- RESOLUTION METHOD FOR AXIS CHIRAL ENANTIOMERS OF LESINURAD
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A resolution method of axial chiral enantiomers of lesinurad (2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetic acid) adopts inexpensive and readily available quinoline natural products and derivatives thereof, such as quinine, cinchonine, quinidine or cinconidine as resolving agents to react with lesinurad racemate in an organic solvent to form a salt, and the salt is dissociated by acidification so as to obtain optically pure (R)- or (S)-2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetic acid. The method can give axial chiral enantiomer of lesinurad in R configuration with a chiral purity ee of up to 100% and a total yield of 90% or more. The obtained axial chiral enantiomer of lesinurad in S configuration can reach a chiral purity ee of up to 99.9% and a total yield of 80% or more.
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Paragraph 0074
(2021/02/26)
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- Synthesis of lesinurad via a multicomponent reaction with isocyanides and disulfides
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An efficient synthesis of Lesinurad a selective uric acid reabsorption (URAT1) inhibitor, is described in this article. The route to synthesis of Lesinurad avoids the use of thiophosgene and the formation of thiols. The key reaction in this synthesis is construction of the 1,2,4-Triazole ring in 72percent yield. The title product is obtained in 45percent yield over 5 steps.
- Li, Yaoqi,Sun, Zhihua
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supporting information
(2020/07/21)
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- Preparation method of Lesinurad
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The invention discloses a preparation method of Lesinurad, and belongs to the technical field of chemical drug synthesis. A compound of the formula Les-03 in the description is prepared from compoundsshown in formulas Les-01 and Les-02 as raw materials, a compound of the formula Les-04 is added, and a compound of the formula Les-05 is prepared. The compound of the Les-05 has high selectivity during coupling, so that the purity of a reaction product is high, post-treatment is facilitated, and quality of an obtained final product is controllable; the compound in Les-07 is prepared from the compound in Les-05 and the compound in Les-06 by Suzuki coupling reaction, the Suzuki coupling reaction has high reliability and good repeatability, and finally Lesinurad is obtained through protecting group removal. The preparation method has the advantages of short process route, high yield and low cost; adopted reagents are non-toxic or low-toxic conventional reagents, and are basically harmless tooperators and basically pollution-free to the environment; the whole process is simple and convenient to operate, the process stability is good, the quality of the obtained final product is controllable and stable, and the method is suitable for commercial production.
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- Resolving method of medicine lesinurad axial chiral enantiomer
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The invention discloses a resolving method of a medicine lesinurad axial chiral enantiomer. An alkamine derivative with optical activity is used as a resolving agent and reacts with a lesinurad racemic body in an organic solvent to form salts; the salts are dissociated to obtain (R)- or (S)-2-(5-bromo-4-(4-cyclopropylnaphthalene-1-yl-4H-1,2,4-triazole-3-sulfenyl)acetic acid with optical activity is obtained. By the method, an S configuration axial chiral enantiomer and an R configuration axial chiral enantiomer with the optical activity ee reaching 93 percent or higher can be obtained.
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Paragraph 0079; 0080; 0081; 0082; 0083
(2017/09/08)
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- A process for the preparation of intermediates to si Lei (by machine translation)
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The invention discloses a compound of formula (I) the method for the preparation of intermediates shows Si Lei. The method can directly introduce triazazole functional group, the reaction yield is up to 96.30%, sulfur generation and avoid the use of toxic reagent such as phosgene. Furthermore, the synthetic route of this invention does not need to ring closing reaction step, a total of six-step reaction of the final product can be obtained, it is simple and convenient to prepare, low cost, is suitable for industrial production. (by machine translation)
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- Method for preparing Lesinurad intermediate
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The invention belongs to the technical field of chemical synthesis, and particularly relates to a new method for preparing a lesinurad intermediate methyl 2-[[4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl]thio]acetate. The method comprises the following steps: (1) using 4-methyl-4H-3-thiol-1,2,4-triazole as the starting raw material to react with methyl bromoacetate or ethyl chloroacetate or phenyl bromoacetate under the action of the deacid reagent to generate methyl (4- methyl-4H-1,2,4-triazol-3-thio)acetate; subjecting the methyl (4- methyl-4H-1,2,4-triazol-3-thio)acetate to N-demethylase to generate methyl (4H-1,2,4-triazole-3-thio)acetate; (3) reacting the methyl (4H-1,2,4-triazole-3-thio)acetate with 1-bromo-4-cyclopropyl-naphthalene or 1-chloro-4-cyclopropyl-naphthalene to form the intermediate methyl 2-[[4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl]thio]acetate. The raw materials do not contain local toxic substances, and the production environment is relatively safe. The obtained product is high in yield and high in purity.
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Paragraph 0030
(2017/01/12)
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- Axially chiral enantiomers of drug Lesinurad
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The invention discloses an axially chiral R-enantiomer and an axially chiral S-enantiomer of the drug Lesinurad. The axially chiral R-enantiomer shows excellent URAT1 inhibition effect, overcomes the problems that a high dosage of Lesinurad racemate leads to renal toxicity and a low dosage Lesinurad racemate cannot produce additional drug effect, and can be applied to treatment or prevention of symptoms of abnormal tissue uric acid levels.
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Paragraph 0085; 0086; 0087; 0088
(2016/10/08)
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- Optically pure thioacetic compound
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The invention belongs to the field of pharmacy and relates to an optically pure thioacetic compound and application thereof to medicine. The optically pure thioacetic compound comprises levorotatory 2-(5-bromo-4-(4-cyclopropyl-naphthalene-1-base)-4H-1,2,4-triazole-3-based sulfenyl) acetic acid and dextral 2-(5-bromo-4-(4-cyclopropyl-naphthalene-1-base)-4H-1,2,4-triazole-3-based sulfenyl) acetic acid.
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- THIO-1,2,4-TRIAZOLE DERIVATIVES AND METHOD FOR PREPARING THE SAME
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Provided is a process for preparing a compound shown as formula (I), comprising a step of contacting a compound shown as formula (II) or a salt thereof with a brominating agent, wherein R1is OR2 or NR3R4; R2 is C1-C6 alkyl or phenyl; each R3, R4 is independently H, C1-C6 alkyl or cycloalkyl, wherein C1-C6 alkyl, cycloalkyl, or phenyl is optionally further substituted by F, Cl, Br, CH3 or CF3. A process for preparing a compound shown as formula (II), a process for preparing a compound shown as formula (V), a process for preparing a compound shown as formula (III), and an intermediate compound as shown as formula (IIa) or formula (Ib) are also provided.
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Paragraph 072-073
(2015/01/09)
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- MANUFACTURE OF 2- (5- BROMO-4 (-CYCLOPROPYLNAPHTHALEN-1-YL) -4H-1,2,4-TRIAZOL-3-YLTHIO) ACETIC ACID
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Described herein are certain processes for the synthesis of compounds of Formula (I):
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Paragraph 0254-0262
(2014/01/18)
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