反应详情

温度

100 °C

3-((4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-one (1611) (13 g, 24.9 mmol) and 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (1612)(6.6 g, 30 mmol) were dissolved in DMF-EtOH-H2O (120 mL, 40 mL, 40 mL). Pd(OAc)2 (1.684 g, 7.5 mmol), PPh3 (3.935 g 15 mmol) and Na2CO3 (13.25 g 125 mmol) were added sequentially. The resulting mixture was degassed and back-filled with argon three times and then stirred at 100° C. for 1 h. The mixture was allowed to cool to RT, filtered through silica gel (10 g) and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (2-20% MeOH/DCM) to afford the product (1613) (9 g, 76% yield) as a slight yellow solid. Then above product was suspended in EtOH (100 mL) and heated to reflux for 30 min. The mixture was allowed to cool to RT, and the solid was collected by filtration. The solid was then suspended in EA (100 mL) and stirred overnight. The precipitate was collected by filtration and further dried in vacuo to afford the desired product, 3-((4-amino-3-(3-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-one (1613)(8.4 g, 69% yield) as a white solid.

1. customThe resulting mixture was degassed
2. additionback-filled with argon three times
3. temperatureto cool to RT
4. filtrationfiltered through silica gel (10 g)
5. concentrationconcentrated in vacuo
6. customThe residue was purified by flash column chromatography on silica gel (2-20% MeOH/DCM)
7. customto afford the product (1613) (9 g, 76% yield) as a slight yellow solid
8. temperatureheated
9. temperatureto reflux for 30 min
10. temperatureto cool to RT
11. filtrationthe solid was collected by filtration
12. stirringstirred overnight
13. filtrationThe precipitate was collected by filtration
14. customfurther dried in vacuo