反应详情

温度

120 °C

1-Methylpiperazine (492 μL, 4.44 mmol) was added to a suspension of 5-chloro-N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(1H-indol-3-yl)pyrimidin-2-amine (Intermediate 76, 612 mg, 1.48 mmol). The mixture was heated at 120° C. for 1 h and was then concentrated in vacuo. The residue was dissolved in CH2Cl2 (25 mL) and washed with water (2×25 mL) and sat. brine (25 mL), then dried (MgSO4) and concentrated in vacuo. Purification by FCC, eluting with 1-10% CH3OH in CH2Cl2 gave the title compound as 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 and diethyl ether to give the title compound (365 mg, 50%) as a yellow/orange solid; 1H NMR: 2.26 (3H, s), 2.47-2.55 (4H, m), 3.07-3.13 (4H, m), 3.93 (3H, s), 6.85 (1H, s), 6.99 (1H, t), 7.16-7.22 (1H, m), 7.48 (1H, d), 8.26 (1H, d), 8.36 (1H, s), 8.42 (1H, d), 8.51 (1H, s), 8.54 (1H, s), 11.88 (1H, s); m/z: ES+ MH+ 494.46.

1. concentrationwas then concentrated in vacuo
2. dissolutionThe residue was dissolved in CH2Cl2 (25 mL)
3. washwashed with water (2×25 mL) and sat. brine (25 mL)
4. dry with materialdried (MgSO4)
5. concentrationconcentrated in vacuo
6. customPurification by FCC
7. washeluting with 1-10% CH3OH in CH2Cl2