反应详情

温度

70 °C

To a mixture of ethyl 3-(2,6-dichloropyridin-3-yl)propan-1-ol (180 mg, 0.873 mmol), 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (439 mg, 0.873 mmol), XantPhos Biphenyl precatalyst (78 mg, 0.087 mmol), and cesium carbonate (854 mg, 2.62 mmol) was added 1,4-Dioxane (7.3 mL) and water (1.5 mL). A steady stream of N2 was bubbled through the reaction mixture for 5 minutes then the mixture was heated to 70° C. for 4 h. The mixture was cooled to ambient temperature, diluted with EtOAc, and washed successively with H2O (1×) and brine (1×). The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography using a gradient of 0-100% EtOAc/CH2Cl2 as eluent. Further purification by preparative TLC using 50% EtOAc/CH2Cl2 as eluent provided the title compound. 1H NMR δ (ppm) (CHCl3-d): 8.01˜7.96 (3H, m), 7.72 (1H, d, J=7.68 Hz), 7.68 (1H, s), 7.56 (1H, d, J=7.70 Hz), 7.23 (2H, t, J=8.6 Hz), 5.95 (1H, br s), 3.78 (2H, q, J=5.76 Hz), 3.24 (3H, s), 3.03 (3H, d, J=4.88 Hz), 2.93 (2H, t, J=7.76 Hz), 2.88 (3H, s), 2.03˜1.97 (2H, m). MS (M+H)+: 545.

1. customA steady stream of N2 was bubbled through the reaction mixture for 5 minutes
2. temperatureThe mixture was cooled to ambient temperature
3. additiondiluted with EtOAc
4. washwashed successively with H2O (1×) and brine (1×)
5. dry with materialThe organic layer was dried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was purified by silica gel column chromatography
9. customFurther purification by preparative TLC