Preparing method of triazole thioglycolic acid compound for curing metabolic arthritis

Abstract

The invention discloses a preparing method of a triazole thioglycolic acid compound for curing metabolic arthritis. According to the method, compound II and compound III are utilized as initial materials and are generated into intermediate compound IV through Suzuki reaction; then nucleophilic substitution happens between the intermediate compound IV and 1,1minute-thiocarbonyl polypyridobisinudazole to generate intermediate compound V; the compound V generates intermediate compound VI through cyclization reaction, and then nucleophilic substitution happens between the compound VI and methyl chloroacetate to generate intermediate compound VII; the intermediate compound VII generates intermediate compound VIII through bromination reaction; and a target product 2-((5-bromine-4-(4-cyclopropyl naphthalene-1-yl)-4H-1,2,4-triazole-3-yl)sulfenyl) acetic acid (I) is generated through hydrolysis reaction. The preparing method is high in selectivity and simple to operate and avoids poisonous reagents and rigorous reacting conditions. Compared with an original synthetic method, the reacting time of the preparing method is shortened, the energy consumption is reduced, and the reaction yield is improved.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and in particular relates to a preparation method of a triazole thioglycolic acid compound for treating gout. Background technique [0002] Lesinuard (Zurampic, RDEA594), the chemical name is 2-((5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl)thio ) Acetic acid, a selective uric acid reabsorption inhibitor developed by AstraZeneca, mainly treats gout by inhibiting renal tubular urate transporter 1 (URAT1) and increasing the excretion of uric acid. Lesinuard was approved by the U.S. Food and Drug Administration (FDA) on December 22, 2015, in combination with a xanthine oxidase inhibitor (XO) for the treatment of hyperuricemia associated with gout for tens of thousands of gout patients Drug therapy offers new options. [0003] At present, the synthesis methods of Lesinuard are mainly divided into the following types: [0004] One, take 1-bromonaphthalene as the synthetic route ...

AI Technical Summary

Problems solved by technology

Although there is no report in the literature on the synthesis of Lesinuard by 15, it is easy to prepare by alkylation reaction

The route is complicated, lengthy, and the yield is low

[0019] In the above-mentioned method for synthesizing Lesinuard, the synthetic route with 1-bromonaphthalene as raw material has the problems of high toxicity, expensive catalyst and harsh reaction conditions; with 4-cyclopropyl-1-naphthalene isothiocyanate as starting material The synthetic route of existing reaction yield is low and the problem that starting material is not easy to obtain; And the synthetic method that takes intermediate compound 6 as raw material or intermediate compound exists the problem of low reaction yield and long reaction time

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