- Preparation method of medicine for treating fascioliasis
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The invention provides a preparation method of Triclabendazole, and relates to a preparation method of Triclabendazole. Compared with the existing synthetic route with many and complex reaction steps,the preparation method provided by the invention has the advantages that the reaction steps are few, the separation is simple and convenient, and the total yield and operability of the reaction are improved.
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Paragraph 0054-0064
(2020/05/09)
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- Synthesis method of triclabendazole
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The invention discloses a synthesis method of triclabendazole, comprising the following steps: reducing 4-chloro-5-(2,3-dichlorophenoxy)-2-nitroaniline as a raw material in an organic solvent by trichlorosilane, thus obtaining an intermediate compound; directly making ring closing reaction with carbon disulfide in the presence of potassium hydroxide, thus preparing an intermediate; enabling the intermediate and dimethyl carbonate to make methylation reaction under DBU catalysis, thus finally preparing triclabendazole. Through the process, a nitro reduction method is improved, the requirementsfor equipment are reduced, and post-treatment steps are simplified; by combining the nitro reduction and the cyclization into a one-step reaction, the operation procedure is simplified and the yield is increased; by changing a feeding sequence in the process of cyclization, the release rate of hydrogen sulfide is controlled, and the influence on environment is reduced. Replacing dimethyl sulfate or methyl iodide with dimethyl carbonate for methylation is more environmentally friendly; the obtained triclabendazole meets the European Pharmacopeas Standards in terms of all indicators, the total yield can reach 55-60%, indicating an obviously improved process and a promising prospect in industrial application.
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Paragraph 0025-0031
(2019/01/13)
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- Method for preparing triclabendazole serving as medicine for animal distomiasis
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The invention relates to a method for preparing triclabendazole serving as a medicine for animal distomiasis. 2,3-dichlorophenol and 3,4-dichloro-5-nitroaniline are used as raw materials and subjected to etherification, reduction reaction, cyclization and methylation to obtain triclabendazole. In the step of etherification, high-alkalinity potassium ethoxide or potassium methoxide is adopted for replacement of potassium hydroxide in the prior art while microwave irradiation heating is performed, and consequently step-by-step preparation of potassium phenoxide is avoided, phase transfer catalysts are not required, 'one-step' etherification is realized, etherification yield is up to 96% or above, product purity reaches 98% or above, and demands of industrial application are met.
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- PROCESS FOR PREPARATION OF TRICLABENDAZOLE
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The present invention discloses a method for preparing Triclabendazole comprising condensing N-(4,5-dichloro-2-ni-trophenyl)acetamide with 2,3-dichlorophenol to obtain 4-chloro-5(2,3-dichlorophenoxy)-2-nitrophenyl acetamide and it to obtain 4-chloro-5(2,3-dichlorophenoxy)-2-nitroaniline; reducing 4-chloro-5(2,3-dichlorophenoxy)-2-nitroaniline in presence of Raney nickel to obtain 4-chloro-5-(2,3-dichlorophenoxy)benzene-1,2-diamine of; cyclising 4-chloro-5-(2,3-dichlorophenoxy)benzene-1,2-diamine in presence of carbondisulfide to obtain 6-chloro-5-(2,3-dichlorophenoxy)-1H-benzimidazole-2-thiol; methylating 6-chloro-5-(2,3-dichlorophenoxy)-1H-benzimidazole-2-thiol using a methylating agent to obtain triclabendazole methanesulfonate salt; converting triclabendazole methanesulfonate salt to hydrochloride salt of Triclabendazole and hydrolysing it to obtain Triclabendazole.
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- PROCESS FOR PREPARATION OF TRICLABENDAZOLE
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The present invention discloses a method for preparing Triclabendazole comprising condensing N-(4,5-dichloro-2-nitrophenyl)acetamide with 2,3-dichlorophenol to obtain 4-chloro-5(2,3-dichlorophenoxy)-2-nitrophenyl acetamide and it to obtain 4- chloro-5(2,3-dichlorophenoxy)-2-nitroaniline; reducing 4-chloro-5(2,3- dichlorophenoxy)-2-nitroaniline in presence of Raney nickel to obtain 4-chloro-5- (2,3-dichlorophenoxy)benzene-l,2-diamine of; cyclising 4-chloro-5-(2,3- dichlorophenoxy)benzene-l,2-diamine in presence of carbondisulfide to obtain 6- chloro-5-(2,3-dichlorophenoxy)-lH-benzimidazole-2-thiol; methylating 6-chloro-5- (2,3-dichlorophenoxy)-lH-benzimidazole-2 -thiol using a methylating agent to obtain triclabendazole methanesulfonate salt; converting triclabendazole methanesulfonate salt to hydrochloride salt of Triclabendazole and hydrolysing it to obtain Triclabendazole.
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- 2H-Benzimidazoles (Isobenzimidazoles). Part 7. A New Route to Triclabendazole and Congeneric Benzimidazoles
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A new synthesis of the selective anthelmintic agent triclabendazole 7 from the readily available 5,6-dichloro-2H-benzimidazole-2-spirocyclohexane 2 by simple steps is described.Analogous benzimidazoles difficult to prepare by conventional methods are similarly obtained.Triclabendazole can exist as a low-melting metastable solid (m.p. 85-90 deg C) convertible by heating or recrystallisation from ethanol into its stable form (m.p. 176-178 deg C).
- Iddon, Brian,Kutschy, Peter,Robinson, Andrew G.,Suschitzky, Hans,Kramer, Walter,Neugebauer, Franz A.
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p. 3129 - 3134
(2007/10/02)
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- SYNTHESIS AND REACTIONS OF 2H-BENZIMIDAZOLE-2-SPIROCYCLOHEXANES : AN APPLICATION OF "UMPOLING"
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The title compounds are available through condensation of an o-phenylenediamine with cyclohexanone followed by oxidation of the resulting product with manganese dioxide.In this article we review their oxidation, reduction, and rearrangement reactions along with their reactions with nitrogen, oxygen, sulphur, and other nucleophiles.As well as the parent compound the reactions of the 5-chloro-, 5,6-dichloro-, 4,6-dibromo-, 5-phenylsulphonyl- and 5-methoxy-derivative are discussed in some detail.Some applications of the methodology developed, particularly to the synthesis of actual or potential benzimidazole anthelminthics, are given also.
- Iddon, Brian
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p. 673 - 701
(2007/10/02)
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