反应详情

A mixture of N-[5-chloro-4-(1-methylindol-3-yl)pyrimidin-2-yl]-N′-(2-dimethylamino-ethyl)-2-methoxy-N′-methyl-5-nitrobenzene-1,4-diamine (Intermediate 98, 553 mg, 1.08 mmol), iron (363 mg, 6.51 mmol) and NH4Cl (43.5 mg, 0.81 mmol) in ethanol (23 mL) and water (7.67 mL) were heated at reflux for 1.5 h. The mixture was then cooled and concentrated in vacuo. The resulting residue was dissolved in CH2Cl2 (100 mL) and CH3OH (10 mL) and this mixture was stirred for 0.25 h and then filtered. The filter cake was washed with further CH2Cl2 and CH3OH and the combined organics were dried (MgSO4) and concentrated in vacuo. Purification by FCC, eluting with 0-5% methanolic ammonia in CH2Cl2 provided a solid. This solid was dissolved in diethyl ether and a small amount of brown precipitate was removed by filtration. The filtrate was concentrated in vacuo to give the title compound (409 mg, 79%) as a brown glass; 1H NMR: (CDCl3) 2.26 (6H, s), 2.38-2.43 (2H, m), 2.68 (3H, s), 2.94-2.98 (2H, m), 3.84 (3H, s), 3.91 (3H, s), 6.71 (1H, s), 7.26-7.36 (2H, m), 7.40 (1H, d), 7.63 (1H, s), 8.09 (1H, s), 8.21 (1H, s), 8.33 (1H, s), 8.67 (1H, d); m/z: ES+ MH+ 480.32.

1. temperaturewere heated
2. temperatureat reflux for 1.5 h
3. temperatureThe mixture was then cooled
4. concentrationconcentrated in vacuo
5. dissolutionThe resulting residue was dissolved in CH2Cl2 (100 mL)
6. filtrationfiltered
7. washThe filter cake was washed with further CH2Cl2 and CH3OH
8. dry with materialthe combined organics were dried (MgSO4)
9. concentrationconcentrated in vacuo
10. customPurification by FCC
11. washeluting with 0-5% methanolic ammonia in CH2Cl2
12. customprovided a solid
13. customa small amount of brown precipitate was removed by filtration
14. concentrationThe filtrate was concentrated in vacuo