Water → 5-chloro-4-(5-chloro-6-(3,3-difluoropyrrolidin-1-yl)pyridin-3-yloxy)-2-fluoro-N-(methylsulfonyl)benzamide

HRID 2048024Notes

Reaction equation

HRID 2048024 reaction equation
C(N(CC)CC)C.[Cl:8][C:9]1[C:10]([O:23][C:24]2[CH:25]=[N:26][C:27](F)=[C:28]([Cl:30])[CH:29]=2)=[CH:11][C:12]([F:22])=[C:13]([CH:21]=1)[C:14]([NH:16][S:17]([CH3:20])(=[O:19])=[O:18])=[O:15].Cl.[F:33][C:34]1([F:39])[CH2:38][CH2:37][NH:36][CH2:35]1.O>CS(C)=O>[Cl:8][C:9]1[C:10]([O:23][C:24]2[CH:25]=[N:26][C:27]([N:36]3[CH2:37][CH2:38][C:34]([F:39])([F:33])[CH2:35]3)=[C:28]([Cl:30])[CH:29]=2)=[CH:11][C:12]([F:22])=[C:13]([CH:21]=1)[C:14]([NH:16][S:17]([CH3:20])(=[O:19])=[O:18])=[O:15]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 249034823,3-Difluoropyrrolidine hydrochlorideHCID 580424375-Chloro-4-[(5-chloro-6-fluoropyridin-3-yl)oxy]-2-fluoro-N-(methylsulfonyl)benzamide

Product 1

HCID 580424205-chloro-4-(5-chloro-6-(3,3-difluoropyrrolidin-1-yl)pyridin-3-yloxy)-2-fluoro-N-(methylsulfonyl)benzamide

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

Triethylamine (0.21 mL, 1.51 mmol) was added to a mixture of 5-chloro-4-[5-chloro-6-fluoropyridin-3-yl)oxy]-2-fluoro-N-(methylsulfonyl)benzamide (Example 19, 150 mg, 0.38 mmol) and 3,3-difluoropyrrolidine hydrochloride salt (60 mg, 0.41 mmol), in DMSO (3.8 mL) and the reaction heated at 80° C. for 120 hours. The mixture was diluted to 5 mL by the addition of water and the mixture purified by preparative HPLC. The title compound was obtained as a beige solid (49 mg, 27%).

Workup

  1. customthe mixture purified by preparative HPLC

Sources & evidence

ORD record
ord-cbf6ff77008b432f9f53e8a1f049e03a
Source dataset
uspto-grants-2013_11
Patent number
US08592629B2

Reaction notes

Loading…