2-Aminothiazole → 1-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide

Participants

Reaction Steps

A solution of perfluorophenyl 1-(2-methoxy-4-(trifluoromethyl)phenyl)isoquinoline-6-sulfonate (INTERMEDIATE LLL) (425.75 mg, 0.775 mmol), thiazol-2-amine (78 mg, 0.775 mmol), and THF (3875 μl) was cooled in an ice-water bath for 15 min, then lithium bis(trimethylsilyl)amide (1M in THF) (1627 μl, 1.627 mmol) was added drop wise. After 30 min, the mixture was warmed to room temperature and loaded onto a 25-g silica gel loading column with DCM. The column was dried under vacuum for 5 min then eluted onto a pre-equilibrated 40-g silica gel column with 0 to 10% MeOH/DCM to give a yellow solid. The mixture was concentrated from DCM (2×). The residue was then taken up in DCM, sonicated, filtered, washed with DCM (3×), and dried under a stream of N2 (g) to give a white solid. The white solid was crushed with a spatula then dried under high vacuum to give 1-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (271 mg, 0.582 mmol, 75% yield) as a white solid: 1H NMR (400 MHz, DMSO-d6) δ ppm=12.89 (br. s., 1H), 8.69 (d, J=5.7 Hz, 1H), 8.55 (d, J=1.8 Hz, 1H), 8.13 (d, J=5.7 Hz, 1H), 7.87 (dd, J=1.9, 8.9 Hz, 1H), 7.70 (d, J=8.9 Hz, 1H), 7.60-7.45 (m, 3H), 7.28 (d, J=4.6 Hz, 1H), 6.87 (d, J=4.6 Hz, 1H), 3.74 (s, 3H); m/z (ESI) 466.2 (M+H)+.

Provenance & Evidence