反应详情

温度

85 °C

A vial containing 4-bromo-1-iodo-2-(trifluoromethyl)benzene was charged with potassium phosphate (0.130 g, 0.614 mmol), followed by a solution of 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 (Intermediate H) (0.100 g, 0.175 mmol) and PdCl2(dppf)-CH2Cl2 (0.014 g, 0.018 mmol) in 1 mL of DMF. The vial was sealed and placed in a shaker block. The block was shaken for three hours at 85° C. The solution was filtered, washed with DMF and concentrated. The resulting solid was treated with a solution of TFA (0.270 mL, 3.51 mmol) in 1 mL of DCM. The vial was shaken at room temperature for two hours. The solution was concentrated and purified via reverse phase HPLC (8 min gradient elution 15 to 75% ACN/H2O, 0.1% TFA modifier) to afford 3-(4-bromo-2-(trifluoromethyl)phenyl)-1-methyl-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide as an off-white solid. 1H NMR (500 MHz, DMSO-d6) δ 3.95 (s, 3 H) 7.40-7.51 (m, 3 H) 7.69 (s, 1 H) 7.92-8.00 (m, 2 H) 8.03 (d, J=1.95 Hz, 1 H) 8.40 (s, 1 H). m/z (ESI) 515.9 (M+H)+.

1. customThe vial was sealed
2. filtrationThe solution was filtered
3. washwashed with DMF
4. concentrationconcentrated
5. stirringThe vial was shaken at room temperature for two hours
6. concentrationThe solution was concentrated
7. custompurified via reverse phase HPLC (8 min gradient elution 15 to 75% ACN/H2O, 0.1% TFA modifier)