Potassium Acetate → 4-Chloro-2-[(1S,11R)-7-oxo-3,6-diazatetracyclo[9.2.1.02,10.03,8]tetradeca-2(10),8-dien-6-yl]pyridine-3-carbaldehyde

温度

80 °C

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 1,4-dioxane (30 mL), 167f (400 mg, 2.0 mmol), 2-bromo-4-chloronicotinaldehyde (1.30 g, 6.0 mmol), and potassium acetate (390 mg, 4.0 mmol). After bubbling nitrogen through the resulting mixture for 30 minutes, Xantphos (110 mg, 0.20 mmol) and tris(dibenzylideneacetone)dipalladium(0) (180 mg, 0.20 mmol) were added and the reaction mixture was heated at 80° C. for 10 h. It was then cooled to room temperature and filtered. The filtrate was partitioned between ethyl acetate (50 mL) and water (30 mL). The aqueous layer was separated and extracted with ethyl acetate (3×30 mL). The combined organic layer was washed with brine (20 mL) and dried over sodium sulfate. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified with silica-gel column chromatography eluting with 2:1 petroleum ether/ethyl acetate to afford 167g (391 mg, 57%) as yellow solid. MS-ESI: [M+H]+ 342.2

1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
2. customAfter bubbling nitrogen through the resulting mixture for 30 minutes
3. temperatureIt was then cooled to room temperature
4. filtrationfiltered
5. customThe filtrate was partitioned between ethyl acetate (50 mL) and water (30 mL)
6. customThe aqueous layer was separated
7. extractionextracted with ethyl acetate (3×30 mL)
8. washThe combined organic layer was washed with brine (20 mL)
9. dry with materialdried over sodium sulfate
10. customThe drying agent was removed by filtration
11. concentrationthe filtrate was concentrated under reduced pressure
12. customThe residue was purified with silica-gel column chromatography
13. washeluting with 2:1 petroleum ether/ethyl acetate

ORDレコード

ord-266562922ed34248a4aa4e3b9b14de8d

出典データセット

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08921353B2