反应详情

A vial was charged with perfluorophenyl 1-(2-chloro-3′-fluoro-5-methoxy-[1,1′-biphenyl]-4-yl)isoquinoline-6-sulfonate (INTERMEDIATE TTTT; 45 mg, 0.074 mmol), 1,2,5-thiadiazol-3-amine (8.21 mg, 0.081 mmol), and THF (0.5 mL) to give a clear solution. The vial was cooled in an ice-water bath for 5 min, then lithium bis(trimethylsilyl)amide (1M in THF) (162 μl, 0.162 mmol) was added drop wise. After 10 min, the mixture was diluted with a small amount of methanol to give a solution which was purified directly by chromatography on silica gel (12-g Redi-Sep Gold column, 0-5% MeOH/DCM) to give 1-(2-chloro-3′-fluoro-5-methoxy-[1,1′-biphenyl]-4-yl)-N-(1,2,5-thiadiazol-3-yl)isoquinoline-6-sulfonamide (22.2 mg, 0.042 mmol, 57.1% yield) as a light-yellow solid. 1H NMR (400 MHz, DMSO-d6) δ=12.50 (br. s., 1H), 8.81-8.69 (m, 2H), 8.50 (s, 1H), 8.18 (d, J=5.4 Hz, 1H), 8.00 (dd, J=1.9, 8.9 Hz, 1H), 7.88 (d, J=8.9 Hz, 1H), 7.65-7.52 (m, 2H), 7.48-7.39 (m, 2H), 7.35-7.29 (m, 1H), 7.27 (s, 1H), 3.70 (s, 3H). m/z (ESI) 527.2 (M+H)+.

1. customto give a clear solution
2. temperatureThe vial was cooled in an ice-water bath for 5 min
3. customto give a solution which
4. customwas purified directly by chromatography on silica gel (12-g Redi-Sep Gold column, 0-5% MeOH/DCM)