SU422137A3 - METHOD OF OBTAINING 1- - Google Patents

Description

This invention relates to a process for the preparation of new and derivative aminopropanes, which have physiological activity and can be used in medical practice.

The proposed method of obtaining new compounds is based on the known reaction of converting the corresponding group, for example, an amide group, to a cyanogen group. As a result of this reaction, new compounds have been obtained that possess valuable physiological properties.

According to the invention, it is proposed to prepare compounds of general formula I

t

2 0CH2-CHOH-CH7-KHR CHg.

where R is a straight or branched alkyl radical with 2-6 carbon atoms from compounds of the general formula (P)

BUT

aOCH -atOH-CH7. -NHR

SNT

where R - has specified. value.

And - translated into the cyano group of the radical, for example, -CONH2 or SG1.ON,

by transferring radical A in a known manner to a cyano group, for example, by dehydration, in the presence of dicyclohexylcarbodimide.

The compounds I according to the invention contain an asymmetric carbon atom in the CHOH group and are therefore both in racemic form and in the form of optical antipodes. The latter can be obtained not only through the cleavage of racemates

common adjuvants such as dibenzoyl-B-tartaric acid, di-toluyl-tartaric acid or O-3-bromocamphor-8-sulphonic acid, but also through the use of optically active starting compounds.

The compounds of formula I according to the invention according to the invention can be converted in the usual way into their physiologically tolerable acid addition salts. Suitable acids are, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, matanesulfonic acid, maleic acid, acetic acid, oxalic acid, lactic acid, tartaric acid, succinic acid or 8-l-lorothofplin. Example 1. 1- (2-cyano-5-methylphenoxy) -2oxy-3-isopropylaminopropane hydrochloride. 12.4 g (0.04 mol) of 1- (2-amino-5-methylphenoxy) -2-hydroxy-3-isopropylaminopropane dichloride are dissolved in a mixture of 50 ml of water and 14 ml of concentrated HC1 and added dropwise at O-5 ° C 5.6 g (0.08 mol) of Na, NO2 dissolved in 10 ml of H2O. This solution is quickly added dropwise at 90 ° C to the second solution obtained from 20 g of copper sulphate, 23.2 g of KCN and 120 ml of water and left to stand at this temperature for 30 minutes. After cooling, the mixture is alkalinized. Extraction is carried out by shaking with chloroform and the organic phase is dried over MgSO4. After distilling off the chloroform, 4.7 g of product remain, which is treated with ether. Insoluble parts are separated. The ethereal phase is acidified with ethereal hydrochloric acid, and a viscous oil is precipitated, which is dissolved in hot acetonitrile. The resulting hydrochloride is cooled and recrystallized from ethanol with the addition of ether. Output 2.1 g, so pl. 168 -170 ° C. Example 2. 1- (2-cyano-5-methylphenoxy) -2oxy-3-vgoro-butylaminopropane hydrochloride. Analogously to example 1 of 6.5 g (0.02 mol) of 1- (2-amino-5 - methylphenoxy) -2 - hydroxy-3-borbutylaminopropane hydrochloride, 10 ml of concentrated PS1, 40 ml of NgO, 2.8 g (0, 04 mol) NaNO2 and 10 ml of H2O receive a solution of the diazonium salt. The latter is mixed with a solution heated to 90 ° C, consisting of 10 g of copper sulfate, 11.2 g of potassium cyanide and 60 ml of H2O, and left to stand at 85-90 ° C for 30 minutes. After cooling, the alkalized precipitated part is basified, the mixture is extracted with chloroform, the organic phase is dried over MgSO4 and the chloroform is distilled off. The residue is purified by chromatography on a column, for example, with silica gel. After evaporation of the fractions with a homogeneous substance, the remaining base is dissolved in a small amount of ether and acidified with ethereal hydrochloric acid. The precipitated hydrochloride is recrystallized from ethanol with the addition of ether. Output 1.8 g, so pl. 113-115 ° C. Example 3. 1- (2-cyano-5-methylphenoxy) -2oxy-3-greg-butylaminopropane hydrochloride. 9.75 g (0.03 mol) of 1- (2-amino-5-methylphenoxy) -2-hydroxy - 3 tert-butylaminopropane dichloride are diazotized in 15 ml of concentrated PS1 and 60 ml of HsC with 4.2 g (0.06 mol ) NaNO2 in 15 ml of P20 at O-5 ° C. The diazonium salt solution is mixed with a solution heated to 90 ° C consisting of 15 g of copper sulphate, 16.8 g of KC1 and 90 ml of H20, and then stirred further for 30 minutes at 85-90 ° C. After cooling, basify with NaOH. The entire mixture is extracted with chloroform, the tar part and the aqueous phase are separated. After the organic phase is washed with water, it is dried over MgSO4 and chloroform is distilled off, and 6.8 g of mass remains, which is recrystallized from ethanol with the addition of ether. Output 4.9 g. After transferring to the hydrochloride as in the above examples, m. Pl. 231-232 ° C. Example 4. 1- (2-cyano-5-methylphenoxy) -2oxy-3- (1,1 - dimethylpropylamino) - propane hydrochloride. Pz 10.2 g (0.03 mol) of 1- (2-amino-5-methylphenoxy) -2-hydroxy-3 - (1,1-dimethylpropylamino) propane dichloride, 15 ml of concentrated HCl and 60 ml of H2O and 4.2 g (0.06 mol) of NaN02 in 15 ml of H2O gives a diazonium solution as described in Example I. This solution is mixed with a hot solution consisting of 15 g of copper sulphate, 16.8 g of NaNO2 and 90 ml of H20 and kept in for 30 minutes at a temperature of approximately 90 ° C. After cooling, it is alkalinized and removed by shaking with chloroform. The diluted portion and the aqueous phase are separated. After the organic phase was dried over MgSO4, chloroform was distilled off, and the residue was purified on a silica gel column. After purification of the fractions containing the product, the solvent mixture is distilled off and the pure base is dissolved in ether. After the addition of the ethereal hydrochloric acid solution, crystalline hydrochloride precipitates. Heg is recrystallized from ethanol with the addition of ether. Output 2.2 g, so pl. 187-188 ° C. Compounds of the formula I with the following characteristics are obtained in a similar manner. Mp, 160-162 ° C (hydrochloride) -C (SPZ) 2-SP2-CH2-SPz 180-183 (hydrochloride) Subject of the invention. Method of obtaining 1- (2-cyano- 5-methylphenxy) -2-hydroxy-3 - alkylaminopropanes of the general formula (I); 2-snon-cng-tcc where R is a straight or branched radical with 2--6 carbon atoms, differing from the fact that in the compound both of fory. the mules (I) are osn-snon-cng-so where R has the indicated meanings A is a 5 ka translatable cyano group, for example, -CONH - or CH-NOH, the latter is converted into a cyano group by a known method, example, by dehydration in the presence of dicyclohexylcarbodiimide and 6, the desired product is isolated in known manner in free form or in salt form in ratssmicheskoy or in optically active form,