Reacción #10425

Ecuación de reacción

cyclopropylamine

2,6-dichloro-5-fluoronicotinamide

oxalyl chloride

→

title compound

Rendimiento 98.5%

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

Rendimiento 98.5%

Disolventes

dichloromethane

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturathe reaction mixture is heated
2. 2
   Temperaturaat reflux for 18 hours
3. 3
   OtroThe solvent is removed in vacuo
4. 4
   workup.DISSOLUTIONthe residue is dissolved in 50 mL of dichloromethane
5. 5
   Otrowhich is also removed in vacuo
6. 6
   workup.DISSOLUTIONThe residue is dissolved in 50 mL of dichloromethane
7. 7
   workup.WAITto come to room temperature over 2 hours
8. 8
   OtroThe solvent is removed in vacuo
9. 9
   Otrothe residue is triturated with 25 mL of dichloromethane, which
10. 10
    Otrois also removed in vacuo

Procedimiento

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.

Fuente