- tris(2-Perfluorohexylethyl)tin azide: A new reagent for preparation of 5-substituted tetrazoles from nitriles with purification by fluorous/organic liquid-liquid extraction
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Summary: The synthesis of a new fluorous tin azide, (C6F13CH2CH2)3SnN3, is reported and this reagent is used to make tetrazoles in both traditional and phase-switching modes. In the traditional mode, the tin azide is reacted with nitriles followed by HCl cleavage to provide the tetrazoles and the fluorous tin chloride (which can be reconverted into the tin azide). In the switching mode, the initial tin tetrazole is purified by fluorous/organic liquid-liquid extraction prior to destannylation. This provides pure products even in incomplete reactions or with impure starting materials, but it only works for smaller nitriles.
- Curran, Dennis P.,Hadida, Sabine,Kim, Sun-Young
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Read Online
- An efficient and telescopic process for valsartan, an angiotensin II Receptor Blocker
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An efficient, telescopic, and scalable process for an antihypertensive drug substance, valsartan with an overall yield of 58%, and ~99.9% purity is described. A simple, and safe process is developed for the recovery of tributyltin chloride from the tributyltin hydroxide, byproduct formed in the tetrazole ring construction, and reused in the synthesis of valsartan.
- Aalla, Sampath,Gilla, Goverdhan,Bojja, Yakambram,Anumula, Raghupathi Reddy,Vummenthala, Prabhakar Reddy,Padi, Pratap Reddy
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Read Online
- Preparation of Tetrazoles from Organic Nitriles and Sodium Azide in Micellar Media
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An effective method for the preparation of 5-substituted tetrazoles from the corresponding nitriles in micellar media is described. It was demonstrated that almost quantitative yields of tetrazoles can be obtained if the amount of water-surfactant is optimized. The advantages of the methods presented over many others currently used are the simplicity, facility of isolation of tetrazole products and elimination of using relatively expensive solvents and reagents.
- Jursic, Branko S.,LeBlanc, Blaise W.
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Read Online
- A short and efficient synthesis of valsartan via a Negishi reaction
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An efficient synthesis of the angiotensin-II inhibitor valsartan (Diovan) is presented. Directed ortho-metalation of 5-phenyl-1-trityl-1H- tetrazole (6) and its Negishi coupling with aryl bromide 5 are the key steps of the synthesis. This method overcomes
- Ghosh, Samir,Kumar, A. Sanjeev,Mehta, G. N.
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Read Online
- An improved synthesis of valsartan
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Biphenyltetrazole group, an important component of sartans, is usually formed in excellent yield by the reaction of 4′-alkylbiphenyl-2- carbonitrile with excessive organotin azide. However, it is restricted in industrial scale because of the difficult post-treatment. In this article, an improved synthetic method for valsartan and the quantitative recovery of tri-n-butyltin chloride are reported. During this process, the tetrazole-Sn complex and excessive organotin azide were decomposed by HCl to furnish tri - n-butyltin chloride, and then reacted with NaF to lead to filterable polymer tributyltin fluoride which was converted again to tributyltin chloride by HCl in ethyl acetate. This approach is facile for the efficient manufacture of sartans using organotin azide to form the tetrazole group and is valuable for industry readers.
- Wang, Guo-Xi,Sun, Bao-Ping,Peng, Cong-Hu
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Read Online
- A PROCESS FOR THE PREPARATION OF HIGHLY PURE VALSARTAN
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Disclosed herein is a process for the preparation and purification of Valsartan. The process according to the invention is capable of removing the toxic nitroamine impurities and providing substantially pure Valsartan.
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Page/Page column 11-16
(2021/06/11)
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- Synthesis of 5-Substituted 1 H-Tetrazoles from Nitriles by Continuous Flow: Application to the Synthesis of Valsartan
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An efficient continuous flow process for the synthesis of 5-substituted 1H-tetrazoles is described. The process involves the reaction between a polymer-supported triorganotin azide and organic nitriles. The polymer-supported organotin azide, which is in situ generated with a polystyrene-supported triorganotin alkoxide and trimethylsilylazide, is immobilized in a packed bed reactor. This approach is simple, fast (it takes from 7.5 to 15 min), and guarantees a low concentration of tin residues in the products (5 ppm). The process was developed to aryl-, heteroaryl-, and also alkylnitriles and was applied for the synthesis of valsartan, an angiotensin II receptor antagonist.
- Carpentier, Florian,Felpin, Fran?ois-Xavier,Zammattio, Fran?oise,Le Grognec, Erwan
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p. 752 - 761
(2020/03/13)
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- 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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- Method for treating azide ions, non-genotoxic impurity Sartan raw material medicine and immediate thereof
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The invention discloses a method for treating azide ions in a system and application thereof to the preparation of a compound with a tetrazolium group and without genotoxic impurities. The method is that the azide ions contained in the hydrogen peroxide treatment system are used. The method is used for preparing the compound with the tetrazolium group and comprises the following preparation steps:enabling a compound containing a cyano group to react with an azide, adding hydrogen peroxide after the reaction to quench and remove excessive sodium azide and further obtaining the compound with the tetrazolium group. The compound prepared by the method does not contain the genotoxic impurities. The method is simple in operation, mild in reaction conditions and suitable for industrial production.
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Paragraph 0105
(2019/05/28)
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- New impurity of valsartan and synthesis method
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The invention discloses a new impurity of valsartan and a synthesis method of the impurity. The method comprises the following steps of: adopting the valsartan to carry out high-temperature reaction in a solvent by using strong base, then adding acid for
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Paragraph 0017-0028
(2018/09/12)
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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 trityl protecting group by removing method of preparing losartan medicine
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The invention discloses a method for preparation of a Sartan drug by removal of a triphenylmethyl protective group. The method includes: under the catalysis of an insoluble weak acid, subjecting a Sartan prodrug and methanol to deprotection reaction, and after complete reaction, conducting aftertreatment to obtain the Sartan drug. The method has the characteristics of low cost, few side product, high quality product, and simple aftertreatment. At the same time, montmorillonite can be taken as insoluble weak acid, and the cost is low, thus being convenient for industrial production.
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Paragraph 0032-0039; 0047-0051
(2018/07/30)
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- Regioselective and Stereoselective Addition of Tetrazole Derivatives to Electron-poor Acetylenic Esters in the Presence of Triphenylphosphine
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Protonation of the highly reactive 1:1 intermediates produced in the reaction between triphenylphosphine and acetylenic esters by tetrazole derivatives leads to the formation of vinyltriphenylphosphonium salts. The cation of these salts undergoes an addition reaction with the counter anion in CH2Cl2at room temperature to yield the corresponding stabilized phosphorus ylides. Elimination of triphenylphosphine from the stabilized phosphorus ylides leads to the corresponding electron-poor N-vinyl tetrazoles in fairly high yields. Structures of N-vinyl tetrazoles were determined by IR,1H NMR,13C NMR and single crystal X-ray structure analyses. The reaction is fairly regioselective and stereoselective.
- Ramazani, Ali,Nasrabadi, Fatemeh Zeinali,?lepokura, Katarzyna,Lis, Tadeusz,Joo, Sang Woo
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- Tetrazolylmethyl quinolines: Design, docking studies, synthesis, anticancer and antifungal analyses
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A new series of 2,5 and 1,5-regioisomers of the tetrazolyl group viz., 3-[(5-benzyl/benzylthio-2H-tetrazol-2-yl) methyl]-2-chloro-6-substituted quinoline 6h-q and 3-[(5-benzyl/benzylthio-1H-tetrazol-1-yl) methyl]-2-chloro-6-substituted quinolines 7h-q were synthesized. Docking studies of all these compounds with DNA as target using PDB: 1AU5 and 453D revealed that the compounds 6h and 6i act as covalent cross linker on the DNA helix of the former and intercalate the latter both with higher C score values. Another set of docking studies in the active pocket of dihydrofolate reductase and N-myristoyl transferase as targets to assess antifungal activity revealed that compounds 6k, 6l, 6p and 7q (with bromo and fluro substituents) showcases different binding modes and hydrogen bonding. Further, the compounds were screened for anticancer activity (primary cytotoxicity) against NCI-60 Human tumor cell line at a single high dose (10?5M) concentration assay. Among the tested compounds, 6h has shown 99.28% of GI against Melanoma (SK-MEL-5) and compound 6i has shown 97.56% of GI against Breast Cancer (T-47D). Further, in vitro antifungal assay against A. fumigatus and C. albicans for these compounds 6h-q and 7h-q revealed potential to moderate activities as compared to the standard.
- Shaikh, Saba Kauser J.,Kamble, Ravindra R.,Somagond, Shilpa M.,Devarajegowda,Dixit, Sheshagiri R.,Joshi, Shrinivas D.
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p. 258 - 273
(2017/02/15)
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- Preparation and purification method of valsartan
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The invention relates to the field of medicinal chemistry and discloses a preparation and purification method of valsartan. The method comprises the steps of (S1) adding L-valine and alcohol to a reaction kettle, slowly dropwise adding thionyl chloride, carrying out heating reflux reaction, adding isopropyl acetate for pulping, carrying out suction filtration to obtain an intermediate 1; (S2) carrying out nucleophilic reaction on the intermediate 1 and a starting material 2 in a solvent under an alkaline condition to obtain an intermediate 2; (S3) carrying out nucleophilic reaction on the intermediate 2 and valeryl chloride in the solvent under the alkaline condition to obtain an intermediate 3; and (S4) carrying out cyclization reaction on the intermediate 3, sodium azide and a catalyst ((-)-sparteine-Cu (II) complex) in the solvent, washing, crystallizing and drying to obtain the valsartan. The sodium azide and the catalyst ((-)-sparteine-Cu (II) complex) are used in the cyclization reaction, and the cyclization yield can reach 90%. According to the purification method, the purity of the raw materials of the valsartan is greater than 99.99%, the content of a solvent residue (ethyl acetate) is smaller than 0.5%, the content of a specific impurity is smaller than 0.1%, other unknown individual impurities are avoided and an enantiomer impurity is not detected.
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Paragraph 0066; 0067; 0068; 0069; 0081-0083; 0090-0098
(2017/10/13)
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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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Paragraph 0062-0063
(2017/08/25)
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- Use of purine compound in treatment or prevention of hyperuricemic or gouty diseases
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The invention belongs to the technical field of medicines, relates to a use of a purine compound in treatment or prevention of hyperuricemic or gouty diseases, and concretely relates to a use of the purine compound concretely is a compound represented by formula (I), a pharmaceutically acceptable salt thereof, a solvate thereof or a composition containing anyone of the compound, the pharmaceutically acceptable salt and the solvate in the preparation of medicines for treating and/or preventing hyperuricemia, gouts, gouty inflammations and uratic nephropathy. In the formula (I), X represents a heteroaryl group selected from nitrogen-containing hetero atoms, Y represents a group selected from aryl groups or heteroaryl groups, the aryl groups or the heteroaryl groups are unsubstituted or are substituted with one or more halogen atoms or C-6 halogenated alkyl groups, m represents 3 or 4, and n represents 0 or 1.
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Paragraph 0147; 0148; 0149
(2017/01/02)
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- A method of preparing the valsartan
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The invention discloses a method for preparing valsartan. The method comprises the following steps: carrying out a first-step reaction on L-valine methyl-ester hydrochloride and 2-cyan-4'-bromomethyl biphenyl, of which the molar ratio is (1-2):1; carrying out a second-step reaction together with pentanoyl chloride; finally carrying out a third-step reaction, so as to obtain a valsartan crude product, wherein the first-step reaction comprises the following steps: by taking acetonitrile as a reaction solvent, carrying out neutral reaction on the L-valine methyl-ester hydrochloride and potassium carbonate; then adding the 2-cyan-4'-bromomethyl biphenyl to react; adding the 2-cyan-4'-bromomethyl biphenyl by 2-6 times, wherein the reaction temperature is 50-65 DEG C; the reaction time is 3-7 hours. By adopting the method for preparing the valsartan, the quantity of byproducts corresponding to valsartan impurities T in the product in the first step is controlled, so as to control the quantity of the valsartan impurities T; furthermore, the other conditions are correspondingly adjusted; generation of other unmanageable impurities also can be avoided. Thus, the high-purity valsartan product can be prepared.
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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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Page/Page column 42
(2015/09/23)
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- COMPOSITIONS AND METHODS FOR DIAGNOSING AND TREATING SALT SENSITIVITY OF BLOOD PRESSURE
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To characterize the urinary exosome miRNome, microarrays were used to identify the miRNA spectrum present within urinary exosomes from ten individuals that were previously classified for their salt sensitivity status. The present application discloses distinct patterns of selected exosomal miRNA expression that were different between salt-sensitive (SS), salt-resistant (SR), and inverse salt-sensitive (ISS) individuals. These miRNAs can be useful as biomarkers either individually or as panels comprising multiple miRNAs. The present invention provides compositions and methods for identifying, diagnosing, monitoring, and treating subjects with salt sensitivity of blood pressure. The applications discloses panels of miRNAs useful for comparing profiles, and in some cases one or more of the miRNAs in a panel can be used. The miRNAs useful for distinguishing SS and SR or ISS and SR subjects. One or more of the 45 miRNAs can be used. Some of the miRNAs have not been previously reported to be circulating. See those miRNAs with asterisks in FIG. 1 and below. The present invention encompasses the use of one or more of these markers for identifying and diagnosing SR, SS, and ISS subjects.
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- PROCESS FOR THE PREPARATION OF ANGIOTENSIN II ANTAGONISTS AND INTERMEDIATES THEREOF
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The present invention relates to an improved process for the preparation of angiotensin receptor antagonists and intermediates thereof. Particularly the present invention relates to an improved process for the preparation of N-(1-oxopentyl)-N-[[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-yl]methyl]-L-valine of Formula 1 via a phosphite salt of Formula-4.H3PO3 preferably a phosphite salt of Formula-4′.H3PO3
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- Synthesis of heteroaromatic derivatives with nitrogen atoms: Tripyrrolyl pyrimidine and tripyrrolyl[1,3,5]triazine
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As a part of a research program related to the synthetic study of pharmacologically and photoconductively interesting pyrrole derivatives, we have synthesized 1-arylpyrroles (3a-e), 9-arylcarbazoles (4a-e), aminophenylpyrroles (6a,b), dipyrrolylbenzenes (7a-c), 2,4,6-tri-pyrrol-1- yl-pyrimidine (8) and 2,4,6-tri-pyrrol-1-yl[1,3,5]triazine (9). We proposed a plausible mechanism for the formation of 9-arylcarbazole.
- Lee,Lee,Jung,Hahn
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p. 501 - 504
(2013/02/22)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF ANGIOTENSIN II ANTAGONISTS AND INTERMEDIATES THEREOF.
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The present invention relates to an improved process for the preparation of angiotensin receptor antagonists and intermediates thereof. Particularly the present invention relates to an improved process for the preparation of N-(l-oxopentyl)-N-[[2''-(lH-tetrazoI-5-yl) [1, 1 ''-biphenyl]-4-yl] methyl]-L- valine of Formula (1) Formula-1 Formula-4.H3P03 via a phosphite salt of Formula-4.H3P03 preferably a phosphite salt of Formula-4''.H3P03 Ph3C N-[2''-1 -triphenylmethyl-tetra zol-5-yl)biphenyl-4-yl)methyl ]-(L)-Valine Benzyl ester H3P03 salt Formula-4''.H3P03 salt.
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- PROCESS FOR THE PREPARATION OF VALSARTAN
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The present invention relates to a process for the preparation of pure Valsartan (I) substantially free from impurities of formulae (Ia), (Ib), and (Ic), which comprises: (i) condensing 2-(4′-bromomethylphenyl)benzonitrile of formula (II) with L-valine methyl ester hydrochloride of formula (V) in the presence of a base in a solvent to produce N-[(2′-cyanobiphenyl-4-yl)methyl]-(L)-valine methyl ester of formula (VI); (ii) treating the compound VI of step (i) with acid followed by treating with base to produce pure compound VI substantially free from dimeric impurity of formula (Via); (iii) reacting the pure compound of formula (VI) with n-valeryl chloride in the presence of a base to produce pure N-valeryl-N-[(2′-cyanobiphenyl-4-yl)methyl]-(L)-valine methyl ester (VII) substantially free from alkene impurity of formula (Vila); (iv) reacting the compound of formula (VII) with trialkyltin chloride and a metal azide in a solvent at a reflux temperature to produce N-(1-oxopentyl)-N-[[2′-(2-tributyltinte-trazol-5-yl)-(1,1′-biphenyl)-4-yl]methyl]-(L)-valine methyl ester of formula (VHIb) free from thermal degradation impurity (Villa); (v) hydrolyzing the compound of formula (VHIb) in the presence of alkaline conditions to produce Valsartan (I).
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- PROCESS FOR PRODUCTION OF BIPHENYL DERIVATIVE
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The invention provides a production method of a biaryltetrazole derivative useful as an intermediate for an angiotensin II receptor antagonist. The method comprises reacting an aryltetrazole derivative with a benzene derivative, deprotecting or reducing the resulting compound, and halogenating the deprotected or reduced compound
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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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- AN IMPROVED PROCESS FOR THE PREPARATION OF VALSARTAN
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The present invention relates to a process for the preparation of pure Valsartan (I) substantially free from impurities of formulae (la), (lb), and (Ic), which comprises: (i) condensing 2-(4'-bromomethylphenyl)benzonitrile of formula (II) with L-valine methyl ester hydrochloride of formula (V) in the presence of a base in a solvent to produce N-[(2'-cyanobiphenyl-4-yl)methyl]-(L)-valine methyl ester of formula (VI); (ii) treating the compound VI of step (i) with acid followed by treating with base to produce pure compound VI substantially free from dimeric impurity of formula (Via); (iii) reacting the pure compound of formula (VI) with n-valeryl chloride in the presence of a base to produce pure N-valeryl-N-[(2'-cyanobiphenyl-4-yl)methyl]- (L)-valine methyl ester (VII) substantially free from alkene impurity of formula (Vila); (iv) reacting the compound of formula (VII) with trialkyltin chloride and a metal azide in a solvent at a reflux temperature to produce N-(l-oxopentyl)-N-[[2'-(2- tributyltintetrazol-5-yl)-(l, l '-biphenyl)-4-yl]methyl]-(L)-valine methyl ester of formula (VHIb) free from thermal degradation impurity (Villa); (v) hydrolyzing the compound of formula (VHIb) in the presence of alkaline conditions to produce Valsartan (I).
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- Highly efficient synthesis of 5-substituted 1H-tetrazoles catalyzed by Cu-Zn alloy nanopowder, conversion into 1,5- and 2,5-disubstituted tetrazoles, and synthesis and NMR studies of new tetrazolium ionic liquids
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A series of 5-substituted 1H-tetrazoles were synthesized through [3+2] cycloaddition reactions between nitriles RCN and NaN3 in the presence of Cu-Zn alloy nanopowder as catalyst. The 1,5-dibutyl, 1-butyl-5-hexyl, 2,5-dibutyl, and 2-butyl-5-hexyl derivatives were then used as building blocks to synthesize several novel tetrazolium ionic liquids (ILs) with EtSO 4-, OTf-, and NTf2- counterions. Whereas alkylation of the 2,5-dialkyltetrazoles selectively gave the N-4 alkylated onium salts, with the 1,5-dialkyl derivatives approximately 1:1 mixtures of two tetrazolium salts were formed by alkylation at N-3 and N-4. The triflate and ethyl sulfate salts are room-temperature ILs that are hydrophilic, whereas the NTf2 salts are low-melting ILs and are hydrophobic. The resulting tetrazolium-based ionic liquids were studied by various multinuclear and 2D NMR techniques including natural abundance 15N and 1H/15N correlations.
- Aridoss, Gopalakrishnan,Laali, Kenneth K.
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experimental part
p. 6343 - 6355
(2011/12/03)
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- PROCESS FOR THE MANUFACTURE OF ORGANIC COMPOUNDS
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The present invention relates to processes for the manufacture of an angiotensin receptor blocker (ARB; also called angiotension Il receptor antagonist or AT1 receptor antagonist) and salts thereof, to novel intermediates and process steps.
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Page/Page column 46-47
(2011/05/11)
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- Process for the manufacture of organic compounds
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The present invention relates to a process for the manufacture of an angiotensin receptor blocker (ARB: also called angiotension II receptor antagonist or AT1 receptor antagonist) and salts, thereof, to novel intermediates and process steps.
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- Synthesis of angiotensin II receptor blockers by means of a catalytic system for C-H Activation
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A highly efficient catalytic system for C-H activation has been worked out that involves inexpensive RuCl3·xH2O and a specific amount of PPh3. This procedure has been successfully applied to a practical synthesis of angiotensin II receptor blockers (ARBs). The residual ruthenium that existed in the reaction mixture was thoroughly removed by treatment with properly selected metal scavengers. The new process permits ready access to the important class of drugs in a highly atom-economical and sustainable manner (Figure presented).
- Seki, Masahiko,Nagahama, Masaki
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p. 10198 - 10206
(2012/02/03)
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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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- METHOD OF REMOVING THE TRIPHENYLMETHANE PROTECTION GROUP
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The present invention relates to a method of removing triphenylmethane protection group. The method for preparing biphenyl benzoic acid derivatives of the present invention is economically advantageous and very excellent in the aspect of improving process in that: process safety is secured by using acidic ion exchange resin in the presence of organic solvent instead of using highly corrosive acid; the reaction takes much less time than do the conventional reactions which use only anhydrous methanol and few sub-reaction does occur; and the ion-exchange resin of the present invention is excellent for mass-processing because the resin can be collected and recycled only by filtration after being used.
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Page/Page column 20
(2010/07/02)
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- PREPARATION OF VALSARTAN
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Processes for preparing valsartan and essentially amorphous valsartan are described.
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Page/Page column 18-19
(2010/08/18)
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- PROCESS FOR PREPARATION OF VALSARTAN INTERMEDIATE
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The present invention provides a process for preparation of a key intermediate of valsartan in a pure form and use of this intermediate for the preparation of valsartan or a pharmaceutically acceptable salt in pure form.
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- New and improved manufacturing process for valsartan
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A new and improved industrially viable manufacturing process for valsartan, an antihypertension drug, is described.
- Kumar N, Senthil,Reddy, Shankar B.,Sinha, Brajesh Kumar,Mukkanti, Kagga,Dandala, Ramesh
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scheme or table
p. 1185 - 1189
(2010/04/22)
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- PROCESSES FOR THE PREPARATION OF INTERMEDIATES OF VALSARTAN
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The present invention relates to processes for the preparation of intermediates of valsartan.
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Page/Page column 7
(2009/08/18)
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- Processes for the preparation of intermediates of valsartan
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The present invention relates to processes for the preparation of intermediates of valsartan.
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Page/Page column 13
(2009/09/05)
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- Unusual detritylation of tritylated tetrazole in Sartan molecules
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Tritylated tetrazole of 2a underwent unusual detritylation under basic reaction condition during the synthesis of methyl ether of olmesartan medoxomil 1. The unusual detritylation was found to be a common feature in the case of all tetrazole containing Sartan molecules (3-7).
- Srimurugan, Sankareswaran,Suresh, Paulsamy,Babu, Balaji,Hiriyanna, Salmara Ganeshbhat,Pati, Hari Narayan
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p. 383 - 384
(2008/09/20)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF VALSARTAN
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The present invention relates to an improved process for the preparation of valsartan compound of formula-1 through novel intermediate compounds. It also relates to a novel process for the preparation of amorphous form of valsartan.
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Page/Page column 19
(2010/11/29)
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- PROCESS FOR THE PREPARATION OF VALSARTAN
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The present invention relates to a process for preparing valsartan from a compound of general formula (I), wherein R is cumyl, trityl or t-butyl. The process comprises a first step, wherein the protective group is eliminated and thereafter the oxazolidinone ring is opened by catalytic hydrogenationin the presence of an organic base. Finally, Valsartanor a pharmaceutically acceptable salt thereofis isolated.
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Page/Page column 10; 12
(2009/01/20)
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- PROCESS FOR PREPARING VALSARTAN
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An N-[(2'-(1-triphenyl methyl tetrazole-5-yl) biphenyl]-4-yl] methyl]-L-valine benzyl ester organic salt of formula (IVA) wherein A represents an organic carboxylic acid, a process for its preparation and its use in the synthesis of valsartan or salts thereof.
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- PROCESS FOR THE PREPARATION OF VALSARTAN AND INTERMEDIATE PRODUCTS
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The present invention relates to a new method for the production of valsartan, a valine derivative having the chemical name is (S)-N-(1 -carboxy-2-methylprop-1 -yl)-N-pentanoyl-N- [2'-(1 H-tetrazol-5-yl)-biphenyl-4-ylmethyl]amine, and pharmacologically ac
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Page/Page column 12; 19-20
(2008/12/06)
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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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- INTEGRASE INHIBITORS - 1
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The present invention describes a method of treatment or prophylaxis of a viral infection in a subject comprising administering to said subject an effective amount of a compound of formula (I) or a pharmaceutically acceptable derivative, salt or prodrug thereof. Compounds of formula (I) are also provided.
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Page/Page column 26-27
(2010/11/28)
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- Safe and fast tetrazole formation in ionic liquids
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The [2+3] cycloaddition of nitriles and azides is reliable for intramolecular reactions, but the hazards with volatile azides in intermolecular reactions are tremendous. Zinc catalysis in aqueous solution is a magnificent improvement, but requires the removal of the zinc salts from the acidic product. Herein, we report safe solvents featuring low vapor pressure and good solubility of NaN3. Ionic liquids based on alkylated imidazoles combined with microwave heating turned out to be a solution for the given tasks.
- Schmidt, Boris,Meid, Daniela,Kieser, Daniel
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p. 492 - 496
(2007/10/03)
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- A PROCESS FOR PURIFICATION OF VALSARTAN
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The present invention relates to a process for purification of Valsartan comprising steps of: (i) crystallizing from an organic solvent (ii) washing the crystallized product obtained in step (i) with a solvent selected from a group consisting of aliphatic
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Page/Page column 6
(2008/06/13)
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- INTERMEDIATES AND PROCESSES FOR THE PREPARATION OF VALSARTAN
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It comprises a preparation process of Valsartan from new salts of Valsartan having the tetrazole moiety protected with a protective group. The process leads to the elimination of the typical impurities due to the preparation process while avoiding its rac
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Page/Page column 26
(2010/11/27)
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- A process for the preparation of angiotensin II antagonistic compounds
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A process for the preparation of angiotensin II antagonists and novel intermediates useful for the synthesis thereof.
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Page/Page column 7
(2008/06/13)
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- PROCESS FOR THE PREPARATION OF ANGIOTENSIN II ANTAGONISTIC COMPOUNDS
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A process for the preparation of angiotensin II antagonists and novel intermediates useful for the synthesis thereof.
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Page/Page column 5
(2010/11/26)
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- Process for obtaining a valsartan salt useful for obtaining valsartan
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The invention relates to a new salt of Valsartan, in particular to the high-purity dilithium salt of Valsartan, its polymorphs and solvates or hydrates thereof, useful for obtaining Valsartan with a high yield. The process for obtaining the dilithium salt of Valsartan (I) comprises i) Coupling of the intermediate (II) with the 2-(1H-tetrazole-5-il)-phenylboronic acid of formula (III), wherein said coupling takes place in the presence of a lithium base, and a mixture of water and water-miscible organic solvent and a palladium catalyst, to give the dilithium salt of Valsartan of formula (I).
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Page/Page column 6-7
(2008/06/13)
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