反应详情

The Buchwald coupled product was prepared according to Procedure H using dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.025 g, 0.053 mmol), 2,5-dimorpholinopyridin-3-amine (0.105 g, 0.40 mmol), 4,8-dichloro-3-methyl-2-(4-methylpyridin-2-yl)quinoline (0.1 g, 0.33 mmol) and Pd2dba3 (0.012 g, 0.013 mmol) and sodium tert-butoxide (0.079 g, 0.83 mmol) in toluene (3.3 mL) at 100° C. for 1.6 h. The crude product was purified by column chromatography on silica gel (0 to 100% DCM/MeOH/ammonium hydroxide (90/9/1)). The desired product was further purified with HPLC (10-90% of 0.1% TFA acetonitrile solution in 0.1% TFA water solution.) The desired fractions were concd then diluted with EtOAc. After washing twice with satd aq. sodium bicarbonate solution, the solvent was removed under reduced pressure to yield pure product 8-chloro-N-(2,5-dimorpholinopyridin-3-yl)-3-methyl-2-(4-methylpyridin-2-yl)-quinolin-4-amine. 1H NMR (400 MHz, CD2Cl2) δ ppm 8.57 (1H, d, J=4.9 Hz), 7.82 (3H, m), 7.57 (1H, d, J=2.5 Hz), 7.43 (1H, dd, J=8.4, 7.4 Hz), 7.27 (1H, d, J=4.3 Hz.), 6.89 (1H, br. s.), 6.22 (1H, br. s.), 3.88 (4H, br. s.), 3.68 (4H, m), 3.20 (4H, br. s.), 2.90 (4H, m), 2.51 (3H, m), 2.39 (3H, s). Mass Spectrum (ESI) m/e=531.2 (M+1).

1. customwas prepared
2. customat 100° C.
3. customfor 1.6 h
4. customThe crude product was purified by column chromatography on silica gel (0 to 100% DCM/MeOH/ammonium hydroxide (90/9/1))
5. customThe desired product was further purified with HPLC (10-90% of 0.1% TFA acetonitrile solution in 0.1% TFA water solution.) The desired fractions
6. additionwere concd then diluted with EtOAc
7. washAfter washing twice with satd aq. sodium bicarbonate solution
8. customthe solvent was removed under reduced pressure