- Synthesis, crystal structural, and spectral characterisation of dabigatran etexilate tetrahydrate
-
Dabigatran etexilate tetrahydrate, C34H49N7O9, has been crystallised at ambient conditions. The colourless crystal was investigated using X-ray crystallography with single crystals and powder techniques, and was characterised by thermogravimetric-differential thermal analysis (TG-DTA) and infrared spectroscopy (IR). The compound was shown to be a tetrahydrate. A dabigatran etexilate molecule and four water molecules form a large ring structure, and intra-molecular hydrogen bonds contribute to the formation of a stable molecule in the unit cell.
- Cai, Zhi-Qiang,Hou, Xu,Kong, Du-Lin,Hou, Ling,Hu, Zhi-Quan
-
-
Read Online
- An improved process for preparation of dabigatran etexilate mesylate
-
An improved process for the preparation of dabigatran etexilate mesylate, wherein the process is substantially free to eliminates the potential impurities. The impurities are formed due to presence of contaminated starting ingredients that is present in commercially available n-hexyl chloro formate. The present invention is to control impurities by using pure n-hexanol in place of n-hexyl chloro formate. Over all yields is good and process can't requires expensive catalysts. Dabigtran is used to prevent strokes in those with arterial fibrillation due to heart valve causes, as well as deep venous thrombosis (DVT). Moreover, the present invention is providing simple, industrial scalable and cost-effective process, which affords good quality and yield.
- Sharif, Sd. Khasim,Ramudu, B. Sri,Nunna, Rambabu,Ramachandran
-
-
Read Online
- Benzenesulfonate and preparation method thereof, and application of benzenesulfonate in preparation of dabigatran etexilate
-
The invention relates to benzene sulfonate represented by a formula 7, a preparation method of the benzene sulfonate, and application of the benzene sulfonate in preparation of dabigatran etexilate. The invention also discloses a method for preparing dabigatran etexilate, wherein the method comprises the following steps: (1) in the presence of a solvent and an acid-binding agent, carrying out an addition reaction on a compound 1 and hydroxylamine hydrochloride to obtain a compound 5; (2) under the action of a reducing agent, carrying out a reduction reaction on the compound 5 and hydrogen, andsalifying with benzenesulfonic acid to obtain benzene sulfonate represented by a formula 7; and (3) carrying out an amidation reaction on the benzene sulfonate represented by the formula 7 and n-hexyl chloroformate to obtain a compound 4, namely dabigatran etexilate. According to the preparation method of the dabigatran etexilate, hydrogen chloride which pollutes the environment and corrodes equipment is not used in a cyano amidination process while industrial iron acetate powder to be eliminated is prevented from being used for reduction, and high-purity dabigatran etexilate can be obtained.
- -
-
Paragraph 0077-0081
(2020/07/02)
-
- 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.
- -
-
-
- Dabigatran etexilate mesylate preparation method
-
The invention belongs to the field of pharmaceutical synthesis, and provides a dabigatran etexilate mesylate preparation method, which comprises: carrying out a ring closure reaction on 3-[(3-amino-4-methylaminobenzoyl)(pyridine-2-yl)amino] ethyl propionate and chloroacetic anhydride to generate N-[[2-(chloromethyl)-1-methyl-1H-benzimidazole-5-yl]carbonyl]-N-2-pyridyl-beta-alanine ethyl ester, carrying out a condensation reaction on the N-[[2-(chloromethyl)-1-methyl-1H-benzimidazole-5-yl]carbonyl]-N-2-pyridyl-beta-alanine ethyl ester and 4-aminobenzamidine dihydrochloride to obtain 3-({2-[(4-amidino-phenylimino)-methylene]-1-methylene-1H-benzimidazole-5-carbonyl}-pyridine-2-imine)-ethyl propionate, carrying out ester forming on the 3-({2-[(4-amidino-phenylimino)-methylene]-1-methylene-1H-benzimidazole-5-carbonyl}-pyridine-2-imine)-ethyl propionate and hexyl chloroformate to obtain dabigatran etexilate, and carrying out salt forming on the dabigatran etexilate and methanesulfonic acid to obtain dabigatran etexilate mesylate. According to the present invention, the route of the method has characteristics of high yield, mild condition and convenient intermediate purification, and meets the requirements of industrial production.
- -
-
-
- Preparation method of non-peptide type thrombin inhibitor dabigatran
-
The invention discloses a preparation method of a non-peptide type thrombin inhibitor dabigatran and belongs to the technical field of medicine chemistry. The technical scheme is characterized by providing the preparation method of the non-peptide type thrombin inhibitor dabigatran; and a synthesis route is as follows: a formula is shown in the description. The preparation method has the advantages of moderate reaction conditions, relatively high yield and low cost and is suitable for industrial production.
- -
-
Paragraph 0023; 0028; 0029; 0034; 0035; 0040
(2019/02/04)
-
- Darbey adds the group ester for an intermediate and its preparation method
-
The invention discloses a novel intermediate form of dabigatran etexilate, wherein the novel intermediate is a salt of 3-[[[2-[[[4-[[ethyoxyl] formimino]phenyl]amino]methyl]-1-methyl-1H-benzimidazole-5-yl]carbonyl](pyridine-2-yl)amino]ethyl propionate as shown in a formula V-A as shown in the specification, and the salt has good purity and stability, can be stored for a long time and can be taken as a process intermediate or a starting raw material for use; and moreover, in the preparation of the subsequent intermediate and the dabigatran etexilate, the reaction operation is simple and convenient, the product purity is high and the industrial application is facilitated.
- -
-
-
- Production process of pradaxa mesylate
-
The invention discloses a production process of pradaxa mesylate. The production process comprises the following steps: (1) preparing an intermediate PR-I; (2) preparing an intermediate PR-II; (3) preparing pradaxa PR-III; (4) refining the pradaxa PR-III; and (5) preparing pradaxa mesylate. The production process is mild in reaction condition, simple in reaction route, convenient in operation, high in selectivity, and capable of shortening the production period; and the obtained pradaxa intermediate is low in water content, the prepared pradaxa mesylate is high in yield and purity, and the maximum impurity is low in impurity content; and the production process is less in emission of three wastes, environmentally friendly, free from requiring the columnar chromatography purification, suitable for the industrialized production, capable of avoiding the requirement of palladium-on-carbon high-pressure hydrogenation on equipment and capable of reducing the risk.
- -
-
Paragraph 0083; 0084; 0098; 0110-0114; 0138; 0139; 0164
(2018/11/22)
-
- Preparation process of Pradaxa
-
The invention discloses a preparation process of Pradaxa. After obtaining a compound 3 with the structural formula as shown in the description, an alkali liquor is added to separate out the compound 3; micro-molecule alcohol is used for refining; under the action of a reaction solvent and an organic alkali, the compound 3 and hexyl chloroformate conduct a condensation reaction to obtain a compound2 with the structural formula as shown in the description; an acid liquor is used for washing, and vacuum concentration is performed till the product is dry; an organic solvent is used for refining;and the compound 2 and methanesulfonic acid are salified to obtain Pradaxa. Through the continuous operation that solid-liquid separation is performed after the alkali liquor is added to separate outthe compound 3, the problems that lots of acid is evaporated to corrode equipment due to vacuum concentration and many degradation impurities are produced by heating are solved. The pickling process is adopted to control specific impurities in a reaction liquid of the compound 2. At last, an appropriate methanesulfonic acid charge ratio and an appropriate charging temperature are adopted to guarantee correct product crystal forms.
- -
-
-
- Preparation method of dabigatran etexilate
-
The invention discloses a preparation method of dabigatran etexilate. The preparation method comprises that (a) an intermediate I or its salt reacts with haloacetic acid or haloacetate under basic conditions to produce an intermediate II, and (b) the intermediate II and DBSM are condensed by a condensing agent and undergo a ring closing reaction to produce dabigatran etexilate. The preparation method has the advantages of mild reaction conditions, cheap and easily available raw materials, simple reaction steps, high atomic utilization rate, simple and controllable operation, high reaction yield, high product purity, controllable quality, less three-waste discharge, and environmental friendliness and is suitable for large-scale industrial production.
- -
-
-
- Preparation method of dabigatran etexilate
-
The invention belongs to the technical field of medicine preparation and particularly relates to a preparation method of dabigatran etexilate. A compound 2 adopted in the preparation method has the characteristics of stable property, no pungent smell, low price and the like. According to the preparation method, the defect that anhydride or acyl chloride compounds are adopted in an existing synthetic route of dabigatran etexilate is overcome, and the compounds have the disadvantages of pungent smell, hygroscopicity and high anhydrous requirement on a reaction system. The reaction process is relatively easily operated and controlled, the synthetic route is short, the byproducts are few, and the cost is low.
- -
-
Paragraph 0025; 0029; 0030
(2018/09/08)
-
- METHOD FOR MANUFACTURING DABIGATRAN ETEXILATE
-
Disclosed is a method for producing dabigatran etexilate. The method for producing dabigatran etexilate according to one embodiment of the present invention comprises: a first step of reacting a compound of chemical formula 1 with a chlorine-based compound to synthesize a compound of chemical formula 2; a second step of reacting the compound of the chemical formula 2 with an ammonium-based compound to synthesize a compound of chemical formula 3; and a third step of reacting the compound of the chemical formula 3 with a chloroformate-based compound.COPYRIGHT KIPO 2017
- -
-
-
- Industrial preparation method of dabigatran
-
The invention discloses an industrial preparation method of dabigatran, and belongs to the field of medicinal chemistry, wherein the preparation method sequentially comprises a condensation reaction, a closed cyclization reaction, a Pinner reaction, and other steps. According to the present invention, the hydrogen chloride/alcohol/ester solution is prepared by using acyl chloride and alcohol as raw materials, such that the problems of corrosion on equipment, high hidden safety danger, environmental pollution and the like caused by the use of hydrogen chloride gas in the prior art are solved; and the reactions in various steps are subjected to the industrial-scale-based optimization, the unnecessary distillation, extraction and re-crystallization process is reduced, the process is simplified, the purification method of the final product dabigatran is improved, the purification efficiency is increased in the case of the ensuring of the process yield and the product quality, the process reproducibility is good, the preparation cost is low, and the method is the ideal industrial preparation method of the dabigatran.
- -
-
-
- A process for preparing darbey adds the group ester method
-
The invention discloses a dabigatran etexilate preparation method. The method comprises the following steps: preparing an intermediate 1, preparing an intermediate 2, preparing an intermediate 3, preparing an intermediate 4, preparing an intermediate 5, preparing an intermediate 6, and preparing dabigatran etexilate. The preparation method has the advantages of cheap and easily available raw materials, easy operation, easy control, high reaction yield, high product purity, and suitableness for the large-scale industrial production of dabigatran etexilate.
- -
-
Paragraph 0028; 0034; 0035; 0041; 0042; 0048
(2017/08/25)
-
- Preparation method for dabigatran etexilate
-
The invention provides a method for preparing dabigatran etexilate. The method comprises the following steps: A) subjecting a compound as shown in a formula I and a compound as shown in a formula II to a reaction in an inert solvent so as to obtain a compound as shown in a formula III, wherein the compound as shown in the formula II comprises an R which is one selected from the group consisting of methyl, ethyl, propyl or isopropyl; B) subjecting the compound as shown in the formula III to activation through a hydrogen chloride solution in an inert solvent, and carrying out a reaction of the activated material and an ammonium salt so as to obtain a product IV; and C) subjecting a compound as shown in a formula IV and a compound as shown in a formula V to a reaction under the action of an acid-binding agent so as to obtain dabigatran etexilate VI. The method provided by the invention has the advantages of low cost, high yield, mild reaction conditions, avoidance of using unstable reagents, etc.
- -
-
-
- Preparation method and intermediate compound of dabigatran etexilate
-
The invention provides a preparation method and an intermediate compound of dabigatran etexilate. Compared with the prior art, the preparation method of the dabigatran etexilate is mild in reaction conditions, simple to operate and high in yield and purity, thereby being suitable for industrial production.
- -
-
Paragraph 0055; 0056; 0057; 0058
(2018/03/13)
-
- 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)
-
- A darbey adds the group ester preparation method
-
The invention relates to a preparation method of Dabigatran etexilate. In a preparation process, acyl chloride or anhydride is used for replacing N, N minute-Carbonyldiimidazole (CDI ) or palladium on activated carbon, which must be used and is expensive in the prior art, the cost is greatly lowered, and used materials are cheap and are easily available, the process is simple and feasible, aftertreatment steps are simplified, column chromatography purification is not needed in whole operation steps, so that the process of the whole preparation method is simplified, and industrialization is convenient to realize; when a compound with a formula 2 is compounded, a sodium amide and ammonium salt system is adopted, and generation of a mass of acid pickle is avoided, so the production is safe, the environment is not polluted, and the preparation process is convenient and easy; when a compound with a formula 1 is compounded, a stable-property compound with a formula 7 is adopted, great convenience is brought for production, and the yield of the Dabigatran etexilate is effectively improved; the total yield of the Dabigatran etexilate prepared by the method reaches 60 to 70 percent.
- -
-
-
- PROCESSES FOR THE PREPARATION OF DABIGATRAN ETEXILATE AND INTERMEDIATES THEREOF
-
The present invention relates to a process for the preparation of dabigatran etexilate of Formula (I), or a pharmaceutically acceptable salt thereof, to processes for the preparation of intermediates of dabigatran etexilate, and to dabigatran etexilate in substantially pure form.
- -
-
Page/Page column 26
(2016/03/14)
-
- Dabigatran etexilate synthesis method
-
The invention belongs to the field of pharmaceutical chemical engineering and relates to a dabigatran etexilate synthesis method. The invention provides the preparation method of dabigatran etexilate with a high yield and good quality and stability. The method has simple processes, is convenient for operation, simplifies post-treatment processes, is free of column chromatography purification in the whole processes and is suitable for industrial production.
- -
-
Paragraph 0011; 0036; 0037
(2017/02/02)
-
- Improved method for preparing Dabigatran etexilate
-
The invention relates to a method for preparing Dabigatran etexilate. The method comprises the specific steps of enabling a compound represented by a formula 1 shown in the description, i.e., 3-[[[2-[[(4-cyanophenyl)amino]methyl]-1-methyl-1H-benzimidazol-5-yl]carbonyl] pyrid-2-ylamino]ethyl propionate to subject to addition reaction with hydroxylamine hydrochloride in the presence of a catalyst in an alcoholic solution, so as to obtain a compound represented by a formula 2 shown in the description, reducing the compound represented by the formula 2 so as to obtain a compound represented by a formula 3 shown in the description, and enabling the compound represented by the formula 3 to subject to amidation reaction with n-hexyl chloroformate in the presence of a catalyst, thereby obtaining a compound represented by a formula 4 shown in the description, i.e., Dabigatran etexilate. Compared with the prior art, the preparation process disclosed by the invention has the advantages that the generation of a large volume of waste acid in the prior art is avoided, the reaction conditions are mild, the control is easy, the yield is high, and the product quality is good, thereby being applicable to industrial production.
- -
-
-
- Preparation method of dabigatran etexilate mesylate
-
The invention discloses a preparation method of dabigatran etexilate mesylate, and belongs to the technical field of medicine. The preparation method comprises the following steps: taking 3-[(3-amino-4-methylaminobenzoyl)pyridine-2-ylamino]ethyl propanoate and N-(4-cyanphenyl)amino acetic acid as the raw materials to synthesize an intermediate (S3); making the intermediate (S3) carry out ring-closure reactions to generate an intermediate (S4); subjecting the intermediate (S4) to acid splitting in the presence of a hydrogen chloride-ethanol solution at first, then carrying out ammonification in the presence of ammonia water to generate an intermediate (S5); carrying out reactions between the intermediate (S5) and n-hexyl chloroformate under an alkaline condition to generate an intermediate (S6); dissolving the intermediate (S6), and finally carrying out reactions between the intermediate (S6) and methylsulfonic acid to obtain dabigatran etexilate mesylate. The preparation method has the advantages of simpleness, controllable and mild conditions, high yield, high product purity, stable product property, and suitability for industrial production.
- -
-
-
- Dabigatran etexilate intermediate synthesis method
-
The invention discloses dabigatran etexilate, an intermediate thereof with a formula (5), and a synthesis method of a derivative thereof. According to the synthesis method, a compound represented by a formula (2) is subjected to a compound represented by a formula (4), such that a compound represented by the formula (5) is obtained; the compound represented by the formula (5) is hydrolyzed, and is subjected to a reaction with 3-(pyridin-2-ylamino)ethyl propionate, such that dabigatran etexilate is prepared.
- -
-
-
- Preparation technique of dabigatran methanesulfonate
-
The invention discloses a preparation technique of dabigatran methanesulfonate. The technique comprises the following steps: 1) by using a compound I and glycine as raw materials, carrying out condensation and salification to obtain a compound II; 2) by using p-halobenzonitrile (III) as a raw material, synthesizing p-halobenzamidine (IV) under the actions of a catalyst and an aminating agent, and carrying out condensation on the p-halobenzamidine (IV) and n-hexyl chloroacetate to obtain a compound V; and 3) carrying out condensation and salification on the compound V and the compound II to obtain the dabigatran methanesulfonate. The synthesis method has the advantages of mild reaction conditions for each step and high selectivity, and is simple to operate. The dabigatran methanesulfonate has high yield and purity. The technique has the advantages of less discharge of three wastes and environment friendliness, does not need column chromatography purification, and is suitable for industrial production.
- -
-
-
- NOVEL ACID ADDITION SALTS OF DABIGATRAN ETEXILATE AND PROCESS FOR THE PREPARATION THEREOF
-
The present invention relates to novel acid addition salts of dabigatran etexilate, process for the preparation and pharmaceutical compositions containing the same. Further, the invention relates to uses of said compositions for post operative prophylaxis of deep vein thrombosis and the prevention of strokes.
- -
-
Page/Page column 13
(2015/03/28)
-
- PROCESS FOR THE PREPARATION OF DABIGATRAN ETEXILATE MESYLATE AND POLYMORPHS OF INTERMEDIATES THEREOF
-
The present invention provides crystalline form of intermediates of Formula 2A, The present invention also provides process for the preparation of dabigatran etexilate mesylate; polymorph of intermediates thereof; particularly processes for the preparation of crystalline form of intermediates. The present invention also relates to the use of crystalline intermediates for the preparation of dabigatran etexilate mesylate.
- -
-
-
- Process For The Preparation Of Benzimidazole Derivatives And Salts Thereof
-
Provided are novel salts of benzimidazole derivatives, preferably salts of benzimidazole derivatives which are useful intermediates in the synthesis of pure 1-methyl-2-[N-[4-(N-n-hexyloxycarbonylamidino)phenyl]aminomethyl]benzimidazol-5-yl-carboxylicacid-N-(2-pyridyl)-N-(2-ethoxycarbonylethyl)amide and its salts.
- -
-
-
- A PROCESS FOR PREPARATION OF DABIGATRAN ETEXILATE MESYLATE AND INTERMEDIATES THEREOF
-
The present invention relates to an improved process for the preparation of Dabigatran etexilate and its acid addition salts thereof, wherein the said process substantially eliminates the potential impurities. The present invention also relates to an intermediate of Dabigatran etexilate and process for preparation thereof.
- -
-
-
- IMPROVED PROCESSES FOR THE PREPARATION OF DABIGATRAN ETEXILATE USING NOVEL INTERMEDIATES
-
Disclosed herein are novel, commercially viable and industrially advantageous processes for the preparation of Dabigatran or a salt thereof, in high yield and purity, using novel intermediate compounds. The novel process solves the drawbacks associated with the prior processes and is commercially viable for preparing Dabigatran and its salts or derivatives thereof.
- -
-
Page/Page column 35
(2015/09/28)
-
- AN IMPROVED PROCESS FOR PREPARATION OF DABIGATRAN ETEXILATE AND PHARMACEUTICALLY ACCEPTABLE ACID ADDITION SALTS THEREOF
-
The present invention provides an improved process for preparation of dabigatran etexilate and pharmaceutically acceptable acid addition salts thereof, particularly mesylate salt. The present invention also provides novel salts of intermediates of Dabigatran etexilate and their polymorphs.
- -
-
Page/Page column 29
(2014/12/12)
-
- PROCESS FOR THE PREPARATION OF BENZIMIDAZOLE DERIVATIVES AND ITS SALTS
-
An dabigatran etexilate intermediate of Formula-6a, and the use in the preparation of dabigatran etexilate thereof.
- -
-
-
- PHARMACEUTICAL INTERMEDIATES AND PROCESS FOR THE PREPARATION THEREOF
-
The present invention relates to a process for the preparation of dabigatran etexilate of the formula or pharmaceutically accepted salts thereof.
- -
-
-
- SYNTHESIS OF DABIGATRAN
-
The present invention relates to a process for preparation of Dabigatran etexilate or pharmaceutically acceptable salt thereof. The present invention relates to novel compounds, in particular Ethyl-3-{[(2-formyl-l-methyl-lH-benzimidazole-5-yl) carbonyl] -(2-pyridinyl) amino} propanoate and Ethyl-3-{[(2-dichloromethyl-l-methyl -lH-benzimidazole-5-yl)carbonyl]- (2-pyridinyl) amino}propanoate and process for preparation thereof. The present invention further relates to the use of these novel compounds in the preparation of Dabigatran etexilate or pharmaceutically acceptable salt thereof.
- -
-
-
- PROCESS FOR THE PREPARATION OF DABIGATRAN ETEXILATE MESYLATE AND POLYMORPHS OF INTERMEDIATES THEREOF
-
The present invention provides crystalline form of intermediates of Formula 2A, Formula 2B and Formula E. The present invention also provides process for the preparation of dabigatran etexilate mesylate; polymorph of intermediates thereof; particularly processes for the preparation of crystalline form of intermediates. The present invention also relates to the use of crystalline intermediates for the preparation of dabigatran etexilate mesylate.
- -
-
-
- 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)
-
- PROCESSES FOR THE PREPARATION OF DABIGATRAN ETEXILATE
-
The present application relates to processes for preparing Dabigatran etexilate, including pharmaceutically acceptable salts or tautomers thereof.
- -
-
Page/Page column 23
(2013/10/21)
-
- IMPROVED PROCESS FOR PREPARATION OF DABIGATRAN ETEXILATE AND ITS NOVEL INTERMEDIATE
-
Provided are intermediates for preparing dabigatran etexilate i.e. isopropanol solvate of l-methyl-2-[N-(4-amidinophenyl)-aminomethyl] benzimidazol-5-yl-carboxylicacid-N-(2-pyridyl)-N-(2-ethoxy carbonyl ethyl)-amide hydrochloride of formula (Vila) and crystalline form II of l-methyl-2-[N-(4-amidinophenyl)-aminomethyl] benzimidazol-5-yl-carboxylic acid-N-(2-pyridyl)-N-(2-ethoxy carbonyl ethyl)-amide hydrochloride of formula (VII).
- -
-
-
- NOVEL POLYMORPH OF DABIGATRAN ETEXILATE
-
Disclosed is a novel polymorph of 3-[(2-{[4-(hexyloxycarbonylaminoimino-methyl)-phenylamino]-methyl}-1-methyl-1H- benzimidazole-5-carbonyl)-pyridin-2-yl-amino]-propionic acid ethyl ester.
- -
-
Page/Page column 11
(2013/09/12)
-
- Design, synthesis and antithrombotic evaluation of novel dabigatran prodrugs containing methyl ferulate
-
A novel series of prodrugs containing dabigatran and methyl (E)-3-(4-hydroxy-2-methoxyphenyl)propenoate (methyl ferulate) were synthesized. All of them reveal the effect of thrombin-induced anti-platelet aggregation in vitro. In addition, in vivo experiment shows that one of the target compounds, X-2 (ED50 = 3.7 ± 1.0 μmol/kg) possesses a more potent activity for inhibiting venous thrombosis than that of dabigatran etexilate (ED50 = 7.8 ± 1.5 μmol/kg).
- Yang, Xiao-Zhi,Diao, Xiao-Juan,Yang, Wen-Hui,Li, Feng,He, Guang-Wei,Gong, Guo-Qing,Xu, Yun-Gen
-
p. 2089 - 2092
(2013/04/24)
-
- 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.
- -
-
-
- 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.
- -
-
Page/Page column 46; 49
(2012/12/13)
-
- PROCESS FOR THE PREPARATION OF BENZIMIDAZOLE DERIVATIVES AND ITS SALTS
-
The Present Invention Provides An Improved Process For The Preparation Of 1-methyl-2-[n-[4-(n-n-hexyloxycarbonylamidino) Phenyl]aminomethyl]benzimidazol-5-yl-carboxylicacid-n-(2-pyridyl)-n-(2-ethoxycarbonylethyl)amide Compound Of Formula-1 And Its Methanesulfonate Salt Compound Of Formula-1a.
- -
-
-
- PROCESS FOR THE MANUFACTURE OF DABIGATRAN ETEXILATE AND INTERMEDIATES THEREOF
-
The present invention relates to a process for the preparation of dabigatran etexilate of the formula (1) or the pharmaceutically accepted salts thereof.
- -
-
-
- PROCESS OF PREPARING A THROMBIN SPECIFIC INHIBITOR
-
A process of preparation of a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R1 and R2 represent H; or either R1 represents ethyl and R2 represents n-hexyloxycarbonyl that applies to industrial scale, novel intermediates useful for the preparation thereof, and processes of preparing said intermediates.
- -
-
-
- SOLID STATE FORMS OF DABIGATRAN ETEXILATE, DABIGATRAN ETEXILATE MESYLATE AND PROCESSES FOR PREPARATION THEREOF
-
Crystalline forms of Dabigatran Etexilate and Dabigatran Etexilate mesylate are described in the present application and processes for preparing the crystalline forms. The present invention also includes pharmaceutical compositions of such crystalline forms of Dabigatran Etexilate and Dabigatran Etexilate mesylate, methods of their preparation and the use of such crystalline forms in the treatment of a patient in need thereof.
- -
-
Page/Page column 21
(2012/03/26)
-
- Synthesis and antithrombotic evaluation of novel dabigatran prodrugs containing a cleavable moiety with anti-platelet activity
-
A novel series of prodrugs consisting of dabigatran and 2-hydroxymethyl-3,5,6-trimethylpyrazine (HTMP) were synthesized. The pharmacological results show that all of them possess the effect of anti-platelet aggregation induced by thrombin in vitro. Moreover, one of those compounds, Y-2 (ED50 = 2.1 ± 1.3 mg/kg) shows more potent activity for inhibiting thrombosis in vivo than that of dabigatran etexilate (ED50 = 4.4 ± 2.2 mg/kg).
- Yang, Xiao-Zhi,Yang, Wen-Hui,Xu, Yun-Gen,Diao, Xiao-Juan,He, Guang-Wei,Gong, Guo-Qing
-
-
- PROCESS FOR THE MANUFACTURE OF DABIGATRAN ETEXILATE
-
An improved process for preparing dabigatran etexilate, as well as analogous compounds of formula 7, is described.
- -
-
-
- IMPROVED PROCESS FOR THE PREPARATION OF 4-(BENZIMIDAZOLYLMETHYLAMINO)-BENZAMIDES AND THE SALTS THEREOF
-
The invention relates to a process for preparing an optionally substituted 4-benzimidazol- 2-ylmethylamino)-benzamidine, characterised in that (a) an optionally correspondingly substituted diaminobenzene is condensed with 2 [4- (1,2,4-oxadiazol-5-on-3-yl)-phenylamino]-acetic acid, (b) i) the product thus obtained is hydrogenated and ii) optionally the amidino group is carbonylated, without isolating the intermediate product of the hydrogenation beforehand; as well as a process for preparing a salt of an optionally substituted 4(benzimidazol-2-ylmethylamino)-benzamidine, wherein (a) an optionally correspondingly substituted diaminobenzene is condensed with 2-[4-(1,2,4-oxadiazol-5-on-3-yl)-phenylamino]-acetic acid, (b) the product thus obtained is hydrogenated, and (c) i) optionally the amidino group is carbonylated and ii) without prior isolation of the intermediate product of the carbonylation the desired salt is isolated.
- -
-
Page/Page column 27-28
(2010/11/27)
-
- IMPROVED PROCESS FOR THE PREPARATION OF THE SALTS OF 4-(BENZIMIDAZOLYLMETHYLAMINO)-BENZAMIDES
-
The invention relates to a process for preparing a salt of an optionally substituted 4-benzimidazol-2-ylmethylamino)-benzamidine, characterised in that (a) an optionally correspondingly substituted diaminobenzene is condensed with 2-[4-(1,2,4-oxadiazol-5-on-3-yl)-phenylamino]-acetic acid, b) i) the product thus obtained is hydrogenated, ii) optionally the amidino group is carbonylated, without isolating the intermediate product of the hydrogenation beforehand and iii) without prior isolation of the intermediate product of the carbonylation the desired salt is isolated.
- -
-
Page/Page column 20; 21
(2010/11/27)
-
