反应详情

温度

80 °C

In an oven-dried, nitrogen cooled flask were placed palladium(II) acetate (438 mg, 1.95 mmol) and (R)-(+)-2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl (1.22 g, 1.95 mmol). N,N-dimethylacetamide (98 mL) was added, and the flask was degassed for three minutes with nitrogen (sparge). Sulfuric acid (0.104 mL, 1.95 mmol) was added, and the flask was degassed for three minutes with nitrogen (sparge). The flask was sealed and heated to 80° C. for 30 minutes. The mixture was cooled to room temperature and added to a separate nitrogen purged flask containing 6-chloro-4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine (7.33 g, 19.5 mmol), zinc cyanide (1.15 g, 9.77 mmol), and zinc (128 mg, 1.95 mmol). The flask was purged with nitrogen for five minutes, then sealed and heated to 100° C. for 3.5 hours. The reaction mixture was cooled to room temperature, filtered, diluted with ethyl acetate, and washed with water and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient) to afford 4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ESI calc'd. for C20H20ClN5 [M+H]+ 366. found 366.

1. customthe flask was degassed for three minutes with nitrogen (sparge)
2. customthe flask was degassed for three minutes with nitrogen (sparge)
3. customThe flask was sealed
4. temperatureThe mixture was cooled to room temperature
5. additionadded to a separate nitrogen purged flask
6. customThe flask was purged with nitrogen for five minutes
7. customsealed
8. temperatureheated to 100° C. for 3.5 hours
9. temperatureThe reaction mixture was cooled to room temperature
10. filtrationfiltered
11. additiondiluted with ethyl acetate
12. washwashed with water and brine
13. dry with materialThe organic layer was dried over sodium sulfate
14. filtrationfiltered
15. concentrationconcentrated under reduced pressure
16. customThe residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient)