SYNTHESIS OF METHYLCARBONYLAMINO-4-BENZOYL-1,2-DIHYDROPYRIDINES AND THEIR CYCLIZATION TO ,9-TETRAHYDRO-2H-PYRIDO[3,4-E]-1,4-DIAZEPIN-2-ONES

The regiospecific reaction of carbonylaminomethylcarbonylamino-4-benzo ylpyridine (6a), or carbonylaminomethylcarbonylamino-4-benzoylpyridine (6b), with either acetyl chloride or ethyl chloroformate, and either n-butylmagnesium chloride or phenylmagnesium bromide afforded the resp ective 1-acetyl (or ethoxycarbonyl)-2-n-butyl (or phenyl)-3-benzyloxy (or t-butoxy) methylcarbonylamino-4-benzoyl-1,2-dihydropyridines 7 in 60-75% yield. Reaction of 1-acetyl (or ethoxycarbonyl)-2-n-butyl (or a minomethylcarbonyl-4-benzoyl-1,2-dihydropyridines 7b, 7f, 7d, 7h with trifluoroacetic acid gave the corresponding 5-phenyl-8-acetyl (or etho xycarbonyl)-9-n-butyl (or ,9-tetrahydro-2H-pyrido[3,4-e]-1,4-diazepin- 2-ones 8a, 8b, 8c, 8d respectively in 45-63% yield. N1-Methylation of 5-phenyl-8-acetyl-9-n-butyl (or ,9-tetrahydro-2H-pyrido[3,4-e]-1,4-dia zepin-2-ones 8a, 8b using sodium hydride and iodomethane yielded the c orresponding N1-methyl derivatives 9a (48%) and 9b (54%). Oxidation of 8,9-tetrahydro-2H-pyrido[3,4-e]-1,4-diazepin-2-one (8d) using p-chlor anil afforded o-5,9-diphenyl-2H-pyrido[3,4-e]-1,4-diazepin-2-one (10). 8,9-tetrahydro-2H-pyrido[3,4-e]-1,4-diazepin-2-one (8a) and the corre sponding 8-ethoxycarbonyl analog 8c exhibited weak anticonvulsant acti vity indicating that 8a and Bc may be acting at the same site as the 7 -halo-1,4-benzodiazepin-2-one class of compounds.