Potassium Phosphate, Tribasic → 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-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)nicotinaldehyde

温度

100 °C

A 50-mL round-bottomed flask equipped with a reflux condenser was charged with 161f (200 mg, 0.40 mmol), 4-chloro-2-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)nicotinaldehyde 139a (132 mg, 0.40 mmol), K3PO4 3 water (213 mg, 0.80 mmol), sodium acetate (66 mg, 0.80 mmol), 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium(II) (16 mg, 0.020 mmol), and acetonitrile (20 mL). After three cycles of vacuum/N2 flush, the mixture was heated at 100° C. under N2 protection for 2 h. Analysis of the reaction mixture by LCMS showed complete conversion to the desired product. 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 30/1) to afford 161g (150 mg, 57%) as yellow solid. MS-ESI: [M+H]+ 663

1. customA 50-mL round-bottomed flask equipped with a reflux condenser
2. customAfter three cycles of vacuum/N2 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 30/1)

ORDレコード

ord-29a7e091f6524f059f265e65d9d63873

出典データセット

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08921353B2