反应详情

A modification of the methods described in Part C of Example 60 was used to treat methyl 3-(4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)-2,2-dimethylpropanoate (7.6 g, 21 mmol) with potassium hydroxide (44 mL of 0.5 M); additional potassium hydroxide (22 mL) was added after refluxing for four hours. After the reaction was heated at reflux for five days, additional potassium hydroxide (11 mL) was added, and the reaction was heated for four more hours. After the reaction with oxalyl chloride (3.7 mL, 42 mmol) was stirred overnight, additional oxalyl chloride (1.0 mL) was added, and then the reaction was stirred for two hours. After the addition of ammonia in methanol (35 mL), the reaction was stirred for one hour and then concentrated. The residue was stirred with saturated aqueous sodium bicarbonate for 30 minutes, isolated by filtration, and recrystallized three times from methanol/water. During the first recrystallization, a solution in methanol was filtered through a 20 micron filter prior to the addition of water. The resulting crystals were dried overnight in a vacuum oven at 70° C. to provide 1.60 g of 3-(4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)-2,2-dimethylpropanamide as light tan crystals, mp 231-233° C.

1. temperatureafter refluxing for four hours
2. temperatureAfter the reaction was heated
3. temperatureat reflux for five days
4. temperaturethe reaction was heated for four more hours
5. stirringthe reaction was stirred for two hours
6. stirringthe reaction was stirred for one hour
7. concentrationconcentrated
8. stirringThe residue was stirred with saturated aqueous sodium bicarbonate for 30 minutes
9. customisolated by filtration
10. customrecrystallized three times from methanol/water
11. customDuring the first recrystallization
12. filtrationa solution in methanol was filtered through a 20 micron
13. filtrationfilter
14. additionto the addition of water
15. customThe resulting crystals were dried overnight in a vacuum oven at 70° C.