反应详情

温度

95 °C

A stirred mixture of 1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-ol (255 g, 999 mmol, prepared using the procedure described in Example 1, Step B), 1-chloro-5-fluoro-4-methyl-2-nitrobenzene (94.7 g, 499 mmol), cesium carbonate (325 g, 1.0 mol) and DMF (2 L) was heated to 95° C. for 6 hours. The reaction was cooled to ambient temperature and partitioned between EtOAc and water. The phases were filtered and then separated. The aqueous phase was re-extracted with EtOAc. The combined organic phases were washed with water, brine, dried (Na2SO4), filtered, and concentrated in vacuo. The crude was purified by Biotage Flash 75 L chromatographic system, eluting with 5% EtOAc/hexanes (12 L), 10% EtOAc/hexanes (6 L), 20% EtOAc/hexanes (6 L), then 30% EtOAc/hexanes (6 L). The product was obtained as a viscous oil (42 g, 9%).

1. customprepared
2. temperatureThe reaction was cooled to ambient temperature
3. custompartitioned between EtOAc and water
4. filtrationThe phases were filtered
5. customseparated
6. extractionThe aqueous phase was re-extracted with EtOAc
7. washThe combined organic phases were washed with water, brine
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe crude was purified by Biotage Flash 75 L chromatographic system
12. washeluting with 5% EtOAc/hexanes (12 L), 10% EtOAc/hexanes (6 L), 20% EtOAc/hexanes (6 L)