Lithium Hexamethyldisilazide → 1-(4-chloro-2-methoxyphenyl)-N-(4-methoxybenzyl)-N-(pyrimidin-4-yl)phthalazine-6-sulfonamide

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Reaction Steps

A round-bottom flask was charged with N-(4-methoxybenzyl)pyrimidin-4-amine (80 mg, 0.371 mmol) and THF (1238 μl) to give a clear solution. The flask was cooled in a dry ice-acetone bath for 5 min, then lithium bis(trimethylsilyl)amide (1M in THF) (371 μl, 0.371 mmol) was added drop wise. The flask was removed from the cooling bath for 3 min, and then re-cooled in the bath. A solution of perfluorophenyl 1-(4-chloro-2-methoxyphenyl)phthalazine-6-sulfonate (128 mg, 0.248 mmol) in THF (1 mL with a 0.5 mL-flask wash) was added drop wise. After another minute, the flask was transferred to an ice-water bath. After 5 min, the mixture was diluted with saturated aq. ammonium chloride and water, then extracted with EtOAc (2×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 50-100% EtOAc/Heptane) to give 1-(4-chloro-2-methoxyphenyl)-N-(4-methoxybenzyl)-N-(pyrimidin-4-yl)phthalazine-6-sulfonamide (50 mg, 0.091 mmol, 36.8% yield) as an off-white solid. m/z (ESI) 548.2 (M+H)+.

Provenance & Evidence