反应详情

温度

100 °C

A mixture of 1.6 g 2-chloro-5-fluoro-N4-[2,2-dimethyl-3,4-dihydro-3-oxo-pyrido[3,2-b][1,4]oxazin-6-yl]-4-pyrimidineamine, 800 mg of 7-aminoisoquinoline, 320 mg of palladium acetate, 320 mg of rac-Binap and 3.68 g cesium carbonate in 32 mL of 1,4-dioxane and 8 mL of NMP was heated at reflux at 100° C. overnight under argon. The reaction was cooled, diluted with CH2Cl2/MeOH and filtered. The filtrate was diluted with water and the organic phase evaporated to give the crude product which was dissolved in acetone/MeOH and evaporated onto silica gel. The material was purified by flash chromatography eluting isocratically with CH2Cl2/2 N ammonia solution in MeOH 15:1 to yield 330 mg of the title compound. 1H NMR (DMSO-d6): δ 8.91 (s, 1H), 8.48 (s, 1H), 8.28 (d, 1H), J=5.4 Hz), 8.16 (d, 1H, J=2.1 Hz), 7.82 (m, 2H), 7.68 (d, 1H, J=6 Hz), 7.51 (d, 1H, J=8.1 Hz), 7.30 (d, 1H, J=8.4 Hz), 1.43 (s, 6H); LCMS: purity: 99%; MS (m/e): 432 (MH+)

1. temperaturewas heated
2. temperatureThe reaction was cooled
3. filtrationfiltered
4. additionThe filtrate was diluted with water
5. customthe organic phase evaporated
6. customto give the crude product which
7. customevaporated onto silica gel
8. customThe material was purified by flash chromatography
9. washeluting isocratically with CH2Cl2/2 N ammonia solution in MeOH 15:1