Ammonia → 2-ethyl-1-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-1H-imidazo[4,5-c]quinolin-4-amine

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Reaction Conditions

Reaction Steps

4-Chloro-2-ethyl-1-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-1H-imidazo[4,5-c]quinoline (2.624 g, 6.451 mmol), 7 N ammonia in methanol (40 mL), and tetrakis(triphenylphosphine)palladium(0) were combined in a pressure vessel and heated at 120° C. for 16 hours. An analysis by HPLC indicated that the reaction was incomplete. The volatiles were removed under reduced pressure, and the residue was dissolved in chloroform. The solution was washed sequentially with aqueous potassium carbonate, water, and brine; dried over magnesium sulfate; filtered; and concentrated under reduced pressure. The resulting dark yellow solid was added to a pressure vessel with 7 N ammonia in methanol (60 mL), and the reaction was sealed and heated at 150° C. for 18 hours. The volatiles were removed under reduced pressure, and the residue was stirred with 0.5 N potassium hydroxide in methanol for 30 minutes. The resulting solid was isolated by filtration, diluted with dichloromethane, purified by column chromatography on silica gel (eluting with 5% to 10% CMA in chloroform), triturated with diethyl ether and filtered, and recrystallized from acetonitrile after a hot filtration. The crystals were isolated by filtration, washed with diethyl ether, and dried to provide 0.139 g of 2-ethyl-1-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-1H-imidazo[4,5-c]quinolin-4-amine as a white powder, mp 232.0-233.0° C.

Provenance & Evidence