SU353411A1 - METHOD OF OBTAINING p-lminoalkancarbonic acids - Google Patents

Description

This invention relates to a process for the preparation of novel aminoalkanoic carboxylic acids not described in the literature, which have pharmacological activity and can be used in medicine.

A method of obtaining compounds of the formula

SNS

R, a sn-c-soon

v

H R3

where RI, R2 and Ra are hydrogen or acyl groups with pharmacological activity. However, in the literature there is no information about obtaining compounds of formula I

NHjRg

I Phs-s-soo

1 I

A method for the preparation of p-aminoalkanecarboxylic acids of the formula I or their salts is proposed, in that a compound of the formula

Y, Nz I I Ph-C-C-y,

1 I R, R.

where YI denotes an amino group or an amino group bound to a Y2 residue;

Y2 is a carboxy-group residue that is esterified into ether or an amidated carboxyl group;

Ph is a phenyl containing at least one hydroxy group, for example, a 3,4-dioxy, 2,6-dioxy or 3,4,5- or 2,3,4-trioxyfenne residue;

RI, Ra, and Hz are as defined,

the Y2 residue is converted to the carboxy group using the local method, using hydrolysis, while simultaneously converting the amino group associated with the Ya residue to the free amine; ogroup. can be modified simultaneously or in stages one nln more primers. The reaction is carried out using conventional hydrolytic, reducing, or hydrogenolytic agents, preferably in the presence of solvents or diluents or mixtures thereof, with cooling or at elevated temperature and / or in the presence of catalytic substances and / or activators, and / or iodine with elevated pressure and / or in an inert gas atmosphere like nitrogen. The cleavage of the resulting isomeric mixtures into pure isomers can be carried out in a known manner. Racemates obtained in which the free hydroxyl groups are substituted in the appropriate case, and, for example, acylated or etherified into ether, can be converted, for example, into salts, and the benefits of using salt with optically active bases as optically active cc-phenylethylamine, a- ( 1-naphthyl) -ethylamine, hiiii or bruch-it, as well as acid addition salts with the corresponding optically active acids. The resulting mixtures of diastereoisomeric salts are divided into separate salts on the basis of physicochemical differences, for example, solubility, crystallisability, etc., and the optically active antipodes are freed from the salts. The racemates can also be separated on the optically active antipodes by fractional crystallization in the appropriate case from an optical solvent, or by chromatography, in particular by top-layer chromatography, on an optically active filler. Mixtures of diastereoisomeric compounds are divided in a well-known way into pure isomeric compounds based on their physicochemical differences (solubility, boiling points, etc.), for example, by fractional crystallization or distillation. Depending on the reaction conditions and starting materials, compounds are obtained in free form or in the form of salts. Salts can be converted in a generally known manner into free compounds. Example 1. 1 g of methyl ester (3-aminor- (3-bromo-4-hydroxyferal) -propionic acid is heated in 10 ml of 1 and sodium hydroxide solution for one hour under reflux. After cooling, neutralized with 7.2 ml 1 and hydrochloric acid. At the same time, p-amnior- (3-bromo-4-oxypheyl) -propionic acid of the formula c drops out: n-c H2-coon, melting point 173 ° C (decomposes). ethanol for 4 hours ( with stirring) under reflux. After cooling, the precipitated crystals are filtered on suction and pereethallized from ether - dimethylformamide. Thus, p-s are obtained but-p - (- 3-bromo-4 - methoxyphenyl) propanoic acid with mp 224-225 ° C. 13 g of p-amino-p- (3-bromo-4-methoxyphenyl) propionic acid with The temperature is added to 65 ml of boron tribromide and at this temperature it is moved for 10 hours. "Then the cooling is stopped and the mixture is kept stirring for 12 hours at room temperature. It is then evaporated to dryness in vacuo and methanol is added to the residue. The methanol solution is dried to dryness in a vacuum. The residue thus obtained was recrystallized from a mixture of methanol, ethyl acetate and ether. In this way, o-p-amino-p- (3-bromo-4-hydroxyphenyl) -propionic acid methyl oxybromide is obtained with m.p. 178-18GS. Example 2. The following compounds were prepared in a similar manner: p-amino- (3 - (3,4 - dioxyphenyl) propionic acid, hydrochloride, m.p., (-) - ramino-p- (3,4-dioxnphenyl) - ironionic acid, (-) - 5-amino-p- (3,4-dioxyphenyl) -pronionic acid; a-methyl-5-amio-p- (3-hydroxyphenyl) - ironionic acid, mp 264-265 ° C; p-amino-p- (3-hydroxyphenyl) -propionic acid, mp 235-236 ° C, (-f) - p-amino-p- (3-hydroxyphenyl) -pronionic acid, (- ) p-amino-p- (3-oxypheyl) -propionic acid; p-amipo-p- (2-hydroxyphenyl) -propionic acid, mp 235-236 ° C, hydrochloride mp 181 - 183 ° C, (+} - p-amino-p- (2-o syphenyl) -propionic acid, (-) - p-amppo- (2-hydroxyphenl) -iroiionic acid. Subject of the invention Method of obtaining p-aminoalkylcarboxylic acids of the formula Ph-CC-COOH II where Ph is phenyl containing at least one hydroxy group, Rb R2, Ra are hydrogen or lower alkyl, also their salts, characterized in that in the compound of the formula Ph-CCY 5 YS is a residue transferable to the carboxy group, for example, esterified to ester or amidated carboxyl group, Ph, Rb Kg and Kz have the indicated values translate the Y2 residue into the carboxy group from-5 known method For example by hydrolysis, b and at the same time associated with residual aminogrunna z is converted to the free aminogrupnu. followed by isolating the desired product in a known manner as a base or salt, as a racemate, million optical optical antipode.