反应详情

温度

100 °C

A solution of 3-{5-(4-chloro-phenyl)-4-oxo-6-[4-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)-phenyl]-4,5-dihydro-pyrazolo[3,4-d]pyrimidin-1-yl}-benzonitrile (prepared as described in example 28, 3.6 g, 6.54 mmol) in N,N-dimethylformamide (70 mL) is degassed with argon for 0.5 h. Then 2-iodopyrazine (2.0 g, 9.82 mmol), cesium carbonate (4.2 g, 13.09 mmol), Pd(dppf)2Cl2 (0.53 g, 0.654 mmol) is added and the resulted mixture is degassed with argon for 0.5 h The reaction mixture is then heated at 100° C. for 1.5 h. The reaction mixture is cooled to rt and diluted with water and extracted with ethyl acetate (3×). The combined organic layer is washed with brine, dried over Na2SO4, concentrated, and purified by column chromatography to afford 3-[5-(4-chloro-phenyl)-4-oxo-6-(4-pyrazin-2-yl-phenyl)-4,5-dihydro-pyrazolo[3,4-d]pyrimidin-1-yl]-benzonitrile. 1H NMR (DMSO-d6, 400 MHz) δ 9.25 (s, 1H), 8.71 (m, 1H), 8.62 (m, 2H), 8.51 (m, 2H), 8.08 (d, 2H), 7.90 (m, 1H), 7.88 (m, 1H), 7.60 (d, 2H), 7.44 (m, 4H); LC-MS calculated for C28H16ClN7O (M+H+) 502.1, found 502.0.

1. customthe resulted mixture is degassed with argon for 0.5 h The reaction mixture
2. temperatureThe reaction mixture is cooled to rt
3. additiondiluted with water
4. extractionextracted with ethyl acetate (3×)
5. washThe combined organic layer is washed with brine
6. dry with materialdried over Na2SO4
7. concentrationconcentrated
8. custompurified by column chromatography