- Axitinib intermediate synthesis method
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The invention relates to an axitinib intermediate synthesis method, and belongs to the field of chemical synthesis, wherein a target compound is obtained through a Vilsmeier reaction, pyranyl protection, a wittig reaction, a reduction reaction and an iodo reaction. According to the present invention, the palladium catalytic reaction is replaced with the wittig reaction, such that the use of the expensive palladium catalyst can be avoided, the post-treatment can be conveniently performed, and the production cost is saved.
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- Preparation method of axitinib intermediate
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The invention provides a preparation method of an axitinib intermediate. The preparation method of the axitinib intermediate comprises the following steps: dissolving (E)-6-nitro-3-[2-(pyridin-2-yl)vinyl]-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (II) into an organic solvent, adding an aqueous Na2S.9H2O solution, preserving heat for reaction, filtering out an insoluble substance while the solutionis hot after a reaction is stopped, adding 50 DEG C hot water into a filtrate, cooling a system to 0 DEG C, filtering, and drying to obtain a yellow brown solid (I). By the preparation method, few byproducts are produced, an operation method is simple, a reaction process is easy to control and reaction post-treatment is simple; the preparation method is low in cost and suitable for industrial production.
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Paragraph 0021-0024; 0025-0028; 0029-0030
(2018/03/24)
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- 2,3-dimethyl-6-urea -2H-indazoles and its preparation method and application
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The invention discloses a 2, 3-dimethyl-6-urea-2H-indazole compound shown by the following general formula (I), medicinal salt or a solvent compound thereof, wherein Ar is substituted or unsubstituted phenyl or aromatic matrix. The invention also discloses a preparation method and application of the compound. The compound can regulate signal transduction of tyrosine kinase, inhibit bad cellular proliferation, and particularly has obvious curative effect for tumors.
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- A process for the preparation of intermediates axi for Nepal the preparation and application of axi for Nepal
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The invention relates to a method for preparing an intermediate of axitinib and application of the intermediate in preparation of axitinib. The preparation method for the intermediate of axitinib 3-iodine-6-nitro-1-(teralin-2H-pyran-2-base)-1H-indazole comprises the following steps that 6-nitroindazole and 3,4-dihydro-2H-pyran react under the action of catalyst so as to protect perssad tetralin-2H-pyran-2-base at N-H site, and the key intermediate with high yield is obtained through iodination at site 3. The application of the intermediate in preparation of axitinib is as follows: Heck coupled reaction is carried out on the intermediate and 2-vinyl pyridine, then nitro reduction and diazo-reaction for iodination are sequentially carried out, finally, the axitinib is obtained after docking of 2-sulfydryl-N-methyl benzamide and deprotection. The related main initial raw materials are easy to purchase in markets, and the method has high yield and high molecule economic efficiency, is efficient and environment-friendly, and is suitable for industrial mass production.
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- Effective Laboratory-Scale Preparation of Axitinib by Two CuI-Catalyzed Coupling Reactions
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The discovery and development of an efficient synthesis route to axinitib is reported. The first-generation route researched by Pfizer implemented two Pd-catalyzed coupling reactions as key steps. In this work, the development of Heck-type and C-S coupling reactions catalyzed by CuI is briefly described, using an economial and practical protocol. Aspects of this route, such as selecting optimal ligands, solvent, and other conditions, are discussed in detail. The scale-up experiment was carried out to provide more than 300 g of active pharmaceutical ingredients of axitinib in Form XLI with 99.9% purity in 39% yield. In short, we provide a new choice of synthesis route to axitinib, through two copper-catalyzed coupling reactions with good yield.
- Zhai, Li-Hai,Guo, Li-Hong,Luo, Yang-Hui,Ling, Yang,Sun, Bai-Wang
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p. 849 - 857
(2015/07/27)
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- VEGFR INHIBITORS CONTAINING A ZINC BINDING MOIETY
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The present invention relates to VEGFR inhibitors and their use in the treatment of cell proliferative diseases such as cancer. The said derivatives may further act as HDAC inhibitors.
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- METHODS FOR PREPARING INDAZOLE COMPOUNDS
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The invention relates to methods for preparing indalzole compounds having formula (I) or pharmaceutically acceptable salts or solvates thereof. Compounds of the formula (I) are useful as anti-angiogenesis agents and as agents for modulating and/or inhibiting the activity of protein kinases, thus providing treatments for cancer or other diseases associated with cellular proliferation mediated by protein kinases.
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Page/Page column 22-23
(2008/06/13)
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- METHODS FOR PREPARING INDAZOLE COMPOUNDS
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The invention relates to methods for preparing compounds of formula (I): or pharmaceutically acceptable salts or solvates thereof. Compounds of the formula (I) are useful as anti-angiogenesis agents and as agents for modulating and/or inhibiting the activity of protein kinases, thus providing treatments for cancer or other diseases associated with cellular proliferation mediated by protein kinases.
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Page/Page column 31-32
(2010/11/30)
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