تفاعل #10425

معادلة التفاعل

cyclopropylamine

2,6-dichloro-5-fluoronicotinamide

oxalyl chloride

→

title compound

المردود 98.5%

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

المردود 98.5%

المذيبات

dichloromethane

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةthe reaction mixture is heated
2. 2
   درجة الحرارةat reflux for 18 hours
3. 3
   أخرىThe solvent is removed in vacuo
4. 4
   workup.DISSOLUTIONthe residue is dissolved in 50 mL of dichloromethane
5. 5
   أخرىwhich 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
   أخرىThe solvent is removed in vacuo
9. 9
   أخرىthe residue is triturated with 25 mL of dichloromethane, which
10. 10
    أخرىis also removed in vacuo

الإجراء التجريبي

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.

المصدر