- 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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- 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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experimental part
p. 986 - 988
(2011/12/16)
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- PROCESS FOR PREPARATION OF 5-SUBSTITUTED TETRAZOLES
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The present invention is a process for preparing sterically hindered 5-substituted tetrazole, which comprises of reacting a nitrile with an organotin halide and an azide in presence of a phase transfer catalyst, in an organic solvent and a co- solvent at reflux temperature for 4 to 20 h.
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Page/Page column 13
(2010/12/18)
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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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- 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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- 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 its intermediates
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The present invention relates to an improved process for the preparation of valsartan and its intermediates in substantially pure enantiomeric form. In particular, the present invention provides a process for preparing benzyl valsartan intermediate substantially free of organotin impurities. The valsartan produced from such benzyl valsartan intermediate requires significantly lower catalyst loading and has superior purity.
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Page/Page column 6
(2010/11/25)
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- INTERMEDIATE COMPOUNDS FOR THE PREPARATION OF AN ANGIOTENSIN II RECEPTOR ANTAGONIST
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It comprises new substituted 4-valinylmethylphenyl boronic acids and their derivatives and also its preparation process. It also comprises a preparation process of Valsartan from such intermediates. The process comprises the reaction of the new 4-valinylmethylphenyl boronic compounds with a (halophenyl)tetrazole compound which proceeds with high yields. The process is particularly advantageous in its practical industrial realization because it avoids the use of azide derivatives and also the use of expensive biphenyl intermediates.
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Page/Page column 29
(2008/06/13)
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- Process for the Preparation of Valsartan and its Intermediates
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The present invention concerns a process for preparing valsartan of Formula I: comprising purifying intermediate benzyl valsartan of Formula IV by crystallizing said benzyl valsartan of lower purity from a first solvent which is a ternary mixture comprising a hydrophilic solvent, a non-polar protic solvent and water; recovering benzyl valsartan from said ternary mixture followed by crystallizing benzyl valsartan from a second solvent comprising a non-polar aprotic solvent or polar aprotic solvent or their mixture; and recovering benzyl valsartan substantially free of organotin impurity; and converting said benzyl valsartan of into valsartan
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Page/Page column 3; 8-9
(2008/06/13)
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- A METHOD OF REMOVING THE TRIPHENYLMETHANE PROTECTING GROUP
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A method of removing the triphenylmethane protecting group from 1-triphenylmethyl-5-(4'-subst. methyl-1,1‘-biphenyl-2-yl)-1H-tetrazoles of general formula I wherein R represents the groups of formulae and where R1, R2 and R3 can be H, a halogen, an unbranched or branched C1-C5 alkyl, C1-C5 hydroxyalkyl, Cl-C5 alkoxy, C1-C5 alkoxymethyl or benzyl, or wherein R2 and R3 can form together a saturated or unsaturated C5-C7 ring, optionally an unsubstituted or substituted aromatic ring, is carried out by solvolysis in a simple anhydrous Cl to C5 alcohol in a neutral or slightly basic medium. The method is suitable for the preparation of drugs, such as the potassium salts of losartan, irbesartan or valsartan or candesartan cilexetil.
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Page/Page column 15
(2008/06/13)
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- PROCESS FOR ISOLATION OF VALSARTAN
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A process for isolation of valsartan is provided. The process forms solid valsartan having a purity of at least 99 %.
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Page/Page column 6
(2008/06/13)
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- PROCESS FOR PREPARATION OF BIPHENYL TETRAZOLE
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The present invention relates to processes for the preparation of pure valsartan. Also provided is a barium salt of valsartan, and a pharmaceutical composition thereof.
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Page/Page column 9
(2008/06/13)
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- PROCESS FOR THE MANUFACTURE OF VALSARTAN
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The present invention relates to a process for the manufacture of Valsartan, 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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- 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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