36 results about "Edoxaban" patented technology

The invention provides a method for separating and purifying edoxaban by chromatography. The separation method is chromatography, and the chromatographic conditions are as follows: the filler is an amylose-tri(3,5-xylylcarbamate) bonded silica gel, and the mobile phase is selected from a mixed solution comprising a non-polar solvent and a polar solvent. By selecting the chromatographic conditions, the edoxaban and seven enantiomers and nonenantiomers thereof can be simultaneously separated, and thus, the method has the characteristics of high speed, high simpleness, high efficiency and the like.

The invention relates to a preparation method of edoxaban and an intermediate thereof. Using compound 1, compound 2 and compound 5 as starting materials, edoxaban is produced through ammonolysis reaction, deprotection reaction, carboxylation reaction and condensation reaction. Compared with the existing technology, this preparation method can The operability is higher, the safety is higher, and the obtained product has high yield and high purity.

The present invention provides 2,2,2-trichloro-1-(4,5,6,7-tetrahydro-5-methylthiazolo[5,4-c]pyridinium-1-yl)ethanone Method for preparing edoxaban from chloride. Among them: 2,2,2-trichloro-1-(4,5,6,7-tetrahydro-5-methylthiazolo[5,4-c]pyridinium-1-yl)ethanone chloride , namely the preparation method of 109C5-11; N 1 -[(1S, 2R, 4S)-2-amino-4-[(dimethylamino)carbonyl]cyclohexyl]-N 2 -(5-Chloro-2-pyridyl)oxalamide bis-methanesulfonate, namely the preparation method of 109T2-31; edoxaban was prepared by using 109C5-11 as an acylating reagent and 109T2-31. The new method avoids the disadvantages of using expensive condensing agent EDCI·HCl and activating agent HOBt in the existing process. The novel method of the invention is beneficial to realize the industrialized scale production of edoxaban p-toluenesulfonate hydrate more economically and efficiently.

The invention discloses a compound sustained-release preparation containing apixaban and a preparation method thereof. The preparation is composed of apixaban granules, edoxaban sustained-release pellets and other pharmaceutically acceptable auxiliary materials. The edoxaban sustained-release pellets are, from the inside to the outside, successively a blank core, an isolation coat layer, and a drug-containing layer, and the drug-containing layer is composed of edoxaban, hydroxypropyl cellulose, and a filler. It is obtained by spraying the drug-containing dispersion solution onto the coated pellet core by the bottom spray coating method to obtain the drug-loaded immediate-release pellets, and then outsourcing the sustained-release coating layer; It is obtained by granulating with microcrystalline cellulose, hydroxypropyl cellulose and croscarmellose sodium. The compound sustained-release preparation of the invention can take effect quickly, release medicine stably for a long time, reduce the number of times patients take medicine, improve compliance, and improve the safety of patient medicine, thereby meeting the needs of treatment and meeting the requirements of clinical medicine.

The present invention relates to an intermediate for preparing edoxaban free base and its preparation method and application. The preparation method of the intermediate comprises the following steps: in an organic solvent, under the action of a base, 5-methyl-4,5,6,7-tetrahydro[1,3]thiazolo[5,4-c] Pyridine-2-carboxylic acid or its salt is reacted with acid chloride to obtain. Using the intermediate, the free base of edoxaban can be synthesized in a low-cost, green, environmentally friendly, simple, efficient and safe manner, and the drug safety of the obtained edoxaban product can be improved. The steps for preparing edoxaban free base are as follows: in an organic solvent, compound (II) and compound (IV) react to obtain; or, in an organic solvent, under the action of a base, compound (II) and compound ( IV) salt reaction, that is, obtained. The structures of compound (II), edoxaban free base, and compound (IV) are respectively as follows.

The invention discloses a preparation method of edoxaban intermediate (1S, 3R, 4R)-3-tert-butoxycarbonylamino-4-hydroxy-cyclohexanecarboxylic acid. According to the preparation method, 3-amino-4-hydroxy-cyclohexane carboxylate represented by formula IV is taken as a raw material, protective reaction with amino protection groups is carried out so as to obtain 3-tert-butoxycarbonylamino-4-hydroxy-cyclohexane carboxylate represented by formula V, enzyme catalyzed esterification resolution reaction is carried out so as to obtain optically pure (1S, 3R, 4R)-3-tert-butoxycarbonylamino-4-hydroxy-cyclohexane carboxylate represented by formula VII, and at last lithium hydroxide hydrolysis is adopted so as to obtain the (1S, 3R, 4R)-3-tert-butoxycarbonylamino-4-hydroxy-cyclohexanecarboxylic acid represented by formula VI. The preparation method possesses following advantages: operation is simple, the preparation method is green, is friendly to the environment, and is high in selectivity and lowin cost, large scale industrialized production can be realized, and it is convenient for industrial popularization.

The invention discloses a method for separating and measuring edoxaban tosylate hydrate and its isomer impurities by chiral high-performance liquid chromatography. The silica gel of methyl phenyl carbamate) is the chiral chromatographic column of filler, and mobile phase is the mixed solution of the methanol-ethanol that adds basic additive. By adopting the method of the present invention, complete separation of Edoxaban from the isomers Edox-II and Edox-III can be realized. The method is convenient to operate, has been verified by the method, has good method specificity, high sensitivity, and precision and accuracy. The method can accurately carry out the quantitative analysis of the isomers Edox-II and Edox-III of the edoxaban toluenesulfonate hydrate raw material drug and its preparations, thereby ensuring that the edoxaban toluenesulfonate hydrate and its preparations quality controllability.