反应详情

温度

120 °C

A mixture of 4-amino-6-chloropyrimidine-5-carbonitrile (0.030 g, 0.192 mmol), 1-(6-fluoro-4-(5-methyl-1,3,4-oxadiazol-2-yl)-3-(pyridin-2-yl)quinolin-2-yl)-ethanamine (0.067 g, 0.192 mmol), and N,N-diisopropylethylamine (0.167 mL, 0.959 mmol) in 1-butanol (1.918 mL) was stirred at 120° C. After 20 h, the mixture was removed from heat and to the cooled mixture was added water (50 mL) and DCM (50 mL). The organic layer was concentrated in vacuo to give the crude material as a light yellow solid. The light yellow solid was absorbed onto a plug of silica gel and purified by silica gel column chromatography eluting with a gradient of 0% to 50% DCM:MeOH:NH4OH (89:9:1) in DCM, to provide 4-amino-6-((1-(6-fluoro-4-(5-methyl-1,3,4-oxadiazol-2-yl)-3-(2-pyridinyl)-2-quinolinyl)ethyl)amino)-5-pyrimidinecarbonitrile as an off-white solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.56-8.62 (1H, m), 8.22-8.29 (1H, m), 7.85-7.93 (3H, m), 7.82 (1H, td, J=7.7, 1.8 Hz), 7.58 (1H, d, J=7.2 Hz), 7.42-7.47 (1H, m), 7.38 (1H, ddd, J=7.6, 4.9, 1.2 Hz), 7.24 (2H, br. s.), 5.54 (1H, quin, J=6.7 Hz), 2.34 (3H, s), 1.39 (3H, d, J=6.7 Hz); LC-MS (ESI) m/z 468.1 [M+H]+.

1. customthe mixture was removed
2. temperaturefrom heat and to the cooled mixture
3. additionwas added water (50 mL) and DCM (50 mL)
4. concentrationThe organic layer was concentrated in vacuo
5. customto give the crude material as a light yellow solid
6. customThe light yellow solid was absorbed onto a plug of silica gel
7. custompurified by silica gel column chromatography
8. washeluting with a gradient of 0% to 50% DCM:MeOH:NH4OH (89:9:1) in DCM