تفاعل #168423

معادلة التفاعل

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

المذيبات

THF

ظروف التفاعل

المعالجة

1. 1
   أخرىThe cooling bath was removed
2. 2
   درجة الحرارةthe 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
   غسيلwashed with sodium thiosulfate (2×) and brine (1×)
6. 6
   تجفيفThe organic layer was dried over magnesium sulfate
7. 7
   ترشيحfiltered
8. 8
   تركيزconcentrated
9. 9
   أخرىThe resulting residue was purified via silica gel chromatography (0-100% ethyl acetate/hexanes)

الإجراء التجريبي

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.

المصدر