반응 #48451

반응 방정식

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

수율 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

수율 15.7%

용매

chloroform

tetrahydrofuran

반응 조건

후처리

1. 1
   농축concentrated
2. 2
   workup.ADDITIONdiluted with saturated aqueous sodium bicarbonate
3. 3
   추출extracted with dichloromethane (2×)
4. 4
   세척The organic layer was washed with water, saturated brine
5. 5
   건조dried over magnesium sulfate
6. 6
   여과filtered
7. 7
   농축concentrated
8. 8
   기타Purification by silica gel chromatography (1%→12% methanol/dichloromethane)

실험 절차

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).

출처