NOVEL METHOD FOR PREPARING LOSARTAN METABOLITE EXP-3174 DIHYDRATE

摘要

The present invention relates to a method for preparing ultra-high purity potassium salts (refer to Chemical Formula 2) of EXP-3174 known as a main metabolite of losartan, and to a method for preparing ultra-high purity EXP-3174·2H2O of Chemical Formula 1 by using the method. The method according to the present invention comprises the following steps: (a) performing a deprotective reaction to the compound of Chemical Formula 4 to prepare the compound of Chemical Formula 3; (b) selectively oxidizing, by using an oxidizing agent, aldehydes of the compound prepared in step (a), and preparing crude EXP-3174·2H2O having a structure of Chemical Formula 1, which has a dehydrate form; (c) heating and refluxing the compound having a structure of Chemical Formula 1, prepared in step (b), in a mixture solvent of water and ethyl acetate, and cooling and filtering the compound; (d) forming KOH and salts from the filtered product obtained in step (c) in a mixture solvent of isopropyl alcohol (IPA) and polar protic solvent to prepare the compound of Chemical Formula 2; and (e) neutralizing the compound of Chemical Formula 2, prepared in step (d), in a mixture solvent of water and ethyl acetate under an acid condition, and performing the process of step (c). According to the present invention, ultra-high purity potassium salts of EXP-3174 and EXP-3174·2H2O, are prepared, in which the content of single impurity does not exceed 0.1%.