Hydrochloric Acid → 1-(2-aminoethoxy)-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-4-amine

Participants

Reaction Steps

To a stirred solution of tert-butyl 2-{[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]oxy}ethylcarbamate (6.0 g) from several batches of Part C in dichloromethane (100 mL) was added m-chloroperbenzoic acid (7.0 g). After about 2 hours, concentrated ammonium hydroxide (35 mL) and water (10 mL) were added. The mixture was cooled in an ice bath and a solution of benzenesulfonyl chloride (3.5 mL) in dichloromethane (25 mL) was added dropwise. The mixture was stirred for 2 hours at room temperature; then dichloromethane (75 mL) and saturated aqueous sodium bicarbonate (35 mL) were added. The aqueous layer was separated and extracted with dichloromethane (2×25 mL). The organic layers were combined, dried over potassium carbonate, filtered, and evaporated to afford an oil. The oil was dissolved in ethanol (50 mL). Concentrated hydrochloric acid (4 mL) was added and the mixture was heated at reflux for 2 days. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in methanol (10 mL) and added to stirred toluene (125 mL) causing an oil to form. The oil was stirred in dichloromethane (75 mL) and 15% sodium hydroxide solution (75 mL) for 2 hours. The layers were separated and the aqueous layer was extracted with dichloromethane (25 mL). The organic layers were combined, dried over potassium carbonate, filtered, and concentrated under reduced pressure to afford 1.3 g of 1-(2-aminoethoxy)-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-4-amine.

Provenance & Evidence