ANALOGIFICATION OF ALPHA-AMINOALKYL-4-HYDROXY-3-UREIDOBENSYL ALCOHOL

摘要

1286225 Benzyl alcohol derivatives SMITH KLINE & FRENCH LABORATORIES 19 April 1971 [17 Feb 1970] 22115/71 Heading C2C The invention comprises novel benzyl alcohol derivatives, pharmaceutically acceptable acid addition salts thereof, and the corresponding novel aminobenzyloxyphenones of the formulµ wherein R is H, C 1-5 alkIl, phenyl, dimethylaminoethyl, or dimethylaminopropyl; R 1 is C 3-5 alkyl C 3-6 cycloalkyl, C 3-6 cycloalkylmethyl or a radical of the formula R 2 is H, CH3 or CH 2 CH 3 ; R 3 and R 4 each are H, OH or OCH3 and R 5 is H or CH 3 , the compounds of the above formulµ are prepared by reacting the appropriate 4-benzyloxy--bromophenones with the corresponding N-benzylamines of the formula followed by, if desired, catalytic hydrogenation. 4 - Benzyloxy - - bromo - 3 - ureidoawtophenone is obtained by brominating 4-benzyloxy-3- ureido-ecetophenone resulting from the action of ammonia on 4-benzyloxy-3-isocyantoacetophenone which is prepared by reacting 3-amino-4-benzyloxyacetophenone with phosgene. 4 - Benzyloxy - - bromo - 3 - (NSP1/SP - methylureido)-acetophenone is made by brominating 4- benzyloxy 3-(NSP1/SP-methylureido)-acetophenone obtained by treating the above named isocyanate with methylamine. By similar processes 4- benzyloxy - 3 - (NSP1/SP - phenylureido) - acetophenone, 4 - benzyloxy - - bromo - 3 - (NSP1/SP - phenylureido)- acetophenone, 4 -beizyloxy - 3 -isocyantobutyro - phenone, 4 -benzyloxy- 3 -ureidobutyrophenone, 4- benzyloxy-3-(N,NSP1/SP-dimethylureido)-acetophenone, 4 - benzyloxy - - bromo - 3 - (N,NSP1/SP - dimethylureido)-acetophenone, and 4 -bemyloxy--bromo-3- 3-ureidoobutyrophenone are prepared. 4 - Benzyloxy- - bromo - 3 - (N- methylureido)-acetophenone is made by brominating 4- benzyloxy- 3- (N-methylureido ) -acetoph enone resulting from the action of sodium cyanate on 4-benzyloxy- 3 -methylaminoccetophenane, which is prepared by hydrolysing 4-benzyloxy-3-(N-methylformamido)-acetophenone, obtained by methylating 4-benzyloxy- 3 -formamidoacetophenone resulting from reaction between ethyl formate and 3-amino-4-benzyloxyacetophenone. Pharmaceutical compositions, having #- adrenergic stimulating activity and suitable for oral or parenteral administration, contain the above novel benzyl alcohol derivative together with suitable pharmaceutical carriers.