反应详情

温度

140 °C

DIPEA (0.105 mL, 0.60 mmol) was added to a mixture of 5-chloro-N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine (Intermediate 20, 0.207 g, 0.5 mmol) and N-methyl-2-(4-methylpiperazin-1-yl)ethanamine (Intermediate 109, 0.079 g, 0.50 mmol) in DMA (5 mL). The mixture was heated in a microwave at 140° C. for 3 h. An additional portion of N-methyl-2-(4-methylpiperazin-1-yl)ethanamine (8 mg, 0.05 mmol) was added and the mixture was heated in a microwave at 140° C. for a further 1 h before being cooled to r.t. The mixture was then concentrated in vacuo and the residue was dissolved in CH3OH. Purification by ion exchange chromatography, using an SCX column and eluting with 1M methanolic ammonia provided crude material after concentration of appropriate fractions in vacuo. Further purification by FCC, eluting with 2-8% CH3OH in CH2Cl2 gave the title compound (0.186 g, 67%) as an orange foam; 1H NMR: (CDCl3) 2.26 (3H, s), 2.32-2.45 (4H, m), 2.45-2.57 (4H, m), 2.61 (2H, t), 2.89 (3H, s), 3.29 (2H, t), 3.98 (3H, s), 6.65 (1H, s), 6.93-7.00 (1H, m), 7.38 (1H, ddd), 7.44 (1H, s), 8.40 (1H, s), 8.49 (1H, d), 8.55 (1H, d), 8.91 (2H, d); m/z: ES+ MH+ 552.59.

1. temperaturethe mixture was heated in a microwave at 140° C. for a further 1 h
2. temperaturebefore being cooled to r.t
3. concentrationThe mixture was then concentrated in vacuo
4. dissolutionthe residue was dissolved in CH3OH
5. customPurification by ion exchange chromatography
6. washeluting with 1M methanolic ammonia
7. customprovided crude material after concentration of appropriate fractions in vacuo
8. customFurther purification by FCC
9. washeluting with 2-8% CH3OH in CH2Cl2