GB1415256A - Alpha-aminomethylbenzyl alcohol derivatives - Google Patents

Abstract

1415256 α - Aminomethylbenzyl alcohols YAMANOUCHI PHARMACEUTICAL CO Ltd 18 Jan 1973 [5 Feb 1972 19 April 1972 23 May 1972] 2733/73 Heading C2C The invention comprises compounds of Formula I in which one of A and B represents a hydrogen atom or a hydroxyl group while the other represents a group of Formula Ia (wherein R<SP>1</SP> 1 which is different from R<SP>2</SP>, represents a hydrogen atom or an alkyl group and R<SP>2</SP> represents a hydrogen atom or a group COR<SP>4</SP> in which R<SP>4</SP> is H or an alkyl group which may have been substituted by a hydroxy, alkoxy or acylamino group), and R<SP>3</SP> represents an alkyl group other than a methyl group or a phenylalkyl group which may have been substituted by a hydroxyl group, an alkyl group, an alkoxy group or an acylamino group and pharmacologically acceptable additive salts thereof. The compounds of Formula I may be prepared by reduction of the corresponding substituted acetophenone and/or by hydrogenolysis of the corresponding benzyl compounds in which benzyl groups are attached to the phenolic oxygen or the amino group attached to R<SP>2</SP>. α-Bromoacetophenones in which the ring is substituted in the 4-position by OH, benzyloxy or NO 2 and in the 3-position by NO 2 , acetylamino or benzyloxyacetylamino groups are prepared by bromination of the corresponding acetophenone. α - (N,N - disubstituted amino)acetophenones substituted in the ring by a 4-benzyloxy group, a 3-group selected from NO 2 , acetylamino, benzyloxyacetylamino, NH 2 and having one N-benzyl group, the other substituent being selected from isopropyl, t-butyl, i-methyl-2- p-hydroxy phenyl ethyl, 1-methyl-2-p-acetylaminophenylethyl and 1-methyl-2-p-methoxyphenylethyl, and 4 - nitro - α - (N-benzyl - N - tertbutyl-amino)acetophenone are prepared by reaction of the correspondingly substituted α-bromo acetophenones with an appropriate amine and the keto groups are reduced with sodium borohydride to obtain the corresponding substituted benzyl alcohols. α - (N,N - disubstituted amino)acetophenones having a 3- or 4-nitro group in the ring are reduced to the corresponding amines by reaction with inon powder or by hydrogenation. The aromatic amino group thus prdouced is formylated by reaction with formic acid in acetic anhydride or with formic acid in the presence of dicyclohexylcarbodiimide. 4 - Benzyloxy - 3 - benzyloxyacetylamino acetophenone and 3-acetylamino-4-benzyloxy acetophenone are prepared from their respective 3-amino compounds by reaction with benzyloxyacetylchloride and acetic anhydride respectively. 4 - Benzyloxy - 3 - methylamino - α - (N- benzyl - N - t - butylamino - methyl)benzyl alcohol is prepared by reduction of the corresponding 3-formylamino compound with LiAlH 4 and is reacted with formic acid in acetic anhydride to obtain the corresponding N-formyl- N-methyl derivative. 3 - Amino - 4 - benzyloxy - α - [N - benzyl - N- (1 - methyl - 2 - p - hydroxy - phenylethyl)aminomethyl]benzyl alcohol is obtained by hydrolysis of the corresponding 3-formylamino compound and is reacted with acetic anhydride or benzyloxyacetylchloride to prepare the corresponding 3-acetylamino or 3-benzyloxyacetylamino compounds respectively. Pharmaceutical compositions having α-adrenergic activity for oral or parenteral or injection administration comprise a compound of Formula I together with a pharmaceutically acceptable diluent or medium.