反应详情

A mixture of 5-chloro-N-[2-methoxy-4-(4-methylpiperazin-1-yl)-5-nitrophenyl]-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine (Intermediate 64, 775 mg, 1.57 mmol), iron (525 mg, 9.40 mmol) and NH4Cl (62.8 mg, 1.17 mmol) was heated at reflux in ethanol (21 mL) and water (7 mL) for 2 h. The mixture was then cooled and filtered through diatomaceous earth (Celite™). The filtrate was concentrated in vacuo and then dissolved into CH2Cl2. This solution was washed with brine, dried (MgSO4) and concentrated in vacuo. Purification by FCC, eluting with 2-6% 7N methanolic ammonia in CH2Cl2 gave the title compound (480 mg, 66%) as a brown gum; 1H NMR: 2.26 (3H, s), 2.52 (4H+DMSO, m), 2.89 (4H, t), 3.68 (3H, s), 4.35 (2H, d), 6.73 (1H, s), 6.99 (1H, d), 7.13 (1H, td), 7.28-7.39 (1H, m), 8.38 (1H, d), 8.39-8.46 (2H, m), 8.82 (1H, d), 8.95 (1H, s); m/z: ES+ MH+ 465.5.

1. temperaturewas heated
2. temperatureThe mixture was then cooled
3. filtrationfiltered through diatomaceous earth (Celite™)
4. concentrationThe filtrate was concentrated in vacuo
5. dissolutiondissolved into CH2Cl2
6. washThis solution was washed with brine
7. dry with materialdried (MgSO4)
8. concentrationconcentrated in vacuo
9. customPurification by FCC
10. washeluting with 2-6% 7N methanolic ammonia in CH2Cl2