Synthetic method of itraconazole key intermediate triazole compounds

Abstract

The invention relates to a synthetic method of triazole compounds of Itraconazole key intermediates, which comprises the steps that: a. cis-bromic ester is reacted with triazole in an organic solvent containing catalyst and alkali so as to obtain the triazole compound crude product, then recrystallization is carried out in the organic solvent so as to obtain the triazole compound refined product. The method for synthetizing the intermediate triazole compounds has the characteristics of simple and convenient operation, short production period, less power consumption, low cost, high safety and good quality, simultaneously, the obtained intermediate triazole compounds have the yield of more than 80 percent, and the isomer impurity content of less than 11 percent, and are more suitable for the large-scale industrial production of Itraconazole.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical chemical synthesis, and relates to a method for preparing a key intermediate of a drug, more specifically a key intermediate of itraconazole: cis-2-(2,4-dichlorophenyl)-2-(1H -1,2,4-triazole-1-methyl)-1,3-dioxolane-4-methanol (abbreviated as "triazoles") synthetic method. Background technique [0002] Itraconazole belongs to a chemically synthesized broad-spectrum antifungal drug, which is a triazole derivative. cocci, Pityrosporum sp., Candida sp. (including Candida albicans, Candida glabrata, and Candida glabrata)], Aspergillus sp., Histoplasma sp., Paracoccidioides brasiliensis, Sporothrix spp. Effective against Fungi, Cladosporium, Blastomyces dermatitidis, and various other yeast and fungal infections. In vitro studies have confirmed that this product can inhibit the synthesis of ergosterol, one of the main components of fungal cell membranes, thereby exerting antifungal effects. Co...

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Problems solved by technology

[0005] There are following deficiencies in the above-mentioned synthetic method: (1) process operation is complex and loaded down with trivial details, need to prepare sodium triazole through earlier, then with cis-bromo ester N-alkylation, finally synthesized through three steps such as sodium hydroxide alkali hydrolysis Triazoles, long production cycle

(2) Because sodium hydride, an extremely flammable and explosive compound, is used in the preparation of sodium triazole, the potential safety hazard is very large, and industrial production is very dangerous (3) the yield is low and only 50% to 60%, and the content of isomer impurities Higher, about 15%, the high content of isomer impurities will lead to high content of related substances in the finished itraconazole product, or even exceed the standard, which seriously affects the internal quality control of itraconazole products

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