- Convenient synthesis of Valsartan via a Suzuki reaction
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An efficient synthesis of the angiotensin II inhibitor Valsartan (Diovan) is presented. The formation of the aryl-aryl bond represents the key step of its synthesis, which has been done by a Suzuki coupling of aryl boronate with 2-bromophenyl oxazoline with good yield and purity. This method overcomes many of the drawbacks associated with the previously reported syntheses.
- Ghosh, Samir,Kumar, A. Sanjeev,Mehta
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Read Online
- Valsartan without genotoxic impurity and preparation method thereof (by machine translation)
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To, valsartan crude: is cyclised to obtain valsartan medoxomil (V), and the valsartan crude product (IV), is purified to obtain valsartan medoxomil (III), to obtain valsartan medoxomil (,) through hydrolysis pH, modulation (II), to obtain the valsartan crude product. pH. The valsartan crude product is obtained by cyclizing the valsartan medoxomil sodium, into salt to obtain valsartan medoxomil,and preparation method of the valsartan medoxomil prepared by the following steps N,N - refining to obtain valsartan medoxomil and, N,N -% of valsartan medoxomil. (by machine translation)
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Paragraph 0085-0088
(2020/05/09)
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- A facile synthesis of 5-(4'-substituted)-[1,1'-biphenyl]-2-yl)-1H-tetrazole: A key intermediate for synthesis of angiotensin II receptor antagonist
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A convenient commercial scale synthesis of 5-(4'-(substituted)-[1,1'-biphenyl]-2-yl)-1H-tetrazole 1 a common intermediate for so many angiotensin II receptors antagonists, has been achieved with high purity using a simple synthetic protocol. The advantage
- Reddy, Kesamreddy Ranga,Reddy, Emani Vijayabhaskar,Shanmukha Kumar
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p. 295 - 300
(2018/09/14)
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- A method for preparing methyl valsartan
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The invention provides a preparation method of valsartan. The preparation method has the technical effects that amide methyl ester and sodium azide are used as raw materials and are catalyzed by amine salt to carry out tetrazole formation reaction; side effects are minimized by controlling the reaction course; main products are furthest generated; unreacted raw materials are recycled and reused; the yield in the preparation method is increased by more than 10% relative to the yields in existing processes; compared with the existing processes, the method has the effect that plenty of high-toxicity wastewater is no longer generated, and is easy to be widely popularized industrially.
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- DEPROTECTION METHOD FOR TETRAZOLE COMPOUND
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The present invention relates to a method of deprotecting a tetrazole compound, useful as an intermediate for angiotensin II receptor blockers, and provides a novel production method of angiotensin II receptor blockers. Provided is a production method of a compound represented by the formula [3] or [4] or a salt thereof, including (i) reducing a compound represented by the formula [1] or [2] or a salt thereof in the presence of a metal catalyst and an alkaline earth metal salt, or (ii) reacting the compound with a particular amount of Br?nsted acid: wherein each symbol is as defined in the present specification.
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- AN IMPROVED PROCESS FOR THE PREPARATION OF N-PENTANOYL-N-[[2'-(1H-TETRAZOL-5-YI)[1,1'-BIPHENYL]-4-YI]METHYL]-L-VALINE
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Disclosed herein is an improved process for the preparation of pure N-Pentanoyl-N-[[2'- (1h-Tetrazol-5-Y1)[1,1'-Biphenyl]-4-Yl]Methyl]-L-Valine employing highly active carbon.
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- Synthesis, pharmacokinetics, and pharmacodynamics studies of valsartan peptide derivatives
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In order to increase the intestinal permeability of valsartan, 14 esters and peptide derivatives of valsartan were chemically synthesized and their absorption characteristics were described. All derivatives were stable and could be better absorbed into th
- Wu, Chun,Hu, Yanpeng,Li, Qianbin,He, Limei,Chen, Jun,Cheng, Zeneng,Li, Yuanjian,Hu, Gaoyun
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experimental part
p. 393 - 400
(2012/08/07)
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- IMPROVED PROCESS FOR PREPARING VALSARTAN
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The invention relates to an improved process for the preparation of valsartan wherein the cycloaddition reaction is performed is an ether as reaction solvent, with a metal salt azide and in the present of zinc halides.
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- AN IMPROVED PROCESS FOR THE PREPARATION OF ANGIOTENSIN II ANTAGONIST
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The present invention provides a method for the preparation of N-(1-oxopentyl)-N-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-L-valine (Valsartan) which comprises; treating N-[[2'-(1-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methy]-L-valine methy
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Page/Page column 10-11
(2008/06/13)
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- INTERMEDIATE COMPOUNDS FOR THE PREPARATION OF ANGIOTENSIN II ANTAGONISTS
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The present invention relates to novel substituted biphenyltetrazole compounds useful as intermediates in the preparation of angiotensin II antagonists, to a process for the synthesis of them and to a process for the conversion thereof to said molecules.
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Page/Page column 30-31
(2010/11/30)
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- Synthesis of valsartan via decarboxylative biaryl coupling
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(Chemical Equation Presented) An efficient synthesis of the angiotensin II inhibitor valsartan (Diovan) is presented. Two routes were evaluated, both making use of an advanced version of our decarboxylative coupling for the construction of the biaryl moiety. Thus, in the presence of a catalyst system consisting of copper(II) oxide, 1,10-phenanthroline, and palladium(II) bromide, 2-cyanocarboxylic acid was coupled with 1-bromo(4-dimethoxymethyl)benzene in 80% yield and with 4-bromotoluene in 71% yield. The valsartan synthesis using 1-bromo(4-dimethoxymethyl)benzene was completed in four steps overall with a total yield of 39%, via a novel route that presents substantial economical and ecological advantages over the literature process, as it is more concise and stoichiometric amounts of expensive organometallic reagents are avoided.
- Goossen, Lukas J.,Melzer, Bettina
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p. 7473 - 7476
(2008/02/12)
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- Efficient synthesis of valsartan, a nonpeptide angiotensin II receptor antagonist
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A highly efficient and convergent approach to the synthesis of the angiotensin II receptor antagonist valsartan (1), one of the most important agents used in antihypertensive therapy today, is described. Directed ortho-metalation of 4-bromotoluene provides the key boronic acid intermediate 11 which was subjected to palladium-catalyzed Suzuki coupling. This method overcomes many of the drawbacks associated with the previously reported syntheses. The saponification of the methyl ester in valsartan was realized in a convenient and economical manner, which is more suitable for industrial production. Georg Thieme Verlag Stuttgart.
- Zhang, Chen,Zheng, Guojun,Fang, Lijing,Li, Yulin
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p. 475 - 477
(2007/10/03)
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- PROCESS FOR PRODUCTION OF (S) -N-PENTANOYL-N-[[2’-(1H-TETRAZOLE-5YL) [1,1’-BIPHENYL]-4-YL]METHYL]-L-VALINE
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The patent relates to a new process of synthesis of an antihypertensive agent, N-pentanoyl-N-[[2'-(1H-tetrazole-5-yl)[1,1'-biphenyl]-4-yl]methyl]-L-valine (1), also known under the generic name of valsartan, by selective reaction of N-pentanoyl-N-[[2'-(1H-tetrazole-5-yl) [1,1'-biphenyl]-4-yl]methyl]-L-valine methyl-ester (14) with metallic or quaternary ammonium trialkylsilanolates by SN2 reaction. The compound 14 was produced in four reaction steps starting from 2N-trityl-5-(4'-methylbiphenyl-2-yl)tetrazole (17) and L-valine methyl-ester (11). Free-radical bromination of the compound 17 with N-bromosuccinimide produced 2N-trityl-5-(4'-bromomethylbiphenyl-2-yl)tetrazole (7), which in the reaction with L-valine methyl-ester (11) results in N-[[2'-(2N-trityl-tetrazole-5-yl)[1,1'-biphenyl]-4-yl]methyl]-L-valine methyl-ester hydrobromide (15). Acylation of the compound 15 with pentanoyl chloride in the presence of trialkylamine bases results in N-pentanoyl-N-[[2'-(2N-trityl-tetrazole-5-yl)[1,1'-biphenyl] -4-yl]methyl]-L-valine methyl-ester (16). Removal of trityl protecting group by strong acids produces the key intermediary, compound 14.
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Page/Page column 17-20; 9
(2010/02/12)
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- ACYL COMPOUNDS
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Compounds of the formula STR1 in which R 1 is an aliphatic hydrocarbon radical which is unsubstituted or substituted by halogen or hydroxyl, or a cycloaliphatic or araliphatic hydrocarbon radical; X 1 is CO, SO 2, or--O--C(=O)--with the carbon atom of the carbonyl group being attached to the nitrogen atom shown in formula I; X 2 is a divalent aliphatic hydrocarbon radical which is unsubstituted or substituted by hydroxyl, carboxyl, amino, guanidino or a cycloaliphatic or aromatic radical, or is a divalent cycloaliphatic hydrocarbon radical, it being possible for a carbon atom of the aliphatic hydrocarbon radical to be additionally bridged by a divalent aliphatic hydrocarbon radical; R. sub.2 is carboxyl which, if desired, is esterified or amidated, substituted or unsubstituted amino, formyl which, if desired, is acetalized, 1H-tetrazol-5-yl, pyridyl, hydroxyl which, if desired, is etherified, S(O) m--R where m is 0, 1 or 2 and R is hydrogen or an aliphatic hydrocarbon radical, alkanoyl, unsubstituted or N-substituted sulfamoyl or PO n H 2 where n is 2 or 3; X 3 is a divalent aliphatic hydrocarbon; R 3 is carboxyl, 5-tetrazolyl, SO. sub.3 H, PO. sub.2 H 2, PO 3 H 2 or haloalkylsulfamoyl; and the rings A and B independently of one another are substituted or unsubstituted; in free form or in salt form, can be prepared in a manner known per se and can be used, for example, as medicament active ingredients.
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