Реакция #168373

Уравнение реакции

potassium fluoride

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

(4aS,7aS)-octahydro-2H-cyclopenta[b]pyrazin-2-one

DIEA

→

4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-[(4aS,7aS)-3-oxooctahydro-1H-cyclopenta[b]pyrazin-1-yl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile

Растворители

DMSO

ethyl acetate

Условия реакции

Обработка

1. 1
   ДругоеThe vial was capped
2. 2
   ТемператураThe mixture was then cooled to room temperature
3. 3
   Промывкаwashed with water and brine
4. 4
   СушкаThe organic layer was dried over magnesium sulfate
5. 5
   Фильтрацияfiltered
6. 6
   Концентрированиеconcentrated
7. 7
   ДругоеPurification by silica gel chromatography (0-20% MeOH in DCM)

Методика

A vial was charged with potassium fluoride (163 mg, 2.81 mmol), 2-bromo-4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile (Preparative Example 3.1, 250 mg, 0.562 mmol), (4aS,7aS)-octahydro-2H-cyclopenta[b]pyrazin-2-one (189 mg, 1.349 mmol), DMSO (1730 μl) and DIEA (491 μl, 2.81 mmol). The vial was capped and heated to 100° C. overnight. The mixture was then cooled to room temperature, diluted with ethyl acetate and washed with water and brine. The organic layer was dried over magnesium sulfate, filtered, and concentrated. Purification by silica gel chromatography (0-20% MeOH in DCM) afforded 4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-[(4aS,7aS)-3-oxooctahydro-1H-cyclopenta[b]pyrazin-1-yl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ESI calc'd. for C27H30ClN7O [M+H]+ 504. found 504.

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