反応 #168283

反応方程式

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

反応条件

後処理

1. 1
   その他the mixture was degassed for three minutes with nitrogen (sparge)
2. 2
   workup.ADDITIONSulfuric acid (0.017 mL) was added
3. 3
   その他the mixture was degassed for three minutes with nitrogen (sparge)
4. 4
   その他The flask was sealed
5. 5
   温度The mixture was cooled to room temperature
6. 6
   workup.ADDITIONadded to a separate nitrogen purged flask
7. 7
   その他The flask was purged with nitrogen for five minutes
8. 8
   その他sealed
9. 9
   温度heated to 100° C. for 3.5 hours
10. 10
    温度The reaction mixture was cooled to room temperature
11. 11
    ろ過filtered
12. 12
    workup.ADDITIONdiluted with ethyl acetate
13. 13
    洗浄washed with water and brine
14. 14
    乾燥The organic layer was dried over sodium sulfate
15. 15
    ろ過filtered
16. 16
    濃縮concentrated under reduced pressure
17. 17
    その他The residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient)

実験手順

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.

出典