反应详情

温度

100 °C

A 25-mL round-bottomed flask equipped with a reflux condenser was charged with 3-(acetoxymethyl)-2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)pyri-din-4-ylboronic acid 116c (165 mg, 0.40 mmol), 146e (141 mg, 0.40 mmol), K3PO4 (170 mg, 0.80 mmol), sodium acetate (66 mg, 0.80 mmol), Pd(dppf)Cl2 (15 mg, 0.020 mmol), and acetonitrile/water (8/0.2 mL). The mixture was subjected to three cycles of vacuum/nitrogen flush and heated at 100° C. under N2 protection for 1 h. Analysis of the reaction mixture by LCMS showed complete conversion to the desired product. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was diluted with dichloromethane (30 mL) and water (30 mL). The organic layer was separated and the water layer was extracted with dichloromethane (2×30 mL). The combined organic extract was dried over Na2SO4, filtered, and concentrated under reduced pressure. The dark residue was purified by silica-gel column chromatography eluting with dichloromethane/methanol (80/1 to 30/1) to afford 146f (115 mg, 45%) as a yellow solid. MS-ESI: [M+H]+ 641.4

1. customA 25-mL round-bottomed flask equipped with a reflux condenser
2. customflush
3. temperatureThe reaction mixture was cooled to room temperature
4. concentrationconcentrated under reduced pressure
5. additionThe residue was diluted with dichloromethane (30 mL) and water (30 mL)
6. customThe organic layer was separated
7. extractionthe water layer was extracted with dichloromethane (2×30 mL)
8. extractionThe combined organic extract
9. dry with materialwas dried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. customThe dark residue was purified by silica-gel column chromatography
13. washeluting with dichloromethane/methanol (80/1 to 30/1)