反应详情

The Buchwald coupled product was prepared according to Procedure H using dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.023 g, 0.047 mmol), 5-morpholinopyridin-3-amine (0.064 g, 0.35 mmol), 4-chloro-5,7-difluoro-3-methyl-2-(4-methylpyridin-2-yl)quinoline (0.09 g, 0.30 mmol) Pd2dba3 (0.011 g, 0.012 mmol) and sodium tert-butoxide (0.071 g, 0.74 mmol) in toluene (2.7 mL) at 120° C. for 10 days. The crude product was purified by column chromatography on basic alumina (0 to 50% hexanes/EtOAc) to give the desired product 5,7-difluoro-3-methyl-2-(4-methylpyridin-2-yl)-N-(5-morpholinopyridin-3-yl)-quinolin-4-amine. 1H NMR (400 MHz, CDCl3) δ ppm 8.55 (1H, d, J=4.9 Hz), 7.95 (1H, d, J=2.2 Hz), 7.81 (1H, d, J=2.2 Hz), 7.65-7.62 (2H, m), 7.20 (1H, m), 6.98-7.07 (2H, m), 6.62 (2H, app t, J=4.5 Hz), 3.86 (4H, t, J=1.9 Hz), 3.20 (4H, t, J=1.9 Hz), 2.48 (3H, s), 2.15 (3H, s). Mass Spectrum (ESI) m/e=448.1 (M+1).

1. customwas prepared
2. customat 120° C.
3. customfor 10 days
4. customThe crude product was purified by column chromatography on basic alumina (0 to 50% hexanes/EtOAc)