Reacción #72011

Ecuación de reacción

Ethyl acetate

cis(±)-4-chloro-N-(3-ethoxypiperidin-4-yl)-5-ethyl-1H-imidazole-2-carboxamide hydrochloride

(1-cyclopropyl-7-fluoro-8-methoxy-4-oxo-1,4-dihydroquinolin-3-yl)carbonyl difluoroborate

→

title compound

Rendimiento 62.0%

cis(±)-7-(4-{[(4-Chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl)-1-cyclopropyl-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

Rendimiento 62.0%

Disolventes

Triethylamine

triethylamine

water

Ethanol

DMSO

Condiciones de reacción

Tratamiento posterior

1. 1
   Lavadothe organic layer was washed with saturated aqueous sodium bicarbonate solution
2. 2
   Secadodried over anhydrous sodium sulfate
3. 3
   Concentraciónconcentration under reduced pressure
4. 4
   workup.STIRRINGthe mixture was stirred at 80° C. for six hours
5. 5
   TemperaturaThe reaction solution was cooled to room temperature
6. 6
   FiltraciónThe resulting solid was collected by filtration
7. 7
   Lavadowashed with ethanol

Procedimiento

Ethyl acetate was added to cis(±)-4-chloro-N-(3-ethoxypiperidin-4-yl)-5-ethyl-1H-imidazole-2-carboxamide hydrochloride obtained in Example (131a) (100 mg, 0.297 mmol), and the organic layer was washed with saturated aqueous sodium bicarbonate solution and dried over anhydrous sodium sulfate. Following concentration under reduced pressure, the residue and (1-cyclopropyl-7-fluoro-8-methoxy-4-oxo-1,4-dihydroquinolin-3-yl)carbonyl difluoroborate obtained in Example (146a) (82 mg, 0.30 mmol) were dissolved in DMSO (0.6 mL). Triethylamine (0.100 mL, 0.721 mmol) was added, and the mixture was stirred at 40° C. overnight. Ethanol (3 mL), water (0.3 mL) and triethylamine (0.3 mL) were added to the reaction solution, and the mixture was stirred at 80° C. for six hours. The reaction solution was cooled to room temperature. The resulting solid was collected by filtration and washed with ethanol to obtain 102.5 mg of the title compound as a pale yellow solid (62%).

Fuente