Reaktion #1518729

Reaktionsgleichung

4-chloro-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinoline

sodium hydride

5-bromo-6′-methoxy-2,3′-bipyridin-3-amine

sodium carbonate

→

N-(5-bromo-6′-methoxy-2,3′-bipyridin-3-yl)-5,7-difluoro-3-methyl-2-(pyridin-2-yl)-quinolin-4-amine

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONUpon complete addition
2. 2
   Temperaturthe mixture was warmed to 70° C
3. 3
   workup.WAITAfter 3 h
4. 4
   Temperaturthe reaction was cooled to rt
5. 5
   ExtraktionThe black mixture was subsequently extracted 5 times with DCM:MeOH (90:10)
6. 6
   ExtraktionThe organic extraction
7. 7
   Waschenwas then washed one time with brine
8. 8
   Trocknendried over anhydrous magnesium sulfate
9. 9
   FiltrationAfter filtration and concentration
10. 10
    Sonstigethe residue was purified on basic alumina (0-35% EtOAc in hexanes)

Vorschrift

A dry flask containing 5-bromo-6′-methoxy-2,3′-bipyridin-3-amine (226.0 mg, 0.81 mmol) in dry DMF (5 mL) was cooled to 0° C., then sodium hydride, 60% dispersion in mineral oil (100.7 mg, 2.52 mmol) was added carefully in portions. The mixture was stirred at 0° C. for 15 min, then 4-chloro-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinoline (353.1 mg, 1.21 mmol) was added in portions. Upon complete addition, the mixture was warmed to 70° C. After 3 h, the reaction was cooled to rt then was carefully treated with 10% sodium carbonate solution. The black mixture was subsequently extracted 5 times with DCM:MeOH (90:10). The organic extraction was then washed one time with brine and dried over anhydrous magnesium sulfate. After filtration and concentration, the residue was purified on basic alumina (0-35% EtOAc in hexanes) to afford a yellow residue as mostly N-(5-bromo-6′-methoxy-2,3′-bipyridin-3-yl)-5,7-difluoro-3-methyl-2-(pyridin-2-yl)-quinolin-4-amine that was used without further purification.

Quelle