反应详情

N-(4-Fluoro-2-methoxy-5-nitrophenyl)-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-amine (Intermediate 127, 300 mg, 0.78 mmol), 8-methyl-2,8-diazaspiro[3.4]octane (Intermediate 47, 118 mg, 0.94 mmol) and DIPEA (0.162 mL, 0.94 mmol) were heated at 100° C. in DMA (4 mL) for 1.75 h. The mixture was then absorbed onto an SCX column, then the column was washed with CH3OH and then eluted with 1:1 7M methanolic ammonia in CH2Cl2. Fractions that contained the desired product were combined and concentrated in vacuo. Purification by FCC, eluting with 2.5% 7N methanolic ammonia in CH2Cl2 gave the title compound (321 mg, 84%) as an orange foam; 1H NMR: 1.62-1.74 (2H, m), 1.74-1.85 (2H, m), 1.91-2.00 (2H, m), 2.00-2.06 (2H, m), 2.38 (3H, s), 2.65 (2H, t), 3.03 (2H, t), 3.71 (2H, d), 3.95 (3H, s), 4.04-4.15 (4H, m), 6.27 (1H, s), 7.01 (1H, d), 8.01 (1H, s), 8.09 (1H, s), 8.33 (1H, d), 8.54 (1H, s); m/z: ES′ MH+ 491.6.

1. customThe mixture was then absorbed onto an SCX column
2. washthe column was washed with CH3OH
3. washeluted with 1:1 7M methanolic ammonia in CH2Cl2
4. concentrationconcentrated in vacuo
5. customPurification by FCC
6. washeluting with 2.5% 7N methanolic ammonia in CH2Cl2