反应详情

温度

120 °C

1-Methylpiperazine (0.453 mL, 4.08 mmol) was added to a suspension of N-(4-fluoro-2-methoxy-5-nitrophenyl)-5-methyl-4-(1-methylindol-3-yl)pyrimidin-2-amine (Intermediate 79, 554 mg, 1.36 mmol) in 2,2,2-trifluoroethanol (10 mL). The mixture was heated in a microwave at 120° C. for 1 h. The mixture was then concentrated in vacuo and the residue was dissolved in CH2Cl2 (50 mL). This solution was washed water (2×50 mL) and sat. brine (50 mL), then dried (MgSO4) and concentrated in vacuo. Purification by FCC, eluting with 1-10% CH3OH in CH2Cl2 gave an orange gum. This gum was dissolved in ethanol (25 mL) and a solid precipitated. This solid was collected by filtration and washed with ethanol to give the title compound (413 mg, 62%) as a yellow/orange solid; 1H NMR: 2.25 (3H, s), 2.39 (3H, s), 2.45-2.54 (4H, m), 3.03-3.10 (4H, m), 3.91 (3H, s), 3.98 (3H, s), 6.86 (1H, s), 7.06 (1H, dd), 7.22-7.28 (1H, m), 7.51 (1H, d), 8.02 (1H, s), 8.07 (1H, s), 8.26-8.30 (1H, m), 8.38 (1H, d), 8.69 (1H, s); m/z: ES+ MH+ 488.29.

1. concentrationThe mixture was then concentrated in vacuo
2. dissolutionthe residue was dissolved in CH2Cl2 (50 mL)
3. washThis solution was washed water (2×50 mL) and sat. brine (50 mL)
4. dry with materialdried (MgSO4)
5. concentrationconcentrated in vacuo
6. customPurification by FCC
7. washeluting with 1-10% CH3OH in CH2Cl2
8. customgave an orange gum
9. customa solid precipitated
10. filtrationThis solid was collected by filtration
11. washwashed with ethanol