Réaction #48451

Équation de réaction

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

Rendement 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

Rendement 15.7%

Solvants

chloroform

tetrahydrofuran

Conditions de réaction

Traitement

1. 1
   Concentrationconcentrated
2. 2
   workup.ADDITIONdiluted with saturated aqueous sodium bicarbonate
3. 3
   Extractionextracted with dichloromethane (2×)
4. 4
   LavageThe organic layer was washed with water, saturated brine
5. 5
   Séchagedried over magnesium sulfate
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated
8. 8
   AutrePurification by silica gel chromatography (1%→12% methanol/dichloromethane)

Mode opératoire

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).

Source