反应详情

A mixture of N-[2-methoxy-4-(4-methylpiperazin-1-yl)-5-nitrophenyl]-4-(1-methy-lindol-3-yl)pyrimidin-2-amine (Intermediate 111, 329 mg, 0.69 mmol), iron (233 mg, 4.17 mmol) and NH4Cl (26.0 mg, 0.49 mmol) in ethanol (12 mL) and water (4 mL) were heated at reflux for 3 h. The mixture was allowed to cool to r.t. and then filtered. The filtrate was concentrated in vacuo. Purification by ion exchange chromatography, using an SCX column and eluting with 0.7M methanolic ammonia gave a brown gum after concentration of appropriate fractions in vacuo. Further purification by FCC, eluting with 0-5% 7N methanolic ammonia in CH2Cl2 gave the title compound (287 mg, 93%) as a light brown gum; 1H NMR: (CDCl3) 2.37 (3H, br s), 2.59 (4H, s), 2.92-2.99 (4H, m), 3.79-3.86 (5H, m), 3.87 (3H, s), 6.71 (1H, s), 7.01 (1H, d), 7.27-7.34 (2H, m), 7.35-7.40 (1H, m), 7.57 (1H, s), 7.78 (1H, s), 8.17 (1H, s), 8.32 (1H, d), 8.47-8.53 (1H, m); m/z: ES+ MH+ 444.54.

1. temperaturewere heated
2. temperatureat reflux for 3 h
3. filtrationfiltered
4. concentrationThe filtrate was concentrated in vacuo
5. customPurification by ion exchange chromatography
6. washeluting with 0.7M methanolic ammonia
7. customgave a brown gum after concentration of appropriate fractions in vacuo
8. customFurther purification by FCC
9. washeluting with 0-5% 7N methanolic ammonia in CH2Cl2