反应 #168283

反应方程式

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

反应条件

后处理

1. 1
   其他the mixture was degassed for three minutes with nitrogen (sparge)
2. 2
   workup.ADDITIONSulfuric acid (0.017 mL) was added
3. 3
   其他the mixture was degassed for three minutes with nitrogen (sparge)
4. 4
   其他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
   其他The flask was purged with nitrogen for five minutes
8. 8
   其他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
    过滤filtered
12. 12
    workup.ADDITIONdiluted with ethyl acetate
13. 13
    洗涤washed with water and brine
14. 14
    干燥The organic layer was dried over sodium sulfate
15. 15
    过滤filtered
16. 16
    浓缩concentrated under reduced pressure
17. 17
    其他The residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient)

实验过程

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.

来源