Potassium Phosphate, Tribasic → 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

Participants

Reaction Conditions

Reaction Steps

A microwave vial was charged with 3-bromo-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide (83.6 mg, 0.164 mmol), (4-chloro-2-(1-methyl-1H-pyrazol-5-yl)phenyl)boronic acid (Intermediate F) (50.4 mg, 0.213 mmol), potassium phosphate (105 mg, 0.492 mmol), and Pd(AmPhos)2Cl2 (5.81 mg, 8.21 μmol). The vial was flushed with Ar, then dioxane (0.6 mL) and water (0.2 mL) were added. The vial was sealed and heated in a microwave reactor for 20 min at 90° C. The mixture was extracted with EtOAc (3×), and the combined organic extracts were concentrated. The crude product was purified by chromatography on silica gel (0 to 100% EtOAc/Heptane) to give 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 (74 mg, 0.119 mmol, 72.6% yield) as an off-white foam. 1H NMR (400 MHz, DMSO-d6) δ=11.81 (s, 1 H), 8.34 (s, 1 H), 8.01-7.94 (m, 1 H), 7.70-7.58 (m, 3 H), 7.55-7.51 (m, 1 H), 7.45 (dd, J=1.9, 8.6 Hz, 1 H), 7.36 (d, J=1.9 Hz, 1 H), 7.16 (s, 1 H), 6.91 (d, J=8.4 Hz, 1 H), 6.45 (d, J=2.4 Hz, 1 H), 6.37 (dd, J=2.4, 8.5 Hz, 1 H), 6.28 (d, J=1.9 Hz, 1 H), 5.08 (s, 2 H), 3.72 (s, 3 H), 3.68 (s, 3 H), 3.21 (s, 3 H). m/z (ESI) 621.0 (M+H)+.

Provenance & Evidence