Lithium Hexamethyldisilazide → N-(3-(2-(2-chloropyriMidin-4-yl)acetyl)-2-fluorophenyl)-2,6-difluorobenzenesulfonamide

Participants

Reaction Conditions

Reaction Steps

To a solution of methyl 3-(2,6-difluorophenylsulfonamido)-2-fluorobenzoate (6.6 g, 19.11 mmol) in tetrahydrofuran (THF) (80 mL) stirred under nitrogen at −30° C. was added the solution of LiHMDS (65 mL, 65 mmol) in tetrahydrofuran dropwise over 40 mins. The reaction mixture was stirred at −5° C. for 2 hours. The reaction mixture was cooled again to −30° C. 2-Chloro-4-methylpyrimidine (2.95 g, 22.94 mmol) in tetrahydrofuran (THF) (10 mL) was added dropwise to the reaction mixture. The reaction mixture was stirred at −10° C. for 1 h, and warmed to room temperature for another 1.5 hours. The reaction mixture was cooled to 0° C. and quenched by addition of the satureated aqueous NH4Cl (80 mL) and extracted with ethyl acetate (100 ml×3). The combined organic layers were washed with water and brine, dried over Na2SO4, filtered and concentrated under reduced pressure to afford the crude product, which was purified by silica gel chromatography with petroleum ether/EtOAc (2:1) to produce the N-(3-(2-(2-chloropyrimidin-4-yl)acetyl)-2-fluorophenyl)-2,6-difluorobenzenesulfonamide (5.05 g, 6.37 mmol, 33.3% yield). LCMS [M+H]+=442.

Provenance & Evidence