Reaktion #9542

Reaktionsgleichung

water

sodium carbonate

7-bromo-2-ethoxymethyl-1-(2-piperazin-1-ylethyl)-1H-imidazo[4,5-c]quinolin-4-amine dihydrochloride

pyridine-3-boronic acid 1,3-propanediol cyclic ester

→

2-ethoxymethyl-1-(2-piperazin-1-ylethyl)-7-(pyridin-3-yl)-1H-imidazo[4,5-c]quinolin-4-amine

Ausbeute 78.9%

Lösungsmittel

toluene

n-propanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe reaction was heated
2. 2
   Temperaturat reflux under nitrogen for three hours
3. 3
   Sonstigeorganic solvent was removed under reduced pressure
4. 4
   ExtraktionThe aqueous mixture was extracted with ethyl acetate (3×)
5. 5
   Waschenthe combined organic fractions were washed sequentially with 2 M aqueous sodium carbonate and brine
6. 6
   Trocknendried over sodium sulfate
7. 7
   Filtrationfiltered
8. 8
   Einengenconcentrated under reduced pressure
9. 9
   Sonstigepurified by flash column chromatography on silica gel (
10. 10
    Wascheneluting with chloroform

Vorschrift

Under a nitrogen atmosphere, triphenylphosphine (0.0409 g, 0.156 mmol), 2 M aqueous sodium carbonate (18.3 mL, 36.5 mmol) and a solution of palladium (II) acetate (0.0117 g, 0.52 mmol) in warm toluene were added to a solution of 7-bromo-2-ethoxymethyl-1-(2-piperazin-1-ylethyl)-1H-imidazo[4,5-c]quinolin-4-amine dihydrochloride (5.28 g, 10.4 mmol) and pyridine-3-boronic acid 1,3-propanediol cyclic ester (1.87 g, 11.5 mmol) in n-propanol (8 mL). The reaction was heated at reflux under nitrogen for three hours then allowed to cool to ambient temperature. Deionized water was added, and organic solvent was removed under reduced pressure. The aqueous mixture was extracted with ethyl acetate (3×), and the combined organic fractions were washed sequentially with 2 M aqueous sodium carbonate and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was combined with material from another run and purified by flash column chromatography on silica gel (eluting with chloroform:methanol in a gradient from 90:10 to 50:50 and 50:50 chloroform:CMA) to provide 3.54 g of 2-ethoxymethyl-1-(2-piperazin-1-ylethyl)-7-(pyridin-3-yl)-1H-imidazo[4,5-c]quinolin-4-amine as a white solid, mp 208–211° C.

Quelle