GB917102A - Phenyloxy and phenylalkoxy benzoic acid aminoalkyl amides - Google Patents

Abstract

The invention comprises amides of the formula <FORM:0917102/IV (b)/1> (wherein "alkylene" is an alkylene radical with 2 or 3 carbon atoms and R1 and R2 are alkyl groups each containing at most 4 carbon atoms, or R1 and R2 together with the adjacent nitrogen atom form a saturated heterocyclic ring system which may also contain other hetero atoms) and their addition salts with pharmacologically acceptable inorganic and organic acids; and the preparation thereof by reaction of a chloride or mixed anhydride of 4-phenyloxy- or a 4-phenylalkoxy-benzoic acid with the appropriate N:N - disubstituted alkylenediamine in an inert solvent. Reference is also made to the use of esters of these substituted benzoic acids, and also to the use of the acids themselves, in this reaction, and to the additional processes (1) reacting a reactive derivative of phenoxy- or a phenylalkoxybenzoic acid with ammonia to give an amide of the formula <FORM:0917102/IV (b)/2> and reacting this with a reactive ester of the appropriate amino-alkanol; and (2) reacting a reactive ester of an alcohol of the formula <FORM:0917102/IV (b)/3> with the appropriate amine, the reactive ester being in turn prepared (a) from a reactive derivative of phenoxy- or a phenylalkoxybenzoic acid and a reactive ester of the appropriate amino-alkanol; or (b) by reaction with the free amino-alkanol and subsequent esterification; or (c) by reaction with an alkyleneimine to give an amide of the formula <FORM:0917102/IV (b)/4> and splitting this with a strong acid. Detailed examples are given and a list of salt-forming acids is provided. 4-Phenoxy-benzoyl chloride and 4-phenyl-alkoxy-benzoyl chlorides are prepared from the acids and thionyl chloride. 4-(31-phenyl-propoxy)-and -(41-phenylbutoxy)-benzoic acids are prepared by reacting the sodium salt of ethyl 4-hydroxy-benzoate with 3-phenyl-propyl bromide and 4-phenyl-butyl bromide respectively and hydrolysing the esters so formed. N-2-aminoethyl-pyrrolidine is prepared from N-2-chloroethyl-pyrrolidine hydrochloride and liquid ammonia at about 100 DEG C. in an autoclave. Aqueous solutions of the acid-addition salts of the invention may be used as injection solutions which are anti-arrhythmics or antifibrillation agents.