反应详情

A mixture of N-{4-[(3aR,6aR)-5-methyl-2,3,3a,4,6,6a-hexahydropyrrolo[3,4-b]pyrrol-1-yl]-2-methoxy-5-nitrophenyl}-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-amine (Intermediate 133, 400 mg, 0.82 mmol), iron (273 mg, 4.89 mmol) and NH4Cl (30.5 mg, 0.57 mmol) in ethanol (12 mL) and water (4 mL) was heated at reflux for 4 h and then stirred at r.t.overnight. Part-purification by ion exchange chromatography, using an SCX column, eluting with 7M methanolic ammonia provided crude material that was concentrated in vacuo onto silica. Purification by FCC, eluting with 0-5% 7N methanolic ammonia in CH2Cl2 provided impure product as a brown gum. Further purification by FCC, eluting with 0-2% 7N methanolic ammonia in CH2Cl2 provided the title compound (123 mg, 33%) as a brown gum; m/z: ES+ MH+ 461.26.

1. temperaturewas heated
2. temperatureat reflux for 4 h
3. customovernight
4. customPart-purification by ion exchange chromatography
5. washeluting with 7M methanolic ammonia
6. customprovided crude material that
7. concentrationwas concentrated in vacuo onto silica
8. customPurification by FCC
9. washeluting with 0-5% 7N methanolic ammonia in CH2Cl2 provided impure product as a brown gum
10. customFurther purification by FCC
11. washeluting with 0-2% 7N methanolic ammonia in CH2Cl2