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

HRID 2048029Notes

Reaction equation

HRID 2048029 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 580423794-methylphenyl 5-chloro-4-({5-chloro-6-[(1R)-2,2,2-trifluoro-1-methylethoxy]pyridin-3-yl}oxy)-2-fluorobenzoate

Product 1

HCID 566442125-chloro-4-({5-chloro-6-[(1R)-2,2,2-trifluoro-1-methylethoxy]pyridin-3-yl}oxy)-2-fluoro-N-(methylsulfonyl)benzamideYield 48%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of methanesulfonamide (105 mg, 1.1 mmol) in THF (4 mL) was added potassium tert-butoxide (126 mg, 1.1 mmol) and the mixture was stirred for 10 minutes at room temperature. A solution of 4-methylphenyl 5-chloro-4-({5-chloro-6-[(1R)-2,2,2-trifluoro-1-methylethoxy]pyridin-3-yl}oxy)-2-fluorobenzoate (Preparation 234, 429 mg, 0.85 mmol) in THF (4 mL) was added and the resulting mixture was stirred at 50° C. for 3 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 partitioned between water and DCM (3×5 mL) and filtered through a phase separation cartridge. The filtrate was concentrated in vacuo to give a crude solid that was purified using trituration with heptanes/acetone 9/1 to give the title compound (199 mg, 48%) as a white solid.

Workup

  1. stirringthe resulting mixture was stirred at 50° C. for 3 hours
  2. temperatureto cool to room temperature
  3. customThe reaction was quenched with water
  4. customThe mixture was partitioned between water and DCM (3×5 mL)
  5. filtrationfiltered through a phase separation cartridge
  6. concentrationThe filtrate was concentrated in vacuo
  7. customto give a crude solid that
  8. customwas purified

Sources & evidence

ORD record
ord-a6253ae1ce93401a86aa49f678f47770
Source dataset
uspto-grants-2013_11
Patent number
US08592629B2

Reaction notes

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