Acetonitrile → 1-(4-chloro-5-cyano-2-methoxyphenyl)-N-(1,3,4-thiadiazol-2-yl)isoquinoline-6-sulfonamide

Participants

Reaction Steps

A vial was charged with perfluorophenyl 1-(4-chloro-5-cyano-2-methoxyphenyl)isoquinoline-6-sulfonate (INTERMEDIATE VVVV, 145.2 mg, 0.268 mmol). 1,3,4-thiadiazol-2-amine (32.6 mg, 0.322 mmol), and cesium carbonate (262 mg, 0.805 mmol). Acetonitrile (1342 μl) was added, and the mixture was stirred for 2 h. The mixture was diluted with EtOAc and 0.5 N aq. HCl. The layers were separated, and the aq. layer was extracted with 10% MeOH/EtOAc (2×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was concentrated from MeOH, then the mixture was filtered through a membrane filter. The collected solid was washed with MeOH (3×), dried under a stream of N2 (g), then dried under vacuum to give 1-(4-chloro-5-cyano-2-methoxyphenyl)-N-(1,3,4-thiadiazol-2-yl)isoquinoline-6-sulfonamide (65.89 mg, 0.144 mmol, 53.6% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ=14.51 (br. s., 1H), 8.80 (s, 1H), 8.70 (d, J=5.7 Hz, 1H), 8.58 (d, J=1.6 Hz, 1H), 8.16 (d, J=5.7 Hz, 1H), 7.98 (s, 1H), 7.89-7.82 (m, 1H), 7.80-7.72 (m, 1H), 7.65 (s, 1H), 3.78 (s, 3H). m/z (ESI) 458.2 (M+H)+.

Provenance & Evidence