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-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine (Intermediate 161, 190 mg, 0.39 mmol), iron (131 mg, 2.34 mmol), NH4Cl (14.62 mg, 0.27 mmol), ethanol (6 mL) and water (2 mL) was heated at reflux for 4 h and then stirred at r.t. overnight. Part-purification was achieved by ion exchange chromatography, using an SCX column and eluting with 7N methanolic ammonia. Appropriate fractions were then concentrated in vacuo onto silica. Purification by FCC, eluting with 0-5% 7N methanolic ammonia in CH2Cl2 provided impure material. The fractions containing desired product were combined and further purified by FCC, eluting with 0-2.5% 7N methanolic ammonia in CH2Cl2 to give the title compound (100 mg, 56%); m/z: ES+ MH+ 457.21.

1. temperaturewas heated
2. temperatureat reflux for 4 h
3. customPart-purification
4. washeluting with 7N methanolic ammonia
5. concentrationAppropriate fractions were then concentrated in vacuo onto silica
6. customPurification by FCC
7. washeluting with 0-5% 7N methanolic ammonia in CH2Cl2 provided impure material
8. additionThe fractions containing desired product
9. customfurther purified by FCC
10. washeluting with 0-2.5% 7N methanolic ammonia in CH2Cl2