

1-(4-amino-3-bromo-5-fluoro-phenyl)-2-tert-butylamino-ethanol hydrochloride

Melting point: 207-20.8°C (decomposition).

1-(4-amino-3-bromo-5-fluoro-phenyl)-2-cyclobutylamino-ethanol hydrochloride

Melting point: 164-166°C (decomposition).

1-(4-amino-3-fluoro-5-iodo-phenyl)-2-cyclopropylamino-ethanol hydrochloride

Melting point: 199-201°C (melting point).

1-(4-amino-3-trifluoromethyl-phenyl)-2-tert-pentylamino-ethanol hydrobromide

Melting point: 174-175°C (decomposition).

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-isopropylamino-

ethanol

Melting point: 104-106°C.

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert-butylamino-ethanol hydrochloride

Melting point: 205-207°C (decomposition).

(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-cyclobutylamino-ethanol hydrochloride

Melting point: 177-178°C.

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert-pentylamino-ethanol hydrochloride

Melting point: 176-178°C (decomposition).

1-(4-amino-3-bromo-5-trifluoromethyl-phenyl)-2-isopropylamino-ethanol hydrochloride

Melting point: 177-179°C (decomposition).

Example 183.

1- ( 4- amino- 3- chloro- 5- nitro- phenyl)- 2- tert.- butylamino- ethanol.

Melting point: 148-149°C.

.Prepared from 1-(4-acetylamino-3-chloro-5-nitro-phenyl)-2-tert-butylamino-ethanol hydrochloride analogous to example 7.

The following compound was prepared analogously: 1-(4-amino-3-bromo-5-nitro-phenyl)-2-tert-butylamino-ethanol.

Q

Melting point: 151-152°C.

Example 184.

1-(4-amino-3-fluoro-phenyl)-2-tert.-butylamino-ethanol.

Melting point of the hydrochloride: 196-197°C (decomposition).

Prepared from 1-(4-amino-3-bromo-5-fluoro-phenyl)-2-tert-butylamino-ethanol analogous to example 14.

The following compound was prepared analogously: 1-(4-amino-3-trifluoromethyl-phenyl)-2-tert-butylamino-ethanol.

Melting point of the hydrochloride: 172-174°C (decomposition).

Example 185.

1-(4- amino- 3- chloro- 5- trifluoromethyl- phenyl)- 2- tert.- butylamino- ethanol.

3.4 g of 1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-bromo-ethanol are dissolved in 25 ml of tert-butylamine and allowed to stand for 20 hours at room temperature. Excess tert-butylamine is evaporated in vacuo and the residue taken up in ether. The ether solution is washed with water, dried over magnesium sulphate and evaporated in vacuo. The evaporation residue is purified chromatographically over a silica gel column with the system chloroform: methanol: conc. ammonia = 90:10:1. The combined fractions with the desired substance thus obtained are brought to dryness in a vacuum. The residue is dissolved in ether and the solution is brought to pH 4 with isopropanolic hydrochloric acid. Thereby 1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert-butylamino-ethanol hydrochloride crystallizes out, which is filtered off and washed with ether o:; melts at 205-207°C (dec.).

Example 186.

1-(4- amino- 3- chloro- 5- trifluoromethyl- phenyl)- 2- tert.- butylamino- ethanol.

Melting point of the hydrochloride: 205-207°C (decomposition).

Prepared according to method f) from 1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-(p-toluenesulfonyloxy)-ethanol and excess tert-butylamine analogous to example 185.

The following compounds are prepared analogously to examples 185 and 186: 1-(4-amino-3-fluoro-phenyl)2-tert-butylamino-ethanol hydrochloride Melting point: 196-197°C (dec.)

1-(4-amino-3-chloro-5-fluoro-phenyl)-2-isopropylamino-ethanol hydrochloride

Melting point: 152-154°C (decomposition).

1-(4-amino-3-chloro-5-fluoro-phenyl)-2-cyclopropylamino-ethanol hydrochloride

Melting point: 175-177°C (decomposition).

1-(4-amino-3-chloro-5-fluoro-phenyl)-2-tert-butylamino-ethanol-

hydrochloride

Melting point: 206-208°C (decomposition).

1-(4-amino-3-chloro-5-fluoro-phenyl)-2-tert-pentylamino-ethanol hydrochloride

Melting point: 187-188°C (decomposition).

1-(4-amino-3-bromo-5-fluoro-phenyl)-2-isopropylamino-ethanol-

hydrochloride

Melting point: 171-173°C (decomposition).

1-(4-amino-3-bromo-5-fluoro-phenyl)-2-tert-butylamino-ethanol hydrochloride

Melting point: 207-208°C (decomposition).

1-(4-amino-3-bromo-5-fluoro-phenyl)-2-cyclobutylamino-ethanol-

hydrochloride

Melting point: 164-166°C (decomposition).

1-(4-amino-3-fluoro-5-iodo-phenyl)-2-cyclopropylamino-ethanol-

hydrochloride

Melting point: 199-201°C (decomposition).

1-(4-amino-3-cyano-5-fluoro-phenyl)-2-isopropylamino-ethanol-

hydrochloride

Melting point: 182-184°C (decomposition).

1-(4-amino-3-cyano-5-fluoro-phenyl)-2-tert-butylamino-ethanol hydrochloride

Melting point: 242-243°C (decomposition).

1-(4-amino-3-cyano-phenyl)-2-cyclobutylamino-ethanol hydrobromide Melting point: from 93°C (decomposition).

1-(4-amino-3-cyano-phenyl)-2-tert-pentylamino-ethanol

Melting point: 143°C.

1-(4-amino-3-chloro-5-cyano-phenyl)-2-propylamino-ethanol-

hydrochloride

Melting point: 187-189°C.

1-(4-axino-3-chloro-5-cyano-phenyl)-2-sec.-i>utilylamino-ethanol-dihydrochloride

Melting point: 190-191°C.

1-(4-amino-3-chloro-5-cyano-phenyl)-2-tert-butylamino-ethanol Melting point: 125-133°C.

1-(4-amino-3-chloro-5-cyano-phenyl)-2-(hydroxy-tert-butylamino)-ethanol hydrochloride

Melting point: 228-230°C (decomposition).

1-(4-amino-3-chloro-5-cyano-phenyl)-2-tert-pentylamino-ethanol hydrochloride

Melting point: 218-220°C (decomposition).

1-(4-amino-3-chloro-5-cyano-phenyl)-2-cyclopentylamino-ethanol hydrochloride

Melting point: 138-144°C.

1-(4-amino-3-chloro-5-cyano-phenyl)-2-[1-(3,4-methylenedidecyl)-2-propylamino]-ethanol hydrochloride

Melting point: 189-192°c.

1-(4-amino-3-bromo-5-cyano-phenyl)-2-isopropylamino-ethanol hydrochloride

Melting point: 186-189°C.

1-(4-amino-3-bromo-5-cyano-phenyl)-2-tert-butylamino-ethanol hydrochloride

Melting point: 213-215°C.

1-(4-amino-3-bromo-5-cyano-phenyl)-2-cyclobylamino-ethanol hydrochloride

Melting point: 215-216°C (decomposition).

1-(4-amino-3,5-dicyano-phenyl)-2-tert-butylamino-ethanol hydrochloride

Melting point: 251-253°C (decomposition).

1-(4-amino-3-trifluoromethyl-phenyl)-2-tert-butylamino-ethanol hydrochloride

Melting point: 172-174°C (decomposition).

1-(4-amino-3-trifluoromethyl-phenyl)-2-tert-pentylamino-ethanol hydrobromide

Melting point: 174-175°C (decomposition).

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-isopropylamiho-ethanol hydrochloride

Melting point: 185-187°C.

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-cyclobutylamino-ethanol hydrochloride

Melting point: 177-178°C.

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert-pentylamino-ethanol hydrochloride

Melting point: 176-178°C (decomposition).

1-(4-amino-3-bromo-5-trifluoromethyl-phenyl)-2-isopropylamino-ethanol hydrochloride

Melting point: 177-179°C (decomposition).

1-(4-amino-3-chloro-5-nitro-phenyl)-2-tert-butylamino-ethanol Melting point: 148-149°C.

1-(4-amino-3-bromo-5-nitro-phenyl)-2-tert-butylamino-ethanol Melting point: 151-152°C.

Example 187.

1-(4-amino-3-bromo-5-fluoro-phenyl)-2-tert-butylamino-ethanol hydrochloride.

1.5 g of 2-tert.-butylamino-1-(3-bromo-5-fluoro-4-nitro-phenyl)-ethanol hydrochloride is dissolved in 40 ml of methanol. After adding 0.6 g of platinum dioxide, hydrogenate with shaking at room temperature and normal pressure until absorption of the theoretical amount of hydrogen. The catalyst is removed and the solution is evaporated to dryness in vacuo.

The crude, solid residue, namely 1-(4-amino-3-bromo-5-fluoro-phenyl)-2-tert-butylamino-ethanol hydrochloride, is partitioned between 2N caustic soda and methylene chloride. The organic phase is separated, washed with water,

dried over sodium sulfate and evaporated to dryness. The remaining oil residue is chromatographed over a chromatography column filled with 80 g of silica gel, whereby a mixture of chloroform and methanol = 10:1 is used as eluent. The eluates containing the substance are combined and evaporated to dryness in vacuo. The residue is taken up in a little isopropanol and acidified to pH 5 with ethereal hydrochloric acid. After adding a little ether, crystallization occurs. The crystals of

suction and wash with a mixture of isopropanol and ether.

Melting point: 207-208°C (decomposition).

■ Wavy compounds were prepared analogously to example 187: 1-(4-amino-3-fluoro-phenyl)-2-tert-butylamino-ethanol hydrochloride Melting point: 196-197°C (decomposition).

1-(4-amino-3-chloro-5-fluoro-phenyl)-2-isopropylamino-ethanol hydrochloride

Melting point: 152-154°C (decomposition).

1-(4-amino-3-chloro-5-fluoro-phenyl)-2-cyclopropylamino-ethanol hydrochloride

Melting point: 175-177°C (decomposition).

1-(4-amino-3-chloro-5-fluoro-phenyl)-2-tert-butylamino-ethanol hydrochloride

Melting point: 206-208°C (decomposition).

1-(4-amino-3-kTor-5-fluoro-phenyl)-2-tert-pentylamino-ethanol hydrochloride

Melting point: 187-188°C (decomposition).

1-(4-amino-3-bromo-5-fluoro-phenyl)-2-isopropylamino-ethanol hydrochloride

Melting point: 171-173°C (decomposition).

1-(4-amino-3-bromo-5-fluoro-phenyl)-2-cyclobutylamino-ethanol hydrochloride

Melting point: 164-166°C (decomposition).

1-(4-amino-3-fluoro-5-iodo-phenyl)-2-cyclopropylamino-ethanol hydrochloride

Melting point: 199-201°C (decomposition).

1-(4-am:-o-3-cyano-5-fluoro-phenyl)-2-isopropylamino-ethanol hydrochloride

Melting point: 182-184°C (decomposition).

1-(4-amino-3-cyano-5-fluoro-phenyl)-2-tert-butylamino-ethanol hydrochloride

Melting point: 242-243°C (decomposition).

1-(4-amino-3-cyano-phenyl)-2-cyclobutylamino-ethanol hydrobromide Melting point: from 193°C (decomposition).

1-(4-amino-3-cyano-phenyl)-2-tert-pentylamino-ethanol Melting point: 14 3°C.

1-(4-amino-3-chloro-5-cyano-phenyl)-2-propylamino-ethanol-hydro-

chloride

Melting point: 187-189°C.

1-(4-amino-3-chloro-5-cyano-phenyl)-2-sec-butylamino-ethanol dihydrochloride

Melting point: 190-191°C.

1-(4-amino-3-chloro-5-cyano-phenyl)-2-tert-butylamino-ethanol Melting point: 125-133°C.

1-(4-amino-3-chloro-5-cyano-phenyl)-2-(hydroxy-tert-butylamino)-ethanol hydrochloride

Melting point: 228-230°C (decomposition).

1-(4-amino-3-chloro-5-cyano-phenyl)-2-tert-pentylamino-ethanol hydrochloride

Melting point: 218-220°C (decomposition).

1-(4-amino-3-chloro-5-cyano-phenyl)-2-cyclopentylamino-ethanol hydrochloride

Melting point: 138-144°C.

1-(4-amino-3-chloro-5-cyano-phenyl)-2-[1-(3,4-meth5_endioxy-phenyl)-2-propylamino]-ethanol hydrochloride

Melting point: 189-192°C.

1-(4-amino-3-bromo-5-cyano-phenyl)-2-isopropylamino-ethanol-

hydrochloride

Melting point: 186-189°C.

1-(4-amino-3-bromo-5-cyano-phenyl)-2-tert-butylamino-ethanol hydrochloride Melting point: 213-215°C.

1-(4-amino-3-bromo-5-cyano-phenyl)-2-rcyclobutylamino-ethanol-

hydrochloride

Melting point: 215-216°C (decomposition).

1-(4-amino-3,5-dicyano-phenyl)-2-tert-butylamino-ethanol-

hydrochloride

Melting point: 251-253°C (decomposition).

1-(4-amino-3-trifluoromethyl-phenyl)-2-tert-butylamino-ethanol hydrochloride

Melting point: 172-174°c (decomposition).

1-(4-amino-3-trifluoromethyl-phenyl)-2-tert-pentylamino-ethanol hydrobromide.

Melting point: 174-175°C (decomposition).

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-isopropylamino-

ethanol

Melting point: 104-106°C.

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert-butylamino-ethanol hydrochloride

Melting point: 205-207°C (decomposition).

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-cyclobutylamino-ethanol hydrochloride

Melting point: 177-178°C.

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert-pentylamino-ethanol hydrochloride

Melting point: 176-178°C (decomposition).

1-(4-amino-3-bromo-5-trifluoromethyl-phenyl)-2-isopropylamino-ethanol hydrochloride

Melting point: 177-179°C (decomposition)•

Example 188.

1-(4- amino- 3- bromo- 5- fluoro- phenyl)- 2- tert.- butylamino- ethanol.

4.8 g of 4-amino-3-bromo-5-fluoro-phenyl-glycolic acid-tert.-butylamide are added to 100 ml of absolute ether, 1.2 g of lithium aluminum hydride and heated to boiling with stirring for 2 hours. Excess lithium aluminum hydride is then split with acetic acid ethyl ester, water, and 2N caustic soda is added and the phases are separated. The aqueous layer is extracted with chloroform and the combined organic phases are dried and evaporated in vacuo. The residue is purified by column chromatography over silica gel with the system chloroform: methanol: conc. ammonia = 90:10:1. The evaporation residue after the fractions containing the substance is dissolved in isopropanol and acidified with ethereal hydrochloric acid to pH 5. After addition of ether, crystallization occurs. The separated hydrochloride of the desired compound is recrystallized from isopropanol.

Melting point: 207-208°C (decomposition).

Wave compounds were prepared analogously to example 188: 1-(4-amino-3-fluoro-phenyl)-2-tert-butylamino-ethanol hydrochloride Melting point: 196-197°C (decomposition).

1-(4-amino-3-chloro-5-fluoro-phenyl)-2-isopropylamino-ethanol-

hydrochloride

Melting point: 152-154°C (decomposition).

1-(4-amino-3-chloro-5-fluoro-phenyl)-2-cyclopropylamino-ethanol hydrochloride

Melting point: 175-177°C (decomposition).

1-(4-amino-3-chloro-5-fluoro-phenyl)-2-tert-butylamino-ethanol-

hydrocarbide

Melting point: 206-208°C (decomposition).

1-(4-amino-3-chloro-5-fluoro-phenyl)-2-tert-pentylamino-ethanol hydrochloride

Melting point: 187-188°C (decomposition).

1-(4-amino-3-bromo-5-fluoro-phenyl)-2-isopropylamino-ethanol-hydro-

chloride

Melting point: 171-173?C (decomposition).

1-(4-amino-3-bromo-5-fluoro-phenyl)-2-cyclobutylamino-ethanol-

hydrochloride

Melting point: 164-166°C (decomposition).

1-(4-amino-3-fluoro-5-iodo-phenyl)-2-cyclopropylamino-ethanol-

hydrochloride

Melting point: 199-201°C (decomposition).

1-(4-amino-3-trifluoromethyl-phenyl)-2-tert-butylamino-ethanol hydrochloride Melting point: 172-174°C (decomposition).

1-(4-amino-3-trifluoromethyl-phenyl)-2-tert-pentylamino-ethanol hydrobromide

Melting point: 174-175°C (decomposition).

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-isopropylamino-

ethanol

Melting point: 104-106°C.

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert-butylamino-ethanol hydrochloride

Melting point: 205-207°C (decomposition).

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-cyclobutylamino-ethanol hydrochloride

Melting point: 177-178°C.

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert-pentylamino-ethanol hydrochloride

Melting point: 176-178°C (decomposition).

1-(4-amino-3-bromo-5-trifluoromethyl-phenyl)-2-isopropylamino-ethanol hydrochloride

Melting point: 177-179°C (decomposition).

Example 189.

1-(4- amino- 3- bromo- 5- fluoro- phenyl)- 2- tert.- butylamino- ethanol.

4.2 g of 4-amino-3-bromo-5-fluoro-phenylglyoxylic acid-tert-butylamide are added to 100 ml of absolute ether 0.75 g of powdered lithium aluminum hydride, stirred mechanically and heated under reflux for 2 hours. 2.0 ml of water, 2.4 ml of 2N caustic soda and 6.0 ml of water are then carefully added to the reaction mixture one after the other. It is filtered off, the organic residue is washed with chloroform and the combined filtrates are evaporated in vacuo. The residue is purified by chromatography on a silica gel column (eluent = chloroform: methanol: conc. ammonia = 90:10:1). The evaporation residue of the desired fractions obtained by vacuum distillation of the solvent is dissolved in isopropanol, ethereal hydrochloric acid is added to pH 5 and further ether is added. The crystallized hydrochloride of the above-mentioned compound is filtered off with suction and recrystallized from isopropanol. Melting point: 207-208°C (decomposition).

. Fluctuating compounds were prepared analogously to example 189: 1-(4-amino-3-fluoro-phenyl)-2-tert-butylamino-ethanol hydrochloride Melting point: 196-197°C (decomposition).

1-(4-amino-3-chloro-5-fluoro-phenyl)-2-isopropylamino-ethanol hydrochloride

Melting point: 152-154°C (decomposition).

1-(4-amino-3-chloro-5-fluoro-phenyl)-2-cyclopropylamino-ethanol hydrochloride

Melting point: 175-177°C (decomposition).

1-(4-amino-3-chloro-5-fluoro-phenyl)-2-tert-butylamino-ethanol-, hydrochloride

Melting point: 206-208°C (decomposition).

1-(4-amino-3-chloro-5-fluoro-phenyl)-2-tert-pentylamino-ethanol hydrochloride

Melting point: 187-188°C (decomposition).

1-(4-amino-3-bromo-5-fluoro-phenyl)-2-isopropylamino-ethanol hydrochloride

Melting point: 171-173°C (decomposition).

1-(4-amino-3-bromo-5-fluoro-phenyl)-2-cyclobutylamino-ethanol hydrochloride

Melting point: 164-166°C (decomposition).

1-(4-amino-3-fluoro-5-iodo-phenyl)-2-cyclopropylamino-ethanol hydrochloride

Melting point: 199-201°C (decomposition).

1-(4-Amino-9-trifluoromethyl-phenyl)-2-tert-butylamino-ethanol hydrochloride

Melting point: 172-174°C (decomposition).

1-(4-amino-3-trifluoromethyl-phenyl)-2-tert.-pentylamino-ethariol hydrobromide Melting point: 174-175°C (decomposition).

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-isopropylamino-ethanol

Melting point: 104-106°C.

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert-butylamino-ethanol hydrochloride

Melting point: 205-207°C (decomposition).

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-cyclobutylamino-ethanol hydrochloride

Melting point: 177-178°C.

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert-pentylamino-ethanol hydrochloride

Melting point: • 176-178°C (decomposition).

1-(4-amino-3-bromo-5-trifluoromethyl-phenyl)-2-isopropylamino-ethanol hydrochloride

Melting point: 177-179°C (decomposition).

Example 190,

1-(4- amino- 3- chloro- 5- trifluoromethyl- phenyl)- 2- tert.- butylamino- ethanol.

Dissolve 3.5 g of 5-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-3-tert.-butyl-oxazolidone-(2) in 13 ml of glacial acetic acid, add at room temperature 13 ml of 45% hydrobromic acid in glacial acetic acid and let stand for an hour. The mixture is then poured onto ice, made alkaline with conc. ammonia and extracted with acetic acid ethyl ester. The organic phase is extracted with 2N hydrochloric acid, made alkaline with conc. ammonia and extracted again with acetic acid ethyl ester. After evaporation of the organic solvent in vacuum, a crude product remains,

which after chromatographic purification over a silica gel column (eluent = chloroform: methanol: conc. ammonia = 90:10:1) gives pure 1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert-butylamino -ethanol.. By dissolving in ether and adding isopropanolic hydrochloric acid, the hydrochloride with a melting point of 205-207°C (decomposition) is obtained from this.

Example 191.

1-( 4- amino- 3- bromo- 5- fluoro- phenyl)- 2- tert,- butylamino- ethanol,

1.5 g of 5-(4-amino-3-bromo-5-fluoro-phenyl)-3-tert-butyl-oxazolidone-(2) is heated in 25 ml of 3N hydrochloric acid for 3 hours at 90 oC» After cooling, filter the slightly fuzzy solution, is brought

at pH 9 with caustic soda and extracted with chloroform. chloroform-

the phase is washed with water, dried over sodium sulfate and evaporated to dryness in vacuo. The oil residue is taken up in a little isopropanol and acidified to pH 5 with ethereal hydrochloric acid. With the addition of a little ether, crystallization occurs. The crystals are suctioned off and washed with a mixture of isopropanol and ether.

Melting point: 207-208°C (decomposition).

Example 192.

1-(4- amino- 3- chloro- 5- cyano- phenyl)- 2- tert.- butylamino- ethanol.

0.5 g of 5-(4-amino-3-chloro-5-cyano-phenyl)-3-tert.-butyl-oxazolidone-(2) (melting point: 115-119°C) is heated with 5 ml of conc. hydrochloric acid for 30 minutes under reflux. It is cooled, ice is added, made alkaline with caustic soda and 1-(4-amino-3-chloro-5-cyano-phenyl)-2-tert-butylamino-ethanol is extracted with chloroform. The product is purified by chromatography on silica gel (eluent = chloroform:methanol = 7:3).

Melting point: 131-135°C, melting point of the hydrochloride: 204-207°C.

The following compounds were prepared analogously to examples 190 and 192: 1-(4-amino-3-fluoro-phenyl)-2-tert•-butylamino-ethanol hydrochloride Melting point: 196-197°C (decomposition).

1-(4-amino-3-chloro-5-fluoro-phenyl)-2-isopropylamino-ethanol hydrochloride

Melting point: 152-154°C (decomposition).

1-(4-amino-3-chloro-5-fluoro-phenyl)-2-cyclopropylamino-ethanol hydrochloride

Melting point: 175-177°C (decomposition).

1-(4-amino-3-chloro-5-fluoro-phenyl)-2-tert-butylamino-ethanol hydrochloride

Melting point: 206-208°C (decomposition).

1-(4-amino-3-chloro-5-fluoro-phenyl)-2-tert-pentylamino-ethanol hydrochloride

Melting point: 187-188°C (decomposition).

1-(4-amino-3-bromo-5-fluoro-phenyl)-2-isopropylamino-ethanol hydrochloride

Melting point: 171-173°C (decomposition).

1-(4-amino-3-bromo-5-fluoro-phenyl)-2-cyclobutylamino-ethanol hydrochloride

Melting point: 164-166°C (decomposition).

1-(4-amino-3-fluoro-5-iodo-phenyl)-2-cyclopropylamino-ethanol hydrochloride

Melting point: 199-201°C (decomposition).

1-(4-amino-3-cyano-5-fluoro-phenyl)-2-isopropylamino-ethanol hydrochloride

Melting point: 182-184°C (decomposition).

1-(4-amino-3-cyano-5-fluoro-phenyl)-2-tert-butylamino-ethanol hydrochloride

Melting point: 242-243°C (decomposition).

1-(4-amino-3-cyano-phenyl)-2-cyclobutylamino-ethanol hydrobromide Melting point: from 193°C (decomposition).

1-(4-amino-3-cyano-phenyl)-2-tert.-pentylamino-ethanol Melting point: 143°C.

1-(4-amino-3-chloro-5-cyano-phenyl)-2-propylamino-ethanol hydrochloride

Melting point: 187-189°C.

1-(4-amino-3-chloro-5-cyano-phenyl)-2-sec-butylamino-ethanol dihydrochloride

Melting point: 190-191°C.

1-(4-amino-3-chloro-5-cyano-phenyl)-2-(hydroxy-tert-butylamino)-ethanol hydrochloride

Melting point: 228-230°C (decomposition).

1-(4-amino-3-chloro-5-cyano-phenyl)-2-tert-pentylamino-ethanol hydrochloride

Melting point: 218-220°C (decomposition).

1-(4-amino-3-chloro-5-cyano-phenyl)-2-cyclopentylamino-ethanol hydrochloride

Melting point: 138-144°C.

1-(4-amino-3-chloro-5-cyano-phenyl)-2-[1-(3,4-methylenedioxy-phenyl)-2-propylamino]-ethanol hydrochloride

Melting point: 189-192°C.

1-(4-amino-3-bromo-5-cyano-phenyl)-2-isopropylamino-ethanol hydrochloride

Melting point: 186-189°C.

1-(4-amino-3-bromo-5-cyano-phenyl)-2-tert-butylamino-ethanol hydrochloride

Melting point: 213-215°C (decomposition).

1-(4-amino-3-bromo-5-cyano-phenyl)-2-cyclobutylamino-ethanol hydrochloride

Melting point: 215-216°C (split nirg) .

1-(4-amino-3,5-dicyano-phenyl)-2-tert-butylamino-ethanol hydrochloride

Melting point: 251-253°C (decomposition).

1-(4-amino-3-trifluoromethyl-phenyl)-2-tert-butylamino-ethanol hydrochloride

Melting point: 172-174°C (decomposition).

1-(4-amino-3-trifluoromethyl-phenyl)-2-tert-pentylamino-ethanol hydrobromide

Melting point: 174-175°C (decomposition).

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-isopropylamino-ethanol

Melting point: 104-106<O*>C.

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-cyclobutylamino-ethanol hydrochloride

Melting point: 177-178°C.

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert-pentylamino-ethanol hydrochloride

Melting point: 176-178°C (decomposition).

1-(4-amino-3-bromo-5-trifluoromethyl-phenyl)-2-isopropylamino-ethanol hydrochloride

Melting point: 177-179°C (decomposition).

1-(4-amino-3-chloro-5-nitro-phenyl)-2-tert-butylamino-ethanol Melting point: 148-149°C.

1-(4-amino-3-bromo-5-nitro-phenyl)-2-tert-butylamino-ethanol Melting point: 151-152°C.

Example 193.

1- ( 4- amino- 3- cyan- 5- fluoro- phenj.) - 2- tert. - butylamino-ethanol.

To a solution of 6 g of selenium dioxide in 36 ml of dioxane

and 1 ml of water is added at 60°C while stirring in portions 10

g 4<1->amino-3'-cyano-5<1->fluoro-acetophenone. It is then heated for 4 hours at reflux temperature. After cooling and with external cooling with ice, 30 ml of tert-butylamine is added dropwise to the solution of 4-amino-3-cyano-5-fluoro-phenylglyoxal thus prepared. After the addition is finished, dilute with 150 ml of ethanol and the undissolved material is filtered off. To the solution containing the crude 4-amino-3-cyano-5-fluoro-phenylglyoxylidene-tert-butylamine, 6 g of sodium borohydride are added in portions while stirring and cooling with ice and allowed to stand at room temperature overnight. Excess sodium borohydride is then destroyed with acetone, water is added and the organic solvent is removed in vacuo. The precipitate that precipitates is filtered off, washed with water and taken up in 200 ml of 2N hydrochloric acid. The hydrochloric acid solution is filtered and then enough 10n caustic soda is added that the pH becomes 6. The aqueous phase is washed with chloroform and then 10n caustic soda is added until a clearly alkaline reaction.

The precipitate is extracted with chloroform, the chloroform solution is washed with water, dried over sodium sulphate and evaporated to dryness in vacuo. The solid residue consisting of 1-(4-amino-3-cyano-5-fluoro-phenyl)-2-tert.-butylamino-ethanol is taken up in 100 ml of absolute ethanol and acidified to pH 6 with ethereal hydrochloric acid. Already during the acidification with ethereal hydrochloric acid, the precipitation of the hydrochloride begins in the form of colorless crystals. The crystallization is made complete by the addition of ether. The crystals are filtered off and washed with ether.

Melting point: 242-243°C (decomposition).

Example 194.

1-(4- amino- 3- chloro- 5- trifluoromethyl- phenyl)- 2- tert.- butylamino- ethanol.

0.4 g of 4-amino-3-chloro-5-trifluoromethyl-phenylglyoxal hydrate is dissolved in 10 ml of methanol, 0.23 g of tert-butylamine is added and allowed to stand for 3 hours at room temperature. The solution is then cooled to -20°C, 0.1 g of sodium borohydride is added and stirred for 20 minutes at -10 to -20°C. It is acidified with 2n hydrochloric acid to pH 2 and brought to pH 9 with 2n ammonia, diluted with water and the methanol is removed in vacuo. The aqueous mixture is extracted with ether, the ether extract is washed with water, dried over magnesium sulfate and evaporated in vacuo. The oil residue is dissolved in a little ether and brought to pH 4 with isopropanolic hydrochloric acid. Crystalline 1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert is obtained. - butylamino-ethanol hydrochloride, which is filtered off and washed with ether. Melting point: 205-207°C (decomposition).

The following compounds were prepared analogously to examples 193 and 194: 1-(4-amino-3-fluoro-phenyl)-2-tert-butylamino-ethanol hydrochloride Melting point: 196-197°C (decomposition.

1-(4-amino-3-chloro-5-fluoro-phenyl)-2-isopropylamino-ethanol hydrochloride

Melting point: 152-154°C (decomposition).

1-(4-amino-3-chloro-5-fluoro-phenyl)-2-cyclopropylamino-ethanol hydrochloride

Melting point: 175-177°C (decomposition).

1-(4-amino-3-chloro-5-fluoro-phenyl)-2-tert-butylamino-ethanol hydrochloride

Melting point: 206-208°C (decomposition).

1-(4-amino-3-chloro-5-fluoro-phenyl)-2-tert-pentylamino-ethanol hydrochloride

Melting point: 187-188°C (decomposition).

1-(4-amino-3-bromo-5-fluoro-phenyl)-2-isopropylamino-ethanol hydrochloride

Melting point: 171-173°C (decomposition).

1-(4-amino-3-bromo-5-fluoro-phenyl)-2-tert-butylamino-ethanol hydrochloride

Melting point: 207-208°C (decomposition).

1-(4-amino~3-bromo-5-fluoro-phenyl)-2-cyclobutylamino-ethanol hydrochloride

Melting point: 164-166°C (decomposition).

1-(4-amino-3-fluoro-5-iodo-phenyl)-2-cyclopropylamino-ethanol hydrochloride

Melting point: 199-201°C (decomposition).

1-(4-amino-3-cyano-5-fluoro-phenyl)-2-isopropylamino-ethanol hydrochloride

Melting point: 182-184°C (decomposition).

1-(4-amino-3-cyano-phenyl)-2-cyclobutylamino-ethanol hydrobromide Melting point: from 19 3°C (decomposition).

1-(4-amino~3-cyano-phenyl)-2-tert.-pentylamino-ethanol Melting point: 14 3°C.

1-(4-amino-3-chloro-5-cyano-phenyl)-2-propylamino-ethanol hydrochloride

Melting point: 187-189°C.

1-(4-amino-3-chloro-5-cyano-phenyl)-2-sec-butylamino-ethanol dihydrochloride

Melting point: 190-191°C.

1-(4-amino-3-chloro-5-cyano-phenyl)-2-tert-butylamino-ethanol Melting point: 125-133°C.

1-(4-amino-3-chloro-5-cyano-phenyl)-2-(hydroxy-tert-butylamino)-ethanol hydrochloride

Melting point: 228-230°C (decomposition).

1-(4-amino-3-chloro-5-cyano-phenyl)-2-tert-pentylamino-ethanol hydrochloride

Melting point: 218-220°C (decomposition).

1-(4-amino-3-chloro-5-cyano-phenyl)-2-cyclopentylamino-ethanol hydrochloride

Melting point: 138-144°C.

1-(4-amino-3-chloro-5-cyano-phenyl)-2-[1-(3,4-methylenedioxy-phenyl)-2-propylamino]-ethanol hydrochloride

Melting point: 189-192°C.

1-(4-amino-3-bromo-5-cyano-phenyl)-2-isopropylamino-ethanol hydrochloride

Melting point: 186-189°C.

1-(4-amino-3-bromo-5-cyano-phenyl)-2-tert-butylamino-ethanol hydrochloride

Melting point: 213-215°C.

1-(4-amino-3-bromo-5-cyano-phenyl)-2-cyclobutylamino-ethanol hydrochloride

Melting point: 215-216°C (decomposition).

1-(4-amino-3,5-dicyano-phenyl)-2-tert-butylamino-ethanol hydrochloride

Melting point: 251-253°C (decomposition).

1-(4-amino-3-trifluoromethyl-phenyl)-2-tert-butylamino-ethanol hydrochloride

Melting point: 172-174°C (decomposition).

1-(4-amino-3-trifluoromethyl-phenyl)-2-tert-pentylamino-ethanol hydrobromide

Melting point: 174-175°C (decomposition).

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-isopropylamino-ethanol

Melting point: 104-106°C.

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-cyclobutylamino-ethanol hydrochloride

Melting point: 177-178°C.

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert-pentylamino-ethanol hydrochloride

Melting point: 176-178°C (decomposition).

1-(4-amino-3-bromo-5-trifluoromethyl-phenyl)-2-isopropylamino-ethanol hydrochloride

Melting point: 177 - 179°C (decomposition).

1-(4-amino-3-chloro-5-nitro-phenyl)-2-tert-butylamino-ethanol Melting point: 148-149°C.

1-(4-amino-3-bromo-5-nitro-phenyl)-2-tert-butylamino-ethanol Melting point: 151-152°C.

Example 195'.'

1-(4- amino- 3- bromo- 5- nitro- phenyl)- 2- tert.- butylamino- ethanol.

2.9 g of 1-(4-amino-3-bromo-phenyl)-2-tert-butylamino-ethanol are dissolved in 15 ml of a mixture of concentrated nitric acid and concentrated sulfuric acid. The solution is heated for one minute at 80-85°C

and poured onto ice.i \ed addition of ammonia, the mixture is made alkaline and then extracted with chloroform. chloroform-

the solution is washed with water, dried and evaporated to dryness in vacuo. The residue is chromatographed over silica gel (eluent = chloroform:methanol = 8:2), and the crude product thus obtained is recrystallized from ethyl acetate. Melting point of 1-(4-amino-3-bromo-5-nitro-phenyl)-2-tert-butylamino-ethanol: 151-152°C.

Example 196.

1-(4-amino-3-chloro-5-nitrophenyl)-2- tert.-butylamino- ethanol.

Melting point: 148-149°C.

Prepared from 1-(4-amino-3-chloro-phenyl)-2-tert-butylamino-ethanol and nitric/sulfuric acid analogous to example 195.

Example 197.

i-(4-amino-3-chloro-5-cyano-phenyl)-2-dimethylamino-ethanol.

0.5 g of 1-acetoxy-1-(4-amino-3-chloro-5-cyano-phenyl)-2-dimethylamino-ethane (melting point: 120-124°C) is stirred in methanol and caustic soda at 20°C for 1 hour. Water is added, the methanol is distilled off under vacuum, the remaining aqueous phase is extracted with chloroform, the chloroform phase is dried over sodium sulphate,

is evaporated to dryness in vacuo, the residue is taken up in isopropanol and the hydrochloride of 1-(4-amino-3-chloro-5-cyano-phenyl)-2-dimethylaminoethanol is brought to crystallisation by the addition of isopropanolic hydrochloric acid.

Melting point: 187-189°C.

Example 198.

1-( 4- amino- 3- cyano- 5- fluoro- phenyl)- 2- dimethylamino- ethanol.

7 g of 1-acetoxy-1-(4-amino-3-cyano-5-fluoro-phenyl)-2-dimethylamino-ethane are dissolved in 100 ml of methanol. 5 ml of 10N aqueous NaOH solution is added to this solution and it is allowed to stand for 1 hour at room temperature. Then dilute with saturated sodium chloride solution and extract exhaustively with chloroform. The chloroform solution is washed with saturated sodium chloride solution, dried over sodium sulphate and evaporated to dryness in vacuo. A colorless oil is obtained. Structural evidence by NMR spectrum (CD3OD): 2.2-2.65 ppm multiplet [8 protons, N-CH3 and N-CH-CH2-n' ] 4.6-4.9 ppm multiplet [4 protons, 3 yield protons and

OH

-ch-ch2-n(],

7.15-7.4 ppm multiplet [2 aromatic protons].

Example 199.

1- ( 4- amino- 3- chloro- 5- cyano- phenyl)- 2- tert.- butylamino- ethanol.

Stir 0.5 g of N-acetyl-N-[2-acetoxy-2-(4-amino-3-chloro-5-cyano-phenyl)-ethyl]-tert-butylamine (melting point: 160-162°C) with methanolic caustic soda for \ hour at 20°C. Water is added, the methanol is distilled off in vacuo, the remaining aqueous phase is extracted with chloroform, the chloroform phase is dried over sodium sulphate, evaporated to dryness and the residue is crystallized from ethanol. 1-(4-amino-3-chloro-5-cyano-phenyl)-2-tert-butylamino-ethanol is obtained.

Melting point: 131-135°C, melting point of the hydrochloride: 204-207°C.

The following compounds were prepared analogously to examples 197-199: 1-(4-amino-3-fluoro-phenyl)-2-tert-butylamino-ethanol hydrochloride Melting point: 196-197°C (decomposition).

1-(4-amino-3-chloro-5-fluoro-phenyl)-2-isopropylamino-ethanol hydrochloride

Melting point: 152-154°C (dec.)

1-(4-amino-3-chloro-5-fluoro-phenyl)-2-cyclopropylamino-ethanol hydrochloride

Melting point: 175-177°C (decomposition).

1-(4-amino-3-chloro-5-fluoro-phenyl)-2-tert-butylamino-ethanol hydrochloride

Melting point: 206-208°C (decomposition).

1-(4-amino-3-chloro-5-fluoro-phenyl)-2-tert-pentylamino-ethanol hydrochloride

Melting point: 187-188°C (decomposition).

1-(4-amino-3-bromo-5-fluoro-phenyl)-2-isopropylamino-ethanol hydrochloride

Melting point: 171-173°C (decomposition).

1-(4-amino-3-bromo-5-fluoro-phenyl)-2-tert-butylamino-ethanol hydrochloride

Melting point: 207-208°C (decomposition).

1-(4-amino-3-bromo-5-fluoro-phenyl)-2-cyclobutylamino-ethanol hydrochloride

Melting point: 164-166°C (decomposition).

1-(4-amino-3-fluoro-5-iodo-phenyl)-2-cyclopropylamino-ethanol hydrochloride

Melting point: 199-201°C (decomposition).

1-(4-amino-3-cyano-5-fluoro-phenyl)-2-isopropylamino-ethanol hydrochloride

Melting point: 182-184°C (decomposition).

1-(4-amino-3-cyano-5-fluoro-phenyl)-2-tert-butylamino-ethanol hydrochloride

Melting point: 242-243°C (decomposition).

1-(4-amino-3-cyano-phenyl)-2-cyclobutylamino-ethanol-hydrobromide-Melting point: from 193°C (decomposition).

1-(4-amino-3-cyano-phenyl)-2-tert-pentylamino-ethanol Melting point: 14 3°C.

1-(4-amino-3-chloro-5-cyano-phenyl)-2-propylamino-ethanol hydrochloride

Melting point: 187-189°C.

1-(4-amino-3-chloro-5-cyano-phenyl)-2-sec-butylamino-ethanol dihydrochloride

Melting point: 190-191°C.

1-(4-amino-3-chloro-5-cyano-phenyl)-2-(hydroxy-tert-butylamino)-ethanol hydrochloride

Melting point: 228-230°C (decomposition).

1-(4-amino-3-chloro-5-cyano-phenyl)-2-tert-pentylamino-ethanol hydrochloride

Melting point: 218-220°C (decomposition).

1-(4-amino-3-chloro-5-cyano-phenyl)-2-cyclopentylamino-ethanol hydrochloride

Melting point: 138-144°C.

1-(4-amino-3-chloro 5-cyanophenyl)-2-[1-(3,4-methylenedioxy-phenyl)-2-propylamino]-ethanol hydrochloride

Melting point: "189-192°C.

1-(4-amino-3-bromo-5-cyano-phenyl)-2-isopropylamino-ethanol hydrochloride

Melting point: 186-189°C.

1-(4-amino-3-bromo-5-cyano-phenyl)-2-tert•-butylamino-ethanol hydrochloride

Melting point: 213-215°C.

1-(4-amino-3-bromo-5-cyano-phenyl)-2-cyclobutylamino-ethanol hydrochloride

Melting point: 215-216°C (decomposition).

1-(4-amino-3,5-dicyano-phenyl)-2-tert-butylamino-ethanol hydrochloride

Melting point: 251-253°C (decomposition).

1-(4-amino-3-trifluoromethyl-phenyl)-2-tert-butylamino-ethanol hydrochloride

Melting point: 172-174°C (decomposition).

1-(4-amino-3-trifluoromethyl-phenyl)-2-tert-pentylamino-ethanol hydrobromide

Melting point: 174-175°C (decomposition).

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-isopropylamino-ethanol

Melting point: 104-106°C.

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert-butylamino-ethanol hydrochloride

Melting point: 205-207°C (decomposition).

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-cyclobutylamino-ethanol hydrochloride

Melting point: 177-178°C.

1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert-pentylamino-ethanol hydrochloride

Melting point: 176-178°C (decomposition).

1-(4-amino-3-bromo-3-trifluoromethyl-phenyl)-2-isopropylamino-ethanol hydrochloride

Melting point: 177-179°C (decomposition).

1-(4-amino-3-chloro-5-nitro-phenyl)-2-tert-butylamino-ethanol Melting point: 148-149°C.

1-(4-amino-3-bromo-5-nitro-phenyl)-2-tert-butylamino-ethanol Melting point: 151-152°C.

Claims (5)

1. Analogy method for the production of new therapies tically active phenylethanolamines of the general formula I where R is a hydrogen, fluorine, chlorine, bromine or iodine atom or a cyano group, R 2 is a fluorine atom, a linear or branched alkyl group, a hydroxyalkyl, aminoalkyl, dialkylaminoalkyl, trifluoromethyl, alkoxy, nitro, cyano, carboxy, caralkyloxy or carbamoyl group, where the alkyl groups contain up to 5 carbon atoms, R^ and R^, which may be the same or different, are hydrogen atoms, linear or branched alkyl, hydroxyalkyl, alkenyl or alkynyl groups with up to 6 carbon atoms, cycloalkyl or cycloalkylalkyl groups with 3-8 carbon atoms, or one optionally with a methylenedioxy group substituted phenylalkyl group, and A means a hydrogen atom or together with R4 the group where R_ means a hydrogen atom or a linear or branched alkyl group, and their optically active antipodes and their physiologically compatible acid addition salts with inorganic or organic acids, characterized in that a) an acetophenone of the general formula II where R^ to R^ is as indicated above, is reduced, or b) for the preparation of compounds of the general formula I, where R^ and R^ are as indicated at the beginning with the exception of alkenyl and alkynyl residues, and R^ means a chlorine, bromine or iodine atom, a compound is halogenated with the general where R2 to R4 are as indicated at the beginning with the exception of alkenyl and alkynyl residues, or from a compound of the general formula IV where R 1 , R 2 and R 3 are as indicated at the outset, X is a protective residue for a hydroxyl group, or a hydrogen atom, is a protecting residue for an amino group or a hydrogen atom, and Y 2 is a protective residue for an amino group or has the meanings given at the outset for R^, with however at least one of the residues X, Y-^ and/or Y 2 meaning one of the above-mentioned protective residues, one or more protective residues are split off, or for the preparation of compounds of the general formula I where R^ denotes a hydrogen atom, a compound of the general formula v is dehalogenated where R 2 to R 3 are as indicated at the outset, and Hal is a chlorine, bromine or iodine atom, or for the preparation of compounds of the general formula I where R 2 means an aminomethyl group, a compound is subjected with the general formula VI where R^ , R^ and R^ are, as indicated at the outset, reduction and then hydrolysis, or f) a compound of the general formula VII where R 1 and R 2 are as indicated at the outset, and z means a chlorine, bromine or iodine atom or a p-toluenesulfonyloxy group, is reacted with an amine of the general formula VIII where R 1 and R 4 are as indicated at the outset, or g) for the preparation of compounds of the general formula I where R 2 does not mean a nitro group, a compound of the general formula IX is reduced where R^, R^ and R^ are as indicated at the beginning, and R,,' have the meanings indicated at the beginning for R2 with the exception of a nitro group, or h) for the preparation of compounds of the general formula I where R does not mean a cyano group and R 2 does not mean a nitro, cyano, carboxy, carbalkoxy or carbamoyl group, a compound of the general formula X is reduced where R^ and R4 are, as stated at the outset, R^' they have . for R^ initially given meanings with the exception of a cyano group, R2" has the initially given meanings with the exception of a nitro-, cyano-, carboxy-, carbaloxy- or carbamoyl group, and A means a carbonyl or hydroxymethylene group, or for the preparation of compounds of the general formula I where R 1 means a hydrogen atom, an oxazolidone is hydrolysed. with the general formula XI where R^, R0 and R^ are as indicated at the outset, or for the preparation of compounds of the general formula I where R^ means a hydrogen atom, an aldehyde of the general formula XII is reduced where R 1 and R 2 are as initially indicated, or the hydrate thereof in the presence of an amine of the general formula Villa where R 3 is as indicated at the outset, or k) for the preparation of compounds of the general formula I where R 2 is a nitro group, a compound of the general formula XIII is nitrated where R^, R^ and R^ are as indicated at the outset, and a compound of the general formula I obtained according to the methods a-k where R 2 means a cyano group is then optionally transferred by means of hydrolysis to the corresponding compound of the general formula I where R 2 means a carbamoyl or carboxyl group, and/or an obtained compound of the general formula I where R 2 means a carbamoyl or carbalkoxy group is optionally transferred to the corresponding compound of the general formula I where R 2 means a carboxyl group, by means of hydrolysis, and/or an obtained compound with the general formula I optionally cleaves into its optically active antipodes, and/or a compound of the general formula I where R^ denotes a hydrogen atom, optionally converted by reaction with an aldehyde - of the general formula XV where R_ has the above meaning, to a compound of formula I where A together with R4 means and/or optionally the compound is transferred to a physiologically compatible acid addition salt with an inorganic or organic acid. 2. Method as stated in claim 1, a-c and f-j, for the production of 1-(4-amino-3-bromo-5-fluoro-phenyl)-2-tert-butylamino-ethanol, characterized in that in the methods a , c and f-j starting materials are used where R^ is bromine, R2 is fluorine, R3 is t-butyl and R4, when present, is hydrogen, and in method b' a starting material of formula "lii where R2, R3 and R4 have above stated meaning. 3. Method as stated in claim 1, a-c and f-j, for the production of 1-(4-amino-3-chloro-5-fluoro-phenyl)-2-tert-butylamino-ethanol, characterized in that in the methods a , c and f-j starting materials are used where R. is chlorine, R2 is fluorine, R^ is cyclopropyl and R^ when present is hydrogen, and in method b a starting material with formula III is chlorinated where R2, R3 and R^ have the above meaning . 4. Procedure as stated in claim 1, a, c, d and f-j, for the production of 1-(4-amino-3-fluoro-phenyl)-2-tert-butylamino-ethanol, characterized in that starting materials are used where R^, when present, is hydrogen, R2 is fluorine, R^ is t -butyl and R 1 , when present, is hydrogen. 5. Method as stated in claim 1, a-c and f-j, for the production of 1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert-butylamino-ethanol, characterized in that in the methods a , c and f-j starting materials are used where R^ is chlorine, R2 is trifluoromethyl, R^ is t-butyl and R4, when present, is hydrogen, and in method b a starting material of formula III is chlorinated where R2, R^ and R^ have meaning stated above.