The invention relates to the technical field of synthesis of
raw material medicines, and particularly discloses a preparation method of
azelastine hydrochloride. The method comprises the following steps: condensing benzoyl hydrazine and 1-methylhexahydroazepine-4-one serving as raw materials, reducing with
sodium borohydride, and reacting to obtain a compound 1; preparing a
solid intermediate compound 2 from the compound 1 and organic binary weak acid; hydrolyzing the compound 2, and cyclizing with a compound 3 to form a compound 4; and salifying the compound 4 by
hydrochloric acid, and separating water by
toluene to obtain a compound 5, namely
azelastine hydrochloride. The intermediate compound 2 prepared by the invention is a
solid, the stability of the intermediate compound 2 is greatly improved compared with that of
hydrochloride obtained in other literatures, the intermediate compound 2 is free of hygroscopicity, the purity can reach 99% or above, the quality risk of subsequent bulk drugs can be greatly reduced, and the process production operation space is larger; and the obtained
azelastine hydrochloride does not contain water and meets related quality standards, the yield is increased to 80% or above compared with other literatures, and the purity can reach 99% or above.