Potassium Phosphate, Tribasic → perfluorophenyl 1-methyl-3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-1H-indole-6-sulfonate

関与物質

反応条件

反応手順

The following reaction was conducted in two separate vials, and the reaction mixtures were combined before purification: A vial was charged with perfluorophenyl 3-bromo-1-methyl-1H-indole-6-sulfonate (52.1 mg, 0.114 mmol), (2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)boronic acid (Intermediate G) (40.1 mg, 0.148 mmol), potassium phosphate (72.7 mg, 0.343 mmol), Pd(AmPhos)2Cl2 (4.04 mg, 5.71 μmol), 1,4-dioxane (428 μl), and water (143 μl). The vial was flushed with Ar, sealed, and heated in a microwave reactor to 90° C. for 30 min. A separate vial was charged with perfluorophenyl 3-bromo-1-methyl-1H-indole-6-sulfonate (180 mg, 0.395 mmol), (2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)boronic acid (139 mg, 0.513 mmol), potassium phosphate (251 mg, 1.184 mmol), Pd(AmPhos)2Cl2 (13.97 mg, 0.020 mmol), 1,4-dioxane (1480 μl), and water (493 μl). The vial was flushed with Ar, sealed, and heated in a reactor to 90° C. for 30 min. The reaction mixtures from both vials were combined, and the combined 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 (10 to 60% EtOAc/Heptane) to give perfluorophenyl 1-methyl-3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-1H-indole-6-sulfonate (250.0 mg, 0.416 mmol, 82% yield) as a pink foam. 1H NMR (400 MHz, CDCl3) δ=8.09-8.01 (m, 1 H), 7.91-7.81 (m, 3 H), 7.76-7.67 (m, 2 H), 7.53 (d, J=2.0 Hz, 1 H), 6.79 (s, 1 H), 6.38 (d, J=1.9 Hz, 1 H), 3.81 (s, 3 H), 3.23 (s, 3 H). m/z (ESI) 602.0 (M+H)+.

情報源と証拠