Preparation method of imiquimod

The invention relates to a preparation method of an antiviral drug imiquimod, wherein the preparation method comprises the steps: (1) with 4-hydroxyquinoline as a starting material, nitrifying to obtain 3-nitro-4-hydroxyquinoline; (2) carrying out chlorination and amination on 3-nitro-4-hydroxyquinoline to obtain 3-nitro-4-isobutyl amine quinoline; (3) carrying out hydrogenation on 3-nitro-4-isobutyl amine quinoline to obtain 3-amino-4-isobutyl amine quinoline, and separating in a formate mode; (4) carrying out cyclization, oxidation and ammoniation on 3-amino-4-isobutyl amine quinoline, carrying out a reaction in a same reactor, and thus obtaining an imiquimod crude product; and (5) preparing a hydrochloride of imiquimod from the imiquimod crude product, purifying, and carrying out alkaline hydrolysis to obtain the high-purity imiquimod. In the method, the imiquimod is prepared from 4-hydroxyquinoline as the starting material, and the total yield can reach 55%; the method has the advantages of high yield, less reaction steps, less discharge of three wastes, mild and more complete reaction conditions, and simple and convenient operation, is suitable for industrialized production, and has relatively high practical value. The obtained product is more stable in quality, and the purity can reach more than 99.7%.