反应详情

温度

100 °C

A mixture of N-(4-((2-chloropyridin-4-yl)oxy)-2,5-difluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (0.100 g, 0.194 mmol, see: Example 1), cyclopropanecarboxamide (0.033 g, 0.388 mmol), Cs2CO3 (0.095 g, 0.291 mmol) and Xantphos (5.05 mg, 8.72 μmmol) in dioxane (2 mL) was sparged with argon, treated with Pd2(dba)3 (2.66 mg, 2.91 μmmol), sparged again with argon, then fitted with a reflux condensor capped with an argon-filled balloon and heated to 100° C. overnight. The mixture was cooled to RT and partitioned between water and EtOAc. The organic layer was washed with brine, dried over MgSO4, concentrated to dryness and purified via silica gel chromatography (EtOAc/Hex) to afford N-(4-((2-(cyclopropanecarboxamido)pyridin-4-yl)oxy)-2,5-difluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (33 mg, 30% yield) as a solid. MS (ESI) m/z: 565.2 (M+H+).

1. customwas sparged with argon
2. additiontreated with Pd2(dba)3 (2.66 mg, 2.91 μmmol)
3. customsparged again with argon
4. customfitted with a reflux condensor
5. customcapped with an argon-
6. additionfilled balloon
7. temperatureThe mixture was cooled to RT
8. custompartitioned between water and EtOAc
9. washThe organic layer was washed with brine
10. dry with materialdried over MgSO4
11. concentrationconcentrated to dryness
12. custompurified via silica gel chromatography (EtOAc/Hex)