反应详情

温度

150 °C

A mixture of ethyl 7-(2-bromo-3-chloro-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoate (Intermediate EB) (200 mg, 0.494 mmol), p-tolylboronic acid (Aldrich) (73.9 mg, 0.544 mmol) and potassium carbonate (205 mg, 1.482 mmol) were combined in a microwave vial. Dioxane (2 ml) was added and the flask was sealed and deoxygenated by evacuation/N2 purge (×3). Pd(Ph3P)4 (57.1 mg, 0.049 mmol) was added and the mixture was de-oxygenated by evacuation/N2 purge (×3) and heated at 150° C. for 3 hours using microwave radiation. The mixture was diluted with water and extracted with EtOAc (×2). The extracts were washed with brine, dried (MgSO4) and evaporated under reduced pressure. The residue was purified by chromatography on silica eluting with 20-100% EtOAc in iso-hexane followed by 10% MeOH in DCM to elute the bis product. Further purification by chromatography on silica eluting with 0-70% EtOAc in iso-hexane afforded a mixture of the titled compound (mono adduct) and the bis adduct (2:1 ratio).

1. customthe flask was sealed
2. customdeoxygenated by evacuation/N2
3. custompurge (×3)
4. custompurge (×3)
5. additionThe mixture was diluted with water
6. extractionextracted with EtOAc (×2)
7. washThe extracts were washed with brine
8. dry with materialdried (MgSO4)
9. customevaporated under reduced pressure
10. customThe residue was purified by chromatography on silica eluting with 20-100% EtOAc in iso-hexane
11. washto elute the bis product
12. customFurther purification by chromatography on silica eluting with 0-70% EtOAc in iso-hexane
13. customafforded