Methanesulfonamide → 5-chloro-4-({5-chloro-6-[(1S)-2,2,2-trifluoro-1-methylethoxy]pyridin-3-yl}oxy)-2-fluoro-N-(methylsulfonyl)benzamide

HRID 2048027Notes

Reaction equation

HRID 2048027 reaction equation
[CH3:1][S:2]([NH2:5])(=[O:4])=[O:3].CC(C)([O-])C.[K+].[Cl:12][C:13]1[C:14]([O:30][C:31]2[CH:32]=[N:33][C:34]([O:38][C@@H:39]([CH3:44])[C:40]([F:43])([F:42])[F:41])=[C:35]([Cl:37])[CH:36]=2)=[CH:15][C:16]([F:29])=[C:17]([CH:28]=1)[C:18](OC1C=CC(C)=CC=1)=[O:19]>C1COCC1>[Cl:12][C:13]1[C:14]([O:30][C:31]2[CH:32]=[N:33][C:34]([O:38][C@@H:39]([CH3:44])[C:40]([F:42])([F:43])[F:41])=[C:35]([Cl:37])[CH:36]=2)=[CH:15][C:16]([F:29])=[C:17]([CH:28]=1)[C:18]([NH:5][S:2]([CH3:1])(=[O:4])=[O:3])=[O:19]

Participants

5

Reactant 3

HCID 72879MethanesulfonamideHCID 23665647Potassium tert-butoxideHCID 580425084-methylphenyl 5-chloro-4-({5-chloro-6-[(1S)-2,2,2-trifluoro-1-methylethoxy]pyridin-3-yl}oxy)-2-fluorobenzoate

Product 1

HCID 566440145-chloro-4-({5-chloro-6-[(1S)-2,2,2-trifluoro-1-methylethoxy]pyridin-3-yl}oxy)-2-fluoro-N-(methylsulfonyl)benzamideYield 27.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of methanesulfonamide (26 mg, 0.28 mmol) in THF (2 mL) was added potassium tert-butoxide (32 mg, 0.28 mmol) and the mixture was stirred for 10 minutes at room temperature. A solution of 4-methylphenyl 5-chloro-4-({5-chloro-6-[(1S)-2,2,2-trifluoro-1-methylethoxy]pyridin-3-yl}oxy)-2-fluorobenzoate (Preparation 230, 108 mg, 0.21 mmol) in THF (2 mL) was added and the mixture was stirred at 50° C. for 10 hours. The reaction mixture was allowed to cool to room temperature. The reaction was quenched with water and acidified with 1N aqueous citric acid solution. The mixture was extracted with DCM (3×5 mL) and filtered using a phase separation cartridge. The filtrate was concentrated in vacuo to give a crude product that was purified by silica gel chromatography eluting with 0-100% EtOAc in heptane to give a product mixture as a white solid. The solid was purified by reverse phase column chromatography eluting with 5-95% CH3CN in water to give a white solid that was further purified using trituration with heptanes/acetone 9/1 to give the title compound (28 mg, 27%) as a white solid.

Workup

  1. stirringthe mixture was stirred at 50° C. for 10 hours
  2. temperatureto cool to room temperature
  3. customThe reaction was quenched with water
  4. extractionThe mixture was extracted with DCM (3×5 mL)
  5. filtrationfiltered
  6. customa phase separation cartridge
  7. concentrationThe filtrate was concentrated in vacuo
  8. customto give a crude product that
  9. customwas purified by silica gel chromatography
  10. washeluting with 0-100% EtOAc in heptane
  11. customto give a product mixture as a white solid
  12. customThe solid was purified by reverse phase column chromatography
  13. washeluting with 5-95% CH3CN in water
  14. customto give a white solid
  15. customthat was further purified

Sources & evidence

ORD record
ord-364608da711b47309a8e10064f54f110
Source dataset
uspto-grants-2013_11
Patent number
US08592629B2

Reaction notes

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