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

Temperature

120 °C

To a stirred solution of dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.026 g, 0.055 mmol), 2,5-dimorpholinopyridin-3-amine (0.110 g, 0.415 mmol), 4,8-dichloro-3-methyl-2-(pyridin-2-yl)quinoline (0.10 g, 0.35 mmol) and Pd2dba3 (0.013 g, 0.014 mmol) in toluene (3.46 mL) was added sodium t-butoxide (0.083 g, 0.865 mmol). The reaction mixture was heated to 120° C. and stirred for 45 min. After which the reaction was cooled to rt and diluted with water (25 mL). The mixture was extracted with EtOAc (3×10 mL) and DCM (1×10 mL). The combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography on basic alumina (0 to 50% EtOAc/hexane) to give the desired product 8-chloro-N-(2,5-di-4-morpholinyl-3-pyridinyl)-3-methyl-2-(2-pyridinyl)-4-quinolinamine. 1H NMR (400 MHz, CDCl3) δ ppm 8.71 (1H, d, J=4.3 Hz), 8.15 (1H, d, J=7.8 Hz), 7.93 (1H, m), 7.82 (1H, d, J=7.4 Hz), 7.76 (1H, br. s.), 7.60 (1H, d, J=2.5 Hz), 7.34-7.47 (2H, m), 6.79 (1H, br. s.), 6.21 (1H, br. s.), 3.93 (4H, br. s.), 3.67-3.79 (4H, m), 3.25 (4H, br. s.), 2.93 (4H, br. s.), 2.49 (3H, s). Mass Spectrum (ESI) m/e=517.2 (M+1).

1. temperatureAfter which the reaction was cooled to rt
2. extractionThe mixture was extracted with EtOAc (3×10 mL) and DCM (1×10 mL)
3. dry with materialThe combined organic layers were dried over magnesium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe crude product was purified by column chromatography on basic alumina (0 to 50% EtOAc/hexane)

ORD record

ord-164ea7213f6640a2b4e03a6b89c898c5

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08940724B2