Cesium carbonate → 2-(5-Bromo-1-methyl-2-oxo-1,2-dihydropyridin-3-ylamino)-5-methyl-4,5-dihydropyrazolo[1,5-a]pyrazin-6(7H)-one

A 100-mL round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 146d (300 mg, 1.8 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (482 mg, 1.8 mmol), cesium carbonate (1.17 g, 3.6 mmol), and 1,4-dioxane (20 mL). After bubbling nitrogen through the suspension for 10 minutes, xantphos (104 mg, 0.18 mmol) and tris(dibenzylideneacetone)dipalladium(0) (82 mg, 0.090 mmol) were added. The system was subjected to three cycles of vacuum/argon flush and heated at reflux for 5 h. It was then cooled to room temperature and filtered. The solid was washed with dichloromethane (2×30 mL). The combined filtrate was concentrated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with dichloromethane/methanol (80/1 to 30/1) to afford 146e (390 mg, 61%) as a yellow solid.

1. customA 100-mL round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
2. customAfter bubbling nitrogen through the suspension for 10 minutes
3. customflush
4. temperatureheated
5. temperatureat reflux for 5 h
6. filtrationfiltered
7. washThe solid was washed with dichloromethane (2×30 mL)
8. concentrationThe combined filtrate was concentrated under reduced pressure
9. customThe residue was purified by silica-gel column chromatography
10. washeluting with dichloromethane/methanol (80/1 to 30/1)

ORD record

ord-09209797ccc84448a712ed990cb4f3fb

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08669251B2