Isopropyl iodide → 1-isopropyl-3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide

Participants

Reaction Conditions

Reaction Steps

A vial was charged with N-(2,4-dimethoxybenzyl)-3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide (Intermediate B) (57.4 mg, 0.088 mmol), cesium carbonate (86 mg, 0.263 mmol), acetonitrile (0.5 mL), and 2-iodopropane (26.3 μl, 0.263 mmol). The vial was sealed and heated to 70° C. for 1 h. The mixture was cooled to room temperature, diluted with water, and extracted with EtOAc (2×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was taken up on in MeOH (1 mL), then acetyl chloride (31.2 μl, 0.438 mmol) was added. After stirring for 1 h, the mixture was concentrated in vacuo. The residue was taken up in a solution of 2N ammonia in methanol, and the resulting slurry was concentrated in vacuo. The crude product was purified by chromatography on silica gel (0 to 10% MeOH/DCM) to give 1-isopropyl-3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide (38.52 mg, 0.070 mmol, 80% yield) as a light-yellow solid. 1H NMR (400 MHz, DMSO-d6) δ=8.36 (s, 1 H), 8.00 (d, J=1.5 Hz, 1 H), 7.96-7.89 (m, 2 H), 7.79-7.75 (m, 1H), 7.70 (d, J=8.5 Hz, 1 H), 7.48 (dd, J=1.7, 8.5 Hz, 1 H), 7.44 (d, J=1.9 Hz, 1 H), 7.09 (s, 1 H), 6.42 (d, J=1.9 Hz, 1 H), 4.86 (td, J=6.5, 13.2 Hz, 1 H), 1.33 (d, J=6.6 Hz, 6 H). m/z (ESI) 547.2 (M+H)+.

Provenance & Evidence