Stannanecarbonitrile, tributyl- → (2,5-Dimorpholinopyridin-3-ylamino)-3-methyl-2-(pyridin-2-yl)quinoline-8-carbonitrile

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 8-chloro-N-(2,5-dimorpholinopyridin-3-yl)-3-methyl-2-(pyridin-2-yl)quinolin-4-amine (0.180 g, 0.35 mmol) in 1-methylpyrrolidin-2-one (3.46 mL) was added palladium bis(trifluoroacetate) (0.017 g, 0.052 mmol), 2-(dicyclohexylphosphino)-2′,4′,6′-triisopropyl-biphenyl (0.050 g, 0.11 mmol) followed by tri-n-butyltin cyanide (0.109 g, 0.35 mmol). The reaction was heated to 160° C. for 36 h. A further 0.3 eq of palladium bis(trifluoroacetate) and 0.6 eq of dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine was added. The reaction was further heated at 160° C. for 3 h. After which, the reaction was cooled to 23° C. The crude product was filtered through a plug of alumina eluting with EtOAc. The organic layer was washed with water, dried over MgSO4 and filtered and evaporated in vacuo. The crude product was purified by column chromatography on alumina (0 to 50% EtOAc/hexane)) to give the desired product 4-((2,5-dimorpholinopyridin-3-ylamino)-3-methyl-2-(pyridin-2-yl)quinoline-8-carbonitrile. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.72 (1H, ddd, J=4.8, 1.8, 1.0 Hz), 8.29 (1H, dd, J=7.1, 1.3 Hz), 8.19 (1H, dd, J=8.5, 1.3 Hz), 8.03-8.08 (2H, m), 7.96 (1H, dt, J=7.9, 1.1 Hz), 7.61-7.65 (2H, m), 7.53 (1H, ddd, J=7.6, 4.8, 1.3 Hz), 6.55 (1H, d, J=2.7 Hz), 3.65 (4H, m), 3.39 (4H, m), 2.95 (4H, m), 2.88 (4H, m), 2.19 (3H, s). Mass Spectrum (ESI) m/e=508.3 (M+1).

Provenance & Evidence