Réaction #168423

Équation de réaction

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

Solvants

THF

Conditions de réaction

Traitement

1. 1
   AutreThe cooling bath was removed
2. 2
   Températurethe 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
   Lavagewashed with sodium thiosulfate (2×) and brine (1×)
6. 6
   SéchageThe organic layer was dried over magnesium sulfate
7. 7
   Filtrationfiltered
8. 8
   Concentrationconcentrated
9. 9
   AutreThe resulting residue was purified via silica gel chromatography (0-100% ethyl acetate/hexanes)

Mode opératoire

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.

Source