GB835802A - Process for the production of new anilides and salts thereof - Google Patents

Abstract

The invention comprises anilides and their acid addition salts of the formula <FORM:0835802/IV (b)/1> wherein R1 and R2 are straight or branched alkylene radicals, Am is a secondary or tertiary amino group or a nitrogen atom forming part of the ring of a heterocyclic base, R3 is chlorine, bromine or methoxy, R4 is hydrogen or when R3 is chlorine or bromine, may also be methyl, and their preparation by reacting an acid anilide of the formula <FORM:0835802/IV (b)/2> with an amine of the formula X1-R2-Am, wherein one of the symbols X1 represents a halogen atom and the other represents the group -NH (alkyl or aralkyl). More generally, the compounds may be prepared by reacting the appropriate substituted aniline or a reactive derivative thereof with an acid HOOC.R1.N (alkyl or aralkyl) -R2-Am or a reactive derivative thereof such as a halide, ester or anhydride. In place of the above amino-acid or derivative thereof, a similar compound containing a group which is subsequently converted into the amino group Am may be used. Products in which Am is a primary or secondary amino group may be further alkylated to secondary or tertiary amino compounds. The products are used as local anaesthetics, suitably in the form of salts such as the sulphate, hydrochloride, hydrobromide, phosphate, acetate, glycolate, citrate, succinate, fumarate, maleate, dihydroxymaleate, methane sulphonate, and hydroxyethane sulphonate. Examples describe the preparation of the 2-chloroanilides of N-b -pyrrolidino - ethyl - N - benzyl - aminoacetic, N - b - pyrrolidinoethyl - N - methyl - amino-acetic, N - b - pyrrolidinoethyl - N - methyl - a -aminopropionic, N - b - diethylaminoethyl - N - methyl - a - aminopropionic, N - b - diethylamino - ethyl - N - methyl - aminoacetic, N - b -piperidinoethyl - N - methyl - aminoacetic, N - b - pyrrolidinoethyl - N - ethyl - aminoacetic, N - b - piperidinoethyl - N - methylaminoacetic, N - b - piperidinoethyl - N - ethylaminoacetic, N - b - diethylaminoethyl - N - ethyl - aminoacetic, N - b - dimethylaminoethyl - N - methyl - aminoacetic and N - b -dimethylaminoethyl - N - ethyl - aminoacetic acids; the 2 - bromoanilides of N - b - diethylaminoethyl - N - methyl - aminoacetic and N-b - pyrrolidinoethyl - N - ethyl aminoacetic acids; the 2-methoxyanilides of N-b -diethylaminoethyl - N - methyl - aminoacetic and N-b - pyrrolidinoethyl - N - methyl - aminoacetic acids and the 2-chloro-5-methyl anilide of N-b -pyrrolidinoethyl - N - methyl - aminoacetic acid. N - Methylaminoacetic acid 2 - chloroanilide is made by the reaction of methylamine with chloracetic acid-2-chloroanilide. Chloracetic acid 2-methoxy-anilide is made by the reaction of chloracetyl chloride with o-methoxyaniline in the presence of sodium acetate.