Oxalyl chloride → 1-Cyclopropyl-3-(2,6-dichloro-5-fluoro-pyridine-3-carbonyl)urea

Participants

Reaction Conditions

Reaction Steps

A solution of 5.8 g (27.8 mmol) of 2,6-dichloro-5-fluoronicotinamide (Chem. Pharm. Bull., 1987; 35:2280) in 60 mL of dichloromethane is treated dropwise with 5.1 g (40 mmol) of oxalyl chloride, and the reaction mixture is heated at reflux for 18 hours. The solvent is removed in vacuo, and the residue is dissolved in 50 mL of dichloromethane, which is also removed in vacuo. The residue is dissolved in 50 mL of dichloromethane, cooled to −20° C. and treated dropwise with 2.28 g (40 mmol) of cyclopropylamine. The reaction mixture is stirred at −20° to −10° C. for ½ hour, then allowed to come to room temperature over 2 hours. The solvent is removed in vacuo and the residue is triturated with 25 mL of dichloromethane, which is also removed in vacuo to give 8.0 g of the title compound, mp 171-173° C.

Provenance & Evidence