Reaktion #74536

Reaktionsgleichung

5-chloro-N-(ethoxymethyl)-2,4-difluoro-N-pyrimidin-4-ylbenzenesulfonamide

5-chloro-N-[(4E)-1-(ethoxymethyl)pyrimidin-4(1H)-ylidene]-2,4-difluorobenzenesulfonamide

5-chloro-N-[(4E)-1-(ethoxymethyl)pyrimidin-4(1H)-ylidene]-2,4-difluorobenzenesulfonamide

4-chloro-2-(1-methyl-1H-pyrazol-5-yl)phenol

potassium carbonate

→

desired product

Ausbeute 27.0%

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

Ausbeute 27.0%

Lösungsmittel

ethyl acetate

dimethyl sulfoxide

Reaktionsbedingungen

Aufarbeitung

1. 1
   Waschenwashed with 1M aqueous sodium hydroxide, water, saturated aqueous sodium chloride solution
2. 2
   Trocknendried over anhydrous sodium sulfate
3. 3
   Einengenconcentrated in vacuo
4. 4
   workup.STIRRINGstirred for 3 hours
5. 5
   Einengenthen concentrated in vacuo
6. 6
   SonstigeThe residue was purified by reverse phase HPLC

Vorschrift

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.

Quelle