211915-84-3Relevant articles and documents
Preparation method of anticoagulant drug dabigatran etexilate and analogues thereof
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Paragraph 0039; 0041-0043, (2020/05/01)
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.
Dabigatran etexilate key intermediate preparation method
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, (2019/10/01)
The invention relates to the field of pharmaceutical intermediates, particularly to an industrial preparation method of a dabigatran etexilate key intermediate. According to the preparation method, astarting raw material is subjected to nitro reduction, amide condensation and cyclization reaction to obtain a key intermediate 3-{2-[(4-cyanophenylamino)methyl]-1-methyl-N-(pyridine-2-yl)-1H-benzo[d]imidazole-5-amido}ethyl propionate. According to the present invention, the preparation method can reduce the production cost, make the production process safe, and improve the yield, and is suitablefor industrial large-scale production.
Synthetic method for pradaxa key intermediate
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Paragraph 0012; 0035-0050, (2018/11/03)
The invention relates to a synthetic method for ethyl [2-[[(4-cyanophenyl)amino]-methyl] -1-methyl-1H-benzimidazol-5-yl]carbonyl] (pyridin-2-yl)amino]propanoate. According to the synthetic method, thereaction formula is as shown in the description. The synthetic method comprises the following steps that 1) a compound SM01 reacts with a coupling reagent CDI in a toluene solution; 2) after the reaction in the step 1) is finished, an obtained reaction solution is cooled, and an SM02 toluene solution is added for reaction; and 3) after the reaction is finished, acetic acid is added, and then thereaction is continued to the end. Compared with the prior art, the synthetic method has the advantages that a solvent is single and does not need to be replaced in the reaction process, the operationis simple and convenient, by-products are few, the yield is high and is 93-96%, a high-purity product of DB02 is easily obtained, the HPLC content is 99% or above, and the method is suitable for industrial production.