反应详情

温度

80 °C

In an oven-dried, nitrogen cooled flask were placed palladium(II) acetate (286 mg, 1.27 mmol) and (R)-(+)-2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl (793 mg, 1.27 mmol). N,N-dimethylacetamide (76 mL) was added and degassed for three minutes with nitrogen (sparge). Sulfuric acid (0.068 mL, 1.27 mmol) was added and 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 racemic 6-chloro-4-(5-chloropyridin-3-yl)-3-[1-(trans-4-methylcyclohexyl)ethyl]-3H-imidazo[4,5-c]pyridine (4.96 g, 12.7 mmol), zinc cyanide (748 mg, 6.37 mmol), and zinc (83 mg, 1.27 mmol). The flask was purged with nitrogen for five minutes and sealed and heated to 80° C. for 16 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 racemic 4-(5-chloropyridin-3-yl)-3-[1-(trans-4-methylcyclohexyl)ethyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ESI calc'd. for C21H22ClN5 [M+H]+ 380. found 380.

1. customdegassed for three minutes with nitrogen (sparge)
2. customdegassed 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 80° C. for 16 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)