반응 #168283

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N,N-dimethylacetamide

(R)-(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl

6-chloro-4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-[(3R)-3-phenylmorpholin-4-yl]-3H-imidazo[4,5-c]pyridine

→

4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-[(3R)-3-phenylmorpholin-4-yl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile

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후처리

1. 1
   기타the mixture was degassed for three minutes with nitrogen (sparge)
2. 2
   workup.ADDITIONSulfuric acid (0.017 mL) was added
3. 3
   기타the mixture was degassed for three minutes with nitrogen (sparge)
4. 4
   기타The flask was sealed
5. 5
   온도The mixture was cooled to room temperature
6. 6
   workup.ADDITIONadded to a separate nitrogen purged flask
7. 7
   기타The flask was purged with nitrogen for five minutes
8. 8
   기타sealed
9. 9
   온도heated to 100° C. for 3.5 hours
10. 10
    온도The reaction mixture was cooled to room temperature
11. 11
    여과filtered
12. 12
    workup.ADDITIONdiluted with ethyl acetate
13. 13
    세척washed with water and brine
14. 14
    건조The organic layer was dried over sodium sulfate
15. 15
    여과filtered
16. 16
    농축concentrated under reduced pressure
17. 17
    기타The residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient)

실험 절차

In an oven-dried, nitrogen cooled flask were combined palladium(II) acetate (70 mg, 0.312 mmol) and (R)-(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (195 mg, 0.313 mmol). N,N-dimethylacetamide (18.7 mL) was added, and the mixture was degassed for three minutes with nitrogen (sparge). Sulfuric acid (0.017 mL) was added, and the mixture 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]-2-[(3R)-3-phenylmorpholin-4-yl]-3H-imidazo[4,5-c]pyridine (1.68 g, 3.14 mmol), zinc cyanide (0.184 g, 1.57 mmol), and zinc (21 mg, 0.32 mmol). The flask was purged with nitrogen for five minutes and 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]-2-[(3R)-3-phenylmorpholin-4-yl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ESI calc'd. for C30H31ClN6O [M+H]+ 527. found 527.

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