Picolinohydrazide → HCID 13649490, compound

Participants

Reaction Steps

Into a suitable reactor are charged N,N-dimethylformamide (159 kg) and 2-pyridinecarboxylic acid hydrazide (25.2 kg) and the mixture is stirred 10-15 minuted at 20°-25° to give a solution. In a separate suitable reactor are charged N,N-dimethylformamide (97 kg) and 11-chloro-5H-pyrrolo-[2,1-c][1,4]benzodiazepine (34.4 kg). The mixture is stirred for 15-30 minutes at 20°-25° to give a solution. This solution is added over 2-3 hours to the preheated solution of 2-pyridinecarboxylic acid hydrazide in N,N-dimethylformamide at 48° to 52°. Once the addition is complete the reaction mixture is further stirred for 2-3 hours at 48° to 52°. The reaction mixture is then heated for 12-15 hours at 72°-75°. The mixture is then cooled to 15°-20° with stirring. The solid is filtered off and washed with N,N-dimethylformamide (28 L). The solid is then stirred in a 1:1 mixture of water and ethanol (140 L) for 30-60 minutes at 20°-25°. The pH is adjusted to about 7 using concentrated ammonium hydroxide solution. The reaction mixture is stirred for 30-60 minutes at 20°-25°. The solid is filtered off, washed with a mixture of ethanol and water (1:1, 50 L) and vacuum dried (60°-70°) to give the title compound as the free base, m.p. 255°-257°.

Provenance & Evidence