GB1092746A - Preparation of acetylenic compounds - Google Patents

Abstract

The invention comprises 3-methyl isopropylamino - 3 - hydroxymethylbut - 1 - yne and 3-benzylmethylamino - 3 - hydroxymethylbut-1-yne, and the process wherein these and other amines of the Formula II <FORM:1092746/C2/1> (wherein R represents a hydrogen atom or a C1- 3 alkyl group, R1 represents an hydroxy, alkoxy, acyloxy, carbamoyloxy, aryloxy or aralkoxy group or a halogen atom, R2 represents alkyl, aryl or aralkyl group, R5 represents an hydrogen atom or an alkyl or aryl group or a cyclopentyl or cyclohexyl group, and each of R13 and R14, which are the same or different, represents an alkyl, hydroxyalkyl or aralkyl group are prepared by treating an oxazolidine of the Formula III <FORM:1092746/C2/2> wherein R6 represents an hydrogen atom or an alkyl, hydroxyalkyl, alkoxy-carbonyl, aryl or aralkyl group) are treated either with lithium aluminium hydride or with Grignard reagent of the formula R7MgX wherein X represents a halogen atom and R7 represents an alkyl, hydroxy alkyl, aryl, or aralkyl group to give a product wherein R1 represents an hydroxy group and, if desired esterifying, etherifying or halogenating this group and forming an acid-addition or quaternary ammonium salt thereof 3 - t - Butyl - 4 - ethyl - 4 - ethynyl - 1,3 - oxazolidine hydrochloride, 3 - t - butyl - 4 - methyl - 4-ethynyl - 1,3 - oxazolidine hydrochloride, 3-benzyl - 4 - methyl - 4 - ethynyl - 1,3 - oxazolidine and 3,4 - dimethyl - 4 - ethynyl - 1,3 - oxazolidine may be prepared by reacting 3-t-butylamino-3-hydroxymethylpent - 1 - yne, 3 - t - butylamino-3 - hydroxymethylbut - 1 - yne, 3 - benzylamino - 3 - hydroxymethylbut - 1 - yne and 3-methylamino - 3 - hydroxymethylbut - 1 - yne respectively with formaldehyde and, where required, converting the resultant free amine into its hydrochloride. 2,3,4-Trimethyl-4-ethynyl-1,3-oxazolidine may be prepared by reacting 3-methylamino - 3 - hydroxymethylbut - 1 - yne with acetaldehyde. 3 - Methylamino - 3 - hydroxymethylbut - 1-yne and its hydrochloride may be prepared by reacting 3 - chloromethylbut - 1 - yn - 3 - ol with sodium hydroxide, treating the resulting 3,4 - epoxy - 3 - methylbut - 1 - yne with hydrochloric acid to give 3-chloro-3-hydroxy-methylbut-1-yne and reacting the latter with methylamine. 3 - Benzyl - 3 - hydroxymethylbut-1-yne and its hydrochloride may be prepared by reacting 3-chloro-3-hydroxymethylbut-1-yne with benzylamine in the presence of coppper bronze.ALSO:Therapeutic compositions with hypotensive activity comprise compounds of the formula <FORM:1092746/A5-A6/1> and non-toxic and quaternary ammonium salts thereof, wherein R represents a hydrogen atom or C1-3 alkyl group, R1 represents a hydroxy, alkoxy, acyloxy, carbamoyloxy, aryloxy or aralkoxy group or a halogen atom, R2 represents an alkyl, aryl or aralkyl group, R5 represents a hydrogen atom or an alkyl, aryl, cyclopentyl or cyclohexyl group, each of R\sv3 and R\sv4 represents, the same or different, an alkyl, hydroxy-alkyl or aralkyl group, together with a suitable carrier.