Water → HCID 57848858, compound

Participants

Reaction Conditions

Reaction Steps

391 mg (1.55 mmol) of 4-(4-methylpiperazin-1-ylmethyl)benzoyl chloride hydrochloride are added to a solution of 0.30 g (0.77 mmol) of tert-butyl 3-amino-5-(N′-methyl-N′-phenylhydrazinocarbonyl)thieno[2,3-c]pyrazole-1-carboxylate in 16 mL of pyridine under argon. The reaction mixture is stirred at a temperature in the region of 25° C. for 16 hours, a further 294 mg (1.16 mmol) of 4-(4-methylpiperazin-1-ylmethyl)benzoyl chloride are then added and stirring is continued for 5 hours. The reaction mixture is then cooled to a temperature in the region of 10° C. and then treated with 50 mL of water. The mixture is extracted twice with 100 mL of ethyl acetate. The organic phases are combined, washed with water to neutral pH, dried over magnesium sulfate, filtered and then concentrated to dryness under vacuum (3 kPa) at a temperature in the region of 30° C. The residue is purified by chromatography on a cartridge of 25 g of silica gel (0.015-0.040 mm), eluting successively with dichloromethane/methanol mixtures (98/2 by volume, and then 97/3, then 96/4 and finally 95/5) at a flow rate of 15 mL/min. The fractions containing the expected product are combined and then concentrated to dryness under reduced pressure (3 kPa) at a temperature in the region of 30° C. 0.14 g of tert-butyl 5-(N′-methyl-N′-phenylhydrazinocarbonyl)-3-[4-(4-methylpiperazin-1-ylmethyl)benzoylamino]thieno[2,3-c]pyrazole-1-carboxylate is thus obtained in the form of an off-white solid melting at 218° C. tert-Butyl 3-amino-5-(N′-methyl-N′-phenylhydrazinocarbonyl)thieno[2,3-c]pyrazole-1-carboxylate is described in example 8. 4-(4-Methylpiperazin-1-ylmethyl)benzoyl chloride may be prepared according to patent WO 03/066 613 A1.

Provenance & Evidence