Potassium Phosphate, Tribasic → 3-(2-cyano-4-(trifluoromethyl)phenyl)-N-(2,4-dimethoxybenzyl)-1-methyl-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)-1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide (0.075 g, 0.131 mmol), 2-bromo-5-(trifluoromethyl)benzonitrile (0.082 g, 0.329 mmol). potassium phosphate (0.098 g, 0.460 mmol), and PdCl2(dppf)-CH2Cl2 (10.74 mg, 0.013 mmol). DMF (0.876 ml) was added, and the vial was flushed with Ar, sealed, and heated to 85° C. for two hours. The reaction was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were washed with brine, dried with sodium sulfate, filtered and concentrated. The material was purified via column chromatography (0 to 100% EtOAc/Heptane) to give 3-(2-cyano-4-(trifluoromethyl)phenyl)-N-(2,4-dimethoxybenzyl)-1-methyl-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide as a light yellow solid. The solid was dissolved in DCM (0.5 ml) and TFA (0.5 ml, 6.49 mmol), and the resulting mixture was stirred for 15 min. The mixture was concentrated in vacuo. The residue was dissolved in acetonitrile, and passed through a PEAX ion exchange column. The column was flushed several times with acetonitrile, then the product was liberated by flushing several times with an 1M HCl solution in 15% MeOH/EtOAc. The solution was concentrated to afford 3-(2-cyano-4-(trifluoromethyl)phenyl)-1-methyl-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide (0.022 g, 0.047 mmol, 36.1% yield) as a pink solid. 1H NMR (400 MHz, DMSO-d6) δ=8.44 (s, 1 H), 8.42 (s, 1 H), 8.17 (s, 1 H), 8.14-8.10 (m, 1 H), 8.07 (d, J=1.2 Hz, 1 H), 7.95 (d, J=8.1 Hz, 1 H), 7.83 (d, J=8.5 Hz, 1 H), 7.60 (dd, J=1.6, 8.5 Hz, 1 H), 4.01 (s, 3 H). m/z (ESI) 464.0 (M+H)+.

Provenance & Evidence