89830-71-7Relevant articles and documents
Preparation method of topiroxostat
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Paragraph 0042-0046, (2021/07/28)
The invention provides a preparation method of topiroxostat, and relates to the technical field of medicine synthesis. The preparation method of the topiroxostat comprises the following steps: carrying out heat-preservation stirring reaction on 4-cyanopyridine and hydrazine hydrate in the presence of a solvent and an alkaline reagent to obtain an intermediate 1; carrying out heating stirring reaction on 4-picolinic acid in the presence of an acidic reagent and hydrogen peroxide to obtain isonicotinic acid nitrogen oxide; carrying out heat-preservation stirring reaction on the intermediate 1 and isonicotinic acid nitrogen oxide under the catalysis conditions of a solvent and a condensing agent to obtain an intermediate 3; carrying out heating stirring reaction on the intermediate 3 in the presence of a solvent and cyanide under the protection of nitrogen to obtain an intermediate 4; and carrying out reflux reaction on the intermediate 4 in the presence of an acidic reagent, cooling to room temperature, and filtering to obtain a topiroxostat solid. According to the invention, the topiroxostat is obtained through hydrazinolysis, oxidation, condensation, cyanidation and cyclization, isonicotinic acid and 4-cyanopyridine are selected as starting materials, the preparation method is low in production cost, high in yield, high in purity and few in three wastes, and the preparation method is suitable for industrial production of the topiroxostat and the intermediate thereof.
Three-Component Reaction of 3,3-Difluorocyclopropenes, s-Tetrazines, and (benzo) Pyridines
Nechaev, Ilya V.,Cherkaev, Georgij V.,Boev, Nikolay V.,Solyev, Pavel N.
, p. 1037 - 1052 (2021/01/09)
A new three-component reaction leading to 1-α-(pyridyl-2-[1,2,4]triazolyl)-2-alkyl-ethanones has been discovered while studying the reactivity of monosubstituted 3,3-difluorocyclopropenes in an inverse electronic demand Diels-Alder (IEDDA) cycloaddition-cycloreversion sequence with s-tetrazines. The reaction involving the above-mentioned reactants and (benzo)pyridine as a third component results in a complex transformation proceeding in mild conditions in a stoichiometric ratio of reactants and has high functional group tolerance (phenols, amides, ethers, carboxylic acids, ketones, and acrylic esters). As a result, simple pyridines are selectively functionalized at the α-position in good isolated yields. The reaction mechanism includes a rare azaphilic [4 + 2]-cycloaddition step between s-tetrazine and intermediate 1-hydroxyindolizine, suggested after byproduct identification and tracked with a deuterium label. To date, it is only the third known example of skewed azaphilic cycloaddition of tetrazine. The reaction is truly three-component and cannot be effectively performed stepwise.
Topiroxostat and preparation method of intermediate of topiroxostat
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Paragraph 0033; 0034; 0035, (2018/06/26)
4-cyanopyridine is taken as a raw material, a compound III is obtained through a reaction, the compound III and a compound IIB undergo an amidation reaction to obtain a compound IV, and a ring-closurereaction is carried out in the function of an acid catalyst to obtain a target topiroxostat molecule. According to the scheme, the raw materials are cheap and are easy to obtain, the product qualityis high, the reaction is simple to operate and is mild, the yield is high, and the waste gas, waste water and industrial residue are less produced. In the reaction process, nitrogen protection isn't required, and a cyaniding reagent isn't used, so that the method has bright industrial prospects.
