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

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 1,4-dioxane (40 mL), 296e (588 mg, 3.0 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (800 mg, 3.0 mmol), and cesium carbonate (1.96 g, 6.0 mmol). After bubbling nitrogen through the suspension for 20 minutes, xantphos (173 mg, 0.30 mmol) and tris(dibenzylideneacetone)dipalladium(0) (137 mg, 0.15 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 (2×15 mL). The combined filtrate was concentrated under reduced pressure. The residue solid was purified by silica-gel column chromatography eluting with dichloromethane/methanol (80/1 to 30/1) to afford 296f (745 mg, 65%) as yellow solid. MS-ESI: [M+H]+ 382.9

1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
2. customAfter bubbling nitrogen through the suspension for 20 minutes
3. customflush
4. temperatureheated
5. temperatureat reflux for 5 h
6. filtrationfiltered
7. washThe solid was washed with dichloromethane (2×15 mL)
8. concentrationThe combined filtrate was concentrated under reduced pressure
9. customThe residue solid was purified by silica-gel column chromatography
10. washeluting with dichloromethane/methanol (80/1 to 30/1)

ORD-Eintrag

ord-c8d60a2b04664c60aad2a2e1ebb75755

Quelldatensatz

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09238655B2