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

HRID 10329Notes

Reaction equation

[Cl:1][C:2]1[N:10]=[C:9]([Cl:11])[C:8]([F:12])=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].[C:13](Cl)(=[O:17])C(Cl)=O.[CH:19]1([NH2:22])[CH2:21][CH2:20]1>ClCCl>[CH:19]1([NH:22][C:13]([NH:6][C:4]([C:3]2[C:2]([Cl:1])=[N:10][C:9]([Cl:11])=[C:8]([F:12])[CH:7]=2)=[O:5])=[O:17])[CH2:21][CH2:20]1

Participants

Conditions

Temperature: -20 °C

Procedure

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.

Workup

temperaturethe reaction mixture is heated
temperatureat reflux for 18 hours
customThe solvent is removed in vacuo
dissolutionthe residue is dissolved in 50 mL of dichloromethane
customwhich is also removed in vacuo
dissolutionThe residue is dissolved in 50 mL of dichloromethane
waitto come to room temperature over 2 hours
customThe solvent is removed in vacuo
customthe residue is triturated with 25 mL of dichloromethane, which
customis also removed in vacuo

Sources & evidence

ORD record: ord-950eac8099204e9080cda488ff8ca284
Source dataset: uspto-grants-2006_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07094780B1

Reaction notes

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