Cesium carbonate → 5-Bromo-3-(5-(2,2-difluoroethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-1-methylpyridin-2(1H)-one

Participants

Reaction Steps

A 50-mL round-bottomed flask equipped with a reflux condenser was charged with 135b (290 mg, 1.43 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (383 mg, 1.43 mmol), cesium carbonate (932 mg, 2.86 mmol), and 1,4-dioxane (20 mL). After bubbling nitrogen through the suspension for 10 minutes, xantphos (82 mg, 0.143 mmol) and Pd2(dba)3 (65 mg, 0.072 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 (30 mL). The combined organic 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 135c (400 mg, 72%) as a yellow solid. MS-ESI: [M+H]+ 387.8

Provenance & Evidence