4-Toluenesulfonyl chloride → HCID 57447065, compound

Participants

Reaction Steps

4-[2-(Ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butanamide (4.3 g, 14 mmol) was treated with mCPBA (6.1 g, 27 mmol), concentrated ammonium hydroxide (50 mL of 29%), and p-toluenesulfonyl chloride (4.6 g, 24 mmol) according to a modification of the method described in Part E of Example 3. The mCPBA addition was carried out at 0° C., and the reaction was carried out in dichloromethane (150 mL). At the end of the reaction the layers were separated, and saturated aqueous sodium bicarbonate (100 mL) and 5% aqueous sodium hydroxide (10 mL) were added to the organic layer. The aqueous layer was extracted with dichloromethane (1.3 L), and the combined extracts were dried over potassium carbonate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (eluting with 90:10 dichloromethane:methanol containing 4 mL/L of ammonium hydroxide) followed by recrystallization five times from ethanol containing a small amount of water. The resulting solid was recrystallized from water:acetonitrile (5:L), dried overnight in a vacuum oven at 70° C., triturated with 25% aqueous ammonium hydroxide, diluted with water, isolated by filtration, recrystallized from ethanol:water, and dried overnight in a vacuum oven at 70° C. to provide 0.4704 g of 4-[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butanamide as tan crystals, mp 233-235° C.

Provenance & Evidence