反应详情

To a solution of [(S)-1-(7-bromo-6-fluoro-1-pyridin-2-yl-1H-benzoimidazol-2-yl)ethyl]-[9-(tetrahydro-pyran-2-yl)-9H-purin-6-yl]amine (267 mg, 0.49 mmol) in dioxane (10 mL) and water (0.5 mL) was added cyclopropylboronic acid (64 mg, 0.75 mmol), cesium carbonate (242 mg, 0.75 mmol) and tetrakis(triphenylphosphine)palladium (0) (57 mg, 0.05 mmol) and the reaction mixture degassed by bubbling argon through the mixture whilst under sonication. The reaction mixture was heated at reflux for 16 h. The reaction mixture was diluted with water and extracted with EtOAc (3×20 mL). The combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to preparative HPLC (C18 Phenomenex column, 10-90% MeCN in water 0.1% formic acid, 25 min gradient) to yield the title compound as a white solid (59 mg, 24%). LCMS (Method C): RT=2.98 min, [M+H]+=499.

1. customthe reaction mixture degassed
2. customby bubbling argon through the mixture
3. customwhilst under sonication
4. temperatureThe reaction mixture was heated
5. temperatureat reflux for 16 h
6. additionThe reaction mixture was diluted with water
7. extractionextracted with EtOAc (3×20 mL)
8. washThe combined organic extracts were washed with brine
9. dry with materialdried (MgSO4)
10. concentrationconcentrated in vacuo
11. customC18 Phenomenex column, 10-90% MeCN in water 0.1% formic acid, 25 min gradient