Reacción #164286

Ecuación de reacción

(R)-1-[4-Chloro-3-(5-fluoro-1H-benzoimidazol-2-yl)-phenyl]-piperidine-3-carboxylic acid hydrochloride

HATU

2-morpholinoethylamine

→

title compound

Rendimiento 29.0%

{(R)-1-[4-Chloro-3-(5-fluoro-1H-benzoimidazol-2-yl)-phenyl]-piperidin-3-yl}-morpholin-4-yl-methanone

Rendimiento 29.0%

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONwere added
2. 2
   Lavadowashed with ammonium chloride solution (2 mL)
3. 3
   Filtraciónfiltered through a phase separator and organic solvent
4. 4
   Otrowas removed
5. 5
   OtroThe crude was then purified by SCX column and flash chromatography (eluent: gradient from cyclohexane:EtOAc/1:1 to 0:1 to EtOAc:NH3 in MeOH (2M)/10:1)
6. 6
   OtroA further purification by preparative HPLC

Procedimiento

Method L—Step a To a mixture of (R)-1-[4-Chloro-3-(5-fluoro-1H-benzoimidazol-2-yl)-phenyl]-piperidine-3-carboxylic acid hydrochloride (obtained as described in general method 3,4, step e) (0.01 g, 0.27 mmol) in dcm (2 mL), HATU (0.10 g, 0.28 mmol), TEA (0.08 mL, 0.56 mmol) and 2-morpholinoethylamine (0.04 g, 0.33 mmol) were added. The reaction mixture was stirred at room temperature overnight, washed with ammonium chloride solution (2 mL), filtered through a phase separator and organic solvent was removed. The crude was then purified by SCX column and flash chromatography (eluent: gradient from cyclohexane:EtOAc/1:1 to 0:1 to EtOAc:NH3 in MeOH (2M)/10:1). A further purification by preparative HPLC was done to obtain 0.03 g of the title compound (29%).

Fuente