反应详情

温度

120 °C

To a stirred solution of X-Phos (0.026 g, 0.055 mmol), 5-morpholinopyridin-3-amine (0.074 g, 0.413 mmol), 4-chloro-5,7-difluoro-3-methyl-2-(pyridin-2-yl)-quinoline (0.10 g, 0.344 mmol) and tris(dibenzylideneacetone)dipalladium(0) (0.013 g, 0.014 mmol) in toluene (3.44 mL) was added sodium t-butoxide (0.083 g, 0.86 mmol). The reaction mixture was heated to 120° C. and stirred for 45 min. The reaction was then cooled to rt and diluted with water (10 mL). The mixture was extracted with EtOAc (2×10 mL) and DCM (1×10 mL). The organic layers were combined and washed with brine (1×20 mL) and dried over magnesium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography on basic alumina (0 to 50% EtOAc in hexanes) to give the desired product 5,7-difluoro-3-methyl-N-(5-(4-morpholinyl)-3-pyridinyl)-2-(2-pyridinyl)-4-quinolinamine. 1H NMR (400 MHz, CDCl3) δ ppm 8.70 (1H, d, J=4.5 Hz), 7.95 (1H, s), 7.78-7.92 (3H, m), 7.62 (1H, d, J=9.8 Hz), 7.33-7.43 (1H, m), 6.97-7.14 (2H, m), 6.60 (1H, br. s.), 3.79-3.94 (4H, m), 3.12-3.30 (4H, m), 2.16 (3H, s). Mass Spectrum (ESI) m/e=434.2 (M+1).

1. temperatureThe reaction was then cooled to rt
2. extractionThe mixture was extracted with EtOAc (2×10 mL) and DCM (1×10 mL)
3. washwashed with brine (1×20 mL)
4. dry with materialdried over magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe crude product was purified by column chromatography on basic alumina (0 to 50% EtOAc in hexanes)