反应详情

温度

0 °C

A mixture of 4-[(2-dimethylaminoethoxy)phenylmethyl]benzoic acid (0.433 g) and 1-hydroxybenzotriazole (0.196 g) in chloroform (7 mL) was cooled to 0° C. and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.277 g) was added in small portions over a 2 minute period. The mixture was stirred for 1 hour and then added dropwise to a chilled (0° C.) solution of 1-(4-aminobutyl)-2-ethoxymethyl-7-(pyridin-3-yl)-1 H-imidazo[4,5-c]quinolin-4-amine (0.400 g) in anhydrous dimethylacetamide (7 mL). The cooling bath was removed and the reaction was stirred for an additional 16 hours. Water was added and the mixture was made acidic by the addition of 4N hydrochloric acid. The aqueous fraction was extracted with diethyl ether (3×) to remove the dimethylacetamide. Sodium hydroxide (10% in water) was added to make the aqueous fraction basic and the aqueous fraction was subsequently extracted with multiple portions of dichloromethane. The organic fractions were combined, washed sequentially with water and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography using a gradient of CMA/chloroform as the eluent. A final recrystallization from acetonitrile provided 0.426 g of N-[4-(4-amino-2-ethoxymethyl-7-(pyridin-3-yl)imidazo[4,5-c]quinolin-1-yl)butyl]-4-[(2-dimethylaminoethoxy)phenylmethyl]benzamide as a white crystalline solid, mp 157.0–161.0° C.

1. additionadded dropwise to
2. customThe cooling bath was removed
3. stirringthe reaction was stirred for an additional 16 hours
4. additionWater was added
5. additionthe mixture was made acidic by the addition of 4N hydrochloric acid
6. extractionThe aqueous fraction was extracted with diethyl ether (3×)
7. customto remove the dimethylacetamide
8. additionSodium hydroxide (10% in water) was added
9. extractionthe aqueous fraction was subsequently extracted with multiple portions of dichloromethane
10. washwashed sequentially with water and brine
11. dry with materialdried over sodium sulfate
12. filtrationfiltered
13. concentrationconcentrated under reduced pressure
14. customThe residue was purified by flash column chromatography
15. customA final recrystallization from acetonitrile