Ammonium Hydroxide → 8-benzyloxy-2-(ethoxymethyl)-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine

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Reaction Steps

mCPBA (60% pure, 27.5 g, 95.9 mmol) was added in small portions over a period of 20 minutes to 8-benzyloxy-2-(ethoxymethyl)-1-propyl-1H-imidazo[4,5-c]quinoline (30.0 g, 79.9 mmol, prepared in Parts A through H of Example 2) in dichloromethane (400 mL). After the reaction was stirred for two hours, it was washed with 1% aqueous sodium carbonate (3×100 mL). The combined aqueous washings were extracted with chloroform (200 mL), and the combined organic fractions were dried over magnesium sulfate and filtered. Trichloroacetyl isocyanate (18.0 g, 95.9 mmol) was added dropwise to the filtrate, and then the reaction was stirred overnight at ambient temperature. Concentrated ammonium hydroxide (100 mL) was slowly added, and the mixture was stirred at ambient temperature for 30 minutes. The organic layer was separated and washed with 1% aqueous sodium carbonate (2×100 mL). The combined aqueous fractions were extracted with chloroform (3×75 mL). The organic fractions were combined, dried over magnesium sulfate, filtered, and concentrated under reduced pressure to yield a dark semi-solid. The crude product was purified on silica gel (1 kg, eluting sequentially with 2% methanol in chloroform and 5% methanol in chloroform) to provide 22 g of 8-benzyloxy-2-(ethoxymethyl)-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine as an off-white solid.

Provenance & Evidence