反应详情

温度

95 °C

6-bromo-4-(4-fluoro-3-(4-methoxypiperidine-1-carbonyl)benzyl)phthalazin-1 (2H)-one (98) (0.2 g, 0.42 mmol), diphenylmethanimine (0.076 g, 0.42 mmol) and cesium carbonate (0.275 g, 0.84 mmol) were added to dioxane (15 mL) and the system was degassed using nitrogen. To this was added diacetoxypalladium (0.019 g, 0.08 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.073 g, 0.13 mmol), the reaction was heated at 95° C. for 2 hours. The reaction mixture was quenched with water (50 mL), extracted with EtOAc (3×50 mL), the organic layer was dried over MgSO4, filtered and evaporated to afford brown gum. This was stirred with 2.0N HCl (5.0 mL) for 1 hour, the reaction mixture was quenched with 2M NaOH (10 mL), extracted with EtOAc (3×15 mL), the organic layer was dried over MgSO4, filtered and evaporated to afford brown gum. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford the desired material as a white solid (0.024 g, 13.87%); 1H NMR (500.133 MHz, DMSO) δ 1.47-1.38 (2H, m), 1.82-1.73 (2H, m), 2.89 (3H, s), 3.23-3.16 (2H, m), 3.27 (2H, s), 3.46-3.41 (1H, m), 4.13 (2H, s), 5.78 (2H, s), 6.87 (1H, d), 7.00 (1H, dd), 7.14 (1H, t), 7.22 (1H, dd), 7.38-7.34 (1H, m), 7.93 (1H, d), 11.60 (1H, s); m/z (LC-MS, ESI+), RT=1.56 (M+H 411).

1. customthe system was degassed
2. customThe reaction mixture was quenched with water (50 mL)
3. extractionextracted with EtOAc (3×50 mL)
4. dry with materialthe organic layer was dried over MgSO4
5. filtrationfiltered
6. customevaporated
7. customto afford brown gum
8. customthe reaction mixture was quenched with 2M NaOH (10 mL)
9. extractionextracted with EtOAc (3×15 mL)
10. dry with materialthe organic layer was dried over MgSO4
11. filtrationfiltered
12. customevaporated
13. customto afford brown gum
14. customThe crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length)
15. additionFractions containing the desired compound
16. customwere evaporated to dryness