反应详情

To a well degassed mixture of 7-bromo-3-methyl-4-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-9H-pyrido[3,4-b]indole-1-carboxamide (0.101 g, 0.188 mmol) and Bis(triphenylphosphine)palladium(II) chloride (0.018 g, 0.026 mmol) in 1,4-dioxane (2.0 mL) in a sealed tube was added tributyl(1-ethoxyvinyl)stannane (0.148 mL, 0.450 mmol) followed by triethylamine (0.052 mL, 0.375 mmol). The resulting mixture was evacuated and charged with nitrogen (2×), immersed in an oil bath at 100° C., and stirred overnight. The mixture was diluted with ethyl acetate, filtered through a pad of CELITE®, and concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran (5 mL) and stirred with 1 N aqueous hydrochloric acid (2 mL) for 2 h. The solution was concentrated under reduced pressure, and the residue was suspended in water. The pH was adjusted to ˜6 with 1 N sodium bicarbonate, and the suspension was extracted with ethyl acetate (3×). The combined organic layers were washed with brine and dried over anhydrous sodium sulfate. Concentration under reduced pressure followed by purification by flash silica gel chromatography using a mixture of ethyl acetate and hexane (50%-62%-75%-88%) afforded 7-acetyl-3-methyl-4-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-9H-pyrido[3,4-b]indole-1-carboxamide (0.051 g, 0.102 mmol, 54% yield) as a pale yellow solid. LC/MS M+1=502.1.

1. customTo a well degassed
2. customThe resulting mixture was evacuated
3. additioncharged with nitrogen (2×)
4. customimmersed in an oil bath at 100° C.
5. additionThe mixture was diluted with ethyl acetate
6. filtrationfiltered through a pad of CELITE®
7. concentrationconcentrated under reduced pressure
8. dissolutionThe residue was dissolved in tetrahydrofuran (5 mL)
9. stirringstirred with 1 N aqueous hydrochloric acid (2 mL) for 2 h
10. concentrationThe solution was concentrated under reduced pressure
11. extractionthe suspension was extracted with ethyl acetate (3×)
12. washThe combined organic layers were washed with brine
13. dry with materialdried over anhydrous sodium sulfate
14. concentrationConcentration under reduced pressure
15. customfollowed by purification by flash silica gel chromatography
16. additiona mixture of ethyl acetate and hexane (50%-62%-75%-88%)