反应详情

To a mixture of 7-chloroimidazo[1,2-c]pyrimidin-5(6H)-one (Preparation H, 10.0 g, 59.0 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (19.0 g, 88.5 mmol) and XPHOS (2.81 g, 5.90 mmol) in isopropyl alcohol (400 mL) was added 2M K3PO4 (88.5 mL, 177 mmol). The mixture was purged with N2 for 15 minutes with vigorous mixing and Pd2dba3 (2.70 g, 2.95 mmol) was added. The mixture was heated at reflux under a N2 atmosphere for 20 hours. The mixture was charged additional 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (6.00 g) and Pd2dba3 (1.00 g) and heated at reflux for an additional 20 hours. The mixture was cooled to ambient temperature and concentrated to an aqueous syrup. The syrup was partitioned into H2O (500 mL) and 50% EtOAc-hexanes (250 mL) and mixed. The mixture was filtered through filter paper and the orange organic layer was removed. The aqueous layer was washed with 50% EtOAc/hexanes and was cooled on an ice bath. The solution was treated with concentrated HCl to pH 6 with stirring and the resulting fine precipitate was collected, washed with H2O and Et2O and dried under vacuum to provide the title compound (9.65 g, 76% yield) as faint grey solid. MS (apci) m/z=216.2 (M+H).

1. customThe mixture was purged with N2 for 15 minutes
2. additionwith vigorous mixing
3. temperatureThe mixture was heated
4. temperatureat reflux under a N2 atmosphere for 20 hours
5. temperatureheated
6. temperatureat reflux for an additional 20 hours
7. concentrationconcentrated to an aqueous syrup
8. customThe syrup was partitioned into H2O (500 mL) and 50% EtOAc-hexanes (250 mL)
9. additionmixed
10. filtrationThe mixture was filtered
11. filtrationthrough filter paper
12. customthe orange organic layer was removed
13. washThe aqueous layer was washed with 50% EtOAc/hexanes
14. temperaturewas cooled on an ice bath
15. additionThe solution was treated with concentrated HCl to pH 6
16. customthe resulting fine precipitate was collected
17. washwashed with H2O and Et2O
18. customdried under vacuum