Acetonitrile → 1-(4-chloro-5-cyano-2-methoxyphenyl)-N-(1,2,4-thiadiazol-5-yl)isoquinoline-6-sulfonamide

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Reaction Steps

A vial was charged with perfluorophenyl 1-(4-chloro-5-cyano-2-methoxyphenyl)isoquinoline-6-sulfonate (INTERMEDIATE VVVV, 154.38 mg, 0.285 mmol), 1,2,4-thiadiazol-5-amine (34.6 mg, 0.343 mmol), and cesium carbonate (279 mg, 0.856 mmol). Acetonitrile (1427 μl) was added, and the mixture was stirred for 1 h. The mixture was diluted with EtOAc and 0.5 N aq. HCl. The layers were separated, and the organic extract was washed with brine, dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 0-10% MeOH/DCM, product eluted over a long period of time). The resulting white solid was taken up in MeOH and filtered. The collected solid was washed with MeOH (2×), dried under a stream of N2 (g), then dried under vacuum to give 1-(4-chloro-5-cyano-2-methoxyphenyl)-N-(1,2,4-thiadiazol-5-yl)isoquinoline-6-sulfonamide (76.6 mg, 0.167 mmol, 58.6% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ=7.43 (d, J=5.7 Hz, 1H), 7.32 (d, J=1.7 Hz, 1H), 7.21 (s, 1H), 6.90 (d, J=5.6 Hz, 1H), 6.70 (s, 1H), 6.62-6.55 (m, 1H), 6.52-6.46 (m, 1H), 6.37 (s, 1H), 2.50 (s, 3H). m/z (ESI) 458.1 (M+H)+.

Provenance & Evidence