Lithium Hexamethyldisilazide → 3-cyano-N-(2,4-di methoxybenzyl)-4-fluoro-N-(5-fluoropyridin-2-yl)benzenesulfonamide

Participants

Reaction Conditions

Reaction Steps

To a −40° C. solution of N-(2,4-dimethoxybenzyl)-5-fluoropyridin-2-amine (Preparation 20, 2.32 g, 8.84 mmol) in THF (60 ml) was added LiHMDS (9.72 ml, 9.72 mmol, 1M in THF) keeping the temperature below −35° C. The reaction mixture was warmed to 0° C. for 40 minutes before re-cooling to −40° C. 3-Cyano-4-fluorobenzene-1-sulfonyl chloride (1.94 g, 8.84 mmol) was added to the reaction mixture as a solution in THF (10 mL) and the reaction mixture allowed to warm to room temperature for 18 hours. The reaction mixture was quenched with saturated ammonium chloride solution (100 mL) and extracted with EtOAc (2×100 mL). The organic layer was washed with saturated brine (100 mL), dried over MgSO4, filtered and the solvent removed under vacuum. The crude material was purified by silica gel column chromatography eluting with 20-40 EtOAc in heptane followed by reverse phase chromatography eluting with 0-100% MeCN in H2O to afford the title compound as a brown gum (2.48 g, 63%).

Provenance & Evidence