反应详情

A mixture of N-[2-methoxy-4-(4-methylpiperazin-1-yl)-5-nitrophenyl]-5-methyl-4-(1-methylindol-3-yl)pyrimidin-2-amine (Intermediate 78, 408 mg, 0.84 mmol), iron (280 mg, 5.02 mmol) and NH4Cl (31.3 mg, 0.59 mmol) in ethanol (24 mL) and water (8.00 mL) was heated at reflux for 3 h. The mixture was cooled and concentrated in vacuo to give a thick slurry. CH2Cl2 (100 mL) and CH3OH (10 mL) were added and the 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 1-7% methanolic ammonia in CH2Cl2 gave the title compound (163 mg, 43%) as a yellow gum which crystallised on standing; 1H NMR: (CDCl3) 2.36 (6H, s), 2.53 (3H, dd), 2.94 (4H, t), 3.69-3.79 (2H, m), 3.83 (3H, s), 3.86 (3H, s), 6.69 (1H, s), 7.24-7.27 (1H, m), 7.29 (1H, dd), 7.33 (1H, dd), 7.36-7.40 (1H, m), 7.49 (1H, s), 7.58 (1H, s), 8.23 (1H, d), 8.26 (1H, s), 8.56 (1H, d); m/z: ES+ MH+ 458.37.

1. temperaturewas heated
2. temperatureat reflux for 3 h
3. temperatureThe mixture was cooled
4. concentrationconcentrated in vacuo
5. customto give a thick slurry
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 1-7% methanolic ammonia in CH2Cl2