Potassium Phosphate, Tribasic → 2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)nicotinaldehyde

Temperatur

100 °C

A 25-mL round-bottomed flask equipped with a reflux condenser was charged with 128d (193 mg, 0.50 mmol), 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-chloronicotinaldehyde 103b (180 mg, 0.50 mmol), 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium(II) (17 mg, 0.025 mmol), K3PO4 (212 mg, 1.0 mmol), sodium acetate (82 mg, 1.0 mmol), acetonitrile (6 mL), and water (0.5 mL). After three cycles of vacuum/argon flush, the mixture was heated at 100° C. for 1 h. Analysis of the reaction mixture by LCMS showed completed conversion to the desired product. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was diluted with dichloromethane (20 mL) and water (10 mL). The aqueous layer was separated and extracted with dichloromethane (3×10 mL). The combined organic layer was dried over Na2SO4 and filtered. The filtrate was 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 128e (190 mg, 65%) as a yellow solid. MS-ESI: [M+H]+ 583.3

1. customA 25-mL round-bottomed flask equipped with a reflux condenser
2. customAfter three cycles of vacuum/argon flush
3. temperatureThe reaction mixture was cooled to room temperature
4. concentrationconcentrated under reduced pressure
5. additionThe residue was diluted with dichloromethane (20 mL) and water (10 mL)
6. customThe aqueous layer was separated
7. extractionextracted with dichloromethane (3×10 mL)
8. dry with materialThe combined organic layer was dried over Na2SO4
9. filtrationfiltered
10. concentrationThe filtrate was concentrated under reduced pressure
11. customThe dark residue was purified by silica-gel column chromatography
12. washeluting with dichloromethane/methanol (80:1 to 30:1)

ORD-Eintrag

ord-f8e736fab7f64558bdaa7aa7ca87f3d6

Quelldatensatz

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08669251B2