A kind of refining method of acotiamide hydrochloride

Abstract

The invention discloses a refining method for hydrochloride acid acotiamide. The refining method comprises the following steps: (1) adding inorganic base into water, stirring for dissolving, adding an organic solvent and crude hydrochloride acid acotiamide, stirring for dissolving, standing for crystallizing, and drying under reduced pressure so as to obtain acotiamide; (2) adding the acotiamide into isopropanol, heating for completely dissolving, filtering, acidizing with concentrated hydrochloric acid until the pH is 1-2, stirring for crystallizing, and drying under reduced pressure so as to obtain the refined hydrochloride acid acotiamide. The refining method can be used for not only removing all the impurities with small polarity after main peak, but also eliminating other impurities in the product, thus remarkably improving the liquid phase purity and effective ingredient content of the product; the purity of refined product reaches over 99.8%, and any individual impurity is less than 0.1%.

Description

technical field [0001] The invention relates to a refining method, in particular to a refining method of acotiamide hydrochloride. It belongs to the field of medical technology. Background technique [0002] Acotiamide hydrochloride hydrate, chemical name: N-[2-(diisopropylamino)ethyl]-2-[(2-hydroxy-4,5-dimethoxybenzoyl)amino]- 4-Thiazole carboxamide hydrochloride trihydrate is a muscarinic M1 and M2 receptor blocker that promotes gastric motility developed by Zeli Company in Japan, and is mainly used for the treatment of functional dyspepsia and other gastrointestinal tracts Diseases such as gastric paralysis, gastroesophageal reflux, irritable bowel syndrome, and constipation. [0003] The main steps of preparing acotiamide hydrochloride hydrate are as follows at present: [0004] [0005] In the compound of formula I, R is methyl or ethyl, the compound of formula II is acotiamide hydrochloride, and the compound of formula III is the final product: acotiamide hydroch...

AI Technical Summary

Problems solved by technology

After the liquid phase detection of the obtained product, it is found that there are impurities with less polarity behind the main peak, which are difficult to remove. If you continue to refine with a mixed solvent of isopropanol and water, there will be no significant reduction. The reason may be that these impurities are less polar. However, isopropanol and water are relatively polar, and it is difficult to refine and remove less polar impurities from solvents with higher polarity.

[0009] There are a lot of literature reports about the refinement and purification of hydrochloride, such as: patent CN1528739 discloses a kind of purification method of levodopa methyl ester hydrochloride, adopts chloroform, carbon tetrachloride or dichloromethane and alcohol solvent, ethyl acetate The mixed solvent of ester, toluene or dimethylformamide is used for recrystallization, and the method of direct recrystallization of hydrochloride is also used, and the impurity with less polarity after the main peak cannot be removed.

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