반응 #168423

반응 방정식

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

Lithium magnesium 2,2,6,6-tetramethylpiperidin-1-ide dichloride

1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione

→

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

용매

THF

반응 조건

후처리

1. 1
   기타The cooling bath was removed
2. 2
   온도the solution warmed to room temperature
3. 3
   workup.STIRRINGstirred for 60 minutes
4. 4
   workup.ADDITIONThe mixture was then diluted with ethyl acetate
5. 5
   세척washed with sodium thiosulfate (2×) and brine (1×)
6. 6
   건조The organic layer was dried over magnesium sulfate
7. 7
   여과filtered
8. 8
   농축concentrated
9. 9
   기타The resulting residue was purified via silica gel chromatography (0-100% ethyl acetate/hexanes)

실험 절차

4-(5-Chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-[(3R)-3-phenylmorpholin-4-yl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile (Example 2.1, Step 4; 180 mg, 0.342 mmol) was taken up in THF (3415 μl) and cooled to −78° C. Lithium magnesium 2,2,6,6-tetramethylpiperidin-1-ide dichloride (1M solution in THF/toluene, 683 μl, 0.683 mmol) was added, and the mixture was stirred at −78° C. for 45 minutes. 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione (244 mg, 0.854 mmol) was then added. The cooling bath was removed, and the solution warmed to room temperature and stirred for 60 minutes. The mixture was then diluted with ethyl acetate and washed with sodium thiosulfate (2×) and brine (1×). The organic layer was dried over magnesium sulfate, filtered, and concentrated. The resulting residue was purified via silica gel chromatography (0-100% ethyl acetate/hexanes) to afford 7-bromo-4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-[(3R)-3-phenylmorpholin-4-yl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile as a white solid that was contaminated with unreacted starting material. MS ESI calc'd. for C30H30BrClN6O [M+1]+, [M+3]+605, 607. found 605, 607.

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