Originator
Erimin,Sumitomo,Japan,1977
Manufacturing Process
To a suspension of 73.9 g of 1-methyl-5-nitro-3-phenylindole-2-carbonitrile in
1.5 liters of dry tetrahydrofuran is added dropwise a solution of 126 g of
boron trifluoride etherate in 220 ml of dry tetrahydrofuran with stirring for 2
hours. After addition, stirring is continued for an additional 3 hours. To the reaction mixture is added dropwise 370 ml of water and then 370 ml of
concentrated hydrochloric acid with stirring under ice-cooling.
The resulting precipitate is collected by filtration, washed with water followed
by ethanol, and dried to give 56.3 g of crude 2-aminomethyl-1-methyl-5-
nitro-3-phenylindole hydrochloride, melting point 263°C to 267°C.
To a suspension of 6.5 g of 2-aminomethyl-1-methyl-5-nitro-3-phenylindole in
65 ml of glacial acetic acid is added dropwise a solution of 6.5 g of chromic
anhydride in 6.5 ml of water at 20°C with stirring. The mixture is stirred at
room temperature overnight and thereto is added 195 ml of water. To the
mixture is added dropwise 100 ml of 28% ammonia water with stirring under
cooling. The resultant precipitate is collected by filtration, washed with water
and dried to give 5.9 g of a crude product having melting point 135°C to
140°C. Fractional recrystallization from ethanol gives 3.8 g of 1-methyl-7-
nitro-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepine-2-one as yellow plates,
melting point 153°C to 156°C. Further recrystallization from the same solvent
gives pale yellow plates having melting point 156°C to 156.5°C.
