Potassium Phosphate, Tribasic → (2-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-{1-methyl-5-[(5-{[(3S)-3-methylmorpholin-4-yl]carbonyl}pyridin-2-yl)amino]-6-oxo-1,6-dihydropyridin-3-yl}pyridin-3-yl)methyl Acetate

Temperatur

100 °C

A 25-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 257a (203 mg, 0.50 mmol), {3-[(acetoxy)methyl]-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridin-4-yl}boronic acid 199e (640 mg, 1.6 mmol), K3PO4 (212 mg, 1.0 mmol), 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium(II) (18 mg, 0.025 mmol), sodium acetate (82 mg, 1.0 mmol), acetonitrile (10 mL), and water (0.2 mL). After three cycles of vacuum/argon flush, the mixture was heated at 100° C. for 2.5 h. Analysis of the reaction mixture by LCMS showed complete 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 (20 mL). The aqueous layer was separated and extracted with dichloromethane (3×20 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 60:1 dichloromethane/methanol to afford 257b (160 mg, 47%) as black solid. MS-ESI: [M+H]+ 680.1

1. customA 25-mL single-neck round-bottomed flask equipped with a magnetic stirrer and 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 (20 mL)
6. customThe aqueous layer was separated
7. extractionextracted with dichloromethane (3×20 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 60:1 dichloromethane/methanol

ORD-Eintrag

ord-710312f538ef485db0e2a54503707d94

Quelldatensatz

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08716274B2