139481-69-9

Basic information

• Product Name: Ethyl-2-Ethoxy-1-[[(2'-(1h-Tetrazol-5-Yl)Biphenyl-4-Yl)Methyl]Benzimidazole]-7-Carboxylate
• Synonyms: Methyl 1-((2'-(2H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)-methyl)-2-ethoxy-1H-benzo[d]imidazole-7-ca;Methyl 1-((2'-(2H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)Methyl)-2-ethoxy-1H-benzo[d]iMidazole-7-carboxylate;methyl 1-((2,-(1H-tetrazol-5-yl)-[1,1,-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate;Methyl 1-((2'-(2H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)-methyl)-2-ethoxy-1H-benzo[d]imidazole-7;Ethyl-2-Ethoxy-1-[[(2'-(1h-Tetrazol-5-Yl)Biphenyl-4-Yl)Methyl]Benzimidazole]-7-Carboxylate;ETHYL2-ETHOXY-1-[[2'-(1H-TETRAZOL-5-YL)METHYL]BENZIMIDAZOLE-7-CARBOXYLATE;Candesartan Methyl Ester;thyl-2-ethoxy-1-[[2'-(1Htetrazol-5-yl-)methyl]benzimidazole]-7-carboxylate
• CAS NO: 139481-69-9
• Molecular Formula: C₂₅H₂₂N₆O₃
• Molecular Weight: 468.515
• EINECS: 1806241-263-5
• Product Categories: Aromatics;Bases & Related Reagents;Heterocycles;Intermediates & Fine Chemicals;Nucleotides;Pharmaceuticals
• Mol File: 139481-69-9.mol

Chemical Properties

• Melting Point: 169-173°C
• Boiling Point: 704.488 °C at 760 mmHg
• Flash Point: 379.861 °C
• Appearance: /
• Density: 1.357 g/cm³
• Storage Temp.: Refrigerator
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 4.15±0.10(Predicted)
• CAS DataBase Reference: Ethyl-2-Ethoxy-1-[[(2'-(1h-Tetrazol-5-Yl)Biphenyl-4-Yl)Methyl]Benzimidazole]-7-Carboxylate(CAS DataBase Reference)
• NIST Chemistry Reference: Ethyl-2-Ethoxy-1-[[(2'-(1h-Tetrazol-5-Yl)Biphenyl-4-Yl)Methyl]Benzimidazole]-7-Carboxylate(139481-69-9)
• EPA Substance Registry System: Ethyl-2-Ethoxy-1-[[(2'-(1h-Tetrazol-5-Yl)Biphenyl-4-Yl)Methyl]Benzimidazole]-7-Carboxylate(139481-69-9)

Safety Data

• Hazardous Substances Data: 139481-69-9(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Ethyl-2-Ethoxy-1-[[(2'-(1h-Tetrazol-5-Yl)Biphenyl-4-Yl)Methyl]Benzimidazole]-7-Carboxylate is used as an intermediate in the preparation of Candesartan (C175575) for the pharmaceutical industry. Candesartan is an angiotensin II receptor antagonist used in the treatment of hypertension and heart failure.
As an intermediate, Ethyl-2-Ethoxy-1-[[(2'-(1h-Tetrazol-5-Yl)Biphenyl-4-Yl)Methyl]Benzimidazole]-7-Carboxylate plays a crucial role in the synthesis process of Candesartan, contributing to the development of this essential medication for cardiovascular health.

Upstream product

• 139481-44-0 methyl 1-[(2'-cyanobiphenyl-4-yl)methyl]-2-ethoxy-benzimidazole-7-carboxylate 
• 21606-04-2 methyl 2-carboxy-3-nitrobenzoate 
• 73833-13-3 acid chloride of 1-methylhydrogen-3-nitrophthalate 
• 603-11-2 3-nitrophthalic acid 
• 57113-90-3 methyl 2-(N-tert-butoxycarbonylamino)-3-nitrobenzoate 
• 856414-36-3 2-Azidocarbonyl-3-nitro-benzoic acid methyl ester 
• 136304-78-4 methyl 3-amino-2-[[(2'-cyanobiphenyl-4-yl)methyl]amino]benzoate 
• 139481-28-0 methyl 2-<<2'-cyanobiphenyl-4-yl)methyl>amino>-3-nitrobenzoate 
• 139481-38-2 methyl 2-amino>-3-nitrobenzoate 
• 150058-27-8 2-ethoxy-1H-benzimidazole-7-carboxylic acid methyl ester 
• 124750-51-2 N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole 

Downstream Products

• 139481-59-7 candesartan 
• 1215298-35-3 methyl 2-ethoxy-1-({2′-[1-(phenylmethyl)-1H-tetrazol-5-yl][1,1′-biphenyl]-4-yl}methyl)-1H-benzimidazole-7-carboxylate 
• 145040-37-5 candesartan cilexetil 
• 139481-72-4 2-Ethoxy-1-[[2'-(N-triphenylmethyltetrazol-5-yl)-biphenyl-4-yl]methyl]benzimidazole-7-carboxylic acid 

Relevant articles and documents

METHOD FOR PREPARING TRITYL CANDESARTAN

The present invention uses a candesartan cyclic compound as a starting material and performs thereon a three-step reaction of forming tetrazole, hydrolysis and adding a protecting group to directly obtain trityl candesartan without separating an intermediate product via crystallization. The operating process is simple and thus is more applicable to industrial production.

Preparation method of candesartan

The invention relates to a preparation method of candesartan. The preparation method comprises the steps of carrying out N-alkylation reaction, deprotection reaction and ester hydrolysis reaction on raw materials including 2-ethoxybenzimidazole-7-carboxylate and a tetrazole compound, so as to obtain the candesartan. According to the preparation method, compounds with high toxicity and large environmental protection pressure such as sodium azide, tributyl tin chloride or tributyl tin azide are not used; and compared with processes in the prior art, the preparation method is simple and convenient in operation and is beneficial to industrial large-scale production.

PROCESS FOR PREPARATION OF CANDESART AN CILEXETIL SUBSTANTIALLY FREE OF DES-CANDESARTAN CILEXETIL IMPURITY

The present invention provides a process for preparation of candeartan cilexetil substantially free of 2,3-dihydro-2-oxo-3-[[2'-(2H-tetrazol-5-yl)[l,l-biphenyl]-4- yl]methyl]-l-[[(cyclohexyloxy)carbonyl]oxy]ethylester-lH-benzimidazole-7- carboxylate (des-candesartan cilexetil) impurity.

METHOD FOR ISOLATING 5-SUBSTITUTED TETRAZOLES

The invention relates to a method for isolating 5-substituted tetrazoles of general formula (I) in which R represents a substituted biphenyl radical during which the ring closure, starting from a corresponding nitrile, is carried out in organic solvents while using alkali, alkaline-earth or organotin azides. The organic phases containing the nitrile and the tetrazol are firstly mixed with water while firstly forming three liquid phases, after which the aqueous phase containing the azide and the phase containing the nitrile are separated out, and the middle organic phase containing the tetrazol is subsequently processed. In the case of ester groups to be saponified, this phase is mixed with alkali lye, after which the organic phase is separated out and the aqueous phase is acidified or otherwise, this phase is immediately acidified and purified.

PROCESS FOR PREPARATION OF CANDESARTAN CILEXETIL

There was provided a process for preparing candesartan cilexetil, the said process comprises hydrogenating a solution of trityl candesartan cilexetil in an alcohol with hydrogen in the presence of a palladium catalyst. Mixture of toluene and methanol was added to 1-(Cyclohexyloxy carbonyloxy)ethyl-2-ethoxy-1-[[2'-(N-triphenylmethyltetrazole-5-yl)biphenyl-4-yl] methyl]benzimidazole-7-carboxylate and hydrogenated at room temperature with hydrogen at atmospheric pressure in the presence of palladium on carbon until the hydrogen uptake was ceased. Filtered over celite bed, washed the bed with a mixture of toluene and methanol, filtrate was collected and concentrated. Co- distilled with acetonitrile, acetonitrile was added, stirred at room temperature, cooled to 0°C. stirred, filtered, washed with chilled acetonitrile and dried to get candesartan cilexetil.

Novel O-[11C]methylated derivatives of candesartan as angiotensin II AT1 receptor imaging ligands: Radiosynthesis and ex vivo evaluation in rats

[11C]Methyl-candesartan and its desethyl derivative ([11C]TH4) were developed as potential radiotracers for imaging angiotensin II (Ang II) type 1 (AT1) receptors. These compounds were synthesized via methylation of tetrazole-protected candesartan using [11C]methyl iodide followed by deprotection through HCl hydrolysis at 65 °C to produce [11C]methyl-candesartan, and 90 °C for [11C]TH4. Ex vivo biodistribution and competition studies were carried out for both [11C]methyl-candesartan and [11C]TH4 to assess tissue retention time course and binding selectivity. Besides the liver, [11C]methyl-candesartan and [11C]TH4 displayed highest tissue retention in the AT1 receptor-rich renal cortex and outer medulla. At tracer doses 15 min post-injection, [11C]methyl-candesartan demonstrated higher specific binding proportion for AT1 receptors, and selectivity for AT1 over Ang II AT2, Mas, β-adrenergic, and α2-adrenergic receptors in rat kidneys compared to [11C]TH4. This study indicates that [11C]methyl-candesartan has potential for in vivo imaging renal AT1 receptors selectively using positron emission tomography.

PROCESS FOR PREPARING CANDESARTAN CILEXETIL

A process for preparing candesartan cilexetil.

CONVERSION OF AROMATIC NITRILES INTO TETRAZOLES

The present invention relates to the conversion of aromatic nitriles to tetrazoles, comprising treatment of the cyano compound with trialkyltin chloride and sodium azide optionally in the presence of a phase transfer catalyst. The process is particularly useful in the perparation of Irbesartan,Candesartan, Losartan and Valsartan.

CRYSTAL AND PROCESS FOR PRODUCING THE SAME

A process for producing crystals of 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimdazole-7-carboxylic acid (compound (I)), characterized by dissolving or suspending the compound (I) or a salt thereof in a solvent comprising an aprotic polar solvent and crystallizing it. By the process, the contaminants which are contained in the compound (I) or its salt and are difficult to remove, such as tin compounds, analogues of the compound (I), and a residual organic solvent, can be easily removed. Crystals of the compound (I) can be efficiently and easily mass-produced in high yield on an industrial scale.

Tri-higher alkyl tin azide and its use

Disclosed are a compound of the formula (R)3 SnN3, wherein R is a C7-18 alkyl, and a process for producing a tetrazolylbenzene compound which comprises reacting a cyanobenzene compound with a (R)3 SnN3. This process is useful for a safe and commercially profitable production of the tetrazolylbenzene compound which is employed for producing a tetrazole derivative having a hypotensive action based on angiotensin II-antagonizing activity or a production intermediate thereof.