반응 #302961

반응 방정식

(1R,2R)—N,N′-dimethylcyclohexane-1,2-diamine

(2R)-1-[3-(4-bromo-2-fluorophenoxy)propyl]-2-methylpyrrolidine

morpholin-4-yl(1H-pyrazol-4-yl)methanone

cesium carbonate

→

titled compound

수율 36.0%

[1-(3-fluoro-4-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxy}phenyl)-1H-pyrazol-4-yl](morpholin-4-yl)methanone

수율 36.0%

용매

N,N-dimethylformamide

반응 조건

후처리

1. 1
   workup.ADDITIONwere added
2. 2
   온도The reaction mixture was cooled to room temperature
3. 3
   여과filtered
4. 4
   기타to remove insoluble materials
5. 5
   농축the filtrate was concentrated under reduced pressure
6. 6
   기타The resulting residue was purified by silica gel column chromatography (eluting solvent: chloroform:methanol=11:1 to 3:1) and NH-type silica gel column chromatography (eluting solvent: chloroform:methanol=10:0 to 100:1)

실험 절차

To a solution of (2R)-1-[3-(4-bromo-2-fluorophenoxy)propyl]-2-methylpyrrolidine obtained in Example 62-(2) (0.72 g) and morpholin-4-yl(1H-pyrazol-4-yl)methanone (0.45 g) in N,N-dimethylformamide (3 mL), cesium carbonate (1.6 g), copper iodide (0.1 g) and (1R,2R)—N,N′-dimethylcyclohexane-1,2-diamine (0.36 mL) were added and the mixture was heated to 130° C., at which it was stirred for 6 hours. The reaction mixture was cooled to room temperature and filtered to remove insoluble materials, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluting solvent: chloroform:methanol=11:1 to 3:1) and NH-type silica gel column chromatography (eluting solvent: chloroform:methanol=10:0 to 100:1) to give the titled compound (0.34 g, 36%) as a colorless solid.

출처