反应详情

To a mixture of 1-{[(3-aminoquinolin-4-yl)amino]methyl}cyclobutanol (23.1 mmol, prepared as described in Part D) in dichloromethane (154 mL) and triethylamine (3.54 mL, 25.4 mmol) at 0° C. was added chloroform (100 mL). The mixture was allowed to warm to room temperature and approximately two thirds of the starting material dissolved. To the mixture was slowly added ethoxyacetyl chloride (88% purity, 3.1 g, 24.3 mmol). The solution was stirred at room temperature for 2 hours. More triethylamine (2 mL) and ethoxyacetyl chloride (88% purity, 1.0 g) were added. After an additional 16 hours, the reaction solution was concentrated under reduced pressure. To the residue was added ethanol (190 mL) and triethylamine (13 mL). The resulting solution was heated at reflux for 20 hours and then was concentrated under reduced pressure to yield a yellow solid. The solid was partitioned between dichloromethane (400 mL) and water (100 mL). The organic layer was washed with water (100 mL) and brine (100 mL), dried over MgSO4, filtered, and concentrated under reduced pressure. The crude product was crystallized from acetonitrile and the crystals were isolated by filtration to provide 4.52 g of 1-{[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}cyclobutanol.

1. dissolutionapproximately two thirds of the starting material dissolved
2. waitAfter an additional 16 hours
3. concentrationthe reaction solution was concentrated under reduced pressure
4. additionTo the residue was added ethanol (190 mL) and triethylamine (13 mL)
5. temperatureThe resulting solution was heated
6. temperatureat reflux for 20 hours
7. concentrationwas concentrated under reduced pressure
8. customto yield a yellow solid
9. customThe solid was partitioned between dichloromethane (400 mL) and water (100 mL)
10. washThe organic layer was washed with water (100 mL) and brine (100 mL)
11. dry with materialdried over MgSO4
12. filtrationfiltered
13. concentrationconcentrated under reduced pressure
14. customThe crude product was crystallized from acetonitrile
15. customthe crystals were isolated by filtration