Lithium Hexamethyldisilazide → 1-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(1,2,5-thiadiazol-3-yl)isoquinoline-6-sulfonamide

Participants

Reaction Conditions

Reaction Steps

1,2,5-thiadiazol-3-amine (28 mg, 0.273 mmol) (Aquila Pharmtech) and perfluorophenyl 1-(2-methoxy-4-(trifluoromethyl)phenyl)isoquinoline-6-sulfonate (Intermediate LLL; 100 mg, 0.182 mmol) were dissolved in THF (1 mL) in a round bottom flask and cooled to 0° C., then lithium bis(trimethylsilyl)amide (1 M in THF, 364 μl, 0.364 mmol) was added and the reaction was stirred for 30 min. The reaction was quenched with saturated ammonium chloride and extracted with EtOAc (3×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated via rotary evaporation. The residue was purified using reverse-phase HPLC with a Waters-Xbridge C18, 19×100 mm, 10 μm column with a gradient 5-95% acetonitrile and water with 0.1% ammonium hydroxide modifier to yield 1-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(1,2,5-thiadiazol-3-yl)isoquinoline-6-sulfonamide. m/z (ESI) 467.0 (M+H)+.

Provenance & Evidence