Potassium Carbonate → 4-({[5-Chloro-6-(3,3,3-trifluoropropoxy)pyridin-3-yl]oxy}methyl)-2,5-difluoro-N-(methylsulfonyl)benzamide

HRID 512025Notes

Reaction equation

HRID 512025 reaction equation
C(=O)([O-])[O-].[K+].[K+].[Cl:7][C:8]1[CH:9]=[C:10]([OH:21])[CH:11]=[N:12][C:13]=1[O:14][CH2:15][CH2:16][C:17]([F:20])([F:19])[F:18].Br[CH2:23][C:24]1[C:36]([F:37])=[CH:35][C:27]([C:28]([NH:30][S:31]([CH3:34])(=[O:33])=[O:32])=[O:29])=[C:26]([F:38])[CH:25]=1>CS(C)=O.Cl>[Cl:7][C:8]1[CH:9]=[C:10]([O:21][CH2:23][C:24]2[C:36]([F:37])=[CH:35][C:27]([C:28]([NH:30][S:31]([CH3:34])(=[O:33])=[O:32])=[O:29])=[C:26]([F:38])[CH:25]=2)[CH:11]=[N:12][C:13]=1[O:14][CH2:15][CH2:16][C:17]([F:18])([F:19])[F:20]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 666669425-Chloro-6-(3,3,3-trifluoropropoxy)pyridin-3-olHCID 666671114-(Bromomethyl)-2,5-difluoro-N-(methylsulfonyl)benzamide

Product 1

HCID 866825664-({[5-Chloro-6-(3,3,3-trifluoropropoxy)pyridin-3-yl]oxy}methyl)-2,5-difluoro-N-(methylsulfonyl)benzamideYield 78.6%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 679Dimethyl SulfoxideSolvent

Procedure

Potassium carbonate (61 mg, 0.229 mmol) was added to a solution of 5-chloro-6-(3,3,3-trifluoropropoxy)pyridin-3-ol (Preparation 67, 45 mg, 0.19 mmol) in DMSO (2 mL) and the reaction mixture was stirred under a nitrogen atmosphere at room temperature for 5 minutes. 4-(Bromomethyl)-2,5-difluoro-N-(methylsulfonyl)benzamide (Preparation 10, 63 mg, 0.19 mmol) was then added and the resulting mixture stirred under nitrogen at room temperature for 120 hours. The reaction mixture was diluted with aqueous hydrochloric acid solution (2 M, 15 mL), extracted with EtOAc (20 mL). The organic layer was washed with aqueous hydrochloric acid solution (2 M, 2×10 mL), dried over magnesium sulfate, filtered and evaporated in vacuo. The resulting crude solid was triturated with TBME/heptane (2:1), washed with heptane and dried in vacuo to yield the title compound as an off-white solid (73 mg, 74%):

Workup

  1. stirringthe resulting mixture stirred under nitrogen at room temperature for 120 hours
  2. extractionextracted with EtOAc (20 mL)
  3. washThe organic layer was washed with aqueous hydrochloric acid solution (2 M, 2×10 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe resulting crude solid was triturated with TBME/heptane (2:1)
  8. washwashed with heptane
  9. customdried in vacuo

Sources & evidence

ORD record
ord-3977a7a4b105426f955c028fdad0c22e
Source dataset
uspto-grants-2015_08
Patent number
US09102621B2

Reaction notes

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