反应详情

温度

90 °C

A mixture of 4-(5-bromo-7-fluoro-2,3-dihydrobenzofuran-2-yl)piperidin-4-ol (0.17 g, 0.531 mmol), 2-chloro-5-propylpyrimidine (0.11 g, 0.691 mmol) and K2CO3 (0.22 g, 1.594 mmol) in DMF (2.6 mL) were heated in 90° C. oil bath for 10 hours. At the conclusion of this period, the reaction mixture was cooled to room temperature, quenched with H2O (5 mL), and then extracted with EtOAc (3×5 mL). The combined organic layers were washed with H2O (3×5 mL) and brine (5 mL), dried (Na2SO4), filtered, and concentrated to yield a residue. The residue was purified by column chromatography (silica gel, hexanes/EtOAc gradient 30 to 40% EtOAc) to afford Compound 1H as a light yellow solid (0.122 g, 52.6% yield). 1H NMR (400 MHz, CDCl3) δ ppm 8.14 (s, 2 H), 6.99-7.10 (m, 2 H), 4.67 (t, J=9.2 Hz, 1 H), 4.47-4.62 (m, 2 H), 3.23-3.41 (m, 3 H), 3.10 (dd, J=15.8, 9.2 Hz, 1 H), 2.39 (t, J=7.6 Hz, 2 H), 1.84-2.00 (m, 2 H), 1.74 (td, J=13.1, 4.8 Hz, 1 H), 1.46-1.66 (m, 4 H), 0.93 (t, J=7.3 Hz, 3 H). LC/MS (m/z)=437 (M+H)+.

1. temperatureAt the conclusion of this period, the reaction mixture was cooled to room temperature
2. customquenched with H2O (5 mL)
3. extractionextracted with EtOAc (3×5 mL)
4. washThe combined organic layers were washed with H2O (3×5 mL) and brine (5 mL)
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated
8. customto yield a residue
9. customThe residue was purified by column chromatography (silica gel, hexanes/EtOAc gradient 30 to 40% EtOAc)