Collect. Czech. Chem. Commun. 1979, 44, 3604-3616

Synthesis of 7-chloro-5-(6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-2-methylamino-3H-1,4-benzodiazepine 4-oxide and of some related compounds

Zdeněk Vejdělek, Miroslav Rajšner, Emil Svátek, Jiří Holubek and Miroslav Protiva

Research Institute for Pharmacy and Biochemistry, 130 00 Prague 3


The base catalyzed condensation of 4-chloronitrobenzene with 2-(cyanomethyl)-6,7,8,9-tetrahydro-5H-benzocycloheptene afforded the 2,1-benzisoxazole derivative VIa which was reduced with iron in acetic acid to the 2-aminophenone VIIa. Its oxime IXa was treated with chloroacetyl chloride in acetic acid and gave the 4-substituted 6-chloro-2-chloromethylquinazoline 3-oxide (Xa). The treatment with methylamine in methanol led to the substitution reaction with a simultaneous ring elargement and the title compound IVa was formed. A similar reaction with 1-methylpiperazine proceeded without rearrangement resulting in the quinazoline XIa. The object of further experiments was the preparation of the lactam Va, the norpethidine derivative XV and some new approaches to intermediates useful in the synthesis of 5-(2-chlorophenyl)-7ethyl-1,3-dihydrothieno[2,3-e]-1,4-diazepin-2-ones.