Реакция #48451

Уравнение реакции

2-oxo-1-(4-piperidinyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine dihydrochloride

triethylamine

Triethylamine

(3R,6S)-3-amino-6-(2,3-difluorophenyl)-7-(hydroxymethyl)azepan-2-one

4-nitrophenyl chloroformate

→

title compound

Выход 15.7%

N-[(3R,6S)-6-(2,3-difluorophenyl)-7-(hydroxymethyl)-2-oxoazepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide

Выход 15.7%

Растворители

chloroform

tetrahydrofuran

Условия реакции

Обработка

1. 1
   Концентрированиеconcentrated
2. 2
   workup.ADDITIONdiluted with saturated aqueous sodium bicarbonate
3. 3
   Экстракцияextracted with dichloromethane (2×)
4. 4
   ПромывкаThe organic layer was washed with water, saturated brine
5. 5
   Сушкаdried over magnesium sulfate
6. 6
   Фильтрацияfiltered
7. 7
   Концентрированиеconcentrated
8. 8
   ДругоеPurification by silica gel chromatography (1%→12% methanol/dichloromethane)

Методика

Triethylamine (0.68 mL, 0.49 mmol) was added to a solution of (3R,6S)-3-amino-6-(2,3-difluorophenyl)-7-(hydroxymethyl)azepan-2-one (57 mg, 0.21 mmol) and 4-nitrophenyl chloroformate (47 mg, 0.23 mmol) in tetrahydrofuran (10 mL) at 0° C. After 30 min, 2-oxo-1-(4-piperidinyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine dihydrochloride (98 mg, 0.34 mmol), triethylamine (0.84 mmol) and chloroform (10 mL) were added and the mixture allowed to warm to ambient temperature. The reaction was stirred overnight, concentrated, diluted with saturated aqueous sodium bicarbonate and extracted with dichloromethane (2×). The organic layer was washed with water, saturated brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (1%→12% methanol/dichloromethane) gave the title compound (17 mg). MS 515.2203 (M+1).

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