反应详情

温度

90 °C

To a 2000 ml flask was charged with 1-[4-(4-Chloro-3-methoxy-phenyl)-piperazin-1-yl]-2-(3-iodo-pyrazolo[3,4-b]pyridin-1-yl)-ethanone (40 g, 78.1 mmol), dppf (3.86 g, 6.96 mmol), Zn(CN)2 (9.6 g, 81.6 mmol), DMF (360 ml) and H2O (20 ml). The resulting suspension was degassed using N2 for 5 min, followed by addition of Pd2(dba)3 (4.24 g, 4.64 mmol). The reaction mixture was heated under N2 at 90° C. for 2 h (monitor by TLC and LC-MS). After cooling to room temperature, diluted with EtOAc (1500 ml), filtered to remove the precipitate and washed with H2O (1000×2 ml), saturated EDTA.4Na (800 ml×2), brine and dried over Na2SO4. After evaporation of the solvent, ether (150 mL) was added and stirred for 2 h. The resulting solid was filtered to give the desired product 30 g (93%) as light yellow powder. Recrystallization from refluxing CH3CN (160 mL) afforded 26 g (80%) light yellow crystals: mp 183-185° C.; Rt=2.38 min; MS (ES) M+H expect 411.1. found 411.1.

1. customThe resulting suspension was degassed
2. customfor 5 min
3. temperatureAfter cooling to room temperature
4. filtrationfiltered
5. customto remove the precipitate
6. washwashed with H2O (1000×2 ml), saturated EDTA
7. dry with material4Na (800 ml×2), brine and dried over Na2SO4
8. customAfter evaporation of the solvent, ether (150 mL)
9. additionwas added
10. filtrationThe resulting solid was filtered