반응 #10425

반응 방정식

cyclopropylamine

2,6-dichloro-5-fluoronicotinamide

oxalyl chloride

→

title compound

수율 98.5%

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

수율 98.5%

용매

dichloromethane

반응 조건

후처리

1. 1
   온도the reaction mixture is heated
2. 2
   온도at reflux for 18 hours
3. 3
   기타The solvent is removed in vacuo
4. 4
   workup.DISSOLUTIONthe residue is dissolved in 50 mL of dichloromethane
5. 5
   기타which 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
   기타The solvent is removed in vacuo
9. 9
   기타the residue is triturated with 25 mL of dichloromethane, which
10. 10
    기타is also removed in vacuo

실험 절차

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.

출처