反应详情

温度

85 °C

A mixture of 2-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-ethanol (Intermediate 3) (0.364 g, 1.19 mol), N2-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-methyl-1H-2-indolecarboxamide (0.485 g, 1.19 mmol), palladium tetrakis(triphenylphosphine) (0.138 g, 0.119 mmol), and sodium carbonate (0.303 g, 2.86 mmol) in DME (12 mL) and water (12 mL) was heated at 85° C. for 4 h then cooled to ambient temperature. The DME was removed in vacuo and the resulting precipitate was collected by filtration and rinsed with water (50 mL) and ether (50 mL) to afford N2-{4-[4-amino-1-(2-hydroxyethyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-1-methyl-1H-2-indolecarboxamide as a tan solid (0.459 g, 1.00 mmol): 1H NMR (d6-DMSO, 400 MHz): δH 9.44 (1H, s), 8.26 (1H, s), 8.12 (1H, d, J=8.0 Hz), 7.70 (1H, d, J=8.0 Hz), 7.59 (1H, d, J=8.4 Hz), 7.29-7.41 (6H, m), 7.15 (1H, t, J=7.4 Hz), 4.90 (1H, t, J=5.8 Hz), 4.41 (2H, t, J=5.8 Hz), 4.04 (3H, s), 3.96 (3H, s), and 3.86 (2H, q, J=5.9 Hz); RP-HPLC (Hypersil C18, 5 μm, 100 Å, 15 cm; 5%-100% acetonitrile—0.1 M ammonium acetate over 15 min, 1 mL/min). Rt 10.52 min. MS: MH+458.2.

1. temperaturethen cooled to ambient temperature
2. customThe DME was removed in vacuo
3. filtrationthe resulting precipitate was collected by filtration
4. washrinsed with water (50 mL) and ether (50 mL)