2,6-Dichlorobenzoyl chloride → 2,6-dichloro-N-(2,6-dichlorobenzoyl)-N-(3,5-difluoropyridin-4-yl)-benzamide

HRID 2366266Notes

Reaction equation

HRID 2366266 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([Cl: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]([Cl:11])[C:3]=1[C:4]([N:19]([C:4](=[O:5])[C:3]1[C:2]([Cl:1])=[CH:10][CH:9]=[CH:8][C:7]=1[Cl:11])[C:18]1[C:17]([F:20])=[CH:16][N:15]=[CH:14][C:13]=1[F:12])=[O:5]

Participants

4

Reactant 2

HCID 783922,6-Dichlorobenzoyl chlorideHCID 27376543,5-Difluoro-4-pyridinamine

Product 1

HCID 866690092,6-dichloro-N-(2,6-dichlorobenzoyl)-N-(3,5-difluoropyridin-4-yl)-benzamideYield 96.7%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

2,6-Dichlorobenzoyl chloride (13.7 mL, 95.6 mmol) was added dropwise, over 10 minutes, to a solution of 3,5-difluoropyridin-4-ylamine (10.37 g, 79.7 mmol) in pyridine (160 mL) at a temperature of between 3 and 5° C., under argon. The reaction mixture was allowed to warm to room temperature over 1 hour and then stirred at room temperature for 2 hours. The volatiles were removed under reduced pressure and the resultant residue was treated with HCl (1N, 120 mL). The resultant suspension was stirred at room temperature for 45 minutes and the precipitate was collected by filtration, washing with water. A mixture of 2,6-dichloro-N-(3,5-difluoropyridin-4-yl)-benzamide and of 2,6-dichloro-N-(2,6-dichlorobenzoyl)-N-(3,5-difluoropyridin-4-yl)-benzamide (22.0 g) was obtained. A suspension of this mixture (22.0 g) in 1N NaOH (200 mL) and MeOH (200 mL) was heated at 65° C. for 7 hours then slowly cooled to room temperature. The pH of the mixture was adjusted to 4-5 by dropwise addition of 12N HCl, controlling the exotherm by the use of an ice-bath. The residue was left standing at room temperature for 18 hours and then the resultant solid was collected by filtration, washing with water, to afford the title compound as an off-white solid (14.65 g, 61% yield over two steps). LCMS (Method D): RT=2.93 min, m/z: 303 [M+H+].

Workup

  1. customThe volatiles were removed under reduced pressure
  2. additionthe resultant residue was treated with HCl (1N, 120 mL)
  3. stirringThe resultant suspension was stirred at room temperature for 45 minutes
  4. filtrationthe precipitate was collected by filtration
  5. washwashing with water
  6. additionA mixture of 2,6-dichloro-N-(3,5-difluoropyridin-4-yl)-benzamide

Sources & evidence

ORD record
ord-169afb59fdde4f16a75afe457f8f0f99
Source dataset
uspto-grants-2014_04
Patent number
US08697708B2

Reaction notes

Loading…