Stannanecarbonitrile, tributyl- → 3-Methyl-2-(4-methylpyridin-2-yl)-4-(5-morpholinopyridin-3-ylamino)-quinoline-8-carbonitrile

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.025 g, 0.053 mmol), tri-n-butyltin cyanide (0.104 g, 0.33 mmol), 8-chloro-3-methyl-2-(4-methylpyridin-2-yl)-N-(5-morpholinopyridin-3-yl)quinolin-4-amine (0.15 g, 0.33 mmol) and Pd2dba3 (0.012 g, 0.013 mmol) in toluene (3.30 mL) was added sodium tert-butoxide (0.079 g, 0.82 mmol). The reaction mixture was heated to 100° C. for 66 h. After which, the reaction mixture was filtered through a plug of alumina eluting with (EtOAc), the filtrate was cond in vacuo. The crude product was purified by column chromatography on alumina (0 to 50% EtOAc in hexanes) to give the desired product. 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 3-methyl-2-(4-methylpyridin-2-yl)-4-(5-morpholinopyridin-3-ylamino)quinoline-8-carbonitrile. 1H NMR (400 MHz, CD2Cl2) δ ppm 8.59 (1H, d, J=5.5 Hz), 8.06 (2H, ddd, J=14.8, 7.9, 1.4 Hz), 7.86 (1H, d, J=2.5 Hz), 7.78-7.83 (1H, m), 7.67 (1H, d, J=2.3 Hz), 7.48 (1H, dd, J=8.5, 7.1 Hz), 7.27 (1H, m), 6.60 (1H, s), 6.43 (1H, t, J=2.3 Hz), 3.75 (4H, m), 3.05 (4H, m), 2.51 (3H, s), 2.36 (3H, s). Mass Spectrum (ESI) m/e=437.1 (M+1).

Provenance & Evidence