Prepn. of 1,4-benzodiazepine cpds. - by reacting e.g. a 2-haloethyl-amino-benzophenone with hexa: methylene tetr:amine in presence of an ammonium salt and water alcohol solvent

摘要

Prepn. of 1,4-benzodiazepines (I) comprises reacting a 2-(2-haloacylamino)- or 2-(2-haloethylamino)-benzophenone (IIe with hexamethylene tetraamine (HMTA) in a solvent mixt. contg. 5-50 (pref. 15-35) vol. % water and a water-miscible alcohol, in the presence of an ammonium salt of an acid of pKa 3.2 or less. (I) is obtd. in higher yields (more than 85%) cf. previous processes (50%) in a shorter reaction time (1/5-1/2 the time previously). Prodn. of by-prods. is lower and isolation of (I) is easier. The process is esp. suitable for the prodn. of e.g. 7-chloro-1-(2,2,2-trifluoroethyl)-5-phenyl-1,3-dihydro-2H-1,4-ben- zodiazepin-2-one and 7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one- . Pref. ammonium salts are NH4Br, NHEI and NH4NO3.