2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 59631092, compound

Participants

Reaction Steps

The Buchwald coupled product was prepared according to Procedure S using of 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-chloro-5,7-difluoro-3-methyl-2-(2-(pyrrolidin-1-yl)pyridin-4-yl)quinoline (0.10 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 5 h. The crude product was purified by column chromatography on silica gel (0 to 100% DCM/methanol/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 aqueous sodium bicarbonate solution, the solvent was removed under reduced pressure to yield pure product 5,7-difluoro-3-methyl-N-(5-morpholinopyridin-3-yl)-2-(2-(pyrrolidin-1-yl)pyridin-4-yl)quinolin-4-amine. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.44 (1H, s), 8.43 (1H, d, J=2.0 Hz), 7.86 (1H, dd, J=8.8, 2.4 Hz), 7.79 (1H, d, J=2.4 Hz), 7.56-7.60 (2H, m), 7.34-7.39 (1H, m), 6.57 (1H, d, J=8.6 Hz), 6.54 (1H, t, J=2.3 Hz), 3.68-3.75 (4H, m), 3.47 (4H, t, J=6.5 Hz), 3.06-3.11 (4H, m), 2.19 (3H, s), 1.95-2.01 (4H, m). Mass Spectrum (ESI) m/e=503.1 (M+1).

Provenance & Evidence