反应详情

温度

100 °C

A glass microwave reaction vessel was charged with (3R)-tert-butyl 3-(6-(1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazol-3-yl)pyrazin-2-yloxy)piperidine-1-carboxylate (1.315 g, 2.17 mmol) and Pd(PPh3)4 (0.125 g, 0.11 mmol). The tube was sealed and evacuated under vacuum and back-filled with N2 (g). A solution of 2-bromo-6-cyclopropylpyrazine (0.562 g, 2.82 mmol) in dioxane (1.8 mL) and 2 M Na2CO3 (5.43 mL, 10.86 mmol) were added. The reaction mixture was stirred and heated at 100° C. for 2 h. After cooling to RT, the organic layer was separated and 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 (80 g), eluting with a gradient of 0% to 40% EtOAc in hexanes, to provide (3R)-tert-butyl 3-(6-(5-(6-cyclopropylpyrazin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yloxy)piperidine-1-carboxylate (0.910 g, 1.52 mmol, 70% yield) as a yellow foam. MS (ESI, pos. ion) m/z: 598.2 (M+1).

1. customA glass microwave reaction vessel
2. customThe tube was sealed
3. customevacuated under vacuum
4. additionback-filled with N2 (g)
5. temperatureAfter cooling to RT
6. customthe organic layer was separated
7. dry with materialdried over anhydrous Na2SO4
8. filtrationfiltered
9. concentrationconcentrated
10. customThe crude material was absorbed onto a plug of silica gel
11. custompurified by chromatography through a Redi-Sep pre-packed silica gel column (80 g)
12. washeluting with a gradient of 0% to 40% EtOAc in hexanes