Potassium Acetate → (S)-4-(5-(5-(2-Ethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-6,7,8,9-tetrahydropyrazino[1,2-a]indol-2(1H)-yl)nicotinaldehyde

온도

100 °C

A 50-mL flask equipped with a reflux condenser was charged with 4-chloro-2-(1-oxo-6,7,8,9-tetrahydropyrazino[1,2-a]indol-2(1H)-yl)nicotinaldehyde 103b (164 mg, 0.50 mmol), (S)-3-(5-(2-ethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one 161f (347 mg, 0.70 mmol), potassium acetate (137 mg, 1.4 mmol), 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium(II) (29 mg, 0.035 mmol), water (5 drops), and acetonitrile (20 mL). After three cycles of vacuum/argon flush, the mixture was heated at 100° C. under argon atmosphere for 3 h. The reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure. The residue was diluted with dichloromethane (50 mL) and water (50 mL). The aqueous layer was separated and extracted with dichloromethane (3×20 mL). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The dark residue was purified by silica-gel column chromatography eluting with dichloromethane/methanol (80/1 to 25/1) to afford 165a (151 mg, 46%) as yellow solid. MS-ESI: [M+H]+ 661

1. customA 50-mL flask equipped with a reflux condenser
2. customAfter three cycles of vacuum/argon flush
3. temperatureThe reaction mixture was cooled to room temperature
4. filtrationfiltered
5. concentrationThe filtrate was concentrated under reduced pressure
6. additionThe residue was diluted with dichloromethane (50 mL) and water (50 mL)
7. customThe aqueous layer was separated
8. extractionextracted with dichloromethane (3×20 mL)
9. dry with materialThe combined organic layer was dried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. customThe dark residue was purified by silica-gel column chromatography
13. washeluting with dichloromethane/methanol (80/1 to 25/1)

ORD 기록

ord-51b73b4ba09042b9a2b9ff7fcbe6be2e

출처 데이터셋

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08921353B2