Refining method of hydroxychloroquine crude product

Abstract

The present invention provides a refining method of a hydroxychloroquine crude product. The refining method comprises two refining processes. In the first refining process, by controlling the use amount of a derivatization reagent and the derivatization reaction temperature, an impurity III is converted into a new impurity easy to remove, the new impurity is removed through a recrystallization mode, the active ingredient hydroxychloroquine hardly participates in the derivatization reaction, the primary refining of the crude hydroxychloroquine product is realized, almost no impurity III exists in the primary refined product, the loss of hydroxychloroquine is low, the yield reaches 90% or above, and the purity reaches 99.5% or above. In the second refining process, a simple recrystallization mode is adopted, the yield of the hydroxychloroquine is high, the yield reaches about 95%, and the purity reaches 99.9%.

Description

technical field [0001] The invention belongs to the technical field of chemical synthesis, in particular to a method for refining crude hydroxychloroquine. Background technique [0002] Hydroxychloroquine Sulfate (Hydroxychloroquine Sulfate, HCQ), chemical name: 2-[[4-[(7-chloro-4-quinolyl)amino]pentyl]ethylamino]-ethanol sulfate. Successfully developed by Winthrop Company, it was first listed in the United States in 1956, and was approved by FDA on May 29, 1998. It is used for the treatment of lupus erythematosus and rheumatoid arthritis. Its chemical structure is as follows: [0003] [0004] Systemic Lupus Erythematosus (SLE) is a multi-system disease involving multiple antibodies in the body. The etiology is unclear and treatment is difficult. The use of antimalarial drugs to treat SLE began in 1950. Dobois found that after 75%-80% of SLE patients were treated with antimalarial drugs, rash, fever, and joint symptoms improved, especially skin lesions. Subsequent stud...

AI Technical Summary

Problems solved by technology

[0008] At present, in the refining process of hydroxychloroquine, impurity III is recrystallized using solvent ethyl acetate, dichloromethane and mixed solvents, which has no obvious effect and is difficult to remove, thus affecting the yield and purity of hydroxychloroquine sulfate

The patent CA2561987A1 discloses a refining method for hydroxychloroquine. During the refining process, an excessive amount of derivatization reagent is used to cause a derivatization reaction of both hydroxychloroquine and impurity III. Lithium oxide is hydrolyzed and finally recrystallized to obtain high-purity hydroxychloroquine. Not only is the operation cumbersome and the yield is low, but also more waste liquid is produced, which is not suitable for industrialized large-scale production

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