Reaktion #10425

Reaktionsgleichung

cyclopropylamine

2,6-dichloro-5-fluoronicotinamide

oxalyl chloride

→

title compound

Ausbeute 98.5%

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

Ausbeute 98.5%

Lösungsmittel

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturthe reaction mixture is heated
2. 2
   Temperaturat reflux for 18 hours
3. 3
   SonstigeThe solvent is removed in vacuo
4. 4
   workup.DISSOLUTIONthe residue is dissolved in 50 mL of dichloromethane
5. 5
   Sonstigewhich 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
   SonstigeThe solvent is removed in vacuo
9. 9
   Sonstigethe residue is triturated with 25 mL of dichloromethane, which
10. 10
    Sonstigeis also removed in vacuo

Vorschrift

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.

Quelle