Lithium Hexamethyldisilazide → 1-chloro-N-(2,4-dimethoxybenzyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide

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Reaction Steps

A solution of N-(2,4-dimethoxybenzyl)thiazol-2-amine (0.546 g, 2.182 mmol) in THF (7 mL) was cooled in a dry ice-acetone bath for 5 minutes. Lithium bis(trimethylsilyl)amide (1M in THF) (2.381 ml, 2.381 mmol) was added dropwise, then the flask was removed from the cooling bath for 5 min. The flask was again cooled into a dry ice-acetone bath for 20 min, resulting in the formation of a thick slurry. A suspension of 1-chloroisoquinoline-6-sulfonyl chloride (0.520 g, 1.984 mmol) in THF (5 mL) was added dropwise, then the cooling bath was removed. The reaction was stirred for one hour. The reaction was quenched with saturated ammonium chloride solution, 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 silica gel chromatography on a 40 g silica column with 0 to 30% EtOAc/Heptane. The product containing fractions were combined and concentrated to afford a white solid. The solid was triturated with methanol and stirred for five minutes. The solution was filtered and the solids were washed with methanol. The solids were dried under a vacuum to afford 1-chloro-N-(2,4-dimethoxybenzyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide as a white solid. m/z (ESI) 498.1 (M+H)+.

Provenance & Evidence