1-Hydroxybenzotriazole → HCID 21984036, compound

Participants

Reaction Conditions

Reaction Steps

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)-1H-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.

Provenance & Evidence