Dimethyl Sulfoxide → Imiquimod

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

A mixture of 4-chloro-1-isobutyl-1H-imidazo[4,5-c]quinoline (II) (3 g, 0.0116 mol), urea (13.8 g, 0.232 mol, 20 equiv.) and DMSO (25 ml) was heated under stirring at 155-160° C. for 12 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 2.45 g of crude imiquimod in 88.5% yield, having a purity of 99.0% (by HPLC, containing 1.0% of the compound II). The crude imiquimod was purified by the method presented in Example 1 to obtain 2.15 g of imiquimod in 87.8% yield; total yield: 77.7%; having a purity of 99-93% (by HPLC).

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