2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → 8-chloro-3-methyl-2-(4-methylpyridin-2-yl)-N-(5-morpholinopyridin-3-yl)quinolin-4-amine

Participants

Reaction Steps

The Buchwald coupled product was prepared according to Procedure H using dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.021 g, 0.044 mmol), 5-morpholinopyridin-3-amine (0.060 g, 0.33 mmol), 4,8-dichloro-3-methyl-2-(4-methylpyridin-2-yl)quinoline (0.084 g, 0.28 mmol) and Pd2dba3 (0.010 g, 0.011 mmol) and sodium tert-butoxide (0.067 g, 0.70 mmol) in toluene (2.8 mL) at 100° C. for 1.6 h. The crude product was purified by column chromatography on alumina (0 to 50% EtOAc in hexanes). 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 cond 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-3-methyl-2-(4-methylpyridin-2-yl)-N-(5-morpholinopyridin-3-yl)quinolin-4-amine. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.70 (1H, s), 8.57 (1H, d, J=4.9 Hz), 8.02 (1H, dd, J=8.6, 1.2 Hz), 7.92 (1H, dd, J=7.5, 1.1 Hz), 7.82 (1H, d, J=2.5 Hz), 7.77 (1H, s), 7.53-7.57 (1H, m), 7.52 (1H, m), 7.34-7.36 (1H, m), 6.57 (1H, t, J=2.3 Hz), 3.68-3.72 (4H, m), 3.05-3.09 (4H, m), 2.47 (3H, s), 2.22 (3H, s). Mass Spectrum (ESI) m/e=446.1 (M+1).

Provenance & Evidence