反应详情

A (3:1) mixture of ethyl 7-(3-chloro-2-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoate (Example 13.2, step 1) (30 mg, 0.072 mmol) and ethyl 7-(2-bromo-3-chloro-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoate (Example 13.1, step 2)(10 mg, 0.025 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (39.4 mg, 0.192 mmol) and potassium carbonate (39.9 mg, 0.288 mmol) in dioxane (2 ml) was degassed by bubbling nitrogen through (×3). Pd(Ph3P)4 (22.22 mg, 0.019 mmol) was added and the mixture was degassed by bubbling nitrogen through (×3). The reaction mixture was heated using microwave radiation at 150° C. for 2 hours. The mixture was diluted with water and extracted with EtOAc (×2). The combined extracts were washed with brine, dried (MgSO4) and evaporated under vacuum. The crude material was purified by ion exchange [Isolute SCX-2 washing with MeOH and eluting with 2M NH3 in MeOH] to give a brown residue. The crude residue was purified by chromatography on silica eluting with 0-100% EtOAc in iso-hexane followed by 10% MeOH/DCM to afford the title compound;

1. customwas degassed
2. customby bubbling nitrogen through (×3)
3. customthe mixture was degassed
4. customby bubbling nitrogen through (×3)
5. temperatureThe reaction mixture was heated
6. customat 150° C.
7. customfor 2 hours
8. additionThe mixture was diluted with water
9. extractionextracted with EtOAc (×2)
10. washThe combined extracts were washed with brine
11. dry with materialdried (MgSO4)
12. customevaporated under vacuum
13. customThe crude material was purified by ion exchange [Isolute SCX-2 washing with MeOH and eluting with 2M NH3 in MeOH]
14. customto give a brown residue
15. customThe crude residue was purified by chromatography on silica eluting with 0-100% EtOAc in iso-hexane