Реакция #10425

Уравнение реакции

cyclopropylamine

2,6-dichloro-5-fluoronicotinamide

oxalyl chloride

→

title compound

Выход 98.5%

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

Выход 98.5%

Растворители

dichloromethane

Условия реакции

Обработка

1. 1
   Температураthe reaction mixture is heated
2. 2
   Температураat reflux for 18 hours
3. 3
   ДругоеThe solvent is removed in vacuo
4. 4
   workup.DISSOLUTIONthe residue is dissolved in 50 mL of dichloromethane
5. 5
   Другоеwhich 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
   ДругоеThe solvent is removed in vacuo
9. 9
   Другоеthe residue is triturated with 25 mL of dichloromethane, which
10. 10
    Другоеis also removed in vacuo

Методика

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.

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