2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → 5,7-difluoro-3-methyl-N-(5-morpholinopyridin-3-yl)-2-(6-(piperidin-1-yl)pyridin-3-yl)quinolin-4-amine

Participants

Reaction Steps

The Buchwald coupled product was prepared according to Procedure S using of dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.020 g, 0.043 mmol), 5-morpholinopyridin-3-amine (0.058 g, 0.32 mmol), 4-chloro-5,7-difluoro-3-methyl-2-(6-(piperidin-1-yl)pyridin-3-yl)quinoline (0.1 g, 0.27 mmol), Pd2dba3 (0.010 g, 0.011 mmol) and sodium tert-butoxide (0.064 g, 0.67 mmol) in toluene (2.7 mL) at 100° C. for 23.3 h. The crude 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 the desired product 5,7-difluoro-3-methyl-N-(5-morpholinopyridin-3-yl)-2-(6-(piperidin-1-yl)pyridin-3-yl)quinolin-4-amine. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.43-8.47 (2H, m), 7.86 (1H, dd, J=8.9, 2.6 Hz), 7.79 (1H, d, J=2.4 Hz), 7.56-7.61 (2H, m), 7.37 (1H, ddd, J=12.5, 9.5, 2.7 Hz), 6.93 (1H, d, J=8.8 Hz), 6.55 (1H, t, J=2.3 Hz), 3.66-3.74 (4H, m), 3.59-3.66 (4H, m), 3.04-3.11 (4H, m), 2.19 (3H, s). Mass Spectrum (ESI) m/e=517.2 (M+1).

Provenance & Evidence