Reaction #42675

Reaction equation

Triethylamine

(3R,6S)-3-amino-6-(2,3-difluorophenyl)-1-(2,2,2-trifluoroethyl)azepane-2-thione

4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carbonyl chloride

water

→

title compound

Yield 55.8%

N-[(3R,6S)-6-(2,3-Difluorophenyl)-2-thioxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide

Yield 55.8%

Solvents

dichloromethane

Conditions

Workup

1. 1
   Temperaturethe mixture heated to reflux
2. 2
   Extractionthe mixture was extracted with dichloromethane (3×)
3. 3
   DryingThe combined organic extracts were dried over sodium sulfate
4. 4
   Filtrationfiltered
5. 5
   Concentrationconcentrated
6. 6
   OtherPurification by silica gel chromatography (100% dichloromethane→95% dichloromethane/methanol)

Procedure

Triethylamine (100 μL, 0.720 mmol) was added to a solution of the bis hydrochloride salt of (3R,6S)-3-amino-6-(2,3-difluorophenyl)-1-(2,2,2-trifluoroethyl)azepane-2-thione (90 mg, 0.240 mmol) and 4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carbonyl chloride (74 mg, 0.264 mmol) in dichloromethane (10 mL) and the mixture heated to reflux. After 18 h, the reaction was allowed to cool to ambient temperature, water was added and the mixture was extracted with dichloromethane (3×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. Purification by silica gel chromatography (100% dichloromethane→95% dichloromethane/methanol) gave the title compound (78 mg). MS 583.2 (M+1).

Source