GB885801A - Tertiary amines and process for their manufacture - Google Patents

Abstract

The invention comprises: (a) 3-tertiary-aminopropanols of the general formula <FORM:0885801/IV (b)/1> (wherein Ph represents an unsubstituted or halogen-, alkyl- or alkoxy-substituted phenyl radical, Py represents a pyridyl radical, which may be alkyl-substituted, R2 represents a hydrogen atom or an alkyl group, and -N = B represents a tertiary amino group) and their acid addition salts and quaternary ammonium compounds; (b) esters of the alcohols of (a) with acids R1COOH (wherein R1 represents an aliphatic hydrocarbon radical), and physiologically tolerable acid addition salts and quaternary ammonium compounds thereof; (c) pharmaceutical preparations comprising the compounds of (b) (see Group VI); (d) the preparation of the compounds of (a) by the process of the examples, which may be summarised as: reacting a compound of the general formula <FORM:0885801/IV (b)/2> with a pyridyl-methyl alkali metal compound, and, if desired, converting the resulting base into an acid addition salt or a quaternary ammonium compound, and/or, if desired, separating mixtures of racemates when such are obtained; (e) preparation of the compounds of (b) by esterifying the alcohols of (a) with an appropriate acid R1COOH or a functional derivative thereof or a ketone corresponding thereto, and, if desired, converting a resulting salt into a free base or a resulting free base into an acid addition salt or a quaternary ammonium compound, and/or splitting a mixture of racemates into its components and/or resolving a racemate into its antipodes. Reference is also made to the use of a pyridyl-methyl Grignard reagent in place of an alkali metal compound in the process of (d), the conversion of a salt of an alcohol of (a) into the free base, and the optical resolution of a racemic alcohol of (a). b -Dimethylamino-a -methylpropiophenone and its b -chloro-derivative are prepared by refluxing propiophenone or b -chloropropiophenone with dimethylamine hydrochloride and paroformaldehyde in aqueous ethanolic hydrochloric acid.ALSO:Pharmaceutical preparations, useful as analgesics, comprise, in admixture or conjunction with a pharmaceutical carrier suitable for enteral or parenteral administration, an ester of the general formula <FORM:0885801/VI/1> (wherein R1 represents an aliphatic hydrocarbon radical, Ph represents an unsubstituted or halogen-, alkyl- or alkoxy-substituted phenyl radical, Py represents a pyridyl radical, which may be alkyl-substituted, R2 represents a hydrogen atom or an alkyl group, and -N=B represents a tertiary amino group) or an acid addition salt (e.g. hydrohalide, sulphate, phosphate, acetate, propionate, glycollate, succinate, maleate, mono- or di-hydroxymaleate, fumarate, malate, tartrate, citrate, benzoate, salicylate, 4-aminosalicylate, 2-phenoxybenzoate, p 2-acetoxybenzoate, or methane-, ethane-or hydroxyethane-sulphonate) or quaternary ammonium salt (e.g. halide or alkanesulphonate) thereof. They may take the form of capsules, tablets, dragees, solutions, suspensions or emulsions, and may contain preserving, stabilizing, wetting or emulsifying agents, salts for varying the osmotic pressure or buffers, or other therapeutically-active substances.