反应详情

A mixture of N-[4-[(3R)-3-dimethylaminopyrrolidin-1-yl]-2-methoxy-5-nitrophenyl]-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine (Intermediate 154, 440 mg, 0.93 mmol), iron (311 mg, 5.56 mmol), NH4Cl (37.2 mg, 0.70 mmol), ethanol (15 mL) and water (5 mL) was heated at reflux for 1.5 h. After cooling the mixture was concentrated in vacuo. The resulting residue was triturated in 10% CH3OH in CH2Cl2 (20 mL) for 15 minutes and then filtered. The residues were triturated again with 10% CH3OH in CH2Cl2 (10 mL) and then filtered. The combined filtrates were washed with brine, dried (MgSO4) and concentrated in vacuo. Purification by FCC, eluting with 0-10% methanolic ammonia in CH2Cl2 gave the title compound (339 mg, 82%) as a yellow solid after trituration with diethyl ether; 1H NMR: 1.73-1.83 (1H, m), 2.00-2.10 (1H, m), 2.20 (6H, s), 2.81-2.90 (1H, m), 2.92-3.00 (2H, m), 3.11-3.16 (1H, m), 3.17-3.24 (1H, m), 3.73 (3H, s), 4.28 (2H, br s), 6.71 (1H, s), 7.07 (1H, td), 7.20 (1H, d), 7.27 (1H, s), 7.37-7.42 (1H, m), 7.97 (1H, s), 8.30 (1H, d), 8.53 (1H, d), 8.76 (1H, s), 8.79 (1H, d); m/z: ES+ MH+ 445.33.

1. temperaturewas heated
2. temperatureat reflux for 1.5 h
3. temperatureAfter cooling the mixture
4. concentrationwas concentrated in vacuo
5. customThe resulting residue was triturated in 10% CH3OH in CH2Cl2 (20 mL) for 15 minutes
6. filtrationfiltered
7. customThe residues were triturated again with 10% CH3OH in CH2Cl2 (10 mL)
8. filtrationfiltered
9. washThe combined filtrates were washed with brine
10. dry with materialdried (MgSO4)
11. concentrationconcentrated in vacuo
12. customPurification by FCC
13. washeluting with 0-10% methanolic ammonia in CH2Cl2