反应详情

温度

80 °C

In a sealed tube was placed a stirred solution of 9-benzyloxy-6-(2-bromo-4-chlorobenzyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (380) (100 mg, 0.194 mmol) in dioxane (3 mL), 3-fluorophenyl boronicacid (27.132 mg, 0.194 mmol), and a 1N solution of potassium carbonate [(80.349 mg, 0.581 mmol) dissolved in 1.06 mL water] was added at room temperature. The reaction mixture was de-gassed with argon by purging for 30 min. Pd(triphenyl phosphine)4 (22.395 mg, 0.019 mmol) and 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (15.911 mg, 0.039 mmol) were added and the reaction mixture was further degassed for another 10 min. The reaction mixture was heated for 30 min at 80° C. (while progress of the reaction was monitored by LC-MS). The reaction was filtered and diluted with water (5 mL) and extract with ethyl acetate (2×20 mL). The combined extracts were dried and concentrated. The resulting crude product was purified by column (using amine bound silica gel) to get 9-benzyloxy-6-(5-chloro-3′-fluoro-biphenyl-2-ylmethyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (383) (65 mg, 63.04%) as an off-white solid.

1. customIn a sealed tube was placed
2. customThe reaction mixture was de-gassed with argon
3. customby purging for 30 min
4. customthe reaction mixture was further degassed for another 10 min
5. filtrationThe reaction was filtered
6. additiondiluted with water (5 mL)
7. extractionextract with ethyl acetate (2×20 mL)
8. customThe combined extracts were dried
9. concentrationconcentrated
10. customThe resulting crude product was purified by column (using amine bound silica gel)