METHOD OF PRODUCING 2-HALOMETHYL-1,4-BENZODIAZEPINES

摘要

1-alkyl-2-halomethyl-1,4-benzodiazepines corresponding to the formula in which R1 represents a C1-4 alkyl group, R2 represents a hydrogen atom, a halogen atom or a trifluoromethyl group, R3 represents a hydrogen or halogen atom and X represents a chlorine or bromine atom, having pharmacological properties, are prepared with improved yield by halogenating the corresponding N1benzoyl-N2-alkyl-N2-phenyl-2-hydroxy-1,3-diaminopropane into the corresponding imidoyl halide and then cyclising that imidoyl halide using a Lewis acid catalyst. The halogenation reaction can be effected directly using phosphorus pentachloride or pentabromide or the 2-hydroxy group of the acyldiaminopropane can first be halogenated using phosphorus oxychloride, oxybromide, trichloride or tribromide or thionyl chloride to give the corresponding 2-haloacyldiamine and the acyl group then halogenated using phosphorus pentachloride or pentabromide to give the imidoyl halide so permitting intermediate purification of the haloacyldiamine.