Refining preparation process of high-purity aprepitant

Abstract

The invention discloses a refining preparation process of high-purity aprepitant. The refining preparation process comprises the following steps: (1) reacting by virtue of intermediates a and b as theraw materials in a solvent A for 1-1.5 hours, so as to obtain an aprepitant crude product; and (2) adding the aprepitant crude product into a solvent B, heating for dissolving, and refining the mixture, so as to obtain an aprepitant pure product. According to the refining preparation process, methyl isobutyl ketone is used as a purifying solvent for purification, so that a relatively good technical effect is achieved, and the contents of main impurity raw material intermediates a and b and process impurities in the aprepitant crude product can be remarkably decreased; and an HPLC detection result shows that the purity of aprepitant reaches above 99.8%, and the impurity limits are all less than 0.1%.

Description

technical field [0001] The invention belongs to the technical field of organic chemistry and relates to a process for refining and preparing high-purity aprepitant. Background technique [0002] Aprepitant is a selective high-affinity antagonist of the human substance P neurokinin 1 (NK1) receptor. Low affinity for serotonin receptor 3 (5-HT3), dopamine receptor, and glucocorticoid receptor targets of other existing drugs for chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea and vomiting (PONV) or no affinity. Aprepitant inhibits cisplatin-induced emesis in the acute and delayed phases, and enhances the antiemetic activity of the 5-HT3 receptor antagonist ondansetron and the glucocorticoid dexamethasone on cisplatin-induced emesis. The structural formula of aprepitant is as follows: [0003] [0004] The synthesis method of the main API is [0005] [0006] The impurity removal method reported in the literature includes recrystallization of e...

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Problems solved by technology

[0006] The impurity removal method reported in the literature includes recrystallization of ethyl acetate, methanol / ethyl acetate, and acetone to remove impurities. By repeating the above purification process, it is found that the residual amount of intermediate a reaches 0.9%, and the residual amount of intermediate b reaches 1%. The effect of multiple purifications is still not obvious, and the API impurity residue below 0.1% cannot be satisfied

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