Реакция #168407

Уравнение реакции

3-{4-(5-chloropyridin-3-yl)-2-[(2-fluorophenyl)carbonyl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-d]pyridin-6-yl}-1,2,4-oxadiazol-5(4H)-one

3-{4-(5-chloropyridin-3-yl)-2-[(2-fluorophenyl)carbonyl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridin-6-yl}-1,2,4-oxadiazol-5(4H)-one

methyl magnesium bromide

→

3-{4-(5-chloropyridin-3-yl)-2-[1-(2-fluorophenyl)-1-hydroxyethyl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-d]pyridin-6-yl}-1,2,4-oxadiazol-5(4H)-one

Растворители

tetrahydrofuran

Условия реакции

Обработка

1. 1
   ДругоеThe reaction was then quenched via the addition of saturated aqueous ammonium chloride
2. 2
   Экстракцияextracted with ethyl acetate (2×)
3. 3
   СушкаThe combined organics were dried over magnesium sulfate
4. 4
   Фильтрацияfiltered
5. 5
   Концентрированиеconcentrated under reduced pressure
6. 6
   ДругоеThe resulting residue was purified via silica gel chromatography (0-10% methanol/DCM)

Методика

To a solution of 3-{4-(5-chloropyridin-3-yl)-2-[(2-fluorophenyl)carbonyl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-d]pyridin-6-yl}-1,2,4-oxadiazol-5(4H)-one (Example 8.1, 44 mg, 0.08 mmol) in tetrahydrofuran (0.8 mL) at −78° C. was added dropwise methyl magnesium bromide (0.054 mL of 3.0 M in diethyl ether, 0.161 mmol). The reaction was stirred and slowly warmed to −20° C. over 3 hours. The reaction was then quenched via the addition of saturated aqueous ammonium chloride and extracted with ethyl acetate (2×). The combined organics were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified via silica gel chromatography (0-10% methanol/DCM) to afford 3-{4-(5-chloropyridin-3-yl)-2-[1-(2-fluorophenyl)-1-hydroxyethyl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-d]pyridin-6-yl}-1,2,4-oxadiazol-5(4H)-one as a white solid. MS ESI calcd. for C29H28ClFN6O3 [M+H]+ 563. found 563.

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