Lithium Hexamethyldisilazide → 1-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(6-(trifluoromethyl)pyrimidin-4-yl)isoquinoline-6-sulfonamide

Participants

Reaction Conditions

Reaction Steps

A round-bottom flask was charged with 6-(trifluoromethyl)pyrimidin-4-amine (0.030 g, 0.182 mmol)) and THF (0.910 ml), and the vessel was cooled to −78° C. for 15 minutes. Lithium bis(trimethylsilyl)amide (0.218 ml, 0.218 mmol),) was then added drop wise over 1 minute. The reaction was stirred for 10 minutes, and then a solution of perfluorophenyl 1-(2-methoxy-4-(trifluoromethyl)phenyl)isoquinoline-6-sulfonate (Intermediate LLL; 0.100 g, 0.182 mmol) in THF (1.6 mL) was added drop wise. The bath was removed, and the resulting mixture was stirred for 45 minutes. The reaction was diluted with saturated ammonium chloride (aq.) solution (30 mL), and was washed with ethyl acetate (20 mL×3). The organic layers were combined, dried over magnesium sulfate, filtered and concentrated. The resulting material was purified via silica gel chromatography (ISCO, 40 g), eluting with 0 to 100% ethyl acetate in heptanes. The fractions were concentrated under reduced pressure to yield 1-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(6-(trifluoromethyl)pyrimidin-4-yl)isoquinoline-6-sulfonamide (0.015 g, 0.028 mmol, 15.60% yield). m/z (ESI) 528.9 (M+H)+.

Provenance & Evidence