反应详情

温度

110 °C

In a large pressure bottle (˜1 L) was added {3-[4-bromo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]phenyl}methanol (22.75 g, 51.3 mMol), 1-ethyl-3-(4-nitrophenyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (21.0 g of a ˜85% pure lot, 52.0 mMol, Intermediate 5), dioxane (400 mL), aq. sat. NaHCO3 (120 mL), and Pd(PPh3)4 (1.5 g, 1.3 mMol). The reaction was purged with N2, capped, and stirred at 110° C. for 16 h. After cooling to RT the reaction was concentrated under vacuum, taken up in EtOAc, washed with H2O, brine, dried (Mg2SO4), filtered, and evaporated to dryness under vacuum. Purification by flash chromatography by silica gel (20 to 30% EtOAc/CH2Cl2) gave the title compound (26.90 g, 90%) as a yellow solid: MS (ES) m/e 580.4 (M+H)+; 1H NMR (400 MHz, DMSO-d6) δ 8.34 (s, 1H), 8.32 (d, J=5.1 Hz, 1H), 8.15 (app. d, 2H), 7.89 (d, J=7.3 Hz, 2H), 7.74 (t, J=7.5 Hz, 1H), 7.61 (app. t, J=7.8 Hz, 2H), 7.54 (app. d, 2H), 7.39-7.43 (m, 2H), 7.32-7.36 (m, 2H), 7.06 (d, J=5.1 Hz, 1H), 6.52 (s, 1H), 5.31 (t, J=5.6 Hz, 1H), 4.57 (d, J=5.3 Hz, 2H), 4.26 (q, J=7.2 Hz, 2H), 1.47 (t, J=7.3 Hz, 3H).

1. customThe reaction was purged with N2
2. customcapped
3. temperatureAfter cooling to RT the reaction
4. concentrationwas concentrated under vacuum
5. washwashed with H2O, brine
6. dry with materialdried (Mg2SO4)
7. filtrationfiltered
8. customevaporated to dryness under vacuum
9. customPurification by flash chromatography by silica gel (20 to 30% EtOAc/CH2Cl2)