Lithium Hexamethyldisilazide → HCID 136409065, compound

Participants

Reaction Steps

A solution of N-(2,4-dimethoxybenzyl)thiazol-2-amine (0.791 g, 3.16 mmol) in tetrahydrofuran (11.57 ml) was cooled in a dry ice-acetone bath for 5 min. Lithium bis(trimethylsilyl)amide (1M in THF) (3.31 ml, 3.31 mmol) was added drop wise, 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 solution of perfluorophenyl 4-oxo-3,4-dihydroquinazoline-7-sulfonate (1.18, 3.01 mmol) in THF (12 mL) was added drop wise, and the reaction was stirred for 30 minutes. An additional equivalent of lithium bis(trimethylsilyl)amide (1M in THF) (3.31 ml, 3.31 mmol) was added and the reaction was stirred for 30 minutes. The reaction was warmed to room temperature and quenched with saturated ammonium chloride solution, diluted with ethyl acetate and washed with water. The aqueous layer was extracted three times with ethyl acetate, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated. The material was dissolved in ethyl acetate and loaded onto a silica cartridge, leaving a tan solid on top. The solid was scraped out of the cartridge and set aside. The remaining material was purified by chromatography on a 40-g silica gel column with 0 to 100% EtOAc/Heptane followed by a 10% MeOH/DCM flush. The product containing fractions were concentrated and combined with the previously isolated material to afford N-(2,4-dimethoxybenzyl)-4-oxo-N-(thiazol-2-yl)-3,4-dihydroquinazoline-7-sulfonamide as a tan solid. (ESI) 481.1 (M+Na)+.

Provenance & Evidence