A solution of ethyl 2,2-dimethyl-3-(2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)propanoate (5.1 g, 15 mmol) and morpholine (5 mL, 60 mmol) was heated at reflux overnight. An analysis by LC/MS indicated the reaction was incomplete. The solution was then heated overnight in a high-pressure vessel at 165° C. Again, an analysis by LC/MS indicated the reaction was incomplete. The volatiles were removed under reduced pressure, and the residue was dissolved in ethanol (30 mL). Aqueous sodium hydroxide (1.35 mL of 50%, 20.0 mmol) was added, and the reaction was stirred for 1.5 hours. The solution was adjusted to pH 7 with the addition of concentrated hydrochloric acid (˜1 mL) and then concentrated under reduced pressure. The residue was dissolved in dichloromethane (75 mL); a solution of oxalyl chloride (2.5 mL, 28 mmol) in dichloromethane (5 mL) was added dropwise over a period of two minutes. The reaction was stirred for 30 minutes, and additional oxalyl chloride (0.5 mL, 6 mmol) was added. The reaction was stirred for 30 minutes and diluted with dichloromethane (75 mL). A solution of morpholine (4.0 mL, 41 mmol) in dichloromethane (10 mL) was then added dropwise, and the reaction was stirred for two hours. The reaction was diluted with dichloromethane (45 mL), washed with saturated aqueous sodium bicarbonate (3×50 mL), dried over potassium carbonate, filtered, and concentrated under reduced pressure. The resulting dark oil was purified by column chromatography on silica gel (eluting with 93:7 dichloromethane:methanol) to provide 5.8 g of 1-(2,2-dimethyl-3-morpholin-4-yl-3-oxopropyl)-2-propyl-1H-imidazo[4,5-c]quinoline as a semi-solid.
