Reaction #9542

Reaction equation

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

Yield 78.9%

Solvents

toluene

n-propanol

Conditions

Workup

1. 1
   TemperatureThe reaction was heated
2. 2
   Temperatureat reflux under nitrogen for three hours
3. 3
   Otherorganic solvent was removed under reduced pressure
4. 4
   ExtractionThe aqueous mixture was extracted with ethyl acetate (3×)
5. 5
   Washthe combined organic fractions were washed sequentially with 2 M aqueous sodium carbonate and brine
6. 6
   Dryingdried over sodium sulfate
7. 7
   Filtrationfiltered
8. 8
   Concentrationconcentrated under reduced pressure
9. 9
   Otherpurified by flash column chromatography on silica gel (
10. 10
    Washeluting with chloroform

Procedure

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.

Source