FUSED-RING BENZODIAZEPINE AND BENZODIAZOCINE DERIVATIVES

摘要

1474252 Pyrimidino-benzodiazepines and pyrimidino-benzodiazocines; intermediates therefor E R SQUIBB & SONS Inc 3 July 1974 [26 July 1973] 29534/74 Heading C2C Novel pyrimidino-benzodiazepines and pyrimidino benzodiazocines of the Formula I wherein m is 1 or 2, n is 2 or 3. R is a hydrogen, fluorine, chlorine or bromine atom or a C 1-4 alkyl, benzyl, phenyl or monosubstituted phenyl radical the substituent being fluorine chlorine, bromine, iodine, C 1-4 alkyl, C 1-4 alkoxy or trifluoromethyl, and R1 is a hydrogen or halogen atom or a C 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkylthio, C 1-4 alkylsulphonyl, phenyl, phenoxy, sulphamyl, di(C 1-4 alkyl)sulphamyl, trifluoromethyl or a mono substitued phenyl or phenoxy radical the substituent being halogen, C 1-4 alkyl, C 1-4 alkoxy or trifluoromethyl, provided that when m is 1, R occupies either the 4- or 5- position of the pyrimidine ring but when m is 1 and R is halogen, it occupies only position-5 and when m is 2 the two R substituents occupy the 4-and 5-positions but only one of them can be halogen and it must occupy the 5-position, are obtained by cyclization of compounds of the Formula IV or V wherein X is a chlorine or bromine atom. Compounds of the formula IV above may be obtained by quaternizing appropriate 2-aminopyrimidines with appropriate o-bromo-phenylethyl or o-bromo-phenylpropyl halides III. Compounds of the Formula V above may be obtained by treating compounds of Formula IV with a water-miscible alcohol and a alkalimetal C 1-3 alkoxide. o - Bromophenylethyl and o - bromophenylpropyl halides of the Formula III may be obtained by halogenating the corresponding o-bromophenylethyl or o-bromophenylpropyl alcohols. o-Bromophenethyl alcohol may be obtained by reacting o-bromobenzyl alcohol with phosphorus tribromide to give o-bromobenzyl bromide, reacting this with sodium cyanide to give obromophenylacetonitrile, reacting this with ethanol and reducing the ethyl-o-bromophenylacetate so produced. 3 - (2 - Bromo - 5 - methylthio)phenyl - 1 - propanol may be obtained by reacting 2-bromo-5- methylthiobenzyl alcohol with phosphorus tribromide and reacting the 2-bromo-5-methylthio benzylbromide so produced with magnesium and ethylene oxide. Pharmaceutical compositions contain compounds of Formula I above as active ingredients.