Lithium Hexamethyldisilazide → HCID 86687520, compound

Participants

Reaction Steps

A solution of perfluorophenyl 1-(pyrrolidin-2-yl)isoquinoline-6-sulfonate 2,2,2-trifluoroacetate (Intermediate ZZZ; 0.350 g, 0.627 mmol) and N-(2,4-dimethoxybenzyl)thiazol-2-amine (0.173 g, 0.689 mmol) in tetrahydrofuran (6.27 ml) was cooled in a dry ice-acetone bath for 10 min. Lithium bis(trimethylsilyl)amide (1M in THF) (1.316 ml, 1.316 mmol) was added drop wise, then the reaction was stirred for 5 minutes. The cooling bath was removed and the reaction was stirred for 30 minutes. The reaction was warmed to room temperature and quenched with saturated ammonium chloride solution (aq), diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated. The filtrate was purified by chromatography on an 80-g silica gel column with 0-100% EtOAc/Heptane followed by a 20% 2.0M ammonia in MeOH/DCM flush to afford N-(2,4-dimethoxybenzyl)-1-(pyrrolidin-2-yl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide as a light yellow solid. m/z (ESI) 511.3 (M+H)+.

Provenance & Evidence