反应 #9542

反应方程式

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

收率 78.9%

溶剂

toluene

n-propanol

反应条件

后处理

1. 1
   温度The reaction was heated
2. 2
   温度at reflux under nitrogen for three hours
3. 3
   其他organic solvent was removed under reduced pressure
4. 4
   萃取The aqueous mixture was extracted with ethyl acetate (3×)
5. 5
   洗涤the combined organic fractions were washed sequentially with 2 M aqueous sodium carbonate and brine
6. 6
   干燥dried over sodium sulfate
7. 7
   过滤filtered
8. 8
   浓缩concentrated under reduced pressure
9. 9
   其他purified by flash column chromatography on silica gel (
10. 10
    洗涤eluting with chloroform

实验过程

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.

来源