2,2-Difluoro-2-(fluorosulfonyl)acetic acid → 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-difluoromethoxy-1-methyl-ethyl)-amide

Participants

Reaction Conditions

Reaction Steps

In a 25 mL pressure tube, 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-hydroxy-1-methyl-ethyl)-amide (60 mg, 0.12 mmol) and copper(I) iodide (14 mg, 0.070 mmol) were combined with acetonitrile (3 mL) to give a light yellow suspension. The mixture was degassed and placed under argon. The reaction mixture was heated to 50° C. in a sand bath. 2,2-Difluoro-2-(fluorosulfonyl)acetic acid (12 μL, 0.112 mmol) was added dropwise slowly to give a light yellow solution. The reaction was stirred for an additional 5 min. The reaction was quenched with water and extracted with ethyl acetate. The combined organics were successively washed with water, saturated sodium bicarbonate, and brine then dried over Na2SO4 and concentrated. The crude material was purified by flash chromatography over silica gel (gradient: 0% to 50% EtOAc in hexanes) to afford 12 mg (18%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-difluoromethoxy-1-methyl-ethyl)-amide as a white solid. MS: [M+H]+=549.

Provenance & Evidence