SE409700B - PROCEDURE FOR THE PREPARATION OF NEW AMINO-PHENYL-ETHANOLAMINES AND THEIR OXAZOLIDINES - Google Patents

Description

R 1 represents a hydrogen, fluorine, chlorine, bromine, iodine atom or a cyano group, R 2 represents a fluorine atom, a straight or branched alkyl group having 1 to 5 carbon atoms, a hydroxyalkyl, aminoalkyl group, 7317035-9 7 , dialkylaminoalkyl, trifluoromethyl, alkoxy, nitro, cyano, carboxy, carbalkoxy or carbamoyl group, and R 4, which may be the same or different, represent hydrogen atoms, straight or branched alkyl groups having 1 to 6 carbon atoms, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkinyl or optionally substituted aralkyl groups and R represents a hydrogen atom or a straight or branched alkyl group. The compounds of the above general formulas I and Ia possess valuable pharmacological properties, in addition to an analgesic, uterine spasmolytic and an antispasmodic effect on the transverse striated muscles, in particular ße-mimetic and / or ßl-blocking action, depending on the substitution one or the other effect star 1 foreground. In particular, the d (+) compounds show a selective effect on the ßl receptors and the l (-) compounds in particular an effect on the ßz- receptors. The new compounds can be prepared according to the following procedure: a) Reduction of an acetophenone of the general formula II,. _ _% R ,, / 3 R1 CO - CH2 - N \ f 34 (II) - HZN Ra wherein B1 - R4 has the meaning given above.

The reduction preferably takes place in a solvent such as meta-. nol, 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 catalytically active hydrogen and at temperatures between -20 ° C and the boiling temperature of the solvent used.

However, the reduction with complex metal hydrides is preferably carried out with sodium borohydride and at room temperature. When using a reaction-prone, complex metal hydride such as lithium aluminum hydride and possibly at elevated temperature, the cyan, carboxy, carbalkoxy or carbamoyl groups mentioned in the definition of the group R2 can be co-reduced at the same time.

If the reduction is carried out with hydrogen in the presence of a catalyst such as Raney nickel, platinum or palladium / animal carbon, they can in the definition of the group R3 and / or the mentioned alkenyl or alkinyl groups be transferred to the corresponding the alkyl groups and / or any benzyl groups present are cleaved off hydrogenolytically. b) "For the preparation of compounds of general formula I, wherein R and H4 have the above definition with the exception of the alkinyl and alkenyl groups and B1 represents a chlorine, bromine or iodine atom: Halogenation of a compound of general formula III , P * R 3 en - en ... WN / 2 aa 4 (In) HZN .R2 wherein RE - Ru has the meaning given above with the exception of the alkenyl and alkinyl groups.

The reaction is carried out with a halogenating agent, e.g. with chlorine, bromine, iodine, tribromophenol bromine or phenyl iodine dichloride, preferably in a solvent, e.g. in 50 - 100% acetic acid or in tetrahydrofuran in the presence of a tertiary organic base, optionally in the presence of a heavy metal such as mercury (II) oxide and suitably at temperatures between 0 and 50 ° C. Per mole of a compound with the general. formula III, which can be used as base or also as salt, e.g. such as mono-, di- or trihydrochloride, 1 mole of halogenating agent or a slight excess is suitably used. If a hydrohalic acid salt is formed during the reaction, this can be directly isolated as such or this can, if desired, be purified again over the base. c) Cleavage of one or more protecting groups of a compound of general formula IV, ox Y | Z 2 n, en - cnz - m __ \ RB »(Iv) v, -n H az wherein B1, R2 and R5 have the meaning given above, X represents a protecting group for a hydroxy group or a hydrogen atom, yl denotes a protecting group for a amino group or a hydrogen atom, Y2 represents a protecting group for an amino group or has for Ru an an. 7317035-9, but at least one of the groups X, Y1 and / or Y2 must constitute one of the above-mentioned protecting groups.

For Y1 and / or Y2 the importance of an aoyl group is especially emphasized, e.g. the acetyl, benzoyl or p-toluenesulfonyl group, or the benzyl group and for X the meaning an acyl group, e.g. the acetyl, benzoyl or p-toluenesulfonyl group, or the trimethylsilyl, benzyl or tetrahydropyranyl (2) group.

If Y1 and / or Y2 denote, for example, a preferred acyl group, the cleavage of this group takes place hydrolytically, e.g. with hydrochloric acid / ethanol or with sodium hydroxide at temperatures up to the boiling temperature of the solvent used. If a compound of the general formula IV H2 denotes a cyano group, this can be saponified simultaneously to a carbamoyl or carboxyl group, if R2 denotes a carbalkoxy or carbamoyl group, it can simultaneously be saponified to the carboxyl group.

When X, Y1 and / or Y2 in a compound of the general formula IV, in which H2 does not constitute a nitro group, for example a benzyl group, the cleavage of this group takes place hydrogenolytically, e.g. with hydrogen in the presence of a catalyst such as palladium on carbon 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 slight overpressure. During the reaction, the alkinyl or alkenyl groups mentioned in the definition of the groups RB and / or R4 can be simultaneously transferred to the corresponding alkyl groups. If X represents, for example, a preferred acyl group, the trimethylsilyl or tetrahydropyranyl (2) group, the cleavage of this group takes place hydrogenolytically, 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, wherein R1 represents a hydrogen atom: r Dehalogenation of a compound of the general formula V, OH I "ß Hal CH - CH2 - N" a (v) HZN - Ra wherein R2 - RÄ has the meaning given above 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 1 methanol, ethanol, acetic 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, using Raney nickel or palladium / carbon, for example the dehalogenation takes place at room temperature and normal pressure. If in a compound of the general formula V R5 and / or R4 denotes an alkenyl or alkinyl group, this can be hydrogenated during the hydrogenolytic dehalogenation to the corresponding alkyl groups and / or a benzyl group, it can be simultaneously hydrogenolytically cleaved off. a compound of the general formula V R 2 a nitro group, the dehalogenation is preferably carried out with triphenylphosphine. e) For the preparation of compounds of general formula I, wherein H2 constitutes the aminomethyl group Reaction of a compound of general formula VI, oH R R 1 ,, / 3 1 cH - C 1 12 - N 2. . nu N (VI) -cn JLN 5 | H wherein B1, R and Ru have the meaning given above with a reducing agent and subsequent hydrolysis.

The reaction takes place in a solvent, preferably by reduction with sodium in pentyl alcohol at temperatures between 0 and 50 ° C and the subsequent hydrolysis of the 1,2,3,4-tetrahydro-quinazoline thus formed, which does not need to be isolated, takes place. preferably with hydrochloric acid at elevated temperature, e.g. at the boiling temperature of the hydrochloric acid used. f) Reaction of a compound of the general formula VII, OH a 'h' ~ 1 CH - C fl è - Z - (VII) HZN, 7z1vozs-9 6 wherein B1 and ha have the meaning given above and Z is a chlorine, bromine or the iodine atom or the p-toluenesulfonyloxy group, with an amine of the general formula VIII, R 4 - wherein R 3 and R 4 have the meaning given above.

The reaction is conveniently carried out in a solvent such as methanol, ethanol, chloroform, tetrachlorohydrocarbon, dioxane or in an excess of the amine of the general formula VIII used and preferably at temperatures between 0 and 100 ° C. However, the turnover can be carried out without solvents. g) For the preparation of compounds of general formula I, in which H2 does not form a nitro group: Reduction or a compound of general formula IX, WR ef '3 C - CH - N R1 H 2 _ \ _ R' * (IX) ' O NI / a 2 R '2 vari Bl, R; and R 4 has the meaning given above and R 2 "has the meaning given above for R 2 'with the exception of the nitro group.

The reduction is suitably carried out with solvents such as water, methanol, ethanol, water / methanol or acetic ester, preferably with atomic hydrogen, e.g. with zinc / glacial acetic acid or iron / hydrochloric acid, with hydrogen in the presence of a catalyst such as Raney nickel, platinum or palladium / carbon, with a complex metal hydride such as lithium aluminum hydride or with stannous chloride / hydrochloric acid, preferably at temperatures between 0 and 100 ° C. h) For the preparation of compounds of general formula I, wherein H1 does not constitute a cyano group and H2 does not constitute nitro, cyano, carboxy, carbalkoxy or carbamoyl groups: Reduction of a compound of general formula X, OR RAW A- É-Nlañ. 4 (x) HZN 7317035-9 wherein R and Ru have the meaning given above, B1 'has the meaning given for R1 with the exception of the cyano group, R2 "has the meaning given for H2 with the exception of nitro, cyano, carboxy, the carbalkoxy or carbamoyl group and A is 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, e.g. with lithium aluminum hydride, with sodium borohydride in the presence of a Lewis acid or with sodium borohydride in pyridine, e.g. at temperatures between 0 and 12000, preferably at the boiling temperature of the solvent used. I i) For the preparation of compounds of general formula I, wherein R4 is a hydrogen atom: Hydrolysis of an oxazolidone of general formula XI, O (II = 0 H1 ÅH /// N - R3 \ ° „2 i (XI) HZN R2 - wherein B1, R2 and RB have the meanings given above.

The hydrolysis is conveniently carried out in a solvent such as water, methanol, ethanol, ethanol / 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. 0 and 110 ° C and depending on the nature of the hydrolyzing agent used, preferably at room temperature or at the boiling temperature of the solvent used.

J) For the preparation of compounds of general formula I, wherein Ru is a hydrogen atom: Reduction of an aldehyde of general formula XII, 31 CO - CHO (XII) H2 !! H 2 wherein R 1 and H 2 are as defined above, or its hydrate, in the presence of an amine of general formula VIIIa, wherein H; has the meaning given above.

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 borohydride or lithium aluminum hydride, with atomic hydrogen or with hydrogen in the presence of a catalyst such as Raney nickel, palladium / carbon or platinum. , suitably at temperatures between -20 and 10 ° C, preferably at temperatures up to the boiling point of the solvent used.

However, the reaction can also take place in such a way that the reduction takes place on an in situ formed compound of the general formula XIIa, H1 co-cH = N-n3 - '(xIIa) H2N R2 wherein R1, R2 and R; has the meaning given above. k) For the preparation of compounds of general formula I, wherein H2 is a nitro group: Nitration of a compound of general formula XIII,. OH n flm en N / R '1 - 2 ~ ~ ___ Ru - (XIII) wherein R1, H3 and Ra have the meaning given above.

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.

The compounds of general formula I obtained according to processes a to k can then, if desired, be decomposed into their optically active antipodes by racemate digestion or by cleavage of a mixture of the diastereomeric compounds of the general formula XIV, 111 cH-crx2-N / (XIV) 9 7317035-9 wherein H1, H2, R; and Ru has the meaning given above, R6 represents a hydrogen atom or an acyl group and R represents a chiral acyl group, and subsequent cleavage of the 7 groups R7, R6 and Ru, if H6 represents an acyl group and Hk an optionally substituted benzyl group.

Such as chiral acyl group R? especially in the case of the nitrogen atom protected optically active Gsaminoacyl groups, e.g. The N-benzyloxycarbonyl-L-alanyl group, or optically active terpenyloxycarbonyl groups, e.g. (-) - the mentyloxycarbonyl group.

The cleavage of a mixture of the diastereomeric compounds of 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 cleavage of the groups H6 and H7 suitably takes place by means of hydrolysis resp. solvolysis 1 presence of water or a suitable alcohol such as methanol, optionally 1 presence of an acid or base and at temperatures between 0 and 10 ° C.

The cleavage of the group R7 can also take place by means of a complex metal hydride such as lithium aluminum hydride in a suitable solvent, e.g. in ether, tetrahydrofuran or dioxane and preferably at temperatures between -eo and 20 ° C. If Re 1 denotes a compound of the general formula XIV the cyano group, this can be co-reduced at the same time.

Depending on the nature of the substituents R6 and R? its cleavage can take place stepwise or even in one step.

If A represents an optionally substituted benzyl group, this cleavage takes place in compounds in which R 2 does not form a nitro group, by means of hydrogenolysis in the presence of a suitable catalyst such as e.g. palladium on carbon or barium sulphate, in a suitable solvent, for example in an alcohol such as 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 H2 in the case of a compound of the general formula XIV denotes the cyano group, this can be co-reduced at the same time. The cleavage of Ru can take place before or after that of the group R6 and R7.

The racemic cleavage of the d, l-form in a compound of the above general formula I preferably takes place by fractional crystallization of a mixture of the diastereomeric salts with an optically active acid, e.g. D (-) - tartaric acid, L (+) - tartaric acid, dibenzoyl-D-tartaric acid, dibenzoyl-L-tartaric acid, (+) - camphor-10-sulfonic acid, L (-) - malic acid, L (+) - mandelic acid, dQ-bromo-camphor-Ûisulfonic acid or 1-kinetic acid. However, the race food cleavage can also take place by column chromatography on an optically active 7317035-9 10 _. _. ~ «Carrier material, e.g. on ethylcellulose.

If, according to processes a) to k), a compound of the general formula I in which H2 is a cyano group is obtained, this can be converted into the corresponding carbamoyl compound and / or a carbamoyl or carbalkoxy compound, these can be converted into the corresponding carboxyl compounds with the general formula I by hydrolysis and / or if a compound of the general formula I is obtained, in which H3 or RÄ constitutes a hydrogen atom, it can, if desired, be transferred with an aldehyde of the general formula XV, H5 - cHo (xv ) wherein R is as defined above, in a corresponding oxazolidine of the general formula Ia.

The reaction with an aldehyde of the general formula XV suitably takes place in a solvent such as ethanol, benzene, toluene or dioxane under water-separating conditions, e.g. in the presence of anhydrous copper (II) sulphate, at temperatures up to the boiling temperature of the solvent used, e.g. at temperatures between 20 and 100 ° C, however, it can also take place without solvent. Particularly advantageously, however, the reaction is carried out by means of a water separator in the presence of a solvent such as benzene or toluene.

The resulting compounds of general formula I and Ia can, if desired, be converted with inorganic or organic acids into their physiologically acceptable acid addition salts with 1, 2 or 3 equivalents of the corresponding acid. Such acids have, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, lactic acid, citric acid, tartaric acid, maleic acid or fumaric acid proved to be suitable.

The compounds of general formula II to XIV used as starting compounds are obtained according to procedures known from the literature. Thus, for example, the compounds of general formula II used as starting materials are obtained by reacting the corresponding 2-haloacetophenone with the corresponding amines.

The compounds of general formula III, IV and V are obtained by reacting the corresponding 2-halo-acetophenone with the corresponding amines and subsequent reduction of the resulting ketone, for example with sodium borohydride, a starting compound of 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 of general formula VI are obtained, for example, by reduction of the corresponding aminoacetylquinazoline with sodium borohydride.

For example, a starting compound of general formula VII is obtained by reacting a corresponding phenylethylene glycol with p-toluenesulfonic acid chloride in the presence of pyridine or by reducing a corresponding aminophenacyl halide with sodium borohydride.

In a starting compound of the general formula IX is obtained, for example, by reduction of a corresponding ketone with sodium borohydride. A starting compound of the general formula X is obtained, for example, by reacting a corresponding acid with a corresponding amine in the presence of a condensing agent such as N, N'-dicyclohexyl-carbodiimide or N, N'-carbonyl-diimidazole or by activation over an acid chloride or a mixed anhydride and subsequent reaction with a corresponding amine, for example by reduction of a corresponding ketocarboxylic acid amide.

A starting compound of the general formula XI is obtained, for example, by halogenation of a corresponding oxazolidone, in which R1 is a hydrogen atom, or by alkylation of a corresponding oxazolidone, in which R3 is 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 dimethyl sulphoxide.

A starting compound of the general formula XIII is conveniently obtained according to a process of the present application.

The starting materials of formulas II - XIII used in processes a) to k) are not always produced in pure form, they can also be suitably used as raw products.

As already mentioned, the new compounds of the general formula I and Ia exhibit valuable pharmacological properties, especially a 52-mimetic and / or beer-blocking effect, whereby depending on its substitution one or the other effect may be in the foreground. In particular, the d (+) compounds show a selective effect on the N1 reoeptors and the l (-) compounds in particular an effect on the ßz reoeptors.

For example, the following substances were tested for their effect on the β-receptors: A = 1- (4-amino-5-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, 7317035-9 bi KIM '' JU @ "U_O 12 _ ..__ H1 _ _ _- 1- (4-amino-3-chloro-5-fluoro-phenyl) -2- tert-butylamino-ethanol hydrochloride, 1- (4-amino-3-fluoro-phenyl) -2-tert-butylamino-ethanol-hydrochloride, 1- (4-amino-5-trifluoromethyl-phenyl ) -2-tert-pentylamino-ethanol hydrobromide, 1- (4-amino-3-chloro-5-trifluoromethyl-phenyl) -2-tert-butylamino-ethanol hydrochloride, 1- (4- amino-3-chloro-5-trifluoromethyl-phenyl) -2-cyclobutylamino-ethanol? -hydrochloride, 1- (4-amino-3-chloro-5-cyano-phenyl) -2-tert-butylamino-ethanol, 1 - (4-amino-3-bromo-5-cyano-phenyl) -2-tert-butylamino-ethanol hydrochloride, 1- (4-amino-3-bromo-5-fluoro-phenyl) - 2-Cyclobutylamino-ethanol hydrochloride, 1- (4-amino-3-fluoro-5-iodo-phenyl) -2-cyc lopropylamino-ethanol-hydrochloride, 1- (4-amino-3-fluoro-5-cyano-phenyl) -2-1-isopropylamino-ethanol-hydrochloride, 1- (4-amino-3-fluoro-5- cyano-phenyl) -2-tert-butylamino-ethanol hydrochloride, 1- (N-amino-3-cyano-phenyl) -2-cyclobutylamino-ethanol hydrobromide, 1- (4-amino-3 -cyan-phenyl) -2-tert-pentylamino-ethanol, - 1- (4-amino-3-chloro-5-cyano-phenyl) -2-propylamino-ethanol hydrochloride, - 1- (4-amino- 5-Chloro-5-cyano-phenyl) -2-sec-butylamino-ethanol hydrochloride, 1- (4-amino-3-chloro-5-cyano-phenyl) -2- (hydroxy-tert.- butylamino) -ethanol hydrochloride, 1- (4-amino-3-chloro-5-cyano-phenyl) -2-tert-pentylamino-ethanol hydrochloride, 1- (4-amino-3 -chloro-5-cyano-phenyl) -2-cyclopentylamino-ethanol-hydrochloride, d 1- (4-amino-3-chloro-5-cyano-phenyl) -2-β- (3,1-methylenedioxy -phenyl) -2--propylamino] ethanol hydrochloride, 1- (4-amino-3-bromo-5-cyano-phenyl) -2-cyclobutylamino-ethanol hydrochloride, 1- (4-amino-3,5 -dicyan-phenyl) -2-tert-butylamino-ethanol hydrochloride, 1- (4-amino-3-bromo-5-nitro-phenyl) -2-tert-butylamino-ethanol and 1- (4-amino -5-k chloro-5-nitro-phenyl) -2-tert-butylamino-ethanol.

The H1-blocking effect was tested as an antagonism against one through a standard dose of 1.0 y / kg i.v. N-isopropyl noradrenaline sulfate triggered tachycardia in cats under anesthesia. From the mean percentage attenuation obtained with the different doses, the increase in heart rate due to N-isopropylphenoradrenaline sulphate was determined by graphical extrapolation to an ED50 value (see Tables II and III).

The ßz-mimetic effect was tested as an antagonism against it by an i.v. dose of 20 μg acetylcholine-triggered bronchospasm in guinea pigs under anesthesia in the Konzett-Rössler test device after i.v. application. Of the percentage attenuations of the bronchospasmes obtained with the different doses, an ED50 value was determined by graphical extrapolation (see Table I).

The A2-blocking effect was tested as an antagonism against the broncholytic effect obtained with 5 Y / kg i.v. N-isopropyl-noradrenaline sulphate in the Konzett-Rössler experimental device on guinea pigs under anesthesia, when bronchospasm was triggered in them with a standard amount of 20 Y / kg i.v. acetylcholine (see Table III).

The acute toxicity of the substances was determined in groups of 10 mice each. The LD50 value, the intravenous dose at which 50% of the animals died within 14 days, was calculated according to the method of Litchfield and Wilooxon (see Tables II and III). 7317035 -9 14 Table I Substance ßz-mimetic action Duration of action nl n? EDSO Y / kg i.v. 'i minutes A 9 5 8.3> 15o - B 5. u 6.7'> 110 c 5 Il 211.0 v30 D 5 L: 10.0> 120 'F. 6 3 18.0> 80 -G 10 5 19.5> 130 H 5 5 6.8> 125 I 11 ll _ 0.20 s 95 J 5 I: 11.8> 140 K 6 3 58.0 s 50 M 6 I: 0.08 H10 N 5 3 0.32 Hm 0 5 3 6.9 Ho P '5 u 3.6 65 Q 5 3. 27,0 50 R 5 3 6,7> 80 s _5 3 10,0> 65 'r 5 3 1,9 H0 U la l: 9,8> 50 v 6 H 2,7> 65 W 5 3 20, 5> 50 x 3 6 3 11.3 Å H5 Z 5 3 '31.5) 80 nl = number of animals / Hos; n - number of doses for reaching ED5O. 15 Table II Substance Effect on 31-recep fi0 P6P fl a LÛSO WE / KH í-V¿ nl ng ED50 X- / km í.v.

A 3 5 13,5 3ü, 5 B - - - 27,2 cu 5 1Is, o 57,0 u D 4 5 8,0 35,1 E us 13,6 - 'ß9,2 F 3 5 3590 _ _ c 5 5 11.6 36.5 H "" "3623 I 5 5 of” Goao J - - - 67.0 xuu 1.5 26.1; L 6 5 1J "m2 M 5 5 0.27 66.1 : N 6 I: 0.022 58, "- 0 5 5 o, o7o ¶ 61.8 p 5 5 0.086 62.0 Q 6 5 0.76 53," R 6 - 6 0.32 H0, H 3 5 í H 0.76 81.8 _T S 'I _ ÛJÜ 33.07 U 6 U 0.70 39.1 v 6 n 1.11 ¶ 13.5 w 6 5 0.078 38.5 X 6 n 0.92, 166, oy 5 2.8 35.8 z 6 11.5 112, "number of animals / Eos number of doses.

Il 7317035-9 7317035-9 o 16 Table III Substance blocking action blocking effect LD5O on the ßl ~ receptors on the ße-receptors mg / kg 1_v_ nl ng ED5o yykg i.v. nl na ED50 \ 7kg i.v.

Ad (+) 7 4 8,4 5 1> 2 ooo 37.2 Dd (+) 6 4 6,2 5 1> 2 000 54,2 Ed (+) 8 3 1,5 4 1> 2 ooo - Gd (+ ) 8 4 12.5 5 -1> 2 ooo 33.2 nl = number of animals number of doses tested on the individual animals.

The novel compounds of general formula I and Ia may optionally be processed in combination with other active substances in conventional pharmaceutical dosage forms. In this case, the single dose amounts to 1 - 10011, but preferably 5 - 50yf.

The invention is further illustrated by the following examples, in which the temperatures refer to degrees Celsius. Example 1. 1- (4-Amino-3-bromo-5-fluoro-phenyl) -2-diethylamino-ethanol 3.4 g of 4'-amino-3'-bromo-2-diethylamino-5'-fluoro -acetophenone hydrochloride was dissolved in 20 ml of methanol. While stirring, a solution of 570 mg of sodium borohydride in 5 ml of water was slowly added at room temperature. By simultaneously adding a hydrochloric acid, the pH was adjusted between pH 3 and pH 6. After the addition of the sodium borohydride solution was completed, the mixture was stirred for a further 30 minutes. at room temperature.

Then 3n hydrochloric acid was added until pH 1 was reached. The hydrochloric acid solution was extracted twice with chloroform, the chloroform extracts were discarded. The aqueous solution was made alkaline with ammonia and extracted thoroughly with chloroform. The chloroform extracts were combined, dried over sodium sulfate and evaporated in vacuo to dryness. A colorless oil remained, which was dissolved in acetic acid ethyl ester.

After addition of ethereal hydrochloric acid, a colorless precipitate precipitated, which was filtered off with suction and dissolved in water. The aqueous solution was made alkaline with sodium hydroxide and extruded with chloroform. The chloroform extract was washed with water, dried over sodium sulfate and evaporated in vacuo.

A colorless oil remained. 2 Structural evidence by NMR spectrum (CDCl 3): 0.85 - 1.2 ppm triplet ÅÉ protons, N (CH2-CH) 2_7Ü 2.4 - 2.9 Ppm multiplet 15 protons, 1N (cH2-) 3; 7. 4.15 ppm Sinsülett (2 protons, NH2), 54.4 - 4.7 ppm Muplet (1 proton, CH), 4.85 ppm singlet (1 proton, OH), 6.9 - 7, 4 ppm multiplet (2 aromatic protons).

Example 2, 1- (4-amino-3-chloro-5-trifluoromethyl-phenyl) -2-tert-butylamino-ethanol hydrochloride 80 g of 4'-amino-2-tert-butylamino-5'- chloro-5'-trifluoromethyl-acetophenone hydrochloride (decomposition between 223 and 2310) was dissolved in 500 ml of methanol and cooled to -150. While stirring, 9.5 g of sodium borohydride were added portionwise over the course of 1 hour, keeping the temperature between -5 and -15 °. After an additional 1 hour at -150, the mixture was acidified with 2N hydrochloric acid and the methanol was removed in vacuo. The remaining aqueous solution was made alkaline with 2N ammonia and extracted with acetic ester. The organic phase was washed with water, dried and added with 50 ml of 4.5N hydrochloric acid in isopropanol. The precipitated hydrochloride of the above substance was filtered off with suction and washed with ethyl acetate and ether. melting point; 205 - 2o7 ° (solar eclipse).

By concentrating the mother liquor, additional substance was recovered.

Example 2. 1- (4-Amino-3-bromo-5-cyano-phenyl) -2-dimethylamino-ethanol hydrochloride 15.2 g 4'-amino-3'-bromo-5'-cyano-2-dimethylamine -acetophenone was dissolved in 300 ml of methanol and added dropwise at room temperature with stirring with a solution of 10 g of sodium borohydride in 100 ml of water.

The mixture was allowed to stand overnight, still present sodium borohydride was decomposed by acidification with hydrochloric acid, the methanol was evaporated in vacuo, the residue was taken up in water, made alkaline with ammonia, extracted three times with about 150 ml each of chloroform, the chloroform solution was washed twice with a small amount of water, dried over sodium sulfate and evaporated to dryness. The residue was taken up in ethanol and slightly acidified with hydrochloric acid / alcohol, whereby 1- (4-amino-5-bromo-5-cyano-phenyl) -2-dimethylamino-ethanol hydrochloride crystallized out. It was recrystallized from ethanol. smäitpunxt; 187-119 °.

Example N. 1- (4-Amino-3-chloro-5-trifluoromethyl-phenyl) -2-tert-pentylamino-ethanol-. -hydrochloride g 0.37 g of 1- (4-amino-3-trifluoromethyl-phenyl) -2-tert-pentylamino-ethanol hydrobromide and 0.2 ml of pyridine were dissolved in 30 ml of tetrahydrofuran and cooling dough to 0 °. 0.5 g of phenyl iodine dichloride was added, the mixture was kept for 2 hours at the said temperature and 0.1 g of phenyl iodine dichloride was added once more. After 20 hours at about 4 °, the solution was evaporated, partitioned between acetic ester and water, made the aqueous extract alkaline with 2N ammonia and extracted again with acetic ester. The organic phase was washed with water, dried and added with a few drops of hydrochloric acid in isopropanol. The precipitated hydrochloride of the above compound was filtered off with suction and washed with ether. smäicpunkt; 176 - 178 ° (dec.).

Example Gel 5. 1- (4-Amino-3-bromo-5-methyl-phenyl) -2-tert-butylamino-ethanol-dihydrochloride 2.6 g of 1- (4-amino-3-methyl-phenyl) -2> tert-butylamino-ethanol hydrochloride was dissolved in 90 ml of 50% acetic acid and added at 0-5 ° with 1.6 g of bromine, dissolved in 5 ml of glacial acetic acid and 1 ml of water. After 15 minutes, unused bromine was destroyed with sodium hydrogen sulphite. It was diluted with water and insoluble by-products were removed by filtration over charcoal.

The filtrate was made alkaline under cooling with sodium hydroxide and extracted with chloroform. After drying over sodium sulfate, the chloroform solution was filtered over carbon and evaporated in vacuo to dryness. The oily bases thus obtained were dissolved in isopropanol and clearly acidified with hydrochloric acid / isopropanol. It was evaporated slightly in vacuo, cooled, filtered off with 1- (4-amino-3-bromo-5-methyl-phenyl) -2-tert-butylamino-ethanol dihydrochloride and recrystallized from isopropanol / ether.

Melting point: from 148 °, decomposition. Example 6. 1- (4-Amino-5-bromo-3-hydroxymethyl-phenyl) -2-tert-butylamino-ethanol 2.0 g of 1- (4-amino-3 -hydroxymethyl-phenyl) -2-tert-butylamino-ethanol was dissolved in 18 ml of glacial acetic acid and 2 ml of water and added dropwise with 1.3 g of bromine. Then the reaction mixture was evaporated, the residue was dissolved in water, made alkaline with 2N ammonia and shaken four times with chloroform. The organic phase was evaporated after drying over sodium sulfate and the residue was purified over a silica gel column with ethanol as eluent. The fractions containing the substance were combined and evaporated in vacuo. The evaporation residue crystallized after standing for a long time under ether. smäitpunkt; 121 - 1219.

Example 7. 7- (4-Amino-3-trifluoromethyl-phenyl) -2-tert-butylamino-ethanol 5.05 g of 1- (4-acetylamino-5-trifluoromethyl-phenyl) -2-tert-butyl- Amino-ethanol hydrochloride was boiled in a mixture of 50 ml of ethanol and 50 ml of 4N sodium hydroxide for 3 hours under reflux. The ethanol was evaporated in vacuo and the precipitated crystallizate was filtered off with suction. After recrystallization from ethanol / water, the melting point was 145 DEG-140 DEG. For transfer to the monohydrochloride, the mixture was dissolved in the calculated amount of hydrochloric acid, evaporated in vacuo to dryness and the solid residue was recrystallized from isopropanol / ether.

Melting point of hydrochloride 172 - 1740 (decomposition).

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) -amino-ethanol (melting point: 98 - 1009) was boiled in a mixture of 10 ml of ethanol and 10 ml of sodium hydroxide for 1.5 hours reflux. The ethanol was distilled off in vacuo and the aqueous phase was extracted with ethyl acetate. The organic extract was washed with water, dried and evaporated in vacuo. The oily residue is thin layer chromatographically uniform (silica 1; chloroform: methanol = 19: 1. Rf value: ^ »0, 5).

Example 9. 1- (4-Amino-3-carboxy-phenyl) -2-tert-butylamino-ethanol 0 g) 1- (4-acetylamino-} -carboxy-phenyl) -2-tert-butylamino- ethanol was dissolved in 6 ml of ethanol and added with 4 ml of concentrated hydrochloric acid.

The mixture was heated for 40 minutes to 700, evaporated in vacuo to dryness and the product was purified by chromatography on silica gel with chloroform-methanol = 3: 2 as eluent. There was obtained 1- (4-amino-3-carboxy-phenyl) -2-tert-butylamino-ethanol, the structure of which was ensured by the nuclear resonance spectrum (CD30D): 1.4 ppm singlet / 9 protons, C (CH3) 5.3 ppm multiplet (2 protons, CH2), 4.5 ppm multiplet (1 proton, CH) 6.8 - 7.8 ppm multiplet (3 aromatic protons).

Example 10. 1- (u-amino-z-tr-1-fluoromethyl-phenyl) -2-cert. -butylamino-ethanol 0.45 g of 1- (4-amino-3-trifluoromethyl-phenyl) -2- (N-benzyl-N-tert-butyl) -amino-ethanol was dissolved in a hydrogenation flask in 10 ml of methanol and 1 ml of hydrochloric acid and hydrogenated in the presence of 50 mg of palladium / carbon catalyst (10%) until 1 mole of hydrogen was taken up. The catalyst was separated by filtration, the solution was evaporated in vacuo and the residue was partitioned between ethyl acetate and 2N ammonia. The organic phase washed with water was dried and evaporated again in vacuo. The residue was crystallized from ethanol / water. melting point: 145 - 147 °.

Example ll. 1- (4-Amino-5-chloro-5-trifluoromethyl-phenyl) -2-tert-butylamino-ethanol hydrochloride 0.76 g 1- (4-amino-3-chloro-5-trifluoromethyl-phenyl) -2- (N-Benzyl-N- '-31-tert-butyl) -aminoethanol was dissolved in a hydrogenation flask in 20 ml of methanol and 1.95 ml in 1N hydrochloric acid and hydrogenated in the presence of 80 mg of palladium / carbon. catalyst (10%) until 1 mole of hydrogen is taken up. The hydrogenation was stopped, the catalyst was removed by filtration and the filtrate was brought to dryness in vacuo. The oily evaporation residue was purified over a column of silica gel using chloroform: methanol: zconc. ammonia = 80: 20: 1 as eluent. The fractions containing the substance were combined and freed in vacuo from the solvent.

The residual crystalline base of the desired compound was transferred with the calculated amount of 1.07n hydrochloric acid in isopropanol in the hydrochloride and recrystallized from ethyl acetate / ether. melting point = 205 - 2o7 ° (solar eclipse).

Example Gel 12. 1- (4-Amino-3-chloro-5-methyl-phenyl) -2-tert-butylamino-ethanol-dihydrochloride 0.7 g 1- (4-amino-3-chloro-5- methyl-phenyl) -2- (N-benzyl-N-cert-butyl) -amino-ethanol hydrochloride was dissolved in 50 ml of methanol and 0.92 ml of 2N hydrochloric acid and hydrogenated in the presence of 50 mg of palladium on wedge ( 10%).

The hydrogenation was stopped when 41 Nml of hydrogen was taken up; the catalyst was filtered off and the filtrate was evaporated to dryness in vacuo. The residue was dissolved in ethanol and precipitated by the addition of ether such as dihydrochloride.

Melting point: from 95 ° (decomposition).

Example Gel 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 was dissolved in 150 ml of methanol and acidified with hydrochloric acid / ethanol to pH 6. This solution was added with 1 g of palladium on carbon (10%) and hydrogenated in a shaker at room temperature and atmosphere. press until the calculated amount of hydrogen has been absorbed. When the catalyst was sucked off, the mixture was evaporated to a small volume. The precipitated crystals were filtered off with suction and recrystallized from ethanol. The colorless crystals of the resulting hydrochloride of the desired substance melted at 174 DEG-176 DEG (sonication).

Example Gel 14. 1- (4-Amino-5-trifluoromethyl-phenyl) -2-cyclopropylamino-ethanol-dihydrochloride 4.1 g 1- (4-amino-5-bromo-5-trifluoromethyl-phenyl) -2- Cyclopropylaminoethanol was dissolved in a hydrogenation flask in 200 ml of methanol and added with 2 g of palladium oxide / barium sulfate catalyst (5%). Hydrogenate until 1 mole of hydrogen is taken up, the catalyst is filtered off and the filtrate is brought to dryness in vacuo. The residue was taken up in water, 21 vzfnizsg-s alkaline with 2N ammonia and the aqueous phase was extracted with ethyl acetate.

The organic extract was washed with water, dried and evaporated again. The solid residue was dissolved in isopropanol and the solution was added with 2 equivalents of hydrochloric acid in isopropanol. The crystallized dihydrochloride of the above compound was filtered off with suction and washed with isopropanol and ether.

Melting point: 141.5 - 1420 (decomposition).

Example Gel 1- 1- (4-Amino-3-trifluoromethyl-phenyl) -2-tert-pentylamino-ethanol hydrobromide 5 g 1- (N-amino-3-bromo-5-trifluoromethyl-phenyl) -2-tert-pentylamino-ethanol hydrochloride was partitioned between ethyl acetate and 2N ammonia.

The organic phase was dried and evaporated in vacuo. The remaining base was dissolved in 100 ml of methanol in a hydrogenation flask, charged with 2.5 g of palladium oxide / barium sulfate catalyst (5%) and hydrogenated until 1 mole of hydrogen was taken up. After the catalyst was removed by filtration, the filtrate was evaporated in vacuo and the solid residue was recrystallized from isopropanol. The resulting hydrobromide of the above compound melted at 1714 DEG-175 DEG (decomposition).

Example Gel 16. 1- (N-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 was dissolved in 100 ml of methanol and 11.6 ml of 2N hydrochloric acid and hydrogenated in the presence of 250 mg of palladium on carbon ( 5%). When 315 ml of hydrogen was taken up, the hydrogenation was stopped, the catalyst was filtered off with suction and the solvent was distilled off in vacuo, the residue was taken up in water and the base was liberated with ammonia; this was extracted with chloroform and chromatographed on a silica gel column. The base, m.p. 96 DEG-980 DEG, was obtained, from which the dihydrochloride decomposed from 1450.

Example Gel 11. 1- (4-Amino-3-aminomethyl-phenyl) -2-tert-butylamino-ethanol 2.0 g of 6- (2-tert-butylamino-1-hydroxy-ethyl) -3 were dissolved. , 4-dihydro-2-methyl-quinazoline in 80 ml of pentyl alcohol, added the mixture portionwise with 7.5 g of sodium within 1 hour and slowly heated the mixture to boiling after another half hour. After boiling for 5 hours, the solution was cooled and added with 100 ml of water. Then 60 ml of concentrated hydrochloric acid were added dropwise, the reaction mixture was stirred for 2 hours and then shaken out twice with ether. The acidic phase was made alkaline with 10N sodium hydroxide, the base was extracted with ether, the ether phase was dried over sodium sulphate and evaporated. The crude product was purified by column chromatography on silica gel with methanol: chloroform (2: 1). After evaporation of the corresponding fraction, 1- (4-amino-5-aminomethyl-phenyl) -2-tert-butylamino-ethanol was obtained as the amorphous substance.

Elemental Analysis C 13 H 25 N 3 O (257.34) Calculated; c 65.78 H 9.76 N 17.70% Found = c 65.50 H 9.61 N 17.58%.

Example 18. 1- (4-Amino-3-bromo-5-carhamoyl-phenyl) -2-dimethylamino-ethanol 2 g 1- (N-amino-3-bromo-5-cyano-phenyl) -2-dimethylamino -ethanol was boiled for 4 hours with a solution of 5 g of sodium hydroxide in 120 ml of 50% ethanol, the ethanol was distilled off, the remaining aqueous solution was diluted with 100 ml of water and extracted three times with chloroform.The chloroform solution was dried over sodium sulfate and evaporated in vacuo The residue was solid and then recrystallized from chloroform, m.p. = from 95 ° (sonar).

Example 19. 1- (4-Amino-β-bromo-5-carboxy-phenyl) -2-dimethylamino-ethanol 2 g lf (4-amino-5-bromo-5-cyano-phenyl) -2-dimethylamino-ethanol cocaine for 4 hours with a solution of 5 g of sodium hydroxide in 120 ml of 50% ethanol. The ethanol was distilled off, the remaining aqueous solution was diluted with 100 ml of water and extracted three times with chloroform. The aqueous phase was neutralized, evaporated to dryness, the residue treated with ethanol, filtered off, the filtrate evaporated and the residue again treated with ethanol and filtered off. Evaporation of the last filtrate left a residue of 1- (4-amino-3,bromo-5-carboxy-phenyl) -2-dimethylaminoethanol, melting at 240 DEG-25 DEG (sonication) and structure was ensured by IR and LIV spectrum: In (KBr); coo 'at 1620 cm -1, NH * at 2000 - 3500 cm -1. Uv (etanc1) = Maxima at 220 and 330 - 340 nm, shoulder at 250 nm.

Example 20. 5- (4-Amino-5-chloro-5-trifluoromethyl-phenyl) -5-tert-butyl-1,3-oxazolidine 1.35 g of 1- (4-amino-3-chloro-5- trifluoromethyl-phenyl) -2-tert-butylamino-ethanol was dissolved in 50 ml of benzene and added to 1.2 ml of 40% aqueous formaldehyde solution. It was evaporated at normal pressure to half volume, added with about 35 ml of benzene and boiled for 5 hours under reflux. Then an additional 1.5 ml of formaldehyde solution was added and the procedure described was repeated three more times.

The mixture was evaporated in vacuo to dryness, dissolved in ether and filtered off from some insoluble precipitates. The filtrate was slightly acidified with ethereal hydrochloric acid and the precipitated product was crystallized by trituration. It was filtered off and recrystallized from acetone / ether. The resulting hydrochloride of the above compound melted at 165 DEG-165 DEG (decomposition).

Example Gel 21. 1- (H-amino-5-fluoro-phenyl) -2-tert-butylamino-ethanol Melting point for hydrochloride 196-197 ° (decomposition).

Prepared according to process a) from 4'-amino-2-tert-butylamino-3'-fluoro-acetophenone hydrochloride and sodium borohydride analogously to Example] Example Gel 22. 1- (4-amino-3-bromo-5-fluoro -phenyl) -2-tert-butylamino-ethanol melting point of hydrochloride = 207-280 ° (dec.).

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

Example Gel 23. 1- (4-Amino-5-chloro-5-trifluoromethyl-phenyl) -2-cyclobutylamino-ethanol Melting point for the hydrochlorylene: 177-178 °.

Prepared according to process a) from 4'-amino-3'-chloro-2-cyclobutylamino--5'-trifluoromethyl-acetophenone hydrochloride and sodium borohydride analogously to Example 2.

Exemge1'24. 1- (4-Amino-3-fluoro-phenyl) -2-cyclopropylamino-ethanol-melting point Prepared according to method c) from 1- (4-ethylamino-3-fluoro-phenyl) -2-cyclopropylamino-ethanol and sodium hydroxide analogously to Example 7.

Example gel 25. 1- (4-amino-3-fluoro-phenyl) -2-tert-butylamino-ethanol Melting point of hydrochloride 196-197 ° (decomposition).

Prepared according to process c) from 1- (4-amino-3-fluoro-phenyl) -2- (N-benzyl-N-tert-butyl) -amino-ethanol hydrochloride and catalytically active hydrogen analogous to Example 13 .

Example Gel 26. 2-Ethylamino-1- (4-amino-5-chloro-5-fluoro-phenyl) -ethanol Melting point of hydrochloride 186-1880 (decomposition).

Prepared according to process a) from 2-ethylamino-4 '- amino -}' - chloro-5'-fluoro-acetophenone and sodium borohydride analogously to Example 1.

Example Gel 27. 1- (4-Amino-3-chloro-5-fluoro-phenyl) -2-isopropylamino-ethanol Melting point of the hydrochloride: 152 - 15 ° (decomposition).

Prepared according to process a) from 4 '-amino-3'-chloro-5'-fluoro-2-1-isopropylamino-acetophenone hydrochloride and sodium borohydride analogously to Example 1. Example 31. 1- (4 -amino-5-chloro-5-fluoro-phenyl) -2-cyclopropylamino-ethanol Melting point of the hydrochloride: 175-177 ° (dec.).

Prepared according to process a) from 4'-amino-5'-chloro-2-cyclopropylamino--5'-fluoro-aetophenone hydrochloride and sodium borohydride analogously to Example 1.

Example Gel 29. 1- (4-Amino-3-chloro-5-fluoro-phenyl) -2-tert-butylamino-ethanol Melting point of the hydrochloride: 206-208 ° (dec.).

Prepared according to process a) from 4'-amino-2-tert-butylamino-3'-chloro-5'-fluoro-aetophenone hydrochloride and sodium borohydride analogous to Example 1.

Example 50. 1- (4-Amino-3-chloro-5-fluoro-phenyl) -2-tert-pentylamino-ethanol Melting point of hydrochloride 187-188 ° (decomposition). Prepared according to process a) from α'-amino-5'-chloro-5'-fluoro-2-tert.- -pentylamino-aetophenone hydrochloride and sodium borohydride analogously to Example 1.

Example 2. 1- (4-Amino-3-chloro-5-fluoro-phenyl) -2- [1- (3,4-methylenedioxy-phenyl) -2-propylamino] Ethanol ° Melting point of the hydrochloride: 119-112 ° ( decomposition).

Prepared according to process a) from 4'-amino-3'-chloro-5'-fluoro-2- [6 (3,4-methylenedioxy-phenyl) -2-propylamino] acetophenone and sodium borohydride analogous to Example 1.

Example 32, 1- (4-Amino-5-chloro-5-fluoro-phenyl) -2-dimethylamino-ethanol Melting point for new hydroxylene = 208 DEG-21 DEG C. (solubilization).

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

Example 53. 1- (4-Amino-5-chloro-5-fluoro-phenyl) -2-diethylamino-ethanol melting point: 39-41 °.

Prepared according to process a) from 4'-amino-3'-chloro-2-diethylamino-5'-fluoro-acetophenone hydrochloride and sodium borohydride analogously to Example 1. 'Example gel 34. 2-ethylamino-1- (4 -amino-3-bromo-5-fluoro-phenyl) -ethanol melting point for the precipitate = 167 - 169 ° (decomposition).

Prepared according to process a) from β-ethylamino-α'-amino-3β-bromo-5'-25'-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 for the new hydrochloride = 171 - 173 ° (decomposition).

Prepared according to process a) from 4'-amino-3'-bromo-5'-fluoro-2-1sopropylamino-aetophenone hydrochloride and sodium borohydride analogously to Example 1.

Example 56. 1- (4-Amino-3-bromo-5-fluoro-phenyl) -2-cyclopropylamino-ethanol melting point of the new hydrocarbon = 185 - 187 ° (decomposition).

Prepared according to process a) from 4'-amino-3'-bromo-2-cyclopropylamino--5'-fluoro-acetophenone and sodium borohydride analogously to Example 1.

Example 57. 1- (4-Amino-3-bromo-5-fluoro-phenyl) -2- (hydroxy-tert-butylamino) -ethanol Melting point 122 DEG-125 DEG.

Prepared according to process a) from 4'-amino-3'-bromo-5'-fluoro-2- (hydroxy-tert-butylamino) -acetophenone hydrochloride and sodium borohydride analogously to Example 1.

Example Gel 38. 1- (4-Amino-3-bromo-5-fluoro-phenyl) -2-tert-pentylamino-ethanol Melting point of the hydrochlorylene = 185 - 187 ° (dec.).

Prepared according to process a) from 4'-amino-3'-bromo-5'-fluoro-2-tert-pentylamino7acetophenone hydrochloride and sodium borohydride analogously to Example 1.

Example 39. 1- (4-Amino-3-bromo-5-fluoro-phenyl) -2- [1- (3,1-methylenedioxy-phenyl) -2-propylamino] -methanol melting point = 126-128 ° .

Prepared according to process a) from 4'-amino-3'-bromo-5'-fluoro-24 / 1- (3, α-methylenedioxy-phenyl) -2-propylamino / polyethophenone and sodium borohydride analogously to Example 1.

Example 40. 1- (4-Amino-3-chloro-5-trifluoromethyl-phenyl) -2-isopropylamino-ethanol melting point = 10 ° -10 °. melting point for nyar ° k10r1aen = 185 - 187 °.

Prepared according to process a) from 4'-amino-3'-chloro-2-1sopropylamino--5'-trifluoromethyl-acetophenone hydrochloride and sodium borohydride analogously to Example 2.

Exemgel H1. 1- (H-amino-3-chloro-5-trifluoromethyl-phenyl) -2-cyclogropylamino-ethanol Melting point: 138 - 1390. Prepared according to process a) from 4'-amino-3 ' Chloro-2-cyclopropylamino-5'-trifluoromethyl-acetophenone and sodium borohydride analogously to Example 2.

Example gel 42. 1- (4-Amino-3-chloro-5-trifluoromethyl-phenyl) -2- (hydroxy-tert-butylamino) -ethanol Melting point of the neo-chloro1a = 219 DEG-220 DEG.

Prepared according to process a) from 4'-amino-3'-chloro-2- (hydroxy-tert-butylamino) -5'-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 for hydrochloride = 176-178 ° (son division).

Prepared according to process a) from 4'-amino-5'-chloro-2-tert.-pentylamino-5'-trifluoromethyl-acetophenone hydrochloride and sodium borohydride analogously to Example 2. 1 Example gel 44. 1- (4-amino -5-chloro-5-trifluoromethyl-phenyl) -2- [2-methyl-4-hydroxy-butyl- - (2) -amino] Letanol melting point for the new hydrochloride = 148 DEG-15 DEG C. (decomposition).

Prepared according to process a) from 4'-amino-3'-chloro-2- [1-methyl-4-hydroxy-butyl- (2) -amino] -15'-trifluoromethyl-acetophenone and sodium borohydride analogous to Example 2.

Example 45. 2- [3-Ethynyl-pentyl- (5) -amino] Cl- (4-amino-5-chloro-5-trifluoromethyl-phenyl) -ethanol melting point for the nyaroxylorene = 185 - 187 ° (decomposition ).

Prepared according to process a) from 2- [3-ethyl-pentyl- (3) -amino] -amino-3'-chloro-5'-trifluoromethyl-aoethophenone hydrochloride and sodium borohydride analogous to Example 2.

Example Gel 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 ° (decomposition).

Prepared according to process a) from 4'-amino-3'-chloro-2- [1- (3,4-methylenedioxy-phenyl) -2-propylamino] 15'-trifluoromethyl-acetophenone hydrochloride and sodium borohydride analogously to examples 2.

Example Gel IIQ 1- (4-Amino-3-chloro-5-trifluoromethyl-phenyl) -2-dimethylamino-ethanol Melting point of neoaro1 ° r1aene = 162 - 164 ° L Prepared according to method a) from 4'-amino-3'- chloro-2-dimethylamino-5'-7317035-9 2? V-trifluoromethyl-acetophenone hydrochloride and sodium borohydride analogously to Example 2.

Example Gel 48. 1L-Amino-3-chloro-5-trifluoromethyl-phenyl) -2- (N-methyl-ethylamino) -ethanol melting point = 48-49 °. Prepared according to process a) from 4'-amino-3'-chloro-2- (N-methyl-ethylamino) -5'-trifluoromethyl-acetophenone hydrochloride and sodium borohydride analogously to Example 2.

Example 49. 1- (4-Amino-3-chloro-5-trifluoromethyl-phenyl) -phidylamino-ethanol Melting point of the hydrochloride: 149-1510.

Prepared according to process a) from 4'-amino-3'-chloro-2-diethylamino-5'-trifluoromethyl-acetophenone hydrochloride and sodium borohydride analogously to Example 2.

Example Gel 50. 1- (4-Amino-3-chloro-5-trifluoromethyl-phenyl) -2- (N-benzyl-N-tert-butyl) -amino-ethanol Oil, thin layer chromatographically uniform (SiO 2; chloroform: meta - zero = 15 = 1; Rf value: 0.75).

Prepared according to process a) from 2'-amino-2- (N-benzyl-N-tert-butyl) -amino-1'-chloro-5'-trifluoromethyl-acetophenone and sodium borohydride analogously to Example 2.

Example 51. 1- (4-Amino-3-bromo-5-trifluoromethyl-phenyl) -2-isopropylamino-ethanol melting point = 102 DEG-105 DEG.

Melting point of the hydrochloride: 177 - 179 ° (decomposition).

Prepared according to process a) from 4'-amino-5'-bromo-2-isopropylamino-5'-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 °.

Melting point of the hydrochloride: 195 - 195.5 ° (decomposition).

Prepared according to process a) from α'-amino-3 '-bromo-2-cyclopropylamino--5'-trifluoromethyl-acetophenone hydrochloride and sodium borohydride analogously to Example 2.

Example 55. 1- (4-Amino-3-bromo-5-trifluoromethyl-phenyl) -2-tert-butylamino-ethanol narrowing point 85-87 °.

Melting point of the hydrochloride: 205 - 9060 (decomposition).

Prepared according to process a) from 4'-amino-3'-bromo-2-tert-butylamino-5'-trifluoromethyl-aetophenone hydrochloride and sodium borohydride analogously to Example 2.

Example 54. 1- (4-Amino-3-bromo-5-trifluoromethyl-phenyl) -2-glycobutylamino-ethanol melting point of the new dry chloride; 189 - 191 ° (decomposition).

Prepared according to process a) from β'-amino-5 '-bromo-2-cyclobutylamino--5'-trifluoromethyl-acetophenone hydrochloride and sodium borohydride analogously to Example 2.

Example 55. 1- (4-Amino-5-bromo-5-trifluoromethyl-phenyl) -2-tert-pentylamino-ethanol Melting point of the hydrochloride: 166.5 - 168.50 (decomposition).

Prepared according to process a) from 4'-amino-3 '-bromo-2-tert-pentylamino-5'-trifluoromethyl-acetophenone hydrochloride and sodium borohydride analogously to Example 2.

Example 56. 2- [3-Ethinyl-pentyl- (5) -amino] -1- (4-amino-3-bromo-5-trifluoromethyl-phenyl) -ethanol Melting point of the hydrochloride: 189 - 1900 (decomposition).

Prepared according to process a) from 2- [3-ethyl-pentyl- (5) -amino / 34'-amino-5'-bromo-5'-trifluoromethyl-acetophenone hydrochloride and sodium borohydride analogous to Example 2.

Example 57. 1- (4-Amino-3-bromo-5-trifluoromethyl-phenyl) -2-dimethylamino-ethanol Melting point of the hydrochloride: 149-1510.

Prepared according to process a) from 4'-amino-5'-bromo-2-dimethylamino-5'-trifluoromethyl-acetophenone hydrochloride and sodium borohydride analogously to Example 2.

Example 58. 1- (4-Amino-5-bromo-5-trifluoromethyl-phenyl] -2- (N-methyl-ethylamino) -ethanol melting point = 52.5 - 53.5 °.

Prepared according to process a) from 4'-amino-3'-bromo-2- (N-methyl-ethylamino) -5'-trifluoromethyl-acetophenone hydrochloride and sodium borohydride analogously to Example 2.

Example 52. 1- (4-Amino-3-bromo-5-trifluoromethyl-phenyl) -2-diethylamino-ethanol melting point for hyarochlorine = 159-160 °.

Prepared according to process a) from 4'-amino-3'-bromo-2-diethylamino-5'-trifluoromethyl-acetophenone hydrochloride and sodium borohydride analogously to Example 2. Example 60. 1- (4-amino-5-methyl -phenyl) -2-tert-butylamino-ethanol melting point for the diaryarocaralene = 100 ° (decomposition). Prepared according to process a) from 4'-amino-3'-methyl-2-tert-butylamino-acetophenone and sodium borohydride analogously to Example 3.

Example gel 61. 1- (4-amino-3-chloro-5-methyl-phenyl); 2-methylamino-ethanol mp: 95-96 °.

Prepared according to process a) from 4'-amino-3'-chloro-5'-methyl-2-methylamino-acetophenone and sodium borohydride analogously to Example 3.

Example gel 62. - 2-Ethylamino-1- (α-amino-3-chloro-5-methyl-phenyl) -ethanol melting point = 107-110.5 °.

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

Example 62. * - 1- (4-amino-3-chloro-5-methyl-phenyl) -2-dimethylamino-ethanol Melting point of hydrochloridene 120 ~ 1250 (decomposition).

Prepared according to process a) from 4'-amino-3'-chloro-2-dimethylamino-5'-methyl-acetophenone hydrochloride and sodium borohydride analogously to Example 1.

Example 64. 1-La-amino-5-chloro-5-methyl-phenyl) -2- (N-methyl-ethylamino) -ethanol Melting point of the hydrochloride: 93-960.

Prepared according to process a) from 4'-amino-3'-chloro-5'-methyl-2- (N-methyl-ethylamino) -acetophenone hydrochloride and sodium borohydride analogously to Example 1. Exemgel 65. 1- (4 -amino-3-chloro-5-methyl-phenyl) -2-diethylamino-ethanol Melting point of hydrochloridene 118 - 222 ° (decomposition).

Prepared according to process a) from 4'-amino-3'-chloro-2-diethylamino-5'-methyl-acetophenone hydrochloride and sodium borohydride analogously to Example 10 Example Gel 66. 1- (4-amino-3-chloro -5-methyl-phenyl) -2- (N-benzyl-N-tert-butyl) -amino-ethanol melting point for the new hydrochloride = zoo - 20 °.

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

Example 67. 1- [4-Amino-5-bromo-5-methyl-phenyl) -2-dimethylamino-ethanol Melting point for the hydroxyovolene = 123 - 1a5 ° (solar refining).

Prepared according to method a) from 4'-amino-3'-bromo-2-dimethylamino-5'-methyl-acetophenone and sodium borohydride analogously to Example 3. 73170-35-9 7317035-9 _, _._____ Example 68 1- (4-Amino-3-bromo-5-methyl-phenyl) -2-ethylamino-ethanol Melting point: 48-500.

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

Example 62. 1- (4-Amino-3-bromo-5-methyl-phenyl) -2- (N-benzyl-N-tert-butyl) -amino-ethanol Prepared according to method a) from 4'- amino-3'-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 (S102; chloroform-methanol = 9: 1, Ef-valuezf-0.9).

Example 70. 1- (3-Ethyl-4-amino-S-chloro-phenyl) -2-diegylamino-ethanol melting point for the new hydrochlorene = 121 - 12 °.

Prepared according to process a) from 3'-ethyl-H'-amino-5'-chloro-2-diethylamino-acetophenone and sodium borohydride analogously to Example 3. Example 71. 1- (5-Ethyl-4-amino- 5-bromo-phenyl) -2-diethylamino-ethanol melting point of the hydrochloride = 132 - 154 °.

Prepared according to process a) from 3'-ethyl-4'-amino-5'-bromo-2-diethylamino-acetophenone and sodium borohydride analogously to Example 3. In Example 72. 1- (4-amino-3-tert. -butyl-5-chloro-phenyl) -2-tert-butylamino-ethanol Melting point of the hydrochloride: from 188 ° (dec.).

Prepared according to process a) from 4 '-amino-3'-tert-butyl-2-tert-butylamino-5'-chloro-acetophenone and sodium borohydride analogously to Example 1.

Example 73. 1- (~-Amino-3-hydroxymethyl-phenyl) -2-dimethylamino-ethanol Prepared from 4'-amino-2-dimethylamino-3'-hydroxymethyl-acetophenone and sodium borohydride analogous to Example 1.

Structural evidence through UV and IR spectra. UV (ethanol): Maximum at 250 nn (E = 0.5), shoulder from 275 and 305 nm (E = 0.1); IR (CH 2 Cl 2): OH at 3600 cm -1, NH 2 at 3380 and 5450 cm -1, N (cH 3) 2 at 2780 and 2830 cm -1. 1- (4-amino-5-hydroxymethyl-phenyl) -2- dletylamino-ethanol Melting point of the dihydrochloride: from 125 ° (decomposition).

Prepared according to process a) from 4'-amino-2-diethylamino-2'ehydroxymethyl-acetophenone and sodium borohydride analogously to Example 1. Example 15. 1- (4-Amino-5-chloro-5- oyan-phenyl) -2-isopropylamino-ethanol Melting point of the hydrochloride: 185 - 1880.

Prepared according to process a) from 4'-amino-3'-chloro-5'-cyano-2-1sopropylamino-acetophenone and sodium borohydride analogously to Example 5.

Example 16. 1- (1H-Amino-3-chloro-5-cyano-phenyl) -2-tert-butylamino-ethanol m.p. = 125 DEG-135 DEG.

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

Example 21. 1- (4-Amino-3-chloro-5-cyano-phenyl) -2-dimethylamino-ethanol Melting point for the new arachloride = 187 - 189 °.

Prepared according to process a) from 4'-amino-3'-chloro-5'-cyano-2-dimethyl-amino-acetophenone and sodium borohydride analogously to Example 5.

Example 18. 1- (4-Amino-3-chloro-5-cyano-phenyl) -2-diethylamino-ethanol melting point = 69-71 °. Prepared according to process a) from 4'-amino-3'-chloro-5'-cyano-2-diethylamino-acetophenone and sodium borohydride analogously to Example 3.

Example 12. In 1- (4-amino-3-bromo-5-cyano-phenyl) -2-isopropylamino-ethanol melting point of new hydroxide = 186 - 189 °.

Prepared according to process a) from 4'-amino-3'-bromo-5'-cyano-2-isopropylamino-acetophenone and sodium borohydride analogously to Example 3.

Example 80. e - II- (4-Amino-5-bromo-α-cyano-phenyl) -2-tert-butylamino-ethanol Melting point of hydrochloride 213-2150.

Prepared according to process a) from 4'-amino-3'-chromo-2-tert-butylamino--5'-cyano-acetophenone and sodium borohydride analogously to Example 3, Example 81. a 1- (4-amino-3- bromo-5-cyano-phenyl) -2-diethylamino-ethanol melting point = 72-74 °.

Prepared according to process a) from H'-amino-3'-bromo-5'-oyan-2-diethyl-. aminoacetophenone and sodium borohydride analogously to Example 5.

Example 82. 1- (4-Amino-3-bromo-5-carboxy-phenyl) -2-tert-butylamino-ethanol melting point = from 218 ° (sonar el.

Prepared according to process a) from 4'-amino-3'-bromo-2-tert.-butylamino--5'-carboxy-acetophenone and sodium borohydride analogously to Example 3. Example 83. 1 - (§-amino-5-chloro-5-methoxy-phenyl) -2-tert-butylamino-ethanol Melting point of the hydrochloride: 175 ~ 1780 (decomposition).

Prepared according to process a) from 4'-amino-2-tert-butylamino-5'4-chloro-5'-methoxy-acetophenone hydrochloride and sodium borohydride analogous to Example 1.

Example 8ü. 1- (4-amino-5-bromo-3-hydroxymethyl-phenyl) -2-dimethylamino-ethanol melting point = 87 - 92 ° § Prepared according to process b) by bromination of 1- (4-amino-3-hydroxymethyl -phenyl) -2-dimethylaminoethanol analogous to Example 6.

Example 85. 1 1- (4-Amino-5-bromo-3-dimethylaminomethyl-phenyl) -2-tert-butylamino-ethanol mp = 127-129 °.

Prepared according to process b) by bromination of 1- (4-amino-} - dimethylaminomethyl-phenyl) -2-tert-butylamino-ethanol analogous to Example 6.

Example 86. 1- (4-Amino-5-bromo-3-dimethylaminomethyl-phegyl) -2-dimethylamino-ethanol Prepared according to method b) by bromination of 1- (4-amino--3-dimethylaminomethyl-phenyl) -2 -dimethylamino-ethanol analogous to Example 6 Structural evidence by NMR spectrum (CDCl / CD OD): 2.2 ppm singlet / 6 protons, N (CH5) 2 / Q 2.35 ppm singlet / 6 protons, N (CH 2) 2 / §'1.8 - 3.0 ppn multiplet (2 protons, CH2), 3.45 ppm singlet (2 protons, CH2), 4, ü - 4.8 ppm multiplet (1 proton, CH), 6, 96 ppm doublet and 7, Ä ppm doublet (2 aromatic protons).

Example 87. 2-Epylamino-1- (4-amino-3-fluoro-phenyl) -ethanol "melting point of the hydrochlorene = 187-188 ° (decomposition) 1 Prepared according to method o) from 1- (4-acetylamino-3- fluoro-phenyl) -2--ethylamino-ethanol and sodium hydroxide analogous to Example 7.

Example 88. 1- (4-Amino-3-fluoro-fepyl) -2-isopropylamino-ethanol melting point for hydrochloride = 156 - 158 ° (decomposition).

Prepared according to process c) from 1- (N-acetylamino-3-fluoro-phenyl) -2-isopropylamino-ethanol and sodium hydroxide analogous to Example 7.

Example 89. 1- (4-Amino-5-fluoro-phenyl) -2-tert-pentylamino-ethanol melting point of the new chloride = 153 - 155 ° (solar unit).

Prepared according to process c) from 1- (4-acetylamino-5-fluoro-phenyl) -2-tert-pentylamino-ethanol and sodium hydroxide analogously to Example 7. Example 90. 1- (4-Amino-ethanol). 3-Fluoro-phenyl) -2-dimethylamino-ethanol Prepared according to process c) from 1- (4-acetylamino-3-fluoro-phenyl) -2-dimethylamino-ethanol and sodium hydroxide analogous to Example 7. Oil; structural evidence by IR and UV spectra. IR (CH 2 Cl 2): OH free at 5550 μm -1, NH 2 v 1a 5570 and 5n 50 am'1, one associates at 5200 - - 5500 am'l, N (cH-) 2 at 2780 and 2850 am'l, aromatic text c = c at 1655 am'1. uv (ethano1) = Maxima at 258 nm (E = 0.6) and 288 nm (E = 0.13).

Example 2. 1- (4-Amino-3-fluoro-phenyl) -2-diethylamino-ethanol melting point for nyraxylarane = 122-125 ° (sonaration).

Prepare according to method C) from 1- (h-acetylamino-5-fluoro-phenyl) -2-diethylamino-ethanol and sodium hydroxide analogously to Example 7.

Example 92. 1- (N-Amino-β-dimethylaminomethyl-phenyl) -2-tert-butylamino-ethanol melting point = 55-59 °.

Prepared according to process c) by saponification of 1- (4-acetylamino--5-dimethylaminomethyl-phenyl) -2-tert-butylaminoethanol with sodium hydroxide / ethanol analogous to Example 7.

Example 93. 1- (4-Amino-3-dimethylaminomethyl-phenyl) -2-dimethylamino-ethanol Prepared according to process c) by saponification of 1- (α-acetylamino-3-dimethylaminomethyl-phenyl) -2-dimethylamino-phenyl ethanol with sodium hydroxide / ethanol analogous to Example 7.

Structural evidence by NMR spectrum (CDCl3): 2.2 ppm singlet / 5 protons, N (CH3) 2 /, 2.35 ppm singlet / 6 protons, N (CH5) 2 /, 1.6-2.9 ppm multi - spot (2 protons, CHF), 5.42 ppm singlet (2 protons, QHP), 4.4-4.8 ppm multiplet (1 proton, CH), 6.6 ~ 7.18 ppm multiplet (3 aromatic protons ).

Examples go. 1- (4-Amino-} -hydroxylmethyl-phenyl) -2-tert-butylamino-ethanol m.p. = 125 DEG-128 DEG. Prepared according to process e) from 1- (4-amino-3-hydroxymethyl-phenyl) -2- - (N-benzyl-N-tert-butyl) -amino-ethanol with hydrogen in the presence of palladium-activated carbon analogous to Example 13.

Example 95. 1- (H-amino-5-chloro-5-hydroxymethyl) -2-tert-butylaminoethanol Prepared according to method c) from 1- (H-amino-5-chloro-5-hydroxymethyl) -phenyl) -2e (N-benzyl-Natert-butyl) -amino-ethanol with hydrogen in the presence of palladium-activated carbon analogous to Example 15. Structural evidence by NMR spectrum (CDCl5): 1.1 ppm singlet / 9 protons, c (cH5) 3/3 2.0-3.6 ppm multiplet (2 prpcpner, cH2), 4.6 ppm singlet (2 protpner, CHQ), 4,2-n, 6 ppm multiplet (1 prptpm, 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 °. Prepared according to process d) from 1- (4-amino-3-bromo-5-trifluoromethyl-phenyl) -E-isopropylaminoethanol and catalytically active hydrogen analogously to Example 14.

Example 97. 1-1α-Amino-3-trifluoromethyl-phenyl) -2-dimethylamino-ethanol mp = 64-66.5 °.

Prepared according to process d) from 1- (4-amino-3-bromo-5-trifluoromethyl-phenyl) -2-dimethylamino-ethanol hydrochloride and catalytically active hydrogen analogously to Example 14.

Example 98. 1- (4-Aminophen 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 active hydrogen analogous to Example 14.

Oil; thin layer chromatographically uniform (Rf value: 0.2; S102; chloroform-methanol: concentrated ammonia = 90: 10: 1); Elemental analysis: C 12 H 17 F 5 N 2 O (262.3) Calculated: c 54.95 H 6.53 N 10.68% Found = c 54.70 H 6.55 N 10.68%.

Example 99. 1- (4-Amino-3-trifluoromethyl-phenyl) -2-diethylamino-ethanol Prepared according to method d) from 1- (4-amino-3-bromo-5-trifluoromethyl-phenyl) -2 -diethylamino-ethanol-hydrochloride and catalytically active hydrogen analogously to Example 1a.

Oil; thin layer chromatographically uniform (Rf value: ^ «0.3, S102, chloroform-methanolzconc.ammoniak = 90: 10: 1); structural evidence by NMR spectrum (CDCl3): 1.1 ppm triplet / 6 protons, N (CH2-§§3) 2 /, 2.55 ppm multiplet / 6 protons, N (CH2-) 3 / Q 4, 5 ppm multiplet (1 proton, CH), 6.7 ppm doublet and 7.5 ppm doublet (2 aromatic protons).

Example 100. 1- (4-Amino-3-methyl-phenyl) -2- (N-benzyl-N-tert-butyl) -amino-ethanol melting point of the dihydropropylene = from 145 ° (sonication).

Prepared according to process d) from 1- (4-amino-3-bromo-5-methyl-phenyl) -2- (N-benzyl-N-tert-butyl) -amino-ethanol with catalytically active hydrogen analogously to Example 16.

Example 10l. 1- (E-amino-3-cyano-phenyl) -2-isopropylamino-ethanol mp = 159-161 °.

Prepared according to process d) from 1- (4-amino-5-bromo-5-cyano-phenyl) -2-isopropylamino-ethanol and catalytically active hydrogen analogously to Example 16.

Example gel 102. 1- (4-amino-3-cyano-phenyl) -2-tert-butylamino-ethanol m.p .: 181-185 °.

Prepared according to process d) from 1- (4-amino-3-bromo-5-cyano-phenyl) -2-tert-butylamino-ethanol and catalytically active hydrogen analogously to Example 16.

Example gel 102. 1- (4-amino-3-gyan-phenyl) -2-dimethylamino-ethanol melting point of the dinhydrochloride; 130 - 135 ° (decomposition).

Prepared according to process d) from 1- (4-amino -} - bromo-5-cyano-phenyl) -2- -dimethylamino-ethanol with catalytically active hydrogen analogously to Example 1f Exemgel 104. 1- (h-afphino- fi- cyano-phenyl) -2-diethylamino-ethanol Prepared according to process d) from 1- (4-amino-3-bromo-5-cyan-phenyl) -2-diethylamino-ethanol and catalytically active hydrogen analogously to examples 16.

Oil; Elemental analysis: C 15 H 19 N 5 O (233.3) 'Calculated: C 67.00 H 8.20 N 18.00% Found =' c 67, oo H 8, no N 17.81%. 2 Exemgel lO§. 5- (N-amino-} -bromo-5-fluoro-phenyl) -5-tert-butyloxazolinedine Melting point of the dihydrochloride: 164-178 ° (dec.).

Prepared from 1- (4-amino-3-bromo® 5-fluoro-phenyl) -2-tert-butylamino-ethanol and HO% formaldehyde solution analogous to Example 20.

Example_lQ§. 1- (4-amino-3-chloro-5-trifluoromethyl-phenyl) -2-tert-butylamino-ethanol Melting point of the hydrochloride: 205-2070 (decomposition).

Prepared according to process c) from 2-tert-butylamino-1- [3-chloro-4- (p-chloro-benzoylamino) -5-trifluoromethyl-phenyl] -ethanol and sodium hydroxide analogous to Example 8.

Example gel 107. 1- (4-amino-5-fluoro-phenyl) -2-tert-butylamino-ethanol Melting point of the hydrochloride: 196 - 1970 (decomposition). Prepared according to process c) from 1- (4-benzoylamino-5-fluoro-phenyl) -2-tert-butylaminoethanol and sodium hydroxide analogous to Example 7.

Example 108. 1- (β-Amino-3-chloro-5-fluoro-phenyl) -β-tert-butylamino-ethanol-Melting point of the hydrochloride; 206 - 208 ° (dec.).

Prepared according to process c) from 2-tert-butylamino-1- (} -chloro-5-fluoro-4-propionylamino-phenyl) -ethanol and sodium hydroxide analogously to Example 7.

Example gel 109. In 1- (4-amino-3-bromo-5-trifluoromethyl-phenyl) -2-cyclopentylamino-ethanol Melting point: 100 - 102.50 (decomposition).

Prepared according to process a) from 4'-amino-3'-bromo-2-cyclopentyl-amino-5'-trifluoromethyl-acetophenone hydrochloride and sodium borohydride analogously to Example 2.

Example gel 110. 1- (4-Amino-3-bromo-5-cyano-phenyl) -2-cyclopropylamino-ethanol 7.5 g of 4'-amino-3'-bromo-5'-cyano-2-cyclopropylamino-acetophenone, dissolved in 200 ml of tetrahydrofuran and 100 ml of water, added at room temperature with 3 g of sodium borohydride and stirred for 1 hour; Excess sodium borohydride was decomposed by the addition of acetone. The insoluble matter was filtered off and the solvent was distilled off in vacuo; the residue was dissolved in hot isopropanol and by adding hydrochloric acid / isopropanol the hydrochloride of 1- (4-amino-3-bromo-5-cyano-phenyl) -2-cyclopropylamino-ethanol was obtained which was recrystallized from isopropanol. melting point: 190 - 193 ° (sonar formation).

Exemgel lll. 1- (4-Amino-3-bromo-5-fluoro-phenyl) -2-cyclobutylamino-ethanol a) 20 g of 4'-amino-3'-bromo-5 '-fluoro-acetophenone were dissolved in 300 ml of roform. While stirring slowly, a solution of β3 ml of bromine in 20 ml of chloroform was added dropwise with stirring. After the addition was complete, the mixture was stirred for another 5 minutes at boiling temperature and then cooled to room temperature. To the crude solution of 4'-amino-3 ', 2-dibromo-5'-fluoro-acetophenone was added dropwise with further stirring and under ice-cooling a mixture of 15 g of cyclobutylamine and 14 ml of triethylamine. After the addition was complete, the mixture was heated to reflux for 2 hours. After cooling, it was washed with water and the organic phase was evaporated in vacuo to dryness. The residue consisted of crude 4'-amino-3'-bromo-2-cyclobutylamino-5'-fluoro-acetophenone. b) The crude ketone obtained under a) was dissolved in 30 ml of tetrahydrofuran. The solution was added with 5 ml of water and then 4.5 g of sodium borohydride was introduced portionwise with stirring and cooling with ice.

The solution was stirred under cooling for 5 hours and then allowed to stand at room temperature overnight. Then the excess sodium borohydride was destroyed with acetone and the solution was evaporated in vacuo to dryness. The residue was partitioned between water and chloroform, the organic phase was extracted three times with 100 ml of 2N hydrochloric acid each, the combined hydrochloric acid extracts were made alkaline with sodium hydroxide and extracted with chloroform. The chloroform solution was washed with water, dried over sodium sulfate and evaporated in vacuo to dryness. The remaining residue of crude 1- (4-amino-5-bromo-5-fluoro-phenyl) -2-cyclobutylamino-ethanol was dissolved in isopropanol and acidified with hydrochloric acid / ether to pH 5. Upon addition of ether, crystallization. The precipitated hydrochloride of the desired compound was recrystallized from isopropanol.

Melting point 164 DEG-166 DEG (decomposition).

Example 112. 1f (4-Amino-3-fluoro-5-iodo-phenyl) -2-1-isopropylamino-ethanol hydrochloride 5.15 g of 1- (4-amino-3-fluoro-phenyl) -2-isopropylamino-ethanol was dissolved in 300 ml of acetic acid, added with 80 g of iodine and 4.0 g of mercuric oxide and stirred vigorously for 2.5 hours at room temperature. Then the solid was filtered off, the dark brown filtrate was decolorized with saturated sodium hydrogen sulphite solution and diluted with water to about 1 liter. While cooling, the mixture was made alkaline with 10N sodium hydroxide and extracted with chloroform. The chloroform phase was dried over sodium sulfate and evaporated in vacuo to dryness. The residue was dissolved in methanol and acidified with ethereal hydrochloric acid to pH 4.5. The solution was evaporated in vacuo to dryness and the solid residue was crystallized from absolute ethanol.

Melting point: 203 - 2050 (decomposition).

Exemgel llj. 1: 1α-amino-3-diethylaminomethyl-phenyl-2-tert, -butylamino-ethanol 6.0 g of 1- (4-acetylamino-3-diethylaminomethyl-phenyl) -2-tert-butylamino-ethanol was boiled 1 a mixture of 50 ml of ethanol and 50 ml of sodium hydroxide for 55 hours under reflux. The ethanol was then distilled off, diluted with water and extracted twice with chloroform.

The organic phase was dried over sodium sulfate and evaporated. After column chromatographic purification (silica gel; methanol), the 1- (4-amino-3-diethylaminomethyl-phenyl) -2-tert-butylamino-ethanol crystallized from petroele. smäitpunkt; 86 - 90 °. 75317035-9 38 Exemgel 114 .. 1- (4-amino-3-cyano-phenyl) -2-cyclopropylamino-ethanol 4 g 1- (4-amino-3-bromo-5-cyano-phenyl) -2-cyclopropylamino -ethanol was dissolved in methanol and hydrogenated after the addition of 1 g of palladium on carbon (10%) at room temperature and a hydrogen pressure of BF5 atm overpressure. After uptake of hydrogen was complete, the mixture was filtered from the catalyst, the filtrate was evaporated in vacuo to dryness and the residue partitioned between dilute sodium hydroxide and chloroform.

Evaporation of the chloroform phase gave 1- (4-amino-3-cyano-phenyl} -2-cyclopropylamino-ethanol as an oil, which was purified by chromatography on silica gel (eluent: chloroform-methanol = 9: 1) and crystallized from isopropanol. by adding ethereal hydrochloric acid such as dihydrochloride.

Melting point: 148 - 15 ° (decomposition).

Example 115. 2-Ethyl-5- (4-amino-3-bromo-5-fluoro-phenyl) -3-tert-butyloxazolidine 5 g 1- (4-amino-3-bromo-5-fluoro-phenyl) phenyl) -2-tert-butylaminoethanol was dissolved in 100 ml of benzene. To this was added 5 g of propionaldehyde and the mixture was heated for 6 hours with a water separator at reflux temperature. Then 5 g of propionaldehyde were added again and heated for a further 3 hours. After cooling, the mixture was evaporated to dryness in vacuo and the residue was chromatographed on a chromatographic column filled with 50 g of silica gel, using benzene as eluent. The eluate containing the substance was purified and evaporated in vacuo to dryness to give the title compound as foam. .

Structural evidence by NMR spectrum (CDCl 3): 0.7 - 1.8 ppm multiplet / 14 protons, -C (CH 5) δ and -CH 2 -CH 3 / Q - 2.5 - 2.95 and 3.1 - 3, 7 ppm 2 multiples / 2 protons Ar-en-cH2-N 4.0 - 4.3 ppm singlet / 2 protons, NH2 / fi l 4.4 - 5.2 ppm multipiet / 2 protons, Ar-gg-CHQ-N <and -o-gg-cH (cH3)? /; 6.8 - 7.35 ppm multiplet / É aromatic šrotoner /. EXAMPLE 116. 1- (4-Amino-5-bromo-5; fluoro-phenyl) -2-cyclopentylamino-ethanol Melting point of the hydrochloride: 167-170 ° (dec.).

Prepared according to process a) from 4'-amine-3'-bromo-2-cyclopentylamino-'5'-fluoro-acetophenone and sodium borohydride analogously to Example III.

Exemgel ll7. 1- (4-Amino-5-bromo-5-fluoro-phenyl) -2-cyclohexylamino-ethanol melting point of the new hydrocarbon = 191-195 ° (decomposition). Prepared according to process a) from β-amino-5'-bromo-2-cyclohexylamino--5'-fluoro-acetophenone and sodium borohydride analogously to Example III.

Example 118. 1- (4-Amino-3-bromo-5-fluoro-phenyl) -2-cycloheptylamino-ethanol melting point for hyarochlorylene: 187-189 ° (separation).

Prepared according to process a) from 4'-amino-5'-bromo-2-cycloheptylamino--5'-fluoro-acetophenone and sodium borohydride analogously to Example III.

Example 112. 1- (4-Amino-5-fluoro-5-iodo-phenyl) -2-cyclopropylamino-ethanol Melting point of the hydrochloride: 199 - 2010 (decomposition).

Prepared according to process a) from 4'-amino-2-cyclopropylamino-3'-fluoro-5'-iodo-acetophenone and sodium borohydride analogously to Example III.

Example 120. 1- (4-Amino-3-fluoro-5-iodo-phenyl) -2-isopropylaminoethanol Melting point of hydrochloride 203 - 205 ° (decomposition).

Prepared according to process a) from 4'-amino-3'-fluoro-2-isopropylamino--5'-iodo-acetophenone and sodium borohydride analogously to Example III.

Example 121. 11β-Amino-5-fluoro-5-iodo-phenyl) -2-cyclobutylaminoethanol Melting point of the hydrochloride: 197 - 1990 (decomposition).

Prepared according to process a) from 4'-amino-2-cyclobutylamino-3'-fluoro-5'-iodo-acetophenone and sodium borohydride analogously to Example III.

Example 122. 1- (4-Amino-3-fluoro-5-1cd-phenyl) -2-tert-butylamino-ethanol melting point of the new hydroxyurea; 207 - 2o9 ° (solar eclipse).

Prepared according to process a) from 4'-amino-2-tert-butylamino-3'-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 ° (dec.).

Prepared according to process a) from 4'-amino-3'-fluoro-2- (hydroxy-tert-butylamino) -5'-iodo-acetophenone and sodium borohydride analogously to Example III.

Example 12%. 2-ethylamino-1- (1H-amino-5-cyano-5-fluoro-phenyl) -ethanol m.p. 216 - 218 ° (dec.).

Prepared according to process a) from 2-ethylamino-4'-amino-5'-cyano-5'-fluoro-acetophenone and sodium borohydride analogously to Example 111.

Example 125. 1- 1- (4-Amino-3-cyano-5-fluoro-phenyl) -2-cyclopropylamino-ethanol Melting point of the hydrochloride: 188 DEG-190 DEG C. (decomposition). Prepared according to process a) from 4'-amino-3'-cyano-2-cyclopropylamino--5'-fluoro-acetophenone and sodium borohydride analogously to Example III.

Example 126. 1- (4-Amino-3-cyano-5-fluoro-phenyl) -2-isopropylamino-ethanol melting point of the new chlorochlorane = 182 - 18u ° (sonar division).

Prepared according to process a) from δ'-amino-3'-cyano-5'-fluoro-2-isopropylamino-acetophenone and sodium borohydride analogously to Example III.

Example 121. 1- (4-Amino-3-cyano-5-fluoro-phenyl) -2-cyclobutylamino-ethanol Melting point of the neochloro1aene = 222 - 224 ° (sonaration).

Prepared according to process a) from 4'-amino-3'-cyano-2-cyclobutylamino-45'-fluoro-acetophenone and sodium borohydride analogously to Example III.

Example 128. 1- (4-Amino-3-cyano-5-fluoro-phenyl) -2-tert-butylamino-ethanol Melting point of the hydrochloride: 242-2H3 ° (dec.).

Prepared according to process a) from 4'-amino-2-tert-butylamino-3'-cyano-5'-fluoro-acetophenone and sodium borohydride analogously to Example III.

Example 122. 1- (4-Amino-3-cyano-5-fluoro-phenyl) -2-cyclopentylamino-ethanol Melting point of the nehydrochlorine = 184-186 ° (solar refining).

Prepared according to process a) from 4'-amino-5'-cyano-2-cyclopentylamino-5'-fluoro-acetophenone and sodium borohydride analogously to Example III.

Example 150. 1- (4-Amino-5-cyano-5-fluoro-phenyl) -2-tert-pentylamino-ethanol Melting point of hydrochloride 172-1750 (decomposition).

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

Example 131. 1- (4-Amino-5-cyano-5-fluoro-phenyl) -2-dimethylaminoethanol Prepared according to process a) from 4'-amino-3'-cyano-2-dimethylaminoethanol. 5'-fluoro-acetophenone and sodium borohydride analogously to Example III.

Oil, structural evidence by NMR spectrum (CD30D): 2.2 - 2.65 ppm multi-OH 1 spot, / 8 pwtones; N-CH; and N-CH-CH 2 ~ N \ / 2 Ä, 6 - 4.9 ppm multiplet, H / Ä protons; 3 exchange protons and -eg-CH2-N \ / Q 7.15 - 7.4 ppm multiplet / 2 aromatic protons /.

Example l§2. 1-QR-amino-3-cyano-5-fluoro-phenyl) -2-diethylamino-ethanol Prepared according to process a) from U'-amino-3'-cyano-2-diethyl-amino-5'-fluoro-acetophenone and sodium borohydride analogously to Example III. Oil, structural evidence by NMR spectrum (CD3OD): 0.85 - 1.2 ppm triplet, / 6 protons; -N (CH2-CH3) 2 / ä 2.45 - 2.85 ppm multiplet / É protons; -N (cH2-cH3) 2 and -en-öñš-N ~ __ ___ OH led / Ä protons; 3 exchange protons and -š fi - CH2- /; 7.1 - 7.4 ppm mnltiplett / Q aromatic protons /.

Example 133-. (1-Amino-3-trifluoromethyl-phenyl) -Eficyclopropylmethyl-amino) -ethanol Melting point of the hydrochloride: 122 - 1270 (decomposition; from 1100 bleaching), Prepared according to method d) from 1- (H-amino-3-bromo- 5-Trifluoromethyl-phenyl) -2- (cyclopropylmethyl-amino) -ethanol and catalytically active hydrogen analogous to Example 114.

Example 134. 1- (4-Amino-3-trifluoromethyl-phenyl) -2-cyclopentylamino-ethanol melting point of hyaroxylorene = 1 hn - 145 °.

Prepared according to process d) from 1- (4-amino-3-bromo-5-trifluoromethyl-phenyl) -2-cyclopentylaminoethanol and catalytically active hydrogen analogously to Example 114.

Example lßâ. 1- (4-amino-5-chloro-5-trifluoromethyl-phenyl) -2- (cyclopropylmethyl-amino) -ethanol melting point of the hydrochloride = 186 - 187 ° (dec.).

Prepared according to process a) from 4'-amino-5'-chloro-2- (cyclopropylmethyl-amino) -5'-trifluoromethyl-acetophenone and sodium borohydride analogously to Example 110.

Example gel 136. 1- (4-Amino-3-chloro-5-trifluoromethyl-phenyl) -2-cyclopentylamino-ethanol Melting point of the hydrochloride: 188-190 ° (dec.).

Prepared according to process a) from 4'-amino-3'-chloro-2-cyclopentylamino--5'-trifluoromethyl-acetophenone and sodium borohydride analogously to Example 110.

Example gel 131. o 1- (4-amino-3-chloro-5-trifluoromethyl-phenyl) -2-cyclohexylamino-ethanol Melting point of the hydrochloride: 213 - 9140 (decomposition).

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

Example 138. g of 1- (4-amino-3-chloro-5-trifluoromethyl-phenyl) -phe-cycloheptylamino-ethanol Melting point of the hydrochloride: 165 - 1650. option 7317035-9 'ne _ dd - Prepared according to process a) amino-3'-chloro-2-cycloheptylamino--5'-trifluoromethyl-acetophenone and sodium borohydride analogously to Example 110.

Example gel 122. 1a (4-amino-3-bromo-5-trifluoromethyl-phenyl) -2- (cyclopropylmethyl-amino) -ethanol Melting point of the hydrochloride: 173 - 1750 (decomposition).

Prepared according to process a) from 4'-amino-3'-bromo-2- (cyclopropylmethyl-amino) -5'-trifluoromethyl-acetophenone and sodium borohydride analogous to Example 110.

Example Gel 140. 1- (4-Amino-3-cyano-phenyl) -2-cyclobutylamino-ethanol Melting point of hydrobromidenz from 93 °, decomposition.

Prepared according to process d) from 1- (4-amino-3-bromo-5-cyano-phenyl) -2-cyclobutylamino-ethanol and catalytically active hydrogen analogously to Example 110. 7 Example gel. 1- (4-amino-3-cyano-phenyl) -2-cyclopentylamino-ethanol melting point = 158-160 °.

Prepared according to process d) from 1- (4-amino-3-bromo-5-cyano-phenyl) -2--cyclopentylamino-ethanol and catalytically active hydrogen analogously to Example 110. 8 Example Gel 142, 1:14 amino -5-cyano-phenyl) -2-tert.; Gentylamino-ethanol m.p. = 143 °.

Prepared according to process d) from 1- (4-amino-3-bromo-5-cyano-phenyl) -2-tert-pentylamino-ethanol and catalytically active hydrogen analogously to Example 110.

Example 142. 1- (4-Amino-3-chloro-5-cyano-phenyl) -2-cyclopropylamino-ethanol melting point of the new chlorochlorine = 175-177 °.

Prepared according to process a) from 4'-amino-3'-chloro-5f-cyano-2-cyclopropylamino-acetophenone and sodium borohydride analogously to Example 110.

Exemgel lüü. 1- (α-Amino-3-chloro-5-cyano-phenyl) -2-propylaminoethanol melting point for the new arocane = 187 - 189 °.

Prepared according to process a) from 4'-amino-3'-chloro-5'-oyan-2-propylamino-acetophenone and sodium borohydride analogously to Example 110.

Example Gel 145. 1- (4-Amino-3-chloro-5-cyano-phenyl) -2-cyclobutylamino-ethanol Melting point of the new hydrochloride = 178 DEG-180 DEG (decomposition) - 43 DEG-17 DEG C. 9A Prepared according to method a) from 4 ' -amino-5'-chloro-5'-cyano-2-cyclobutylamino-acetophenone and sodium borohydride analogously to Example 110.

Example 146. 1- (N-amino-} -chloro-5-cyano-phenyl) -2-sec-butylamino-ethanol melting point of the new oxide = 190 - 191 °.

Prepared according to process a) from 4'-amino-2-sec-butylamino-5'-chloro--5'-cyano-acetophenone and sodium borohydride analogously to Example 110.

Example gel 141. 1- (N-amino-3-chloro-5-cyano-phegyl) -2- (hydroxy-tert-butylamino) -ethanol Melting point of the by-chloride: 228 - 230 ° (decomposition).

Prepared according to process a) from H'-amino-3 '-chloro-5'-cyano-2- (hydroxy-tert-butylamino) -acetophenone and sodium borohydride analogous to Example 110.

Example 148. 1- (4-Amino-} -chloro-5-cyano-phenyl) -2-cyclopentylamino-ethanol melting point for the new smoke = 138 - 144 °.

Prepared according to process a) from 4'-amino-3'-chloro-5'-cyano-2-cyclopentylamino-acetophenone and sodium borohydride analogously to Example 110.

Example 149. 1 1- (4-Amino-3-chloro-5-cyanophenyl) -2-tert-pentylaminoethanol Melting point for the new smoke = 218 DEG-220 DEG (sunflower).

Prepared according to process a) from 4'-amino-3'-chloro-5'-oyan-2-tert-pentylamino-acetophenone and sodium borohydride analogously to Example 110.

Example Gel 15o.- 1- (4-Amino-3-chloro-5-cyan-phenyl) -2-cycloheptylamino-ethanol Melting point of the hydrochloride: 235-237 ° (dec.).

Prepared according to process a) from 4'-amino-3'-chloro-5'-cyano-2-cycloheptylamino-acetophenone and sodium borohydride analogously to Example 110.

Exemgel lâl. 1- (β-amino-3-chloro-5-cyano-phenyl) -2- [1- (3,4-methylenedioxy-phenyl) -2-propylamino] -ethanol melting point of the hydroxide = 189-119 °.

Prepare according to process a) from 4'-emine-5'-xylor-5'-cyano-2- [1- (3,4-methylendloxy-phenyl) -2-propylamino] -acetophenone and sodium borohydride analogous to Example 110.

Exemgel 1§2. 1- (4-amino-3-bromo-5-cyano-phenyl) -2-cyclobutylamino-ethanol Melting point of the hydrochloride: 215-216 ° (dec.).

Prepared according to process a) from 4'-amino-3'-bromo-5'-cyano-2-cyclo-butylamino-acetophenone and sodium borohydride analogously to Example 110. 7317035-9 c now Example 152. 1- (4-amino- 3-bromo-5-cyano-phenyl) -2- (hydroxy-tert-butylamino) fetanol Melting point of the hydrochloride: 221 - 2220.

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

Example 1- 1- (4-Amino-3-bromo-5-cyano-phenyl) -2-cyclopentylamino-ethanol smalupunk for the new hydrochloride; 177 °.

Prepared from 4'-amino-3'-bromo-5'-cyano-2-cyclopentylamino-acetophenone and sodium borohydride analogously to Example 110.

Example 155. 1- (Efamino-3-bromo-5-cyano-phenyl) -2-tert-pentylamino-ethanol c melting point of the new hydrochloride; 202 - 2o1 + ° (decomposition).

Prepared according to process a) from 4'-amino-3'-bromo-5-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 for the hyarokioria: 209 - 220 ° (decomposition).

Prepared according to process a) from 4'-amino-3'-bromo-5'-cyano-2-cyclohexylamino-acetophenone and sodium borohydride analogously to Example 110.

Example 151. 1- (4-Amino-3,5-dicyan-phenyl) -2-cyclopropylamino-ethanol Melting point of the hydrochloride: 222 - 2230 (decomposition).

Prepared according to process a) from 4'-amino-2-cyclopropylamino-3 ', 5'-dicyane-acetophenone and sodium borohydride analogously to Example 110.

Example l§8. 1- (4-amino-3,5-dicyan-phenyl) -2-isopropylamino-ethanol melting point for the neodrecioria; 224 - 226 ° (dec.).

Prepared according to process a) from 4'-amino-5 ', §'-dicyan-2-isopropylamino-acetophenone and sodium borohydride analogously to Example 110.

Example 159. 1-LH-amino-3,5-dicyan-phenyl) -2-cyclobutylamino-ethanol Melting point of the hydrochloride: 258 ° (decomposition).

Prepared according to process a) from 4'-amino-2-cyclobutylamino-3 ', 5'- -dicyane-acetophenone and sodium borohydride analogously to Example 110.2 Example 160. 1-LH-amino-3,5-dicyan-phenyl) -2 -sec / butylamino-ethanol Melting point of the hydrochloride: 197 - 1990.

Prepared according to process a; from 4'-amino-2'-sec-butylamino-3 ', 5'-dicyano-acetophenone and sodium borohydride analogously to Example 110. Example Gel 161. 1- (4-Amino-3,5-dicyan -phenyl) -2-tert-butylamino-ethanol narrowing point for new chloroyldenium = 251 - 253 ° (sonareling).

Prepared according to process a) from 4'-amino-2-tert-butylamino-3 ', 5'-dioyanacetophenone and sodium borohydride analogously to Example 110.

Example Gel 162. A 1- (4-Amino-3,5-dicyan-phenyl) -2- (hydroxy-tert-butylamino) -ethanol melting point of the hydrochlorylene; 240 - 241 ° (south division).

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

Example 162. 1- (4-Aminophae, 5-dieyan-phenyl) -2-cyclopentylamino-ethanol melting point for the new hydroxyl chloride = 214-216 °.

Prepared according to process a) from 4'-amino-2-cyclopentylamino-3 ', 5'-dicyan-aetophenone and sodium borohydride analogously to Example 110.

Example gel 164. 2 1- (4-amino-3,5-dicyan-phenyl) -2-tert-pentylamino-ethanol Melting point of the hydrochloride: 231 - 253 ° (dec.).

Prepared according to process a) from 4'-amino-3 ', 5'-dicyan-2-tert.-pentylamino-acetophenone and sodium borohydride analogously to Example 110.

Example 165. 1- (N-Amino-3,5-dicyan-phenyl) -2- [1- (3,4-methylenedioxy-phenyl) -2-propylamino] -ethanol Melting point of the hydrochloride: 219-222 (dec. ).

Prepared according to process a) from 4 '-amino-3', 5'-dicyan-2- [1- (3, H--methylenedioxy-phenyl) -2-propylamino] -acetophenone and sodium borohydride analogous to Example 110.

Example 166. 1- (4-Amino-3-chloro-5-diethylaminomethyl-phenyl) -2-tert-butylamino-ethanol m.p. = 65-69 °.

Prepared according to process a) from 4'-amino-2-tert-butylamino-3'-chloro-5'-diethylaminomethyl-acetophenone and sodium borohydride analogously to Example 110.

Example 167. 1- (4-Amino-3-bromo-5-diethylaminomethyl-phenyl) -2-tert-butylamino-ethanol m.p. = 96-100 °.

Prepared according to process a) from 4 '-amino-3'-bromo-2-tert-butylamino-5'-diethylaminomethyl-acetophenone and sodium borohydride analogously to Example 110. 7317035-9 Ä6 Example 168. 1- (4 -amino-3-chloro-5-nitro-phenyl) -2-tert-butylamino-ethanol melting point = 148 - 149 °.

Prepared according to process a) from 4'-amino-2-tert-butylamino-3'-chloro-5'-nitro-acetophenone and sodium borohydride analogously to Example 110.

Example 162. 1- (4-Amino-bromo-5-nitro-phenyl) -2-tert-butylamino-ethanol m.p. = 151-152 °.

Prepared according to process a) from 4'-amino-3'-bromo-2-tert-butylamino--5'-nitro-acetophenone and sodium borohydride analogously to Example 110.

Example 120. 5- (4-Amino-3-b-fomo-5-fluoro-phenyl) -3-tert-butyl-f-isopropyl-oxazolidine Prepared from 1- (4-amino-5-bromo-5-fluoro-phenyl -2-tert-butyl-aminoethanol and isobutyraldehyde analogously to Example 115.

Amorphous substance; structural evidence by NMR spectrum (CDCl 3) 0.85 - 1.2 ppm ¿multipletc / 15 protons, -c (cH) and) cH-cH (cH¿) 2 /; 1.5 - 1.85 ppm multiplet / 1 proton, p) cH-gg (cH3) 2/3 2.5 - 2, § “56E 3.2 - 3.7 ppm 2 multiplets / 2 protons, Ar -çH-CH2-Nif / 2 5.9 - 4.2 ppm singlet / 2 protons, NH2 /; 4.4 - 4.9 ppm multiplet / P protons, Ar-CH-CH2-Ni and -O-gg-çH (CH3) 2 / § 6.8 - 7.3 ppm multiplet / 2 aromatic protons /.

Example 171. 5- (4-Amino-5-bromo-5-fluoro-phenyl) -3-tert-butyl-oxazolidine melting point for the dihydroxylurea = 164-178 ° (separation).

Prepared from 1- (U-amino-3-bromo-5-fluoro-phenyl) -2-tert-butylamino-ethanol and formaldehyde analogous to Example 115.

Example 112. - 5- (4-Amino-3-chloro-5-trifluoromethyl-phenyl) -3-tert-butyl-2-methyl-oxazolidine '* melting point for the new hydroxylurea = 199-220 ° (sonar division).

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

Example 172. 1-1- (4-amino-5-fluoro-phenyl) -2-tert-butylamino-ethanol and d-1- (4-amino--3-fluoro-phenyl) -2-tert.- butylamino-ethanol a) 11- (4-acetylamino-5-fluoro-phenyl) -2- (N-benzyl-N-tert-butyl) -amino-O- (N-carbobenzoxy-Lphanyl) -ethanol and dl - (4-Acetylamino-5-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 1-300 ml of absolute tetrahydrofuran, 14.5 g of N, N'-carbonyldiimidazole were added and the mixture was stirred for 3 hours at room temperature. Then a solution of 10 gd, 11- (4-acetylamino-3-fluorophenyl) -2- (N-benzyl-N-tert-butyl) -amino-ethanol in 200 ml of absolute tetrahydrofuran and a pea-sized piece of sodium was added and stirred for 12 days at room temperature. The mixture was then evaporated to dryness in vacuo and the residue partitioned between chloroform and water. The chloroform phase was dried over sodium sulfate and evaporated in vacuo to dryness. The two diastereomeric esters thus obtained, mixed, showed different Rf values by thin layer chromatography (silica gel G, Merck; chloroform: acetone = 10: 1).

The above evaporation residue was purified over a silica gel chromatography column, without separating the diastereomeric esters. (500 g silica gel; eluent Chloroform acetone = 10: 1).

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

/ B / âg4 = 10101 ° (c = 2.0; methanol); Rf value = 0.27. The mother liquor obtained above was evaporated in vacuo to dryness.

The diastereomeric ester with the largest Rf value (Br = 0.33) was isolated over a chromatography column (100 g silica gel; eluent: Chloroform acetone = 20: 1): Colorless oil, consisting of dl- (4-acetylamino -3-Fluoro-phenyl) -2- (N-benzyl-N-tert-butyl) -amino-O- (N-carbobenzoxy-L-alanyl) -ethanol. / a / âgä = _65? (e .-. 2.0; methanol), Rf value = 0.33. b) g 11- (4-amino-5-fluoro-phenyl) -2-tert-butylamino-ethanol 2 g 1-1- (4-acetylamino-5-fluoro-phenyl) -2- (N-benzyl- N-tert-butyl) -amino-O- (N-carbobenzoxy-L-alanyl) -ethanol was dissolved in 60 ml of ethanol.

The solution was added with 20 ml of 5N sodium hydroxide and heated for 4 hours at reflux temperature. After cooling, the mixture was partitioned between chloroform and water and the aqueous phase was extracted four more times with chloroform. The combined chloroform solutions were dried over sodium sulfate and evaporated in vacuo to dryness. The residue, consisting of 11- (4-aceto-3-fluoro-phenyl) -2- (N-benzyl-N-tert-butyl) -aminoethanol, was dissolved in 50 ml of methanol and acidified with hydrochloric acid / ether to pH 6, was added with 0.2 g of palladium on carbon (10%) and hydrogenated at room temperature and 5 atm. pressure in a Parr device until no more hydrogen is absorbed. After sucking off the catalyst, the mixture was evaporated in vacuo to dryness and the solid residue consisting of 11- (4-amino-3-fluoro-phenyl) -2-tert-butylamino-ethanol hydrochloride was crystallized from isopropanol after addition of ether. 7317035 -9 48 melting point; 199 DEG-200 DEG (solar water) / .alpha. = -123.3 DEG (C = 1.0; methanol). c) dl- (4-amino-3-fluoro-phenyl) -2-tert-butylamino-ethanol The oily dl- (4-acetylamino-3-fluoro-phenyl) obtained above - -2- - (N-benzyl- The N-tert-butyl) -amino-O- (N-carbobenzoxy-L-alanyl) -ethanol was dissolved in 30 ml of ethanol. The solution was added with 10 ml of 5N sodium hydroxide and heated to reflux for 4 hours. After cooling, the mixture was partitioned between chloroform and water and the aqueous phase was extracted four more times with chloroform.

The combined chloroform solutions were dried over sodium sulfate and evaporated in vacuo to dryness. The residue, consisting of d-1- (4-amino-3-fluoro-phenyl) -2- (N-benzyl-N-tert-butyl) -amino-ethanol, was dissolved in 25 ml of methanol and acidified with ethereal hydrochloric acid to pH 6, was added with 0.1 g of palladium on carbon (10%) and hydrogenated at room temperature and 5 atm. pressure in a Parr device until no more hydrogen is absorbed. After the catalyst was filtered off with suction, the mixture was evaporated to dryness in vacuo and the solid residue, consisting of dl- (4-amino-3-fluoro-phenyl) -2--tert-butylamino-ethanol hydrochloride, was crystallized from isopropanol after the addition of ether. melting point = 198 - 200 ° (south division).

/ G / ê24 = + 124.4 ° (c = 1, lä2; methanol).

Example gel 124. dl- (4-amino-5-chloro-5-trifluoromethyl-phenyl) -2-tert-butylamino-ethanol and 1-1- (4-amino-3-chloro-5-trifluoromethyl-phenyl) - 2-tert-butylamino-ethanol a) d, 11- (4-amino-3-chloro-5-trifluoromethyl-phenyl) -2-tert-butylamino-O-O (-); mentoxycarbonyl / Letanol To a solution of 8.8 gd, 1- (1- (4-amino-3-chloro-5-trifluoromethyl-1-phenyl) -2-tert-butylamino-ethanol in 50 ml of pyridine was added dropwise with stirring and at 20 ° 56.6 ml of a 0.5 molar solution of chloroformic acid - (-) - menthyl ester in toluene. After 2 hours, the solution was evaporated in vacuo to dryness. The oily residue was first decomposed with water and taken up after decanting the supernatant solution into ether. The ethereal solution was washed successively with water, 2n ammonia (whereby a precipitate falling between the phases goes into solution) and again with water. The ether solution dried with magnesium sulphate was brought to pH 6 with Än isopropanolic hydrochloric acid. The mixture of the hydrochloride of the said diastereomeric compounds crystallized out. It was filtered off and washed with ether. In thin layer chromatograms, silica gel G, Merck, with butyl acetate: cyclohexane = 9: 1 showed the crystallizate two equally strong spots with approximate Rf values of 0.45 and 0.55. b) Separation of d- and 1-1- (4-amino-5-chloro-5-trifluoromethyl-phenyl) -2-tert-butylamino-O- [11-mentoxycarbonyl] methanol 3.0 g of the above-obtained mixture of the hydrochloride of d- and 1-1- (4-amino-3-chloro-trifluoromethyl-phenyl) -2-tert-butylamino-O- - ((-) - mentoxycarbonyl / Letanol was suspended in a small amount of water, shaken with ether, added with 5.0 ml of 2N ammonia and shaken until everything is dissolved. The ether phase was separated, washed with water, dried over sodium sulfate and evaporated in vacuo. The oily residue was chromatographed on a silica gel column (6.5 cm in diameter, 107 kg in length, 2.2 kg of silica gel) with a mixture of butyl acetate and cyclohexane (19: 1) (flow rate 120 ml / hour). Pure fractions with an Rf value of 0.55 were combined and freed from solvent in vacuo. The residue was crystallized from petroleum ether (b.p.: 40-60 °). D-1- (4-Amino-3-chloro-5-trifluoromethyl-phenyl) -2-tert-butylamino-O - [(-) - mentoxycarbonyl] ethanol was obtained. melting point: 95, 5 - 96, 5 °. / 5 / §2¿ = + 74.1 ° (c = 1.0; chloroform).

When the fractions containing the mixtures of the diastereomeric compounds were separated and those which could be added a further chromatographic separation, the fractions containing the solid were combined with an Rf value of 0.45 and evaporated in vacuo. Recrystallization once of the residue obtained from petroleum ether gave chromatographically pure 1-1- (4-amino-5-chloro-5-trifluoromethyl-phenyl) -2-tert-butylamino-O - / (- ) -mentoxycarbonyl / acetanol.

Melting point: 102 - 1040. / a / sg, = -273.5 ° (c = 1.0; chloroform). c) dl- (4-amino-3-chloro-5-trifluoromethyl-phenyl) -2-tert-butylamino-ethanol 1.6 g dl- (4-amino-5-chloro-5-trifluoromethyl-phenyl) -2-tert-Butylamino-O - [(-) - menthoxycarbonyl / letanol was dissolved in 16 ml of methanol and allowed to stand for 65 hours at about 200. The mixture was evaporated in vacuo and the residue was purified by column chromatography (silica gel; chloroform nolz-concentrated ammonia = 90: 10: 1). The fractions of the desired substance were combined and evaporated in vacuo. The residue was dissolved in ethyl acetate and the solution was added with the calculated amount of 4N hydrochloric acid in isopropanol, whereby the hydrochloride of the said compound crystallized out.

Melting point: Slow decomposition over 1940.

/ Dr / ÉÉÄ = + 154.9 ° (c = -. 1.0; methanol). 7317035-9? 50 g i _. 1) (11- (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-phenyly-2-tert-butylamino-O - [(-) - menthoxycarbonyl] ethanol by solvolysis with methanol and chromatographic purification analogous to the example of the enantiomeric compound.

Melting point of the hydrochloride: over 94 ° C slow decomposition. / byšâg = -154.80 (c = 1.0; methanol).

Example 115. dl- (4-amino-3-bromo-5-fluoro-phenyl) -2-tert-butylamino-ethanol and 1-1- (α-amino-5-bromo-5-fluoro-phenyl) Q-tert-butylamino-ethanol 205 gd, 11- (4-amino-3-bromo-5-fluoro-phenyl) -2-tert-4-butylamino-ethanol and 118 g of dibenzoyl-D-tartaric acid were dissolved in 2.5 liters of hot ethanol, filtered and allowed to stand for one day at room temperature to crystallize. The resulting product was recrystallized 6 times from methanol-ether to give the pure d- [1- (α-amino-5-bromo-5-fluoro-phenyl) -2-tert-butylamino-ethanol / α-dibenzoyl- Dftartrate with melting point 206 - 208 ° _ (decomposition). fi q (3âg = + 332.9 ° (c = 2.0; methanol). The salt was dissolved in methanol and concentrated ammonia while heating and the base was crystallized by adding water.

The base obtained was dissolved in absolute ethanol, neutralized with absolute ethanolic hydrochloric acid and the crystallization of d1- (α-amino-3-prom-5-fluoro-phenyl) -2-tert-butylamino-ethanol-hydrochloride was completed. it by adding ether. melting point = 234 - 235 ° (decomposition). x / bar: = + 132.0 ° (c = 2.0; methanol).

The mother liquor of the precipitate of d- [1- (4-amino-3-bromo-5-fluoro-phenyl) -2-tert-butylamino-ethanol / dibenzoyl-D-tartrate and the first from the recrystallization were combined, evaporated to a smaller volume and by adding concentrated ammonia and water the base was precipitated. 10 g of 1- (4-amino-3-bromo-5-fluoro-phenyl) -2-tert-butylamino-ethanol (1-form enriched) thus obtained were dissolved in 1.8 liters of absolute ethanol and added. with a solution of 82 g of dibenzoyl-L-tartaric acid in 500 ml of absolute ethanol, evaporated to a volume of 1 liter and allowed to stand for 3 days at room temperature for crystallization. The crude product obtained was recrystallized six times from methanol / ether to give 1- [1- (4-amino-5-bromo--5-fluoro-phenyl) -2-tert-butylamino-ethanol / Edibenzoyl-L- tartrate in pure form. melting point = 204 - 2o6 ° (sönderae1n1ng) ._ «_ / h75§§. = _35o¿2 ° (0 = 2,0; methanol). 7317035-9 51 The salt was dissolved in methanol and concentrated ammonia while heating and the base precipitated by adding water. The resulting base was dissolved in absolute ethanol, neutralized with absolute ethanolic hydrochloric acid, and by the addition of ether, 1- (N-amino-}-bromo-5-fluoro-phenyl) -2-tert-butylamino-ethanol was brought the hydrochloride to crystallize. smäitpunkt; 218 - 22 ° (dec.). [α] D = 133.9 ° (c = 2.0; methanol).

Example 176. d-1- (4-Amino-5-chloro-5-fluoro-phenyl) -2-tert-butylamino-ethanol Melting point of the hydrochloride: P10-211 ° (decomposition). [α] D = + 139.7 ° (c = 2.0; methanol).

Prepared from d, 11 - (β-amino-5-chloro-5-fluoro-phenyl) -2-tert-butylamino-ethanol by fractional crystallization of the dibenzoyl-D-tartrate analogously to Example 175. amino-3-chloro-5-fluoro-phenyl) -2-tert-butylamino-ethanol Melting point of the hydrochloride: 209 - 2100 (dec.) = δ = 139.2 ° (c = 2.0; methanol) .

Prepared from d, 1- 1- (4-amino-5-chloro-5-fluoro-phenyl) -2-tert-butylamino-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 hydroxy chloride: 197-199 ° (dec.). / two = + 59.9 ° (0 = 2.0; methanol). Prepared from d, 1-1- (4-amino-5-chloro-5-cyano-phenyl) -2-tert-butylamino-ethanol by fractional crystallization of the dibenzoyl-D-tartrate analogous to Example 175. 1- 1- (4-amino-3-chloro-5-cyano-phenyl) -2-tert-butylamino-ethanol Melting point of the hydrochloride: 199-202 ° (dec.). / or / ñâ fi = -59.85 ° (c = 2.0; methanol).

Prepared from d, 1-1- (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. dl- (α-Amino-3-chloro-5-fluoro-phenyl) -2-tert-butylamino-ethanol 0.26 g dl- (4-amino-5-fluoro-phenyl) -2-tert .-butylamino-ethanol hydrochloride and 0.2 ml of pyridine were dissolved in 50 ml of tetrahydrofuran and cooled to 0 DEG. 0.5 g of phenyl iodine dichloride was added, the mixture was kept for 2 hours at the said temperature and a further 0.1 g of phenyl iodine dichloride was added. After 20 hours at about Mo., the solution was evaporated, partitioned between acetic ester and water, the aqueous extracts made alkaline with 2N ammonia and extracted again with acetic ester; The organic phase was washed with water, dried and evaporated in vacuo to dryness. The residue was dissolved in absolute ethanol, neutralized with ethanolic hydrochloric acid and the hydrochloride of the said compound was brought to crystallization by adding ether.

Melting point: 210 - 2110 (decomposition). / byšâ fi = + 139.6 ° (c = 2.0; methanol).

Example Gel 119. dl- (4-amino-3-bromo-5-fluoro-phenyl) -2-tert-butylamino-ethanol 0.26-g dl- (4-amino-3-fluoro-phenyl) -2- tert-butylamino-ethanol hydrochloride was dissolved in 30 ml of 50% acetic acid and added dropwise at 0-50 with 0.16 g of bromine, dissolved in 5 ml of glacial acetic acid and 1 ml of water. After 15 minutes, the reaction mixture was evaporated, the residue was dissolved in water, made alkaline with 2N ammonia and extracted with chloroform. The chloroform solution was dried over sodium sulfate and evaporated in vacuo to dryness. The residue was transferred by dissolving in ethanol, neutralizing with ethanolic hydrochloric acid and adding ether to the hydrochloride of said compound. melting point = 25k - 235 ° (decomposition). / öy3ê fi '= + 132.0 ° (0 = 2.0; methanol).

Example gel 180. 1- (4-amino-3-cyano-phenyl) -2-cyclobutylamino-ethanol Melting point of the hydrobromide: from 1930 (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, m.p. = 1.5 °. 1- (4-amino-3-trifluoromethyl-phenyl) -2-tert-butylamino-ethanol, melting point of the hydrochloride: 172-174 ° (dec.). 1- (N-amino-3-trifluoromethyl-phenyl) -2-tert-pentylamino-ethanol, melting point of the hyarobromylene = 174 DEG-175 DEG (sonar unit). Example Gel 181. 1- (4-Amino-3-chloro-5-fluoro-phenyl) -2-isopropylamino-ethanol Melting point of the hydrochloride: 152 DEG-15 DEG C. (decomposition).

Prepared from 1- (4-amino-5-fluoro-phenyl) -2-isopropylamino-ethanol hydrochloride and chlorine analogously to Example 4.

In analogy to Examples 4, 5 and 112, the following compounds were prepared: 1- (4-amino-5-chloro-5-fluoro-phenyl) -2-cyclopropylamino-ethanol-52; _ 7¶7m_wN 7317035-9 53 _ -hydrochloride, m.p. = 175 - 177 ° (s8nderae1n1ng). 1- (4-Amino-3-chloro-5-fluoro-phenyl) -2-tert-butylamino-ethanol-hydrochloride, m.p .: 206-208 ° (dec.). 1- (4-amino -} - chloro-5-fluoro-phenyl) -2-tert-pentylamino-ethanol hydrochloride, m.p .: 187-188 ° (dec.). 1- (4-amino-3-bromo-5-fluoro-phenyl) -2-1-isopropylamino-ethanol hydrochloride, m.p. = 171 DEG-173 DEG (sonar). . 1- (4-Amino-3-bromo-5-fluoro-phenyl) -2-tert-butylamino-ethanol-hydrochloride, m.p. = 207-220 ° (dec.). 1- (4-amino-3-bromo-5-fluoro-phenyl) -2-cyclobutylamino-ethanol hydrochloride, m.p. = 164 DEG-166 DEG (sonication). 1- (4-Amino-5-fluoro-5-iodo-phenyl) -2-cyclopropylamino-ethanol hydrochloride, m.p. = 199-220 ° (decomposition). 1- (4-amino-3-chloro-5-cyano-phenyl) -2-propylamino-ethanol hydrochloride, m.p. 187 - 189 °. 1- (--quino-3-chloro-5-cyano-phenyl) -2-sec-butylamino-ethanol-d1-hydrochloride, m / mmmm = 1¶> -1 °. 1- (4-amino-3-chloro-5-cyano-phenyl) -2-tert-butylamino-ethanol, m.p. = 125 DEG-133 DEG. 1- (4-Amino-3-chloro-5-cyano-phenyl) -2- (hydroxy-tert-butylamino) -ethanol hydrochloride, m.p. = 228 DEG-230 DEG (sunflower). 1- (4-Amino-3-chloro-5-cyano-phenyl) -2-tert-pentylamino-ethanol hydrochloride, m.p. = 218 DEG-220 DEG (sonication). 1- (α-amino-3-chloro-5-cyano-phenyl) -2-cyclopentylamino-ethanol hydrochloride, melting point fi = 138-114 °. 1- (4-amino-3-chloro-5-cyano-phenyl) -2- [1- (3,4-methylenedioxy-phenyl) -8-2-propylamino] Letanol hydrochloride, m.p. = 189-192 °. 1- (4-amino-3-bromo-5-cyano-phenyl) -2-isopropylamino-ethanol-hydrochloride, m.p .: 186-189 °. 7317035-9 S 1- (4-amino-3-bromo-5-cyano-phenyl) -2-tert-butylamino-ethanol-hydrochloride, m.p. = 213 DEG-215 DEG. 1- (4-amino-5-bromo-5-cyano-phenyl) -2-cyclobutylamino-ethanol hydrochloride, m.p .: 215-216 ° (dec.). 1- (4-amino-3-chloro-5-trifluoromethyl-phenyl) -2-isopropylamino-ethanol, m.p. = 104-166 °. 1- (4-Amino-5-chloro-5-trifluoromethyl-phenyl) -2-tert-butylamino-ethanol hydrochloride, m.p. = 205 DEG-207 DEG (sonication). 1- (4-amino-3-chloro-5-trifluoromethyl-phenyl) -2-cyclobutylamino-ethanol hydrochloride, m.p. 177 DEG-178 DEG. 1- (4-amino-3-chloro-5-trifluoromethyl-phenyl) -2-tert-pentylamino-ethanol hydrochloride, m.p .: 176-178 ° (dec.). 1- (4-Amino-5-bromo-5-trifluoromethyl-phenyl) -2-1-isopropylamino-ethanol hydrochloride, m.p. = 177 DEG-179 DEG (sonication). 1- (4-amino-3-chloro-5-nitro-phenyl) -2-tert-butylamino-ethanol, m.p. 148 DEG-149 DEG. 7 1- (4-amino-3-bromo-5-nitro-phenyl) -2-tert-butylamino-ethanol, melting point = 151 - 152 °.

Example 182. 1- (4-Amino-3-chloro-5-fluoro-phenyl) -2-isopropylamino-ethanol Melting point of the hydrochloride: 152-1540 (decomposition).

Prepared from 1- (α-acetylamino-3-chloro-5-fluoro-phenyl) -2-isopropylamino-ethanol hydrochloride analogous to Example 7 or from 1- (4-amino-5-chloro--5-fluoro- phenyl) -2- (N-benzyl-N-isopropyl) -aminoethanol analogous to Example 10.

Analogously, the following compounds were prepared: 1- (4-amino-3-chloro-5-fluoro-phenyl) -2-cyclopropylamino-ethano-hydrochloride, m.p. = 175-177 ° (decomposition). 1- (4-Amino-3-chloro-5-fluoro-phenyl) -2-tert-pentylamino-ethanol hydrochloride, melting point = 187-188 ° (decomposition). 1- (4-amino-3-bromo-5-fluoro-phenyl) -2-isopropylamino-ethanol hydrochloride, m.p. = 171 DEG-175 DEG (decomposition).

H 7317035-9 55 1- (4-Amino-3-bromo-5-fluoro-phenyl) -2-tert-methylamino-ethanol hydrochloride, m.p. = 207 DEG-208 DEG (dec.). 1- (4-amino-3-bromo-5-fluoro-phenyl) -2-cyclobutylamino-ethanol hydrochloride, m.p .: 164-166 ° (dec.). 1- (4-amino-3-fluoro-5-iodo-phenyl) -2-cyclopropylamino-ethanol hydrochloride, m.p. = 199-220 ° (decomposition). 1- (4-Amino-5-trifluoromethyl-phenyl) -2-tert-pentylamino-ethanol-hydrobromide, m.p. = 17 DEG-175 DEG (sonication). 1- (Amino-5-chloro-5-trifluoromethyl-phenyl) -isopropylamino-ethanol, m.p. = 104-166 °. 1- (4-amino-3-chloro-5-trifluoromethyl-phenyl) -2-tert-butylamino-ethanol hydrochloride, melting point 205 DEG-207 DEG (decomposition). 1- (4-amino-3-chloro-5-trifluoromethyl-phenyl) -2-cyclobutylamino-ethanol-hydrochloride, m.p. = 177-178 °. 1- (4-Amino-3-chloro-5-trifluoromethyl-phenyl) -β-tert-pentylamino-ethanol hydrochloride, m.p. = 176 DEG-178 DEG (sonication). 1- (4-amino-3-bromo-5-trifluoromethyl-phenyl) -2-isopropylamino-ethanol hydrochloride, m.p. = 177 DEG-179 DEG (dec.).

Example 183. - 1- (4-Amino-3-chloro-5-nitro-phenyl) -2-tert-butylamino-ethanol m.p. = 18 DEG-149 DEG.

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

Analogously, the following compound was prepared: 1- (4-amino-3-bromo-5-nitro-phenyl) -2-tert-butylamino-ethanol, m.p. = 151-152 °.

Example 184. 1- (4-Amino-Q-fluoro-phenyl) -2-tert-butylamino-ethanol Melting point of hydrochloride: 196 - 1970 (decomposition).

Prepared from 1- (4-amino-3-bromo-b-fluoro-phenyl) -β-tert-butylamino-ethanol analogous to Example 1a.

Analogously, the following compound was prepared: 1- (4-amino-3-trifluoromethyl-phenyl) -2-tert-butylamino-ethanol, melting point of the hydrochloride: 172-174 ° (dec.).

Exemgel l8§. 1- 14-amino-3-chloro-5-trifluoromethyl-phenyl) -2-tert-butylamino-ethanol 3 3; 4 g 1- (4-amino-3-chloro-5-trifluoromethyl-phenyl) -2- bromo-ethanol was dissolved in 25 ml of tert-butylamine and allowed to stand for 20 hours at room temperature. The excess tert-butylamine was evaporated in vacuo and the residue was taken up in ether. The ether solution was washed with water, dried over magnesium sulfate and evaporated in vacuo. The evaporation residue was purified by chromatography on a silica gel column using the chloroform-methanol system. ammonia = 90: 10: 1. The resulting combined fractions with the desired substance were brought to dryness in vacuo. The residue was dissolved in ether, and with isopropanolic hydrochloric acid the solution was brought to pH 4. 1- (4-amino-3-chloro-5-trifluoromethyl-phenyl) -2-tert-methylamino-ethanol hydrochloride crystallized out, which was filtered off with suction and wash dough with ether and melt at 2o5 - 2o7 ° (decomposition).

Example 186. 8 1- (4-Amino-3-chloro-5-trifluoromethylphenyl) -2-tert-butylaminoethanol Melting point of the hydrochloride: 205-207 ° (dec.).

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

In analogy to Examples 185 and 186, the following compounds were prepared: See 1- (4-amino-3-fluoro-phenyl) -2-tert-butylamino-ethanol-hydrochloride, m.p. = 196-197 ° (sonication). d 1- (4-amino-3-chloro-5-fluoro-phenyl) -2-isopropylamino-ethanol hydrochloride, m.p. = 152 DEG-154 DEG (sunflower). 1- (4-Amino-3-chloro-5-fluoro-phenyl) -2-cyclopropylamino-ethanol-hydrochloride, m.p. = 175-177 ° (solubility). le (4-amino-3-chloro-5-fluoro-phenyl) -2-tert-butylamino-ethanol hydrochloride, m.p .: 206-2080 (dec.). 1- (4-Amino-3-chloro-5-fluoro-phenyl) -2-tert-pentylamino-ethanol hydrochloride, m.p. 187 DEG-188 DEG (sonication). 1- (4-Amino-3-bromo-5-fluoro-phenyl) -2-1-isopropylamino-ethanol hydrochloride, m.p. = 171 DEG-173 DEG (Sand @ rinein) - 7317035-9 57 1- (4- amino-3-bromo-5-fluoro-phenyl) -2-tert-butylamino-ethanol hydrochloride, m.p. = 207 DEG-208 DEG (decomposition). 1- (H-amino-3-bromo-5-fluoro-phenyl) -2-cyclobutylamino-ethanol hydrochloride, m.p. = 16u - 166 ° (dec.). 1- (4-amino-3-fluoro-5-iodo-phenyl) -2-cyclopropylamino-ethanol hydrochloride, m.p. = 199-220 ° (decomposition). 1- (h-amino-3-cyano-5-fluoro-phenyl) -2-isopropylamino-ethanol hydrochloride, m.p. = 182-18 ° (dec.). 1- (4-Amino-3-cyano-5-fluoro-phenyl) -2-tert-butylamino-ethanol-hydrochloride, m.p. 1- (4-amino-3-cyano-phenyl) -2-cyclobutylamino-ethanol hydrobromide, melting point: from 93 ° (decomposition). 1- (4-amino-3-cyano-phenyl) -2-tert-pentylamino-ethanol, m.p. = 143 °. 1- (4-Amino-3-chloro-5-cyano-phenyl) -2-propylamino-enanol-hydrochloride, m.p. 187-1890. 1- (4-Amino-3-chloro-5-cyano-phenyl -2-sec-butylamino-ethanol-dihydrochloride, m.p. = 190 DEG-191 DEG. 1- (M-amino-3-chloro-5-cyano-phenyl) -2-tert-butylamino-ethanol, m.p. = 125 DEG-133 DEG. 1- (4-Amino-3-chloro-5-cyano-phenyl) -2- (hydroxy-tert-butylamino) -ethanol hydrochloride, m.p. 228-250 ° (dec.). 1- (4-amino-3-chloro-5-cyano-phenyl) -2-tert-pentylamino-ethanol-hydrochloride, m.p. = 218 DEG-220 DEG (dec.). 1- (4-amino-3-chloro-5-cyano-phenyl) -2-cyclopentylamino-ethanol-hydrochloride, melting point = 158 - 144 °.

A 1- (4-amino-3-chloro-5-cyano-phenyl) -2- [1- (5,4-methylenedioxy-phenyl) -2-propylamino] -ethanol hydrochloride, m.p. = 189 DEG-19 DEG. . 1- (4-Amino-3-bromo-5-cyano-phenyl) -2-isopropylamino-ethanol hydrochloride, m.p .: 186-1890. 1- (4-amino-3-bromo-5-one). -cyan-phenyl) -2-tert-butylamino-ethanol-hydrochloria; melting point = 215 - 215 °. 1- (4-amino -} - bromo-5-cyano-phenyl) -2-cyclobutylamino-ethanol hydrochloride, m.p. = 215-216 ° (son division). 1- (4-Amino-3,5-dicyan-phenyl) -2-tert-butylamino-ethanol-hydroxylofia, m.p. 251 DEG-255 DEG (sonication). 1- (4-Amine-3-trifluoromethyl-phenyl) -2-tert-butylamino-ethanol-hydrochloride, m.p. = 172 DEG-17 DEG C. (dec.). 1- (H-amino-3-trifluoromethyl-phenyl) -2-tert-pentylamino-ethanol-hydrobromide, pain point: 171: 175 ° (decomposition). 1- (4-amino-3-chloro-5-trifluoromethyl-phenyl) -2-isopropylamino-ethanol hydrochloride, m.p. = 185-187 °. 1- (4-Amino-3-chloro-5-trifluoromethyl-phenyl) -2-cyclobutylamino-ethanol hydrochloride, m.p. = 177-178 °. 1- (4-Amino-5-chloro-5-trifluoromethyl-phenyl) -2-tert-pentylamino-1-ethanol hydrochloride, m.p .: 177 DEG-1780 (decomposition). 1- (4-Amino-3-bromo-5-trifluoromethyl-phenyl) -2-1-isopropylamino-ethanol hydrochloride, m.p. = 177 DEG-179 DEG (sonication). 1- (4-amino-3-chloro-5-nitro-phenyl) -2-tert-butylamino-ethanol, m.p. = 148-149 °. 1- (4-amino-3-bromo-5-nitro-phenyl) -2-tert-butylamino-ethanol, m.p. 151 - 152 °.

Example Gel 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 was dissolved in 40 ml of methanol. After adding 0.6 g of platinum dioxide, the mixture was hydrogenated with shaking at room temperature and normal pressure until the theoretical amount of hydrogen was taken up. The catalyst was removed and the solution was evaporated in vacuo to dryness. The crude solid residue of 1- (4-amino-3-bromo-5-fluoro-phenyl) -2-tert-butylamino-ethanol hydrochloride was partitioned between 2N sodium hydroxide and methylene chloride. The organic phase was separated, washed with water, dried over sodium sulfate and evaporated to dryness in vacuo. The residual oily residue was chromatographed on a chromatography column, filled with 80 g of silica gel, using a mixture of chloroform and methanol = 10: 1 as eluent. The eluate containing the substance was combined and evaporated in vacuo to dryness. The residue was taken up in a small amount of isopropanol and acidified with ethereal hydrochloric acid to pH 5. After the addition of a small amount of ether, the crystallization occurred. The crystals were filtered off and washed with a mixture of isopropanol and ether. melting point = 207 - 2o8 ° (sun unit).

In analogy to Example 187, the following compounds were prepared: 1- (N-amino-3-fluoro-phenyl) -2-tert-butylamino-ethanol hydrochloride. melting point = 196 - 197 ° (decomposition). 1- (4-amino-3-chloro-5-fluoro-phenyl) -2-isopropylamino-ethanol hydrochloride, m.p. = 152 - 15h ° (solar unit). 1- (4-Amino-3-chloro-5-fluoro-phenyl) -2-cyclopropylamino-ethanol hydrochloride, m.p. = 175 DEG-177 DEG (sonication). 1- (4-amino-3-chloro-5-fluoro-phenyl) -2-tert-butylamino-ethanol-hydrochloride, m.p .: 206-208 ° (dec.). 1- (4-amino-3-chloro-5-fluoro-phenyl) -2-tert-pentylamino-ethanol hydrochloride, m.p .: 187-188 ° (dec.). 1- (N-amino-3-bromo-5-fluoro-phenyl) -2-isopropylamino-ethanol hydrochloride, m.p. = 171-173 ° (dec.). 1- (4-Amino-3-bromo-5-fluoro-phenyl) -2-cyclobutylamino-ethanol hydrochloride, m.p. 16A-1660 (dec.). 1- (4-Amino-3-fluoro-5-iodo-phenyl) -β-cyclopropylamino-ethanol hydrochloride, m.p. = 199-220 ° (sonication). 1- (4-amino-5-cyano-5-fluoro-phenyl) -2-isopropylamino-ethanol hydrochloride, m.p. = 182-184 ° (dec.). 1- (4-amino-3-cyano-5-fluoro-phenyl) -2-tert-butylamino-ethanol-hydrochloride, m.p. = 242-243 ° (solar unit). 1- (4-amino-3-cyano-phenyl) -2-cyclobutylamino-ethanol hydrobromide, melting point: from 1950 (decomposition). 7317035-9 60 1- (4-amino-5-cyanophenyl) -2-tert-pentylaminoethanol, melting point: 143 °. 1- (4-amino-5-chloro-5-cyano-phenyl) -2-propylamino-ethanol hydrochloride, m.p. = 187-198 °. 1- (4-Amino-3-chloro-5-cyano-phenyl) -2-sec-butylamino-ethanol-dihydrochloride, m.p. = 190 DEG-191 DEG. 1- (4-amino-3-chloro-5-cyano-phenyl) -2-tert-butylamino-ethanol, m.p. = 125 DEG-133 DEG. 2- (4-Amino-3-chloro-5-cyano-phenyl) -2- (hydroxy-ether-butylamino) -ethanol hydrochloride, m.p. = 228 DEG-250 DEG (dec.). 1- (N-amino-3-chloro-5-cyano-phenyl) -2-tert-pentylamino-ethanol hydrochloride, m.p. = 218 DEG-220 DEG (sonication). 1- (4-amino-3-chloro-5-cyano-phenyl) -2-cyclopentylamino-ethanol hydrochloride, m.p .: 138-1440. 1- (4-amino-3-chloro-5-cyano-phenyl) 2- [1- (3,4-methylenedioxy-phenyl) -2-propylamino] Letanol hydrochloride, m.p. = 189 DEG-192 DEG. 1- (4-amino-3-bromo-5-cyano-phenyl) -2-isopropylamino-ethanol-hydrochloride, m.p. = 186-198 °. 1- (4-Amino-3-bromo-5-cyano-phenyl) -2-tert-butylamino-ethanol hydrochloride, m.p. = 215 DEG-215 DEG. 1-8 1- (4-amino-3-bromo -5-cyano-phenyl) -2-cyclobutylamino-ethanol-hydrochloride, m.p. = 215-216 ° (sonication) 1- (H-amino-3,5-dicyan-phenyl) -2-tert-butylamino ethanol hydrochloride, m.p. = 251 DEG-255 DEG (solar water) 1- (N-amino-3-trifluoromethyl-phenyl) -2-tert-butylamino-ethanol hydrochloride, m.p. = 172 DEG-174 DEG. (Decomposition) 1- (4-amino-5-trifluoromethyl-phenyl) -2-tert-pentylamino-ethanol-hydrobromide, m.p. = 174 DEG-175 DEG (sonication). amino-5-chloro-5-trifluoromethyl-phenyl) -2-isopropylamino-ethanol, melting point 10 -106 °. 1- (α-amino-5-chloro-5-trifluoromethyl-phenyl) -2-tert. -butylamino-ethanol hydrochloride, m.p. = 205 DEG-207 DEG (decomposition) 1- (4-amino-3-chloro-5-trifluoromethyl-phenyl) -2-oligobutylamino-ethanol hydrochloride, m.p. = 177-178 1- (4-amino-5-chloro-5-trifluoromethyl-phenyl) -2-tert-pentylamino-ethanol hydrochloride, m.p .: 176-178 ° (decomposition). 1- (4-amino-3-bromo-5-trifluoromethyl-phenyl) -2-isopropylamino-ethanol hydrochloride, m.p. = 177 DEG-179 DEG (sonication).

ExemEel 188. 1- (4-Amino-5-bromo-5-fluoro-phenyl) -2-tert-butylamino-ethanol 4.8 g of 4-amino-3-bromo-5-fluoro-phenylglycolic acid tert-butylamide were added to 100 ml absolute ether with 1.2 g of lithium aluminum hydride and heated with stirring for 2 hours until boiling. Thereafter, the sodium hydroxide solution was added with acetic acid ethyl ester, concentrated water and sodium hydroxide and the phases were separated. The aqueous layer was extracted with chloroform and the combined organic phases were dried and evaporated in vacuo. The residue was purified by column chromatography over silica gel using the chloroform: methanol: conc. ammonia = 90: 10: 1. The evaporation residue with the fractions containing the substance was dissolved in isopropanol and acidified with ethereal hydrochloric acid to - pH 5. After addition of ether, crystallization occurred. The precipitated hydrochloride of the desired compound was recrystallized from isopropanol. sma1epunkc = 207 - 2o8 ° (sönaeraelning).

In analogy to Example 188, the following compounds were prepared: g 1- (4-amino-5-fluoro-phenyl) -2-tert-butylamino-ethanol hydrochloride, m.p. = 196 DEG-197 DEG (sonar). 1- (h-amino-5-chloro-5-fluoro-phenyl) -2-isopropylamino-ethanol hydrochloride, m.p. = 152-15 ° (dec.). 1- (M-amino-3-chloro-5-fluoro-phenyl) -2-cyclopropylamino-ethanol-hydrochloride, 1 'melting point: 175-177 ° (dec.). 1- (4-Amino-5-chloro-5-fluoro-phenyl) -2-tert-butylamino-ethanol-hydrochloride, m.p. = 206-280 ° (dec.). 1- (4-amino-3-chloro-5-fluoro-phenyl) -2-tert-pentylamino-ethanol-hydrochloride, m.p. 187-1880 (dec.). 1- (4-amino-3-bromo-5-fluoro-phenyl) -2-isopropylamino-ethanol-hydrochloride, m.p. = 171 DEG-173 DEG (sonication). 1- 1- (4-Amino-3-bromo-5-fluoro-phenyl) -2-cyclobutylamino-ethanol hydrochloride, melting point = 16 h - 166 ° (sonication). 1- (4-amino-3-fluoro-5-iodo-phenyl) -2-cyclopropylamino-ethanol hydrochloride, melting point; 199 - 2o1 ° (decomposition). 1- (4-Amino-3-trifluoromethyl-phenyl) -2-tert-butylamino-ethanol-hydrochloride, m.p. = 172 DEG-174 DEG (sonication). 1- (4-amino-3-trifluoromethyl-phenyl) -2-tert-pentylamino-ethanol-hydrobromide, m.p. = 174 DEG-175 DEG (dec.). 1- (4-amino-5-chloro-5-trifluoromethyl-phenyl) -1-isopropylamino-ethanol, m.p. = 104 DEG-106 DEG. 1- (4-gmino-3-chloro-5-trifluoromethyl-phenyl) -2-tert-butylamino-ethanol hydrochloride, m.p. = 205-27 ° (dec.). 1- (4-amino-3-chloro-5-trifluoromethyl-fepyl) -2-cyclobutylamino-ethanol hydrochloride, m.p. = 177-178 °. 1- (4-amino-5-chloro-5-trifluoromethyl-phenyl) -2-tert-pentylamino-ethanol hydrochloride, m.p .: 176-178 ° (dec.). 1- (4-Amino-3-bromo-5-trifluoromethyl-phenyl) -2-isopropylamino-ethanol hydrochloride, m.p. = 177 DEG-179 DEG (sonication).

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 was added to 100 ml of absolute ether with 0.75 g of powdered lithium aluminum hydride, stirred mechanically and heated for 2 hours under reflux. Then the reaction mixture was added in succession with 2.0 ml of water, 2.4 ml of 2N sodium hydroxide and 6.0 ml of water.

It was filtered off with suction, the inorganic residue was washed with chloroform and the combined filtrates were evaporated in vacuo. The residue was purified by chromatography on a silica gel column (eluent = chloroform: methanol: conc. Ammonia = 90: 10: 1). The evaporation residue of the solvent obtained by vacuum distillation of the solvent. The desired fractions were dissolved in isopropanol, added with ethereal hydrochloric acid to pH 5 and additional ether was added. The crystallized hydrochloride of the above compound was filtered off with suction and recrystallized from isopropanol. sma1tpunxt = 207 - 2o8 ° (decomposition).

In analogy to Example 189, the following compounds were prepared: 1- (4-amino-5-fluoro-phenyl) -2-tert-butylamino-ethanol hydrochloride Melting point: 196-197 ° (dec.). 1- (N-amino-5-chloro-5-fluoro-phenyl) -2-isopropylamino-ethanol hydrochloride, m.p. = 152-15 ° (sonarel). 1- (H-amino-5-chloro-5-fluoro-phenyl) -2-cyclopropylamino-ethanol-hydrochloride, m.p .: 175-177 ° (dec.). 1- (H-amino-5-chloro-5-fluoro-phenyl) -2-tert-butylamino-ethanol-hydrochloride, m.p .: 206-2080 (dec.). 1- (4-Amino-3-chloro-5-fluoro-phenyl) -2-tert-pentylamino-ethanol hydrochloride, m.p. = 187-188 ° (sol.). 1- (amino-3-bromo-5-fluoro-phenyl) -2-isopropylamino-ethanol hydrochloride, m.p. = 171 DEG-175 DEG (decomposition). 1- (4-amino-3-bromo-5-fluoro-phenyl) -2-cyclobutylamino-ethanol hydrochloride, m.p .: 164 DEG-166 DEG (dec.). 1- (4-Amino-5-fluoro-5-iodo-phenyl) -2-cyclopropylamino-ethanol-4-hydrochloride, m.p. = 199-220 ° (sunflower). 1- (4-amino-3-trifluoromethyl-phenyl) -2-tert-butylamino-ethanol-hydrochloride, m.p. = 172 DEG-17 DEG C. (decomposition). 1- (H-amino-5-trifluoromethyl-phenyl) -2-tert-pentylamino-ethanol-hydrobromide, m.p. = 17n - 175 ° (sonaration). 1- (α-amino-3-chloro-5-tr fluoromethyl-phenyl) -2-isopropylamino-731-ethanol, m.p .: 1014-106 °. 1- (4-amino-5-chloro-5-trifluoromethyl-phenyl) -2-tert-butylamino- Ethanol hydrochloride, m.p. 205 DEG-207 DEG (decomposition) 1- (4-amino-3-chloro-5-trifluoromethyl-phenyl-2-cyclobutylamino-ethanol hydrochloride, m.p .: 177 DEG-178 DEG. 1- (1H-amino-5-chloro-5-trifluoromethylphenyl) -β-tert-pentylamino-ethanol hydrochloride, m.p. 176 DEG-178 DEG (sonar unit). 1- (N-amino-3-bromo- 5-trifluoromethyl-phenyl) -2-isopropylamino-ethanol hydrochloride, m.p. = 177-179 ° (dec.).

Example Gel 190. 1- (4-Amino-5-chloro-5-trifluoromethyl-phenyl] -2-tert-butylamino-ethanol 3.5 g 5- (4-amino-3-chloro-5-trifluoromethyl-phenyl) -} - tert.-butyloxazolidone- (2) was dissolved in 15 ml of glacial acetic acid, added at room temperature with 15 ml of 45% hydrobromic acid in glacial acetic acid and allowed to stand for 1 hour, then the mixture was poured onto ice, made alkaline with concentrated ammonia and extracted with acetic acid ethyl ester, the organic phase was extracted with 2N hydrochloric acid, the acidic solution was made alkaline with concentrated ammonia and extracted again with acetic ester.

After evaporation of the organic solvent in vacuo, a crude product remained which, after chromatographic purification on a silica gel column (eluent = chloroform-methanol-conc. Ammonia = 90: 10: 1) gave pure 1- (4-amino-5-chloro-5-trifluoromethyl-phenyl ) -2-tert-butylamino-ethanol.

Dissolving in ether and adding isopropanolic hydrochloric acid gave the hydrochloride, m.p. 205 DEG-207 DEG (dec.).

Example 121. 1- (4-Amino-3-bromo-5-fluoro-phenyl) -2-tert-butylamino-ethanol 1.5 g of 5- (4-amino-5-bromo-5-fluoro-phenyl -3-tert-butyl-oxazolidone- (2) was heated in 25 ml of a hydrochloric acid for 3 hours at 90 °. After cooling, the slightly cloudy solution was filtered, brought to pH 9 with sodium hydroxide and extracted with chloroform. The chloroform phase was washed with water, dried over sodium sulfate and evaporated in vacuo to dryness. The oily residue was taken up in a small amount of isopropanol and acidified with ethereal hydrochloric acid to pH 5. After the addition of a small amount of ether, crystallization took place. The crystals were filtered off and washed with a mixture of isopropanol and ether. Melting point: 207 - 2080 (decomposition). r; Example 72. 1- (4-Amino-3-chloro-5-cyano-phenyl) -2-tert-butylamino-ethanol 0.5 g of 5- (4-amino-3-chloro -5-cyano-phenyl) -5-tert-butyl-oxazolidinone- (2) (m.p. = 115-119 °) was charged with 5 ml of concentrated hydrochloric acid for 30 minutes under reflux. It was cooled, added to ice, the mixture was made alkaline with sodium hydroxide and 1- (α-amino-3-chloro-5-cyano-phenyl) -2-tert-butylaminosethanol was extracted with chloroform. The product was purified by chromatography on silica gel (eluent: Chloroform: methano1 = 7 = 5). Melting point = 151 - 155 °; Melting point of the new chloride = 204 - 207 In analogy to Examples 190 - 192, the following compounds 1- (4-amino-3-fluoro-phenyl) -2-tert-butylamino-ethanol-hydrochloride melting point were prepared: 196 - 1970 (decomposition). 1- (H-amino-3-chloro-5-fluoro-phenyl) -2-isopropylamino-ethanol hydrochloride, melting point = 152 - 15h ° (solar refining). 1- (4-Amino-3-chloro-5-fluoro-phenyl) -2-cyclopropylamino-ethanol-hydrochloride, m.p. = 175-177 ° (sonication). 1- (4-amino-5-chloro-5-fluoro-phenyl) -2-tert-butylamino-ethanol-O-hydrone chloride, m.p. = 206-280 ° (dec.). 1- (β-amino-3 Chloro-5-fluoro-phenyl) -2-tert-pentylamino-ethanol hydrochloride, m.p. = 187 DEG-188 DEG (decomposition). [1- (β-amino-3-bromo-5-fluoro-phenyl) - 2-1 isopropylamino-ethanol hydrochloride, m.p. = 171 DEG-175 DEG (dec.) 1- (4-amino-5-bromo-5; fluoro-phenyl) -2-cyclobutylamino-ethanol hydrochloride, melting point: 164 - 1660 (decomposition) 1- (H-amino-3-fluoro-5-iodo-phenyl) -2-cyclopropylamino-ethanol hydrochloride, melting point = 199-220 ° (decomposition). 1- ( 4-amino-5-cyano-5-fluoro-phenyl) -2-1-isopropylamino-ethanol-hydrochloride, melting point: 182-1840 (decomposition) 1- (H-amino-3-cyano-5- fluoro-phenyl) -2-tert-butylamino-ethanol- -neydroxyuride, m.p. = Que - 2u5 ° (solubility). 1- (α-amino-3-cyano-phenyl) -2-cyclobutylamino-ethanol hydrobromide, melting point = from 195 ° (solar flow) - 7317035-9 1- (4-amino-3-cyano-phenyl) -2-terpentylamino-ethanol, melting point: 143 °.

In 1- (4-amino-5-chloro-5-cyano-phenyl) -2-propylamino-ethanol hydrochloride, m.p. = 187-198 °. 1- (β-Amino-3-chloro-5-cyano-phenyl) -2-sec. -butylamino-ethanol-dihydrochloride, 2 melting point = 190 - 191 ° - 1- (4-amino-3-chloro-5-cyano-phenyl) -2- (hydroxy-tert-butylamino) -ethanol hydrochloride , melting point = 228 - 23o ° (south division). . 1- (4-amino-3-chloro-5-cyano-phenyl) -2-tert-pentylamino-ethanol-hydrochloride, m.p. = 218 DEG-220 DEG (dec.). 1- (4-amino-3-chloro-5-cyano-phenyl) -2-cyclopentylamino-ethanol hydrochloride, m.p. = 138 DEG-144 DEG. 1- (4-amino-3-chloro-5-cyano-phenyl) -2- [1- (3,4-methylenedioxy-phenyl) -2-propylamino] -ethanol hydrochloride, m.p. = 189 DEG-192 DEG. N- (4-amino-3-bromo-5-cyano-phenyl) -2-1-isopropylamino-ethanol hydrochloride, m.p. = 186-198 °. 1- (4-4mino-}-bromo-5-cyano-phenyl) -2-tert-butylamino-ethanol-hydrochloride, m.p .: 213-2150 (dec.). 1- (4-amino-3-bromo-5-cyano-phenyl) -2-cyclobutylamino-ethanol hydrochloride, m.p. 215 DEG-216 DEG (dec.). 1- (4-aminoene, 5-dicyan-phenyl) -2-tert-butylamino-ethanol hydrochloride, m.p. = 251-255 ° (dec.). 1- (4-amino-5-trifluoromethyl-phenyl) -2-tert-butylamino-ethanol-hydrochloride, m.p. = 172 DEG-174 DEG (sonar). 1- (4-Amino-3-trifluoromethyl-phenyl) -2-tert-pentylamino-ethanol-hydrobromide, m.p. 174 DEG-175 DEG (sonar). 1- (H-amino-3-chloro-5-trifluoromethyl-phenyl) -2-isopropylamino-ethanol, melting point = 10 -4-166 °. 66 V - w „WMV * Im ffff I: __ 1 rr fl, 6 ,, 7317035-9 1- (4-amino-3-chloro-5-trifluoromethyl-phenyl) -2-cyclobutylamino-ethanol hydrochloride, m.p. = 177 - i78 °. 1- (4-Amino-3-chloro-5-trifluoromethyl-phenyl) -2-tert-pentylamino-ethanol hydrochloride, m.p. 176 DEG-178 DEG (dec.). 1- (4-amino-3-bromo-5-trifluoromethyl-phenyl) -2-isopropylamino-ethanol hydrochloride, m.p. = 177 DEG-179 DEG (sonication). 1- (4-amino-3-chloro-5-nitro-phenyl) -2-tert-butylamino-ethanol, m.p. = 148-149 °. 1- (4-amino-5-bromo-5-nitro-phenyl) -2-tert-butylamino-ethanol, m.p. = 151 DEG-152 DEG.

Example Gel 123. 1- (4-Amino-3-cyano-5-fluoro-phenyl) -2-tert-butylamino-ethanol In a solution of 6 g of selenium dioxide in 36 ml of dioxane and 1 ml of water was introduced at 60 ° with stirring 10 g of H'-amino-3'-cyano-5'-fluoro-acetophenone portionwise. The mixture was then heated for 4 hours at reflux temperature. To the solution of .alpha.-amino-3-cyano--5-fluoro-phenylglyoxal thus prepared, 30 ml of tert-butylamine were added dropwise after cooling and under external cooling with ice. After the addition was complete, it was diluted with 150 ml of ethanol and filtered off with insoluble constituents. The solution containing crude 4-amino-3-cyano-5-fluoro-phenylglyoxylidene-tert-butylamine was added with stirring and cooling with ice portionwise with 6 g of sodium borohydride and allowed to stand overnight at room temperature. Then the excess sodium borohydride was destroyed with acetone, added with water and the organic solvent was removed in vacuo. The precipitate which precipitated was filtered off with suction, washed with water and taken up in 200 ml of hydrochloric acid. The hydrochloric acid solution was filtered off and then added with so much 10N sodium hydroxide that pH 6 was reached. The aqueous phase was washed with chloroform and then further added with 1N sodium hydroxide to a clear alkaline reaction. The precipitate was extracted with chloroform, the chloroform solution was washed with water, dried over sodium sulfate and evaporated in vacuo to dryness. The solid residue of 1- (4-amino--3-cyano-5-fluoro-phenyl) -2-tert-butylamino-ethanol was taken up in 100 ml of absolute ethanol and acidified with ethereal hydrochloric acid to pH 6. Already un - where the acidification with ethereal hydrochloric acid began the separation of the hydrochloride in the form of colorless crystals. The crystallization was completed by the addition of ether. The crystals were filtered off and washed with ether. e melting point = ene - 2h5 ° (decomposition). 7317035-9 68 __H_A de __M_f Exemgel 194. 1- (4-amino-3-chloro-5-trifluoromethyl-phenyl) -2-tert-butylamino-ethanol 0.4 g H-amino-3-chloro-5- trifluoromethyl-phenylglyoxal hydrate was dissolved in 10 ml of methanol, added with 0.5 g of tert-butylamine and allowed to stand for 3 hours at room temperature. Then the solution was cooled to 0.1 ° C, stirred with 0.1 g of sodium borohydride and stirred for 20 minutes at -10 - -200. It was acidified with 2N hydrochloric acid to pH 2 and then with 2N ammonia to pH 9, rinsed with water and the methanol removed in vacuo. The aqueous mixture was extracted with ether, the ether extract was washed with water, dried over magnesium sulphate and evaporated. 1 vacuum.

The oily evaporation residue was dissolved in a small amount of ether and given with isopropanolic hydrochloric acid pH H. Crystalline 1- (4-amino-3-chloro-5-trifluoromethyl-phenyl) -2-tert-butylamino-ethanol-hydro- chlor1d, "which was filtered off with suction and washed with ether. mp; 205 - 2 ° C (dec.).

In analogy to Examples 193 and 194, the following compounds were prepared: 1- (N-amino-3-fluoro-phenyl) -2-tert-butylamino-ethanol hydrochloride m.p .: 196-197 ° (dec.). 1- (4-Amino-3-chloro-5-fluoro-phenyl) -2-isopropylamino-ethanol-hydrochlororial - melting point = 152 - 154 ° (solubilization). 1- (4-Amino-5-chloro-5-fluoro-phenyl) -2-cyclapropylamino-ethanol hydrochloride, 7 'Melting point: 175 - 177 ° (reconstitution). . 1- (4-amino43-chloro-5-fluoro-phenyl) -2-tert-butylamino-ethanol-hydrochloride, m.p. 206 DEG-208 DEG (decomposition). 1- (H-amino-3-chloro-5-fluoro-phenyl) -ether ether-pentylamino-ethanol-hydrochloride, melting point = 187-188 ° (solar refining). 1- (4-Amino-3-bromo-5-fluoro-phenyl) -2-isopropylamino-ethanol hydrochloride, m.p. = 171 DEG-173 DEG (dec.). 1- (4-amino-5-bromo-5-fluoro-phenyl) -2-tert-butylamino-ethanol-4-hydrochloride, m.p .: 207-2080 (dec.). 1- (4-amino-3-bromo-5-fluoro-phenyl) -2-cyclobutylamino-ethanol-α-hydrochloride, ~7 mp: δ - 166 ° (dec.). 1- (H-amino-5-fluoro-5'-N-phenyl) -cyclopropylamino-ethanol-hydrophane. 69 1311135-211 chloride, melting point: 199> 20l ° (decomposition). 1- (4-amino-5-cyano-5-fluoro-phenyl) -2-1-isopropylamino-ethanol-hydrochloride, m.p. = 182-184 ° (dec.). 1- (4-Amino-3-cyano-phenyl) -2-cyclobutylanino-ethanol hydrobromide, m.p. = 195 ° (solubilization). 1- (N-amino-3-cyano-phenyl) -2-tert-pentylamino-ethanol, m.p. 1- (4-amino-3-chloro-5-cyano-phenyl) -2-propylamino-ethanol-hydrochloride, m.p .: 187 DEG-189 DEG. 1- (4-amino-5-chloro-5-cyano-phenyl) -2-sec-butylamino-ethanol-dihydrochloride, m.p. = 190-191 °. 1- (4-amino-3-chloro-5-cyano-phenyl) -2-tert-butylamino-ethanol, m.p .: 125-133 °. 1- (4-Amino-3-chloro-5-cyano-phenyl) -2- (hydroxy-tet.-butylamino) -ethanol hydrochloride, m.p. = 228 DEG-230 DEG (decomposition). 1- (4-Amino-3-chloro-5-cyano-phenyl) -2-tert-pentylamino-ethanol hydrochloride, m.p. = 218 DEG-220 DEG (decomposition). 1- (N-amino-5-chloro-5-cyano-phenyl) -2-cyclopentylamino-ethanol-hydrochloride, m.p. 138 DEG-14 DEG. . 1- (N-amino-3-clear-5-cyano-phenyl) -2- [1- (3,1-methylenedioxy-phenyl) -2-propylamino] -ethanol hydrochloride, m.p. = 189-192 °. 1- (4-Amino-5-bromo-5-cyano-phenyl) -2-isopropylamino-ethanol / hydrochloride, melting point = 186 - 189 °. 1- (4-Amino-3-bromo-5-cyano-phenyl) -2-tert-butylamino-ethanol hydrochloride, m.p. = 213 DEG-215 DEG. 1- (4-amino-3-bromo-5-cyano-phenyl) -2-cyclobutylamino-ethanol-hydrochloride, m.p. 215-2160 (dec.). 1- (4-amino-3,5-dicyan-phenyl) -2-tert-butylamino-ethanol-hydrochloride, m.p .: 251-2530 (dec.). 731.70? 55-9 i, 70 if uW__ 1- (4-amino-3-trifluoromethyl-phenyl) -2-tert-butylamino-ethanol-hydrochloride, m.p .: 172-174 ° (dec.). 1- (4-Amino-3-trifluoromethyl-phenyl) -2-tert-pentylamino-ethanol-hydrobromide, m.p. = 174 DEG-175 DEG (solar unit). 1- (Ephamino-3-chloro-5-trifluoromethyl-phenyl) -2-isopropylamino-ethanol, m.p. = 10 -4-10 °. 1- (4-amino-3-chloro-5-trifluoromethyl-phenyl) -2-cyclobutylamino-ethanol hydrochloride, m.p. 177-178 °. 1- (4-amino-3-chloro-5-trifluoromethyl-phenyl) -2-tert-pentylamino-ethanol hydrochloride, m.p. = 176-178 ° (dec.). 1- (4-amino-3-bromo-5-trifluoromethyl-phenyl) -2-isopronylamino-ethanol hydrochloride, m.p. = 177 DEG-179 DEG (sonication). 1- (4-amino-3-chloro-5-nitro-phenyl) -2-tert-butylamino-ethanol, m.p. = 148-149 °. 1- (4-amino-3-bromo-5-nitro-phenyl) -2-tert-butylamino-ethanol, m.p. = 151-152 °.

Example Gel 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- butylaminoethanol was dissolved in 15 ml of a mixture of concentrated nitric acid and concentrated sulfuric acid. The solution was heated for 1 minute to 80-850 and then poured onto ice. By adding ammonia, the mixture was made alkaline and then extracted with chloroform. The chloroform solution was washed with water, dried and evaporated in vacuo to dryness. The residue was chromatographed on silica gel (eluent: chloroform: methanol = 8: 2) and the crude product thus obtained was recrystallized from ethyl acetate. Melting point of 1- (4-amino-3-bromo-5-nitro-phenyl) -2-tert-butylamino-ethanol: 151-125 °.

Example 126. 1- (4-Amino-chloro-5-nitro-phenyl) -2-tert-butylamino-ethanol mp = 148-149 °.

Prepared from 1- (4-amino-3-chloro-phenyl) -2-tert-butylamino-ethanol and nitric acid / sulfuric acid analogous to Example 195. Example 71 12- 1- [N-amino-3-chloro-5 -cyan-phenyl) -2-dimethylamino-ethanol 0.5 g of 1-acetoxy-1- (4-amino-5-chloro-5-cyano-phenyl) -2-dimethylamino-ethane (melting point: 120 - 124 ° ) was stirred in methanolic sodium hydroxide at 20 ° for 1 hour. They were added with water, the methanol was distilled off in vacuo, the remaining aqueous phase was extracted with chloroform, the chloroform phase was dried over sodium sulphate, 1 vacuum was evaporated to dryness, the residue was taken up in isopropanol and the hydrochloride of 1- (4-amino-3-chloro -5-cyano-phenyl) -2-dimethylamino-ethanol by adding isopropanolic hydrochloric acid to crystallization. melting point = 187 - 189 °.

Example Gel 198. 1- (4-Amino-5-cyano-5-fluoro-phenyl) -2-dimethylamino-ethanol 7 g of 1-acetoxy-1- (4-amino-3-cyano-5-fluoro-phenyl) - 2-Dimethylamino-ethane was dissolved in 100 ml of methanol. To this solution was added 5 ml of 1N aqueous NaOH solution and the mixture was allowed to stand for 1 hour at room temperature. It was then diluted with saturated brine and extracted thoroughly with chloroform. The chloroform solution was washed with saturated brine, dried over sodium sulfate and evaporated in vacuo to dryness. A colorless color was obtained.

Structural evidence by NMR spectrum (CD3OD): OH 2.2 - 2.65 ppm multiplet / Q protons; N-CH; and N-è fl-CH2-Ni: / S 4.6 - 4.9 ppm multiplet / ü protons; 3 exchange protons and OH -šg-CH2-Ni: /; 7.15 - 7, ü ppm multiplet /? aromatic protons.

Example Gel 192. 1- (4-Amino-3-chloro-5-cyano-phenyl) -2-tert-butylamino-ethanol 0.5 g N-acetyl-N- [2-acetoxy-2- (H -amino-3-chloro-5-cyano-phenyl) -ethyl / L-tert-butylamine (m.p .: 160 - 1620) was stirred with methanolic sodium hydroxide for 1/2 hour at 200. They were added with water, the methanol was distilled off. in vacuo, extracted the remaining aqueous phase with chloroform, dried the chloroform phase over sodium sulfate, evaporated in vacuo to dryness and crystallized the residue from ethanol; 1- (N-amino-3-chloro-5-cyano-phenyl) -2-tert-butylamino-ethanol was obtained. melting point = 131 - 135 °; melting point for nyar0k10r1den = 204 - 2o7 °.

Analogous to Example 19? ~ 199, the following compounds 7317035-9 1- (β-amino-5-fluoro-phenyl) -2-tert-butylamino-ethanol hydrochloride were prepared, m.p. = 196-197 ° (dec.). 1- (4-amino-3-chloro-5-fluoro-phenyl) -2-isopropylamino-ethanol-hydrochloria, m.p. = 152-154 ° (dec.). 1smä1cpunkt = 187 - 188 ° (decomposition). 1- (72-amino-3-chloro-5-fluoro-phenyl) -2-cyclopropylamino-ethanol; hydrochloride; smä1cpgnxb = 175 - 177 ° (sönaeraelning). 1- 1- (4-amino-3-chloro-5-fluoro-phenyl) -2-tert-butylamino-ethanol-7-hydrochloride, m.p. = 206 DEG-208 DEG (sonar). S 1- (4-Amino-5-chloro-5-fluoro-phenyl) -2-tert-pentylamino-ethanol-7-hydroxyl chloride, § 1- (4-amino-3-bromo-5-fluoro-phenyl) -2-1sopropylamino-ethanol hydrochloride, m.p. = 171 DEG-173 DEG (sonication). 1- (4-Amino-3-bromo-5-fluoro-phenyl) -2-tert-butylamino-ethanol-hydrochloride, m.p. 207 DEG-208 DEG (sunflower). 1- (4-Amino-3-bromo-5-fluoro-phenyl) -2-cycloputylamino-ethanol hydrochloride, m.p. = 16 DEG-166 DEG (sunflower). 1- (4-Amino-5-fluoro-5-iodo-phenyl) -2-cyclopropylamino-ethanol hydrochloride, m.p. = 199-220 ° (son division).

1- (H-amino -} - cyano-5-fluoro-phenyl) -1H-propylamino-ethanol hydrochloride, m.p .: 82 DEG-18 DEG C. (decomposition). 1- (4-Amino-5-cyano-5-fluoro-phenyl) -2-tert-butylaminophetanol hydrochloride, m.p. = 242 DEG-243 DEG (sonication). 1- (4-amino-3-cyano-phenyl) -2-cyclobutylamino-ethanol hydrobromide, m.p. = from 193 ° (decomposition). 1- (4-amino-3-cyano-phenyl) -2-tert-pentylamino-ethanol, m.p. = 143 °. 1- (4-amino-3-chloro-5-cyano-phenyl) -2-propylamino-ethanol hydrochloride, m.p. = 187-198 °. 1- (4-Amino-3-chloro-5-cyano-phenyl) -2-sec-butylamino-ethanol-dihydrochloride, m.p. = 180 DEG-191 DEG. 1- (4-Amino-3-chloro-5-cyano-phenyl) -2- (hydroxy-tert-butylamino) -5-ethanol hydrochloride, m.p. = 228 DEG-230 DEG (decomposition). 1- (4-Amino-5-chloro-5-cyano-phenyl) -2-tert-pentylamino-ethanol-7-hydrochloride, m.p. = 218 DEG-220 DEG (decomposition). 1- (4-amino-3-chloro-5-cyano-phenyl) -2-cyclopentylamino-ethanol hydrochloride, m.p. = 158 DEG-144 DEG. 1- (4-amino-5-chloro-5-cyano-phenyl) -2- [1- (3,4-methylenedioxy-phenyl) -2-propylamino] ethanol hydrochloride, m.p. = 189-192 °. 1- (4-amino-5-bromo-5-cyano-phenyl) -2-isopropylamino-ethanol hydrochloride, m.p. = 186-198 °. 1- (U-amino-3-bromo-5-cyano-phenyl) -2-tert-butylamino-ethanol-hydrochloride, m.p. = 215 DEG-215 DEG. 1- (4-Amino-3-bromo-5-cyano-phenyl) -2-cyclobutylamino-ethanol hydrochloride, m.p. = 215-216 ° (solubilization). 1- (N-amino-3,5-dicyan-phenyl) -2-tert-butylamino-ethanol hydrochloride, m.p. = 251 DEG-255 DEG (dec.). 1- 1- (4-amino-j-trifluoromethyl-phenyl) -2-tert-butylamino-ethanol hydrochloride, m.p. = 172 DEG-174 DEG (dec.). 1- (4-quino-3-trifluoromethyl-phenyl) -2-terb.-pentylamino-ethanol-hydrobromide, m.p. 174 DEG-175 DEG (dec.). 1- (4-amino-3-chloro-5-trifluoromethyl-phenyl) -2-isopropylamino-ethanol, m.p. 104-106 °. ; 1- (α-amino-3-chloro-5-trifluoromethyl-phenyl) -2-tert-butylamino-ethanol hydrochloride, m.p. = 205 DEG-207 DEG (decomposition). 1- (4-amino-3-chloro-5-trifluoromethyl-phenyl) -2-cyclobutylamino-ethanol hydrochloride, melting point = 177-178 °. 1- (4-amino-3-chloro-5-trifluoromethyl-phenyl) -2-tert-pentylamino-ethanol hydrochloride, m.p. = 176-178 ° (dec.). 1- (4-amino-3-bromo-3-trifluoromethyl-phenyl) -2-isopropylamino-ethanol hydrochloride, m.p .: 177-1790 (decomposition). 7317035-9 7H 1- (4-amino-3-chloro-5-nitro-phenyl) -2-nerve.-butylamino-ethanol 1,1 mp = 148-149 °. 1- (4-amino-5-bromo-5-nitro-phenyl) -2-tert-butylamino-ethanol, m.p. = 151 DEG-152 DEG.

Example 200. 1 Tablets containing 1- (1- (4-amino-3-chloro-5-cyano-phenyl) -2-tert-butylamino-ethanol hydrochloride Composition: 1 tablet contains: Active substance 0.01 mg Milk sugar 82, H9 mg Potato starch 33.00 mg Polyvinylpyrrolidone 4.00 mg Magnesium stearate 0.50 mg 120.00 mg Preparation method: The active substance and PVR were dissolved in ethanol. The mixture of milk sugar and potato starch was moistened evenly with the active substance / granulation solution. Moisture sieving took place with a mesh width of 1.5 mm.

Then the mixture was dried at 500 and dry sieving was performed with 1.0 mm mesh. The granules thus obtained were mixed with magnesium stearate and compressed into tablets.

Tablet weight: 120 mg, punch; 7 mm, flat.

Exemgel 201. 2 2 Dragees with 5γ- 1- (4-amino-3-chloro-5-cyano-phenyl) -2-tert-butylaminoa-ethanol Composition z 1 dragee core contains: Active substance 0.005 mg Milk sugar 82.495 mg Potato starch 53,000 mg Polyvinylpyrrolidone 4,000 mg Magnesium stearate 0,500 mg 120,000 mg Preparation procedure: Dragé core analogous to Example 200.

Core weight: 120 mg, - _ punch: 7 mm, arched. 5 The core was coated in a known manner with a casing, which 1 consisted mainly of sugar and talc. The finished dragees were polished with beeswax. 5; Weight: 200.0 mg. 7317035-9 75 Example gel 202. 9 Gelatin capsules with 10-1- (α-amino-3-chloro-5-cyano-phenyl) -2-tert-butyl-amino-ethanol Composition: 1 capsule contains: Active substance 0.010 mg Milk sugar 59,990 mg Maize starch 60,000 mg 120,000 mg Preparation method: The active substance was intensively mixed with milk sugar and maize starch and filled into gelatin capsules of suitable size.

Kapse1fy11n1ng = 12o, o mg.

Example 203.

Ampoules with leaf 1- (4-amino-3-bromo-5-fluoro-phenyl) -2-tert-butylamino-ethanol hydrochloride Composition: 1 ampoule contains: Active substance 0.01 mg Citric acid 2.5 mg Sodium hydrogen phosphate 7.5 mg Saline 4.6 mg Ampoule water ad 2.0 ml Preparation procedure: The active substance, the buffer substance and the saline were dissolved in 1 ampoule water and then filtered sterile. 1 9 Filling: In brown ampoules to 2 ml under protective gassing (N2) ster111ser1ng = ao minutes at 12o °.

Example Gel 204. 9 Suppositories with 10 .mu.l 1- (4-amino-3-chloro-5-cyano-phenyl) -2-tert-butylamino-ethanol Composition: 1 suppository contains: Active substance 0.01 mg Suppository mass (eg Witepsol W H5) l 699.99 mg l 700.00 mg Preparation procedure: In the molten and to 400 cooled suppository mass, the finely powdered active substance was stirred by means of a dip homogenizer and the mass was poured at 57 ° 1 slightly pre-cooled forms. 'suppository weight 1.7 H. 7317035-9 76 Exemgel 205.

Syrup with 10 .mu.l 1- (A-amino-3-bromo-5-fluoro-phenyl) -2-tert-butylamino-ethanol hydrochloride Composition: 100 ml of syrup contains: Active substance 0.0000l g Benzoic acid 0, 1 g Tartaric acid _ 1.0 g Sugar «50.0 g Orange flavor 1.0 g Food red 00.05 g Dest water 100.0 ml Preparation procedure: 7 Approx. 60 g of distilled water was heated to 800 and benzoic acid, tartaric acid, the active substance, the dye and sugar were dissolved in turn. After cooling to room temperature, the flavoring agent was added and the mixture was filled to the indicated volume. The syrup was filtered.

Example 206.

Dragees with 25 .mu.l of 1- (4-amino-3-chloro-5-trifluoromethyl-phenyl) -2-tert-butylamino-ethanol hydrochloride Composition: 1 dragee core contains: Active substance 0.025 mg Milk sugar 82.475 mg Potato starch. 33,000 mg Polyvinylpyrrolidone 4,000 mg Magnesium stearate - 0.500 mg 120,000 mg Preparation method: l ¿Analogous to Example 200.

Example 202.

Ampoules with 20 μl 1- (4-amino-3-chloro-5-trifluoromethyl-phenyl) -2-tert-butylamino-ethanol hydrochloride Composition: 1 ampoule contains: Active substance I 0.02 mg Citric acid 2 .5 mg / mg Sodium hydrogen phosphate 7.5 mg Saline 4.6 mg Ampoule water ad 2.0 ml Preparation procedure: Analogous to Example 203. In 1.1, free 77 Exemgel 208.

Tablets with 5-yl dl- (4-amino-5-fluoro-phenyl) -2-tert-butylamino-ethanol hydrochloride Composition: 1 tablet contains: Active substance 0.05 mg Milk sugar 82, H5 mg Potato starch 53, 00 mg Polyvinylpyrrolidone 4.00 mg Magnesium stearate 0.50 mg 120.00 mg Preparation procedure: Analogous to Example 200.

Tablet weight: 120 mg, punch: 7 mm, flat.

Example gel 209. 1 Dragees with 25, dl- (4-amino-5-fluoro-phenyl) -2-tert-butylamino-ethanol-hydrochloride Composition: 1 dragee core contains: 'Active substance o, o25 mg Milk seekers 82, 1175. mg Potato starch 33,000 mg Polyvinylpyrrolidone ~ 4,000 mg Magnesium stearate 0.500 mg 120,000 mg Preparation method: Dragé core analogous to Example 201.

Core weight: 120 mg, punch: 7 mm, arched. 7317035-9 The core was coated in a known manner with a casing which consisted mainly of sugar and talc. The finished dragees were polished with beeswax.

Weight: 200.0 mg.

Example 210.

Gelatin capsules with 25) f dl- (4-amino-5-fluoro-phenyl) -2-tert-butyl-amino-ethanol hydrochloride Composition: 1 capsule contains: Active substance 0.025 mg Milk sugar 59.975 mg Maize starch 60,000 mg 120,000 mg 7317035-9 78, Ä f HJ- _, W__ _ M-. ___., Preparation procedure: Analogous to Example 202.

Example 211. Ampoules of 20; f dl- (4-amino-5-fluoro-phenyl) -2-tert-butylamino-ethanol hydrochloride Composition of 1 ampoule contains: (01 09 Active substance 5 0.02 mg Citric acid 2.5 mg Sodium hydrogen phosphate 7.5 mg Salt 4.6 mg Distilled water ad 2.0 mg Preparation procedure: Analogous to Example 203.

Example P12.

Suppositories with 50 .mu.l of 1- (4-amino-5-fluoro-phenyl) -2-tert-butylamino-ethanol hydrochloride Composition containing the suppository contains: Active substance 0.05 mg suppository mass 692,95 mg l 700.00 mg Preparation procedure: I Analogous to Example 204.

Example 213 7 Syrup containing 25-yl dl- (4-amino-3-fluoro-phenyl) -2-tert-butylamino-ethanol hydrochloride per 5 ml Composition: In 100 ml of syrup contains: Active substance 0.0005 g Benzoic acid 0.1 g Tartaric acid 1.0 g Sugar 50.0 g Orange flavor 1.0 g Food red _ 0.05 g Distilled water per 100.0 ml Preparation procedure: Analogous to Example 205. h / l

Claims (2)

A process for the preparation of novel amino-phenyl-ethanolamines of the general formula I, if the '' n R1 li CH N '// I 3 CI _ 2 "" "* -n IA H2I R2 wherein R1 represents a hydrogen, fluorine, chlorine, bromine, iodine atom or a cyanide group. R2 represents a fluorine atom, a straight or branched alkyl group having 1 to 5 carbon atoms, a hydroxyalkyl, aminoalkyl, adialkylaminoalkyl, trifluoromethyl, alkoxy, nitro, cyano, carboxy, carbalkoxy or carbamoyl group. and R 4, which may be the same or different, represent hydrogen atoms, straight or branched alkyl groups having 1-6 carbon atoms, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkinyl or one having a methylenedioxy group or a phenylalkyl group, mono or disubstituted by hydroxy or methoxy groups, - 'H' A represents a hydrogen atom or together with R4 a group of the formula & _, CH - Rs, wherein H5 represents hydrogen or a straight or branched alkyl group, _ and their optically active antipodes and their physiologically tolerable acid addition salts with inorganic or organic acids, characterized in that: a) an acetophenone of the general formula II, RH N _ // f 3 -C - R1 C0 2. ___ \ _ R "(II) HER Ra wherein R 1 - R 4 have the meaning given above, are reduced or b) for f Composition of compounds of general formula I, in which H3 and R2 have the meaning given above with the exception of alkenyl and alkinyl groups and R1 represents a chlorine, bromine or iodine atom, a compound of general formula III is halogenated, 7317035-9 80 OH 1 CH - CH - _R_, / 'I 3 N 2 “\\ _ nu (In) HZN H2 wherein Ra - RÄ has the meaning given above with the exception of alkenyl and alkinyl groups, or c) from a compound of the general formula IV, OX _ 1 HN Y2 R CH - C - gs Y1 "'I? u Ra wherein R1, -R2 and H3 have the meaning given above, X represents a protecting group for a hydroxy group or a hydrogen atom, Y1 represents a protecting group for an amino group or a hydrogen atom, Y2 represents a protecting group for an amino group or has the one for Ru mentioned above meaning, however, at least one of the groups X, Y1 and / or Y2 must constitute the above-mentioned protecting group, one or more protecting groups are cleaved or d) for the preparation of compounds of the general formula I, in which R forms a hydrogen atom, a compound with the general l a- 'formula V, H31 CH - CHZ - N' "“ * ~ RÅ (V) HZN Ra wherein H2 - RÄ has the meaning given above and Hal represents a chlorine, bromine or iodine atom, or e) for preparation of compounds of general formula I, wherein R 2 is an aminomethyl group, a compound of general formula VI is then reduced and hydrolyzed, fe n h H / H 3 '1 / cH - C112 - N In RÅ N (VI) CH / H \ 1W 3 | H wherein R 1, H 3 and Ru have the above b or f) a compound of the general formula VII, OH - I '1 cn - cnz - z' (VII) HN 2 Ra wherein R 1 and R 2 are as defined above, and Z is a chlorine, bromine or iodine atom or a p-toluenesulfonyloxy group, is reacted with an amine of the general formula VIII, / Rß-H - N (VIII) \ R4 wherein H3 and H4 have the meaning given above, or g) for the preparation of compounds of the general formula I , wherein R 2 does not form a nitro group, a compound of the general formula IX is reduced, f 'R 111 cn _ cnz - N / 3 _ Ra (IX) OZN / R2' wherein E1, R3 and RÄ have the meaning given above, and R 2 'has the meaning given for H 2 with the exception of the nitro group, or n) for the preparation of compounds of general formula I, wherein R 1 does not form a cyano group and H 2 does not constitute nitro, cyano, carboxy, carbalkoxy or carbamoyl groups, a compound of the general form X, '731-' az n R \ n is reduced; A-c-Ni 5 DR ”<> I X -1 HZN k Ru 5 wherein R3 and En have the meaning given above, 'B1' has the meaning given for B1 above with the exception of the cyano group. R 2 "has the meaning given above for H 2 with the exception of nitro, cyano, carboxy, carbalkoxy or carbamoyl groups and A is a carbonyl or a hydroxymethylene group, or i) for the preparation of compounds of general formula I, wherein 1 % is a hydrogen atom, an oxazolidone of the general formula XI is hydrolyzed by C = O H1 cH N - a; s \ CHZ / (m) ä HZN. H2 wherein R1, R2 and R5 have the meaning given above, or j) for the preparation of compounds of general formula I, wherein H4 is a hydrogen atom, an aldehyde of general formula XII, R1 CO - CHO HN (XII) is reduced H 2 wherein R 1 and R 2 are as defined above, or its hydrate in the presence of an amine of the general formula VIIIa, n 3 H - N <(vzxza) H wherein H 3 is as defined above, or k) for the preparation of compounds with the general. formula I, wherein 32 is a nitrogrwpn, the nitrene a compound with the allnïn- v | in formula XIII, nqnß 731703549 83 bn,. RÖ n, cH-cH2-N \ Rh (XIII) /. Wherein R 1, R 5 and R a are as defined above, and a compound of the general formula I obtained according to methods a * - k), wherein R 2 is a cyano group, is then transferred, if desired, by hydrolysis to the corresponding compound with the general formula I, wherein H 2 is a carbamoyl or carboxyl group, and / or a obtained compound of the general formula I, wherein R 5 is a carbamoyl or carbalkoxy group, is transferred, if desired, by hydrolysis into the corresponding compound of the general formula I, wherein R 2 is a carboxyl group, and / or a resulting compound of general formula I is cleaved if desired in its optically active antipodes and / or is converted to a compound of general formula I, wherein R 3 or Ru is a hydrogen atom, if so. is desired, by reaction with an aldehyde of the general formula XV, H5 - cHo (XV) wherein H5 is a hydrogen atom or a straight or branched alkyl group, in an oxazolidine of the general formula Ia, 111. cH N - R \ / 5 (Ia) CH2 112m wherein R1, R2 and H3 and R5 have the meaning given above and / or are transferred, if desired, in a physiologically tolerable acid addition salt with an inorganic or organic acid. IN 2. A process according to claim 1, characterized in that a obtained racemate of the general formula I is then, if desired, cleaved by means of racemate cleavage or a mixture of the diastereomeric compounds of the general formula XIV, on? In RB R1 a _ cnz - 1: / \ R4 (xIv) rm 'ln' 73170353-9 84 wherein R1, H2, R3 and R4 have the meaning given above, R6 represents a hydrogen atom or an acyl group and R7 a chiral acyl group, is split in its pure diastereomers and then the group R7 and optionally ¶ R4, if this constitutes an optionally substituted benzyl group, and R6, if this does not constitute hydrogen, is cleaved. A process according to claim 1 for the preparation of 1- (4-amino-β-bromo-S-fluoro-phenyl) -2-tert-butylamino-ethanol and its acid addition salts. A process according to claim 1 for the preparation of 1- (4-amino-silyl-5-cyano-phenyl) -2-tert-butylamino-ethanol and its acid additions. A process according to claim 1 for the preparation of 1- (4-amino-3-fluoro-5-iodo-phenyl) -2-cyclopropylamino-ethanol and its acid addition salts. A process according to claim 1 for the preparation of 1- (4-amino-3-fluoro-5-cyano-phenyl) -2-isopropylamino-ethanol and its acid addition salts. A process according to claim 1 for the preparation of 1- (4-amino-3,5-dicyan-phenyl) -2-tert-butylamino-ethanol and its acid addition salts. A process according to claim 1 for the preparation of 1- (4-amino-3-bromo-5-nitro-phenyl) -2-tert-butylamino-ethanol and its acid addition salts. ' 9. A process according to claim 1 for the preparation of 1- (4-amino-3-chloro-5-trifluoromethylphenyl) -2-tert-butylamino-ethanol hydrochloride. PROMISED PUBLICATIONS: Sweden 306 749 (12 q: 32/21), 365 199 (C070 91/40), 366 539 (C076 91/40), 381 660 (C070 263/04), 396 597 (C076 91/40) AH