反应详情

温度

80 °C

A round bottom flask was charged with tris(dibenzylidineacetone)dipalladium(0) (0.066 g, 0.072 mmol) and di-tert-butyl-(2′,4′,6′-triisopropyl-biphenyl-2-yl)-phosphane (0.061 g, 0.14 mmol) in 1,4-dioxane (10 mL) to give a black solution which was degassed via vacuum/nitrogen purge (3 times). The mixture was heated to about 80° C. for about 10 min. To the reaction mixture were added 2-bromo-6-(5-methoxy-1-methyl-1H-indol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine (0.35 g, 0.72 mmol, Example #20, Step D) and tert-butyl hydrazinecarboxylate (0.142 g, 1.08 mmol), followed by sodium tert-butoxide (0.104 g, 1.08 mmol). The mixture was heated at about 80° C. for about 20 min. The reaction mixture was cooled and filtered through Celite®. The filter pad was further rinsed with EtOAc (40 mL). The filtrate was concentrated under reduced pressure and purified by silica gel chromatography eluting with a gradient of 0-100% EtOAc in heptane to give tert-butyl 2-(6-(5-methoxy-1-methyl-1H-indol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazine-carboxylate (0.272 g, 70%): LC/MS (Table 1, Method d) Rt=1.78 min; MS m/z: 539 (M+H)+.

1. customto give a black solution which
2. customwas degassed via vacuum/nitrogen
3. custompurge (3 times)
4. temperatureThe mixture was heated at about 80° C. for about 20 min
5. temperatureThe reaction mixture was cooled
6. filtrationfiltered through Celite®
7. washThe filter pad was further rinsed with EtOAc (40 mL)
8. concentrationThe filtrate was concentrated under reduced pressure
9. custompurified by silica gel chromatography
10. washeluting with a gradient of 0-100% EtOAc in heptane