Preparation method of anticoagulant drug dabigatran etexilate and analogues thereof
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.
-
Paragraph 0060; 0062; 0069-0070
(2020/05/01)
Preparation method of high-purity dabigatran etexilate
The invention discloses a preparation method of high-purity dabigatran etexilate, prepared by subjecting ethyl 3-[[[2-[[(4-cyanophenyl)amino]methyl]-1-methyl-1H-benzimidazole-5-yl]carbonyl]pyridine-2-ylamino]propanoate to alcoholysis and aminolysis to obtain a compound 4, and subjecting the compound to esterification reaction with hexyl chloroformate; recrystallization is performed after the esterification reaction; the recrystallization employs a recrystallization solvent that is ethyl acetate, isopropyl acetate or n-butyl acetate. The recrystallization solvent can decrease the content of the byproduct compound 7 in dabigatran etexilate to 1% and below, particularly to 0.5% and below for ethyl acetate, with the loss of dabigatran etexilate less than 5%; the purifying process is economical and practical and is suitable for industrial large-scale production.
-
Paragraph 0006; 0018; 0019
(2017/08/27)
Synthesis, characterization and suppression of impurities during optimization of dabigatran etexilate
The synthetic methods for two impurities of dabigatran etexilate are firstly described, and both of two impurities are characterized by NMR and MS spectral data. The suppression of impurities as well as the optimization process of dabigatran etexilate is also disclosed.
Chen, Yu,Liang, Jun,Chen, Huansheng,Yuan, Li
p. 1699 - 1710
(2013/09/12)
DABIGATRAN ETEXILATE AND RELATED SUBSTANCES, PROCESSES AND COMPOSITIONS, AND USE OF THE SUBSTANCES AS REFERENCE STANDARDS AND MARKERS
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.
-
(2012/12/13)
More Articles about upstream products of 1408238-36-7