Dimethyl Sulfoxide → Imiquimod

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-chloro-1-isobutyl-1H-imidazo[4,5-c]quinoline (II) (4 g, 0.0154 mol), urea (18.5 g, 0.308 mol, 20 equiv.) and DMSO (26 ml) was heated under stirring at 145-150+C for 24 hours. Then, the reaction mixture was cooled to 80° C. and water (52 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 (25 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 3.13 g of crude imiquimod in 84.8% yield, having a purity of 99.4% by HPLC, (containing 0.6% of the compound II). The crude imiquimod was purified by the method presented in Example 1 to obtain 2.75 g of imiquimod in 87.8% yield; total yield: 74.4%; having a purity of 99.93% (by HPLC).

Provenance & Evidence