Реакция #168377

Уравнение реакции

triethylamine

4-(5-chloropyridin-3-yl)-2-((2S,4R)-2-(hydroxymethyl)-4-methoxypyrrolidin-1-yl)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile

oxalyl chloride

DMSO

→

3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile

Растворители

dichloromethane

dichloromethane

dichloromethane

Условия реакции

Обработка

1. 1
   workup.STIRRINGThe reaction was stirred for 30 min at −40° C
2. 2
   Температураthe reaction was warmed to room temperature
3. 3
   workup.STIRRINGstirred overnight
4. 4
   ДругоеThe reaction mixture was quenched with saturated aqueous NaHCO3 (30 mL)
5. 5
   ДругоеThe dichloromethane layer was separated
6. 6
   ЭкстракцияThe aqueous layer was extracted with dichloromethane (20 mL)
7. 7
   ПромывкаThe combined dichloromethane layers were washed with brine (50 mL)
8. 8
   Сушкаdried over Na2SO4
9. 9
   Фильтрацияfiltered
10. 10
    Концентрированиеconcentrated in vacuo
11. 11
    ДругоеThe residue was purified by column chromatography on silica gel
12. 12
    Промывкаeluting with EtOAc/isohexane

Методика

A solution of oxalyl chloride (0.160 ml, 1.826 mmol) in dichloromethane (5 ml) was cooled to −78° C., and a solution of DMSO (0.259 ml, 3.65 mmol) in dichloromethane (2.5 ml) was slowly added. The reaction was warmed to −60° C. After 10 min of stirring, a solution of 4-(5-chloropyridin-3-yl)-2-((2S,4R)-2-(hydroxymethyl)-4-methoxypyrrolidin-1-yl)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile (452 mg, 0.913 mmol) in dichloromethane (5 ml) was slowly added. The reaction was stirred for 30 min at −40° C. Then triethylamine (0.764 ml, 5.48 mmol) was added, and the reaction was warmed to room temperature and stirred overnight. The reaction mixture was quenched with saturated aqueous NaHCO3 (30 mL). The dichloromethane layer was separated. The aqueous layer was extracted with dichloromethane (20 mL). The combined dichloromethane layers were washed with brine (50 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on silica gel, eluting with EtOAc/isohexane to give 4-(5-chloropyridin-3-yl)-2-(2S,4R)-2-formyl-4-methoxypyrrolidin-1-yl)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ESI calc'd. for C26H29ClN6O2 [M+H]+ 493. found 493.

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