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

温度

100 °C

A 50-mL round-bottomed flask equipped with a reflux condenser was charged with 326b (160 mg, 0.46 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 (300 mg, 0.69 mmol), K3PO4 (195 mg, 0.92 mmol), sodium acetate (75 mg, 0.92 mmol), 1,1′-bis(diphenylphosphino) ferrocenedichloropalladium(II) (42 mg, 0.046 mmol), acetonitrile (10 mL), and water (6 drops). The system was subjected to three cycles of vacuum/nitrogen flush and heated at 100° C. under N2 protection for 1.5 h. LCMS Analysis 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 extract was dried over Na2SO4, filtered, and concentrated under reduced pressure. The dark residue was purified by gel-silica column chromatography eluting with 60:1 dichloromethane/methanol to afford 326c (130 mg, 45%) as a black solid. MS-ESI: [M+H]+ 621.3

1. customA 50-mL round-bottomed flask equipped with a reflux condenser
2. customflush
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. extractionThe combined extract
10. dry with materialwas dried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure
13. customThe dark residue was purified by gel-silica column chromatography
14. washeluting with 60:1 dichloromethane/methanol

ORDレコード

ord-00078c1ba56b4c8b8a9789bfe0b43aa4

出典データセット

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09238655B2