- Asymmetric Catalytic Epoxidation of Terminal Enones for the Synthesis of Triazole Antifungal Agents
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An enantioselective epoxidation of α-substituted vinyl ketones was realized to construct the key epoxide intermediates for the synthesis of various triazole antifungal agents. The reaction proceeded efficiently in high yields with good enantioselectivities by employing a chiral N,N′-dioxide/ScIII complex as the chiral catalyst and 35% aq. H2O2 as the oxidant. It enabled the facile transformation for optically active isavuconazole, efinaconazole, and other potential antifungal agents.
- Feng, Xiaoming,He, Qianwen,Liu, Xiaohua,Zhang, Dong,Zhang, Fengcai
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p. 6961 - 6966
(2021/09/11)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF TRIAZOLE DERIVATIVES
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The present invention relates to an improved process for the preparation of triazole derivatives such as ravuconazole and isavuconazole.
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- Preparation method of isavuconazole intermediate
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The invention provides a preparation method of an isavuconazole intermediate. Specifically, the present invention provides a method for preparing (2R,3S)-1-(1H-1,2,4-triazol-1-yl)-2-(2,5-difluorophenyl)-3-cyano-2-butanol (an intermediate 10) by carrying out a ring-opening reaction on (2R,3S)-2-(2,5-difluorophenyl)-3-methyl-2-[(1H-1,2,4-triazol-1-yl)methyl]ethylene oxide (an intermediate 9) and trimethylcyanosilane in the presence of tetrabutylammonium fluoride (TBAF). The product obtained by the method provided by the invention has high purity and yield, and the method has mild conditions, iseasy to control, and is suitable for industrial mass production.
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Paragraph 0079-0088
(2019/12/09)
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- Method for manufacturing isavuconazole or ravuconazole
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The invention provides a method for manufacturing a triazole compound isavuconazole or ravuconazole which is enriched by a diastereoisomer and enantiomer. The method comprises the following steps: a Reformatsky reaction is carried out between ketone and dihalogeno metal propionitrile; an enantiomer mixture is generated, and separation is carried out. The method can obviously reduce steps for synthesis of isavuconazole or ravuconazole, yield of products is improved, and production cost is reduced.
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Paragraph 0055; 0056; 0058; 0061; 0063; 0064-0067; 0078
(2017/08/27)
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- Preparation method of isavuconazole intermediate
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The invention belongs to the technical field of chemical drug intermediate preparation and relates to a preparation method of an isavuconazole intermediate. The preparation method is a 4-(2-((2R, 3R)-3-(2, 5-difluorophenyl)-3-hydroxy-4-(1H-1, 2, 4-triazole-1-yl)butane-2-yl)thiazole-4-yl)benzontrile preparation method. The 4-(2-((2R, 3R)-3-(2, 5-difluorophenyl)-3-hydroxy-4-(1H-1, 2, 4-triazole-1-yl)butane-2-yl)thiazole-4-yl)benzontrile has a structural formula (I) shown in the description.
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- Preparation method of isavuconazole and isavuconazole prepared through method
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The invention relates to a preparation method of isavuconazole and isavuconazole prepared through the method.The preparation method comprises the following steps that 1, diflurophenyl acetylchloride, triazole, CuI, potassium carbonate and first organic solvent are sequentially added into a reaction kettle, reacting under stirring is performed at the temperature of 80 DEG C-100 DEG C, and then purifying is performed to obtain a first product; 2, propionitrile, a catalyst and second organic solvent are added into a reaction container, the temperature is lowered to minus 20 DEG C-minus 5 DEG C, the second organic solvent containing the first product is dropwise added, reacting and purifying are performed to obtain a second product, and a mixture composed of C-9 primary amine quinine and copper pigment alkali is adopted as the catalyst; 3, the second product is added into another reaction container, diethylphosphorodithioate, water and mixed isopropanol solvent are added into the reaction container, heating is performed until the temperature is increased to 80 DEG C-90 DEG C, reacting under stirring and purifying are sequentially performed, and a third product is obtained; 4, the third product, 2-bromo-4'-acetylbenzonitrile and third organic solvent are mixed, react under stirring at the temperature of 60 DEG C-70 DEG C and then purified, and the isavuconazole is obtained.Accordingly, a novel synthetic route is redesigned, and the reaction steps are reduced.
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Paragraph 0019; 0024
(2016/10/10)
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- Process for the manufacture of enantiomerically pure antifungal azoles as ravuconazole and isavuconazole
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A new technical process for preparation of enantiomerically pure antifungal compounds of formula I by resolution of the racemates has been disclosed.
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Page/Page column 8-9
(2011/04/25)
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- Azoles for treatment of fungal infections
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Azole derivatives of the formula I wherein R14, R15are each independently hydrogen or fluorine, T is a group of the formula: wherein R9is pyrrolidinyl or a group A—NH—B—, A is hydrogen or straight-chain or branched C1-C5alkyl; B is straight-chain or branched C1-C4alkylene, —CH2—CONH—CH2or —CH2CH2CH2—CH(NH2); and X?is a pharmaceutically acceptable anion; and pharmaceutically acceptable salts of said compounds, and hydrates and solvates of the compounds of formula I and the salts thereof can be used in the production of medicaments for treating fungal infections and mycoses.
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