反应详情

温度

100 °C

A mixture of N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(1-methylindol-3-yl)pyrimidin-2-amine (Intermediate 129, 300 mg, 0.76 mmol), 8-methyl-2,8-diazaspiro[3.4]octane (Intermediate 47, 115 mg, 0.92 mmol), DIPEA (0.158 mL, 0.92 mmol) and DMA (4 mL) was heated at 100° C. for 1 h. The mixture was then absorbed onto an SCX column, and the column was washed with CH3OH. The column was then eluted with 1:1 methanoic ammonia in CH2Cl2 and fractions containing the desired product were combined and concentrated in vacuo. Purification by FCC, eluting with 1.5% CH3OH in CH2Cl2 gave the title compound (209 mg, 55%) as an orange solid; 1H NMR: 1.71 (2H, dt), 2.00-2.10 (2H, m), 2.40 (3H, s), 2.67 (2H, t), 3.74 (2H, d), 3.88 (3H, s), 3.96 (3H, s), 4.11 (2H, d), 6.31 (1H, s), 7.12 (1H, t), 7.20 (1H, d), 7.25 (1H, dd), 7.52 (1H, d), 8.02 (1H, s), 8.28-8.34 (2H, m), 8.36 (1H, d), 8.63 (1H, s); m/z: ES+ MH+ 500.6.

1. customThe mixture was then absorbed onto an SCX column
2. washthe column was washed with CH3OH
3. washThe column was then eluted with 1:1 methanoic ammonia in CH2Cl2 and fractions
4. additioncontaining the desired product
5. concentrationconcentrated in vacuo
6. customPurification by FCC
7. washeluting with 1.5% CH3OH in CH2Cl2