反应详情

The Buchwald coupled product was prepared according to Procedure H using dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.018 g, 0.039 mmol), 2,5-dimorpholinopyridin-3-amine (0.077 g, 0.29 mmol), 4-chloro-5,7-difluoro-3-methyl-2-(2-methyl-4-(trifluoromethyl)phenyl)quinoline (0.090 g, 0.24 mmol), Pd2dba3 (7.74 mg, 8.46 μmol) and sodium tert-butoxide (0.058 g, 0.61 mmol) in toluene (2.4 mL) at 120° C. for 4 h. The crude product was purified by column chromatography on basic alumina (0 to 50% hexanes/EtOAc) to give the desired product N-(2,5-dimorpholinopyridin-3-yl)-5,7-difluoro-3-methyl-2-(2-methyl-4-(trifluoromethyl)phenyl)quinolin-4-amine. 1H NMR (400 MHz, CDCl3) δ ppm 7.75 (1H, br. s), 7.58-7.66 (4H, m), 7.38 (1H, m), 7.06 (1H, m), 6.26 (1H, br. s.), 3.93 (4H, br. s), 3.80 (4H, app t, J=4.1 Hz), 3.20 (4H, br. s.), 3.01 (4H, app t, J=4.4 Hz), 2.25 (3H, s), 1.94 (3H, s). Mass Spectrum (ESI) m/e=600.2 (M+1).

1. customwas prepared
2. customat 120° C.
3. customfor 4 h
4. customThe crude product was purified by column chromatography on basic alumina (0 to 50% hexanes/EtOAc)