Trichloroacetyl isocyanate → 2-ethoxymethyl-1-propyl-8-(pyridin-3-ylmethoxy)-1H-imidazo[4,5-c]quinolin-4-amine

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Reaction Steps

The crude 2-ethoxymethyl-5-oxido-1-propyl-8-(pyridin-3-ylmethoxy)-1H-imidazo[4,5-c]quinoline from Part A was dissolved in 50 mL of dichloromethane and trichloroacetyl isocyanate (540 mg, 2.85 mmol) was added dropwise. The reaction was monitored by thin layer chromatography and once the starting material was consumed, 2 mL of concentrated ammonium hydroxide was added. The reaction was stirred for 30 minutes and then passed through a column containing cation-exchange resin. The column was washed with methanol to remove impurities followed by elution of the desired product from the column with 2M ammonia in methanol. The volatiles were removed under reduced pressure. The resulting residue was dissolved in dichloromethane and purified by column chromatography on a HORIZON HPFC system. A silica gel cartridge was used eluting with a gradient of 0-8% methanol in dichloromethane. The solid was further purified by recrystallization from acetonitrile to give 2-ethoxymethyl-1-propyl-8-(pyridin-3-ylmethoxy)-1H-imidazo[4,5-c]quinolin-4-amine as light amber crystals, mp 190.0-191.0° C.

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