反应详情

温度

105 °C

A screw-cap vial was charged with 4-chloro-5,7-difluoro-3-methyl-2-(5-(methylsulfonyl)pyridin-3-yl)quinoline (40 mg, 0.11 mmol), 2,5-dimorpholinopyridin-3-amine (28.7 mg, 0.11 mmol), tris(dibenzylideneacetone)dipalladium (0) (10.0 mg, 11.0 μmol), X-Phos (10.3 mg, 0.022 mmol), sodium tert-butoxide (31.3 mg, 0.33 mmol), and toluene (1.1 mL). The reaction was stirred at 105° C. for 30 min, then cond. The resulting residue was partitioned between DCM and water, and extracted twice with DCM. The combined organic layer was dried over magnesium sulfate and cond, and the crude product was purified by flash chromatography (basic alumina, 0-60% EtOAc in hexanes). This afforded N-(2,5-dimorpholinopyridin-3-yl)-5,7-difluoro-3-methyl-2-(5-(methylsulfonyl)pyridin-3-yl)quinolin-4-amine. Mass Spectrum (ESI) m/e=597.0 (M+1). 1H NMR (500 MHz, CDCl3) δ ppm 9.26 (1H, d, J=2.2 Hz), 9.16 (1H, s), 8.56 (1H, s), 7.89 (1H, s), 7.72 (1H, s), 7.63 (1H, s), 7.09 (1H, s), 6.43 (1H, s), 3.88-4.08 (4H, m), 3.85 (4H, br. s.), 3.23 (4H, br. s.), 3.08 (4H, br. s.), 2.18 (3H, s), 1.57 (3H, s).

1. customThe resulting residue was partitioned between DCM and water
2. extractionextracted twice with DCM
3. dry with materialThe combined organic layer was dried over magnesium sulfate and cond
4. customthe crude product was purified by flash chromatography (basic alumina, 0-60% EtOAc in hexanes)