Abstract:

Imiquimod was synthesized from raw material 2 ,4-dihydroxyquinoline via 7 reaction steps including nitration, chlorination , amination , reduction of nitro group , cyclization , henzylamination and dehenzylation. The average yield of 2 ，4-dihydroxy-3-nintroquinoline (Ⅱ reached 99% by reusing the mother liquid of nitration for 7 times. 4-(2-methylpropylamino) -2-chloro-3-nitroquinoline (Ⅳ) was reduced to 4-( 2-methylpropylamino) -3-amino-
2-chloroquinoline ( V) hy iron powder and hydrochloric acid in 95%ethanol ， anhydrous K₂ CO₃ with proper quantity was added to the reaction mixture to make the hyproduct ferric oxide easy to filtrate off from the solution of V , the yield of V was 76%. With the improved synthesis procedure , the intermediates ohtained from the nitration , the amination , the reduction of nitro group , the cyclization and the henzylamination were pure enough to he directly used in the next reaction without further purification , thus simplifying the synthesis procedure with an overall imiquimod yield of more than 45%.

Key words: 2, 4-dihydroxyquinoline, imiquimod, immune response modifier, synthesis