Dimethyl Sulfoxide → Imiquimod

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-chloro-1-isobutyl-1H-imidazo[4,5-c]quinoline (II) (3 g, 0.0116 mol), urea (6.9 g, 0.116 mol, 10 equiv.) and DMSO (20 ml) was heated under stirring at 140° C. for 35 hours. Then, the reaction mixture was cooled to 80° C. and water (30 ml) and 46% aqueous NaOH solution were added to produce a pH of 10-11. The mixture was stirred at ambient temperature for 1 hour and a precipitate was collected by filtration. The wet compound was treated with water (20 ml) at 70-80° C. under stirring for 1 hour. A solid was collected by filtration from the hot mixture, washed with water (3×20 ml) and methanol (20 ml) and dried at 80° C. under reduced pressure overnight to yield 2.4 g of crude Imiquimod in 87.6% yield, having 99.0% purity (by HPLC, containing 1.0% of compound II).

Provenance & Evidence