Nitrazolam synthesis

Yield:-

Reaction Conditions:

in water;

Steps:

12 1-Methyl-8-nitro-6-phenyl-4H-s-triazolo[4,3-a]-[1,4]benzodiazepine.

EXAMPLE 12 1-Methyl-8-nitro-6-phenyl-4H-s-triazolo[4,3-a]-[1,4]benzodiazepine. A stirred mixture of 1,3-dihydro-7-nitro-5-phenyl-2H-1,4-benzodiazepine-2-thione (2.97 g.; 0.01 mole), acetic acid hydrazide (2.21 g.; 0.03 mole) and 1-butanol (100 ml.) ws refluxed for 1.5 hours with a slow stream of nitrogen bubbling through the reaction mixture. The resulting mixture was concentrated in vacuo. The residue was suspended in water and extracted with methylene chloride. The extract was dried over anhydrous potassium carbonate and concentrated in vacuo. The residue was chromatographed on silica gel (200 g.) with 2% triethylamine-3% methanol-95% ethyl acetate (by volume). The product thus obtained was crystallized from methanol-ethyl acetate to give 0.83 g. (26%) of 1-methyl-8-nitro-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine of melting point 233°-234° C.

References:

US3987052,1976,A