反应详情

A vial was charged with perfluorophenyl 1-methyl-3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-1H-indole-6-sulfonate (Intermediate E) (32.98 mg, 0.055 mmol), thiazol-2-amine (7.14 mg, 0.071 mmol), and THF (0.4 mL) to give a clear solution. Lithium bis(trimethylsilyl)amide (1M in THF) (137 μl, 0.137 mmol) was added dropwise over 5 min, and the resulting solution was stirred overnight. In the morning, acetic acid (0.03 mL) was added, resulting in a viscous mixture. The mixture was diluted with DCM/MeOH, transferred to a flask, and concentrated in vacuo. The crude product was purified by chromatography on silica gel (0 to 5% MeOH/DCM) to give 1-methyl-3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)-1H-indole-6-sulfonamide (20.6 mg, 0.040 mmol, 72.6% yield) as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ=7.96-7.83 (m, 3 H), 7.78-7.71 (m, 1 H), 7.60-7.43 (m, 2 H), 7.40 (d, J=1.9 Hz, 1 H), 7.21 (s, 1 H), 7.12 (s, 1 H), 6.79 (d, J=4.6 Hz, 1 H), 6.36 (s, 1 H), 3.80 (s, 3 H), 3.22 (s, 3 H). m/z (ESI) 518.2 (M+H)+.

1. customto give a clear solution
2. customresulting in a viscous mixture
3. customtransferred to a flask
4. concentrationconcentrated in vacuo
5. customThe crude product was purified by chromatography on silica gel (0 to 5% MeOH/DCM)