2-Chloro-6-fluorobenzoyl chloride → 2-chloro-N-(2-chloro-6-fluorobenzoyl)-N-(3,5-difluoropyridin-4-yl)-6-fluorobenzamide

HRID 2366257Notes

Reaction equation

[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[C:3]=1[C:4](Cl)=[O:5].[F:12][C:13]1[CH:14]=[N:15][CH:16]=[C:17]([F:20])[C:18]=1[NH2:19]>N1C=CC=CC=1>[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[C:3]=1[C:4]([N:19]([C:4](=[O:5])[C:3]1[C:7]([F:11])=[CH:8][CH:9]=[CH:10][C:2]=1[Cl:1])[C:18]1[C:17]([F:20])=[CH:16][N:15]=[CH:14][C:13]=1[F:12])=[O:5]

Participants

Conditions

Temperature: 0 °C

Procedure

2-Chloro-6-fluorobenzoyl chloride (13.6 g, 71.6 mmol) was added dropwise, over 10 minutes, to a solution of 3,5-difluoro-pyridin-4-ylamine (7.7 g, 59.3 mmol) in pyridine (100 mL) at 0° C. under argon and the reaction mixture was stirred at 0° C. for 3 hours. The volatiles were removed under reduced pressure and the resultant residue was treated with 1N HCl (100 mL). The resultant suspension was stirred at room temperature for 2 hours and then the solid was collected by filtration, washing with water. A mixture of 2-chloro-N-(3,5-difluoropyridin-4-yl)-6-fluorobenzamide, LCMS (Method E): RT=2.83 min, m/z: 287 [M+H+], and of 2-chloro-N-(2-chloro-6-fluorobenzoyl)-N-(3,5-difluoropyridin-4-yl)-6-fluorobenzamide LCMS (Method E): RT=3.96 min, m/z: 443 [M+H+], (23 g) was obtained which was used in the following step without further purification.

Workup

customThe volatiles were removed under reduced pressure
additionthe resultant residue was treated with 1N HCl (100 mL)
stirringThe resultant suspension was stirred at room temperature for 2 hours
filtrationthe solid was collected by filtration
washwashing with water
additionA mixture of 2-chloro-N-(3,5-difluoropyridin-4-yl)-6-fluorobenzamide, LCMS (Method E)

Sources & evidence

ORD record: ord-cd7b35310e634f81a6d7e340ad891d4e
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08697708B2

Reaction notes

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