反应详情

tert-Butyl {4-[(3-amino-7-bromoquinolin-4-ylamino)methyl]benzyl}carbamate (8.46 g, 18.5 mmol), triethylamine (2.25 mL) and dichloromethane (92 mL) were combined. Ethoxyacetyl chloride (2.92 g, 24 mmol) was added dropwise to the mixture. The reaction was stirred for an additional 1.5 hours and then concentrated under reduced pressure. Ethanol (92 mL) and triethylamine (10.31 mL) were added to the residue and the reaction was heated at reflux temperature for 1.5 hours. A precipitate formed. The reaction was cooled to room temperature and then concentrated under reduced pressure. The residue was dissolved in dichloromethane and washed sequentially with water and saturated aqueous sodium chloride. The organic fraction was dried over magnesium sulfate, filtered, and concentrated under reduced pressure. An initial purification by flash column chromatography eluting with a gradient of CMA in chloroform (2–10%) was followed by recrystallization from acetonitrile to provide 3.4 g of tert-butyl[4-(7-bromo-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-ylmethyl)benzyl]carbamate as yellow-orange crystals.

1. concentrationconcentrated under reduced pressure
2. additionEthanol (92 mL) and triethylamine (10.31 mL) were added to the residue
3. temperaturethe reaction was heated
4. temperatureat reflux temperature for 1.5 hours
5. customA precipitate formed
6. concentrationconcentrated under reduced pressure
7. dissolutionThe residue was dissolved in dichloromethane
8. washwashed sequentially with water and saturated aqueous sodium chloride
9. dry with materialThe organic fraction was dried over magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. customAn initial purification by flash column chromatography
13. washeluting with a gradient of CMA in chloroform (2–10%)
14. customwas followed by recrystallization from acetonitrile