Potassium Carbonate → 5-chloro-4-[4-chloro-2-(1-methyl-1H-pyrazol-5-yl)phenoxy]-2-fluoro-N-pyrimidin-4-ylbenzenesulfonamide

HRID 46258Notes

Reaction equation

HRID 46258 reaction equation
[Cl:1][C:2]1[C:3](F)=[CH:4][C:5]([F:22])=[C:6]([S:8]([N:11](COCC)[C:12]2[CH:17]=[CH:16][N:15]=[CH:14][N:13]=2)(=[O:10])=[O:9])[CH:7]=1.ClC1C(F)=CC(F)=C(S(/N=C2/N=CN(COCC)C=C/2)(=O)=O)C=1.[Cl:47][C:48]1[CH:53]=[CH:52][C:51]([OH:54])=[C:50]([C:55]2[N:59]([CH3:60])[N:58]=[CH:57][CH:56]=2)[CH:49]=1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.C(OCC)(=O)C>[Cl:1][C:2]1[C:3]([O:54][C:51]2[CH:52]=[CH:53][C:48]([Cl:47])=[CH:49][C:50]=2[C:55]2[N:59]([CH3:60])[N:58]=[CH:57][CH:56]=2)=[CH:4][C:5]([F:22])=[C:6]([S:8]([NH:11][C:12]2[CH:17]=[CH:16][N:15]=[CH:14][N:13]=2)(=[O:9])=[O:10])[CH:7]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 59436509(NE)-5-chloro-N-[1-(ethoxymethyl)pyrimidin-4-ylidene]-2,4-difluorobenzenesulfonamide2×HCID 594366195-chloro-N-(ethoxymethyl)-2,4-difluoro-N-pyrimidin-4-ylbenzenesulfonamideHCID 1355532144-Chloro-2-(1-methyl-1H-pyrazol-5-yl)phenol

Product 1

HCID 468415015-chloro-4-[4-chloro-2-(1-methyl-1H-pyrazol-5-yl)phenoxy]-2-fluoro-N-pyrimidin-4-ylbenzenesulfonamideYield 27%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of 5-chloro-N-(ethoxymethyl)-2,4-difluoro-N-pyrimidin-4-ylbenzenesulfonamide and 5-chloro-N-[(4E)-1-(ethoxymethyl)pyrimidin-4(1H)-ylidene]-2,4-difluorobenzenesulfonamide and 5-chloro-N-[(4E)-1-(ethoxymethyl)pyrimidin-4(1H)-ylidene]-2,4-difluorobenzenesulfonamide (Preparation 719) used as a mixture of three regioisomers, (64 mg, 0.18 mmol), 4-chloro-2-(1-methyl-1H-pyrazol-5-yl)phenol (Preparation 89) (37 mg, 0.18 mmol) and potassium carbonate (37 mg, 0.26 mmol) in dimethyl sulfoxide (1 mL) was stirred at room temperature for 19 hours then diluted with ethyl acetate (30 mL), washed with 1M aqueous sodium hydroxide, water, saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was taken up in trifluoroacetic acid (1 mL) and stirred for 3 hours then concentrated in vacuo. The residue was purified by reverse phase HPLC to give 29 mg (27%) of the desired product as a white solid.

Workup

  1. washwashed with 1M aqueous sodium hydroxide, water, saturated aqueous sodium chloride solution
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated in vacuo
  4. stirringstirred for 3 hours
  5. concentrationthen concentrated in vacuo
  6. customThe residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-66c51af93b99491e8cbb653fbe700209
Source dataset
uspto-grants-2013_09
Patent number
US08541588B2

Reaction notes

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