Lithium Hexamethyldisilazide → 5-chloro-N-(2,4-dimethoxybenzyl)-2,4-difluoro-N-(pyrimidin-2-yl)benzenesulfonamide

Participants

Reaction Conditions

Reaction Steps

A solution of (2,4-dimethoxybenzyl)-pyrimidin-2-yl-amine (Preparation 12, 736 mg, 3 mmol) in anhydrous tetrahydrofuran (20 mL) was cooled to −78° C. before the addition of a 1M solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (3.30 mL, 3.30 mmol). The reaction was allowed to warm to 0° C. for 30 minutes before cooling again to −78° C. The resulting solution was added to a solution of 3-chloro-4,6-difluorobenzenesulfonyl chloride (890 mg, 3.6 mmol) in tetrahydrofuran (10 mL) at −78° C. After 30 minutes at this temperature the reaction was warmed to room temperature and stirred for 24 hours. The reaction was quenched by the addition of saturated aqueous ammonium chloride solution and extracted into ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography (50-100% dichloromethane in heptane gradient elution) to afford the title compound as a white solid (260 mg, 19%).

Provenance & Evidence