反应详情

温度

80 °C

To a 50 mL round bottom flask was added CuCl (0.035 g, 0.36 mmol), Cs2CO3 (0.467 g, 1.43 mmol), 1,1′-bis(diphenylphosphino)ferrocene (0.020 g, 0.04 mmol), tert-butyl (3R)-3-((6-(5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)-2-pyrazinyl)oxy)-1-piperidinecarboxylate 10a (0.200 g, 0.36 mmol), Pd(OAc)2 (4.02 mg, 0.02 mmol), and 2-isopropoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazine (0.189 g, 0.72 mmol, CombiPhos Catalysis). The flask was sealed and evacuated under vacuum and backfilled with N2. DMF (2.7 mL) was added, and the reaction mixture was stirred at 80° C. for 18 h. The reaction was filtered through a 0.45 M filter and then diluted in water and extracted with EtOAc (3×). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (12 g), eluting with a gradient of 0% to 50% EtOAc in hexane, to provide tert-butyl (3R)-3-((6-(5-(6-(1-methylethoxy)-2-pyrazinyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)-2-pyrazinyl)oxy)-1-piperidinecarboxylate (0.130 g, 0.21 mmol, 59% yield) as a light-yellow oil. MS (ESI, pos. ion) m/z: 616.2 (M+1).

1. customThe flask was sealed
2. customevacuated under vacuum
3. additionDMF (2.7 mL) was added
4. filtrationThe reaction was filtered through a 0.45 M
5. filtrationfilter
6. additiondiluted in water
7. extractionextracted with EtOAc (3×)
8. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
9. filtrationfiltered
10. concentrationconcentrated
11. customThe crude material was absorbed onto a plug of silica gel
12. custompurified by chromatography through a Redi-Sep pre-packed silica gel column (12 g)
13. washeluting with a gradient of 0% to 50% EtOAc in hexane