تفاعل #168283

معادلة التفاعل

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

ظروف التفاعل

المعالجة

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

الإجراء التجريبي

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.

المصدر