反应详情

温度

80 °C

To a solution 6-benzyl-8-chlorobenzo[c][2,7]naphthyridin-5(6H)-one (640 mg, 2.00 mmol) in toluene (12 mL) at room temperature, was added cesium carbonate (975 mg, 2.99 mmol) and N-Boc L-Leucinol (1287 mg, 5.99 mmol) and the mixture was degassed with nitrogen for 5 min. The mixture was then treated with di-tert-butyl(2′,4′,6′-triisopropyl-[1′,1′-biphenyl]-2-yl)phosphine (508 mg, 1.197 mmol) followed by palladium(II)acetate (448 mg, 2.00 mmol) and degassed for another 10 min. The reaction mixture was sealed and heated at 80° C. After overnight stirring the reaction mixture was cooled to room temperature and filtered through diatomaceous earth (Celite®). The bed was washed with ethyl acetate and the combined filtrate was concentrated under reduced pressure to afford crude product which was purified by combi flash (ethyl acetate/petroleum ether) to afford (S)-tert-butyl (1-((6-benzyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (500 mg, 0.738 mmol, 37% yield) as an off-white solid. LC/MS (ESI) m/e 502.3 [(M+H)+, calcd for C30H36N3O4 502.4]; LC/MS retention time (method D): tR=1.26 min.

1. customthe mixture was degassed with nitrogen for 5 min
2. customdegassed for another 10 min
3. customThe reaction mixture was sealed
4. temperaturewas cooled to room temperature
5. filtrationfiltered through diatomaceous earth (Celite®)
6. washThe bed was washed with ethyl acetate
7. concentrationthe combined filtrate was concentrated under reduced pressure
8. customto afford crude product which
9. customwas purified by combi flash (ethyl acetate/petroleum ether)