反应详情

温度

90 °C

A vial was charged with 3-bromo-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide (324 mg, 0.636 mmol), (2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)boronic acid (Intermediate G) (223 mg, 0.827 mmol), potassium phosphate (405 mg, 1.908 mmol), and Pd(AmPhos)2Cl2 (22.52 mg, 0.032 mmol), 1,4-dioxane (2.4 mL), and water (0.8 mL). The vial was flushed with Ar, sealed, and heated in a microwave reactor to 90° C. for 40 min. The reaction mixture was diluted with water and extracted with EtOAc (2×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The crude product was purified by chromatography on silica gel (50 to 100% EtOAc/Heptane) to afford 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 (335.1 mg, 0.512 mmol, 80% yield) as a yellow foam that was about 90% pure as assessed by NMR. 1H NMR (400 MHz, DMSO-d6) δ=11.92 (d, J=2.4 Hz, 1 H), 8.34 (s, 1 H), 8.00 (dd, J=0.4, 1.8 Hz, 1 H), 7.95-7.87 (m, 2 H), 7.79-7.76 (m, 1 H), 7.71 (d, J=8.6 Hz, 1 H), 7.49 (dd, J=1.9, 8.6 Hz, 1 H), 7.41 (d, J=1.9 Hz, 1 H), 7.20 (d, J=2.7 Hz, 1 H), 6.92 (d, J=8.4 Hz, 1 H), 6.45 (d, J=2.4 Hz, 1 H), 6.40-6.34 (m, 2H), 5.09 (s, 2 H), 3.72 (s, 3 H), 3.68 (s, 3 H), 3.19 (s, 3 H). m/z (ESI) 655.2 (M+H)+.

1. customThe vial was flushed with Ar
2. customsealed
3. additionThe reaction mixture was diluted with water
4. extractionextracted with EtOAc (2×)
5. dry with materialThe combined organic extracts were dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customThe crude product was purified by chromatography on silica gel (50 to 100% EtOAc/Heptane)