Hydrochloric Acid → 3-(4-chloro-2-(1-methyl-1H-pyrazol-5-yl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide 3-(4-chloro-2-(1-methyl-1H-pyrazol-3-yl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide

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Reaction Steps

A vial was charged with 3-(4-chloro-2-(1-methyl-1H-pyrazol-5-yl)phenyl)-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide (Intermediate A) (28.44 mg, 0.046 mmol) in methanol (0.5 mL). Hydrogen chloride (4M in 1,4-dioxane) (114 μl, 0.458 mmol) was added, and the resulting mixture was stirred for 30 min. The mixture was diluted with DCM and concentrated in vacuo. The residue was suspended in MeOH, then filtered through Celite® (diatomaceous earth). The filtrate was concentrated, and the residue was dissolved in methanol and loaded onto a 500 mg SCX-2 ion exchange column. The column was eluted with methanol, then with a solution of 2N ammonia in methanol. The basic fractions were concentrated to give 3-(4-chloro-2-(1-methyl-1H-pyrazol-5-yl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide 3-(4-chloro-2-(1-methyl-1H-pyrazol-3-yl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide (19.36 mg, 0.041 mmol, 90% yield) as a light-yellow solid. 1H NMR (400 MHz, DMSO-d6) δ=11.57 (br. s., 1 H), 8.05 (s, 1 H), 7.85 (dd, J=0.5, 1.6 Hz, 1 H), 7.71-7.58 (m, 2 H), 7.54 (d, J=8.5 Hz, 1 H), 7.49 (d, J=2.2 Hz, 1 H), 7.43-7.33 (m, 2 H), 7.23-7.04 (m, 1 H), 6.93 (d, J=2.6 Hz, 1 H), 6.30 (d, J=1.9 Hz, 1 H), 3.19 (br. s., 1 H). m/z (ESI) 471.0 (M+H)+.

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