147403-65-4

Basic information

• Product Name: (Z)-Methyl 2-ethoxy-3-((2'-(N'-hydroxycarbaMiMidoyl)biphenyl-4-yl)Methyl)-3H-benzo[d] iMidazole-4-carboxylate
• Synonyms: (Z)-Methyl 2-ethoxy-3-((2'-(N'-hydroxycarbaMiMidoyl)biphenyl-4-yl)Methyl)-3H-benzo[d] iMidazole-4-carboxylate;(Z)-Methyl 2-ethoxy-1-((2'-(N'-hydroxycarbaMiMidoyl)biphenyl-4-yl)Methyl)-1H-benzo[d]iMidazole-7-carboxylate;2-Ethoxy-1-[[2'-[(hydroxyaMino)iMinoMethyl][1,1'-biphenyl]-4-yl]Methyl]-1H-benziMidazole-7-carboxylic Acid Methyl Ester;(Z)-Methyl 2-ethoxy-3-((2'-(N'-hydroxycarbaMiMidoyl)biphenyl-4-yl)Methyl)-3H-benzo[d] iMidazole-4-ca;Methyl 2-ethoxy-1-((2'-(N-hydroxycarbamimidoyl)-[1,1'-biphenyl]-4-yl)methyl)-1H-benzo[d]imidazole;InterMediate of Azilsartan;Methyl 2-ethoxy-1-((2'-(N-hydroxycarbaMiMidoyl)-[1,1'-biphenyl]-4-yl)Methyl)-1H-benzo[d]iMidazole-7-carboxylate;2-Ethoxy-1-｛[2'-(N'-hydroxycarbaMiMidoyl)biphenyl-4-yl]Methyl｝-1H-benzo[d]iMidazole-7 -carboxylic acid Methyl ester
• CAS NO: 147403-65-4
• Molecular Formula: C₂₅H₂₄N₄O₄
• Molecular Weight: 444.48246
• EINECS: 1592732-453-0
• Product Categories: Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 147403-65-4.mol

Chemical Properties

• Melting Point: 207-209℃
• Boiling Point: 657.2±65.0 °C(Predicted)
• Appearance: /
• Density: 1.29
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• Solubility: Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly)
• PKA: 6.77±0.69(Predicted)
• CAS DataBase Reference: (Z)-Methyl 2-ethoxy-3-((2'-(N'-hydroxycarbaMiMidoyl)biphenyl-4-yl)Methyl)-3H-benzo[d] iMidazole-4-carboxylate(CAS DataBase Reference)
• NIST Chemistry Reference: (Z)-Methyl 2-ethoxy-3-((2'-(N'-hydroxycarbaMiMidoyl)biphenyl-4-yl)Methyl)-3H-benzo[d] iMidazole-4-carboxylate(147403-65-4)
• EPA Substance Registry System: (Z)-Methyl 2-ethoxy-3-((2'-(N'-hydroxycarbaMiMidoyl)biphenyl-4-yl)Methyl)-3H-benzo[d] iMidazole-4-carboxylate(147403-65-4)

Safety Data

• Hazardous Substances Data: 147403-65-4(Hazardous Substances Data)

Usage

Uses

1. Pharmaceutical Industry:
(Z)-Methyl 2-ethoxy-3-((2'-(N'-hydroxycarbaMiMidoyl)biphenyl-4-yl)Methyl)-3H-benzo[d] iMidazole-4-carboxylate is used as an intermediate in the synthesis of angiotensin II receptor antagonists, specifically for the development of Azilsartan (A926900) derivative. This application is due to its chemical properties that allow it to be a key component in the creation of drugs that help regulate blood pressure and treat hypertension.
2. Chemical Research and Development:
As a white solid with unique chemical properties, (Z)-Methyl 2-ethoxy-3-((2'-(N'-hydroxycarbaMiMidoyl)biphenyl-4-yl)Methyl)-3H-benzo[d] iMidazole-4-carboxylate can be used in various chemical research and development projects. Its specific properties make it a valuable compound for further exploration and potential development of new drugs or materials.
3. Drug Synthesis and Design:
The compound's structure and properties make it a potential candidate for use in drug synthesis and design, particularly in the development of new pharmaceuticals targeting specific receptors or biological pathways. Its role as an intermediate in the synthesis of angiotensin II receptor antagonists highlights its potential in this application.

Upstream product

• 1403477-45-1 methyl 2-ethoxy-1-((2'-(N'-(methoxycarbonyloxy)carbamimidoyl)biphenyl-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylate 
• 139481-44-0 methyl 1-[(2'-cyanobiphenyl-4-yl)methyl]-2-ethoxy-benzimidazole-7-carboxylate 

Downstream Products

• 147403-03-0 azilsartan 
• 147404-82-8 2-ethoxy-1-[[2'-[N'((ethoxycarbonyl)oxy)carbamimidoyl][1,1-biphenyl]-4-yl]methyl]-1H-benzimidazole-7-carboxylic acid methyl ester 
• 1403474-78-1 methyl 2-oxo-3-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)-2,3-dihydro-1H-benzo[d]imidazole-4-carboxylate 
• 147403-52-9 methyl 2-ethoxy-1-((2′-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)-1H-benzo[d]-imidazole-7-carboxylate 
• 1417576-00-1 (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-oxo-3-((2’-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)-[1,1’-biphenyl]-4-yl)methyl)-2,3-dihydro-1H-benzo[d]imidazole-4-carboxylate 
• 1417576-01-2 (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-ethoxy-1-((2′-(4-ethyl-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)-biphenyl-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylate 
• 1397836-49-5 1-[(2'-(N'-hydroxycarbamimidoyl)[1,1'-biphenyl]-4-yl)methyl]-2-ethoxy-1H-1,3-benzodiazole-7-carboxylic acid 
• 1449029-77-9 (5-methyl-2-oxo-2H-1,3-dioxol-4yl)methyl 2-ethoxy-1-[(4-(2-[N-hydroxy-carbamimidoyl]phenyl)phenyl)-methyl]-1H-1,3-benzodiazole-7-carboxylate 
• 1449029-78-0 (5-methyl-2-oxo-1,3-dioxol-4-yl) methyl 2-ethoxy-1-[(2'-{N'-[(ethoxycarbonyl)oxy]carbamimidoyl}-biphenyl-4-yl)-methyl]-1H-benzimidazole-7-carboxylate 
• 1449029-80-4 (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-ethoxy-1-{[2'-(N'-{[(4-nitrophenoxy)carbonyl]oxy}carbamimidoyl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-carboxylate 
• 147404-82-8 methyl 2-ethoxy-1-[[2'-(ethoxycarbonyloxy-carbamimidoyl)biphenyl-4-yl]methyl]benzimidazole-7-carboxylate 
• 147404-76-0 methyl 1-[(2'-carbamoylbiphenyl-4-yl)methyl]-2-ethoxybenzimidazole-7-carboxylate 

Relevant articles and documents

Synthesis technology for continuously preparing azilsartan in micro-channel reactor

The invention discloses a synthesis technology for continuously preparing azilsartan in a micro-channel reactor. The technology comprises the following steps: (1) adding SM-1, an aqueous hydroxylaminesolution and triethylamine into anhydrous ethanol, and performing a reaction to obtain an intermediate TAK1; (2) preparing a homogeneous solution A from the TAK1, triethylamine and dioxane; (3) preparing a homogeneous solution B from solid phosgene and dioxane; (4) dissolving sodium hydroxide in water to prepare a homogeneous solution C; (5) respectively pumping the homogeneous solution A and thehomogeneous solution B into a microstructure mixer I in a micro-channel reaction device at the same time, performing mixing, and introducing the obtained mixed solution into a microstructure reactorI; (6) respectively pumping the homogeneous solution C and the effluent of the microstructure reactor I into a microstructure mixer II in the micro-channel reaction device at the same time while step(5) is carried out, performing mixing, and introducing the obtained mixed solution into a microstructure reactor II; and (7) collecting the effluent of the microstructure reactor II to obtain the product azilsartan.

High-purity, small-particle-diameter and low-solvent-residue azilsartan bulk drug and preparation method thereof

The present invention discloses a high-purity, small-particle-diameter and low-solvent-residue azilsartan bulk drug and a preparation method thereof. The purity of the azilsartan bulk drug is more than or equal to 99.9%; the particle size of D90 is less than or equal to 20 [mu]m; and the solvent residue is less than or equal to 500 ppm. The present invention also discloses a high-purity intermediate used for preparing the azilsartan bulk drug and a preparation method thereof, wherein the purity of the intermediate is more than or equal to 99.9%.

A method for preparing [...]

The invention relates to an azilsartan (a hypertension treating medicine) preparation method, and belongs to the field of medicines. The method has the beneficial effects that a compound 1 serves as an initial raw material of the reaction, the azilsartan is prepared through three reaction steps of hydroxylammonium chloride addition, ethyl chloroformate acylation and cyclization hydrolysis under the alkali action, and the cyclization and hydrolysis reaction steps of the prior art are combined into one step, so that conventional 4-5 steps are reduced to three steps, and the reaction time is shortened; and the yield is increased, the content of ethyoxyl-removing impurities is greatly reduced, experimental operations are simplified, the cost is lowered, the azilsartan with high purity is obtained, the high performance liquid chromatography (HPLC) purity is more than 99.5%, and the ethyoxyl and amide-removing impurities are all less than 0.1%.

Method for simply and conveniently synthesizing azilsartan

The invention relates to the field of medicine, and discloses a method for simply and conveniently synthesizing azilsartan. According to the method, 1-[(2'-(hydroxyl guanyl)[1,1-biphenyl]-4-radical) methyl]-2-ethoxylated-1H-benzimidazole-7-methyl formate is mixed with a carbonylation reagent, water serves as a solvent, and reaction is performed at 25 DEG C to obtain O-acylation intermediate; the O-acylation intermediate is mixed with an alkaline reagent, water serves as a solvent, reflux reaction is carried out at 100 DEG C, filtration is carried out, 1mol/L of diluted hydrochloric acid is used for adjusting the pH value to 3-4, suction filtration is carried out, and the solvent is recrystallized to obtain the azilsartan. The method for simply and conveniently synthesizing the azilsartan has the advantages that two steps of reactions of cyclization and hydrolyzation are combined into one step under the alkali action, the azilsartan is obtained with two steps in an aqueous phase, the synthesis steps are reduced, the operation is simple and convenient, and the water is used as the solvent, so that method has very high industrial application value.

Preparation method of Azilsartan low in amide impurity content

The invention discloses a preparation method of Azilsartan low in amide impurity content. According to the preparation, in a step of preparation of an intermediate III from an intermediate II, a metalchelating agent, and a phase transfer catalyst are added. The preparation method of Azilsartan low in amide impurity content is capable of controlling influences of trace metal ions (especially ironions) in a reaction solvent, and ensuring that almost no amide impurity is contained in a reaction solution, so that product purity is increased effectively, yield is increased correspondingly, the practicality is high, and industrial application requirements are satisfied.

Preparation method of Azilsartan intermediate

The invention relates to a preparation method of Azilsartan intermediate. The preparation method includes: allowing a compound 1-[(2'-cyanobiphenyl-4-base)methyl]-2-ethyoxyl benzimidazole-7-carboxylic acid methyl ester to have reaction with hydroxylamine hydrochloride under an anhydrous weak alkali condition. The preparation method has the advantages that the method is few in side reactions, amide impurities can be controlled within 1%, yield and product purity can be increased, and products can be directly used for the next-step reaction without being purified; the method is simple in post-treatment operation, the target product can be separated out by directly dropwise adding water after the reaction, and the method is suitable for industrial production.

Angiotensin II receptor antagonists and its key process for the preparation of intermediates (by machine translation)

This invention has offered a kind of angiotensin II receptor antagonists arab League Qi Shatan and its key intermediate 2-ethoxy-1 - [[ 2 - (N-hydroxy ammonia-methyl-imino) biphenyl-4-yl] - 1H-benzimidazole-7-carboxylic acid methyl ester preparation method, the 1 - [(2-cyano-biphenyl-4-yl) methyl] - 2-ethoxy-benzimidazole-7-carboxylic acid methyl ester with hydroxylamine hydrochloride in water and organic solvent in the mixed solvent prepared by reaction under alkaline conditions 2-ethoxy-1 - [[ 2 - (N-hydroxy ammonia-methyl-imino) biphenyl-4-yl] - 1H-benzimidazole-7-carboxylic acid methyl ester. The 2-ethoxy-1 - [[ 2 - (N-hydroxy ammonia-methyl-imino) biphenyl-4-yl] - 1H-benzimidazole-7-carboxylic acid methyl ester and the halogenated alkane ethyl chloroformate in a solvent, the reaction is under alkaline conditions 2-ethoxy-1 - [[ 2 - [[ ( ethoxycarbonyl ) oxy] amidino] [1,1-biphenyl] - 4-yl] methyl] - 1H-benzimidazole-7-carboxylic acid methyl ester, hydrolysis to obtain arab League Qi Shatan in alkaline conditions. The method of the invention greatly reduces the production cost, improving the yield and purity of product, is suitable for industrial production. (by machine translation)

Aitch sand smooth process for the preparation of intermediates

The invention relates to the technical field of azilsartan intermediate preparation method. According to the invention, a compound 1-[(2'-cyanobiphenyl-4-group)methyl]-2-ethoxy benzimidazole-7-methyl carboxylate is subject to a reaction with an aqueous solution of hydroxylamine, such that the intermediate is prepared. In prior arts, amide impurities with an amount equal to that of the products are generated. With the method provided by the invention, the impurities are greatly reduced, such that the yield is increased. In prior arts, the reaction time is 48 hours, and yet a small amount of raw materials is not reacted. With the method provided by the invention, the reaction time is 24 hours, and the reaction is sufficiently carried out, such that the efficiency is improved. In a post-processing process, complicated steps of acid extraction and alkali ionization are not required. When the reaction id finished, the materials are cooled, and the target product can be precipitated directly.

Aitch sand smooth intermediate and its preparation method (by machine translation)

The invention discloses Aitch sand smooth intermediate and its preparation method. The preparation method comprises the following steps: in the solvent, compound 2B with hydroxylamine mixing, reaction, get compound 3B can be. The invention method for preparing the Aitch of less impurity, short reaction time, the higher process yield, high purity of the product, is suitable for industrial production. (by machine translation)

Aitch sand smooth intermediate and its and Aitch of preparation method

The invention discloses a preparation method of an intermediate 5B and azilsartan 1. The preparation method of the azilsartan 1 comprises the following steps: 1) in a solvent, mixing a compound 2B with hydroxylamine to react to obtain a compound 3B; 2) in a solvent, mixing the compound 3B prepared in the step 1) with chloroformate to react under the action of alkali to obtain a compound 4B; 3) in a solvent, carrying out cyclization reaction on the compound 4B prepared in the step 2) to obtain a compound 5B; and 4) in a solvent, carrying out esterolysis reaction on the compound 5B prepared in the step 3) under the action of alkali to obtain the azilsartan 1, wherein R is a C6-C10 aryl group or C1-C4 straight-chain or branched-chain alkyl group. The preparation method of the azilsartan intermediate 5B is described as the step 3). The preparation method has the advantages of fewer impurities, short reaction time, higher technical yield and higher product purity, and is suitable for industrial production.