- Preparation method of anticoagulant drug dabigatran etexilate and analogues thereof
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The invention discloses a preparation method of an anticoagulant drug dabigatran etexilate and analogues thereof. The preparation method comprises the following steps: 3-[(3-amino-4-methylaminobenzoyl)pyridin-2-ylamino]propionic acid ethyl ester (DGM1) and isopropyl 2-(4-cyanophenylamino)acetate (DGM2) which are taken as reaction initial raw materials undergo a docking reaction under the action ofan alkali reagent and a condensing agent to prepare an intermediate DG1; the intermediate DG1 reacts in an alcohol solvent to produce imino ester, and acid catalysis and ammonia reaction are carriedout to prepare a formamidine compound; an intermediate DG2 reacts with n-hexyl chloroformate under the action of the alkali reagent to remove one molecule of water and form an amido bond in order to obtain dabigatran etexilate; and the dabigatran etexilate analogues DG-D1 to DG-D4 are prepared from the dabigatran etexilate and its intermediate DG2. The preparation method of the dabigatran etexilate and analogues thereof has the advantages of short and feasible synthesis route, simplicity in operation, high product yield is high, and suitableness for large-scale industrial production.
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Paragraph 0056-0059
(2020/05/01)
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- Synthesis method of benzimidazole compound K
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The invention provides a synthesis method of a benzimidazole compound K. The method includes the steps of: 1) producing a compound 2 from a compound 1 under the action of a reducing agent; 2) subjecting the compound 2 and an acylation reagent to cyclization to generate a compound 3; 3) producing a compound 5 from nitrobenzamide 4 and hexyl chloroformate in the existence of strong base; 4) conducting catalytic hydrogenation on the compound 5 under certain hydrogen pressure to reduce nitro into amino so as to generate a compound 6; and 5) producing the compound 3 and the compound 6 into the benzimidazole compound K under certain temperature in the existence of sodium iodide and weak base, with the synthetic route shown as the specification. The method provided by the invention adopts cheap and easily available raw materials to achieve oriented synthesis of the benzimidazole compound K by 5-step reaction, the obtaine product has no need for purification, the aftertreatment of each step is simple, and the product is convenient to obtain. Therefore, the method is suitable for large-scale synthesis, and provides standard substances for quality research.
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- A preparation darbey adds the group ester amide the method of impurity (by machine translation)
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The present invention relates to the field of organic synthesis technology, in particular to a kind of preparation darbey adds the group ester amidation method of the impurity, the method to 4-aminobenzoic amidine-Carbamic N-own ester as the raw material, prepared by the hydrolysis reaction of hydrolysis product, then the hydrolysis product and the 3 - [(3-amino-4-methyl-aminobenzoyl) pyridin-2-yl-amino] propionic acid ethyl ester under the action of catalyst and undergo condensation, get darbey adds the group ester amide impurity, the method can be obtained through the two step process of the finished product darbey adds the group ester amide impurity, the method is simple, easy to operate, and does not need the chromatographic separation is a compound of high purity can be obtained, to darbey adds the group ester control the quality of the drug impurities provide a high-purity of the substance. (by machine translation)
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Paragraph 0030; 0031; 0034; 0035
(2016/11/24)
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- DABIGATRAN ETEXILATE AND RELATED SUBSTANCES, PROCESSES AND COMPOSITIONS, AND USE OF THE SUBSTANCES AS REFERENCE STANDARDS AND MARKERS
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The present invention relates to dabigatran etexilate and related substances and use of the substances as reference standards and markers. There are also provided processes of detecting the substances in samples of dabigatran etexilate, or pharmaceutically acceptable salts or solvates thereof, and also for analyzing the purity of samples of dabigatran etexilate, or pharmaceutically acceptable salts or solvates thereof.There are still further provided processes of preparing dabigatran etexilate and related substances, and pharmaceutical compositions containing the same.
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