1403474-70-3

Basic information

• Product Name: 1H-BenziMidazole-7-carboxylic acid, 1-[[2'-(2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)[1,1'-biphenyl]-4-yl]Methyl] -2-ethoxy-, ethyl ester
• Synonyms: 1H-BenziMidazole-7-carboxylic acid, 1-[[2'-(2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)[1,1'-biphenyl]-4-yl]Methyl] -2-ethoxy-, ethyl ester;1-[[2'-(2,5-Dihydro-5-oxo-1,2,4-oxadiazol-3-yl)[1,1'-biphenyl]-4-yl]methyl]-2-ethoxy-1H-benzimidazole-7-carboxylic acid ethyl ester;ethyl 2-ethoxy-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)-[1,1'-biphenyl]-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylate;Ethyl 2-ethoxy-1-((2'-(5-oxo-2,5-dihydro-1,2,4-oxadiazol-3-yl)-[1,1'-biphenyl]-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylate;ethyl ester of azilsartan
• CAS NO: 1403474-70-3
• Molecular Formula: C₂₇H₂₄N₄O₅
• Molecular Weight: 484.50326
• EINECS: 200-258-5
• Mol File: 1403474-70-3.mol

Chemical Properties

• Appearance: /
• Density: 1.34±0.1 g/cm3 (20 ºC 760 Torr)
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 6.99±0.20(Predicted)
• CAS DataBase Reference: 1H-BenziMidazole-7-carboxylic acid, 1-[[2'-(2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)[1,1'-biphenyl]-4-yl]Methyl] -2-ethoxy-, ethyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: 1H-BenziMidazole-7-carboxylic acid, 1-[[2'-(2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)[1,1'-biphenyl]-4-yl]Methyl] -2-ethoxy-, ethyl ester(1403474-70-3)
• EPA Substance Registry System: 1H-BenziMidazole-7-carboxylic acid, 1-[[2'-(2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)[1,1'-biphenyl]-4-yl]Methyl] -2-ethoxy-, ethyl ester(1403474-70-3)

Safety Data

• Hazardous Substances Data: 1403474-70-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
1H-BenziMidazole-7-carboxylic acid, 1-[[2'-(2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)[1,1'-biphenyl]-4-yl]Methyl] -2-ethoxy-, ethyl ester is used as an impurity in the production of Azilsartan (A926900). As an analgesic and anti-inflammatory drug, Azilsartan contains angiotensin II antagonists, which help in managing pain and inflammation by blocking the action of angiotensin II, a potent vasoconstrictor.
The presence of this compound as an impurity in Azilsartan may have implications for the drug's efficacy, safety, and overall quality. It is essential to monitor and control the levels of this impurity during the manufacturing process to ensure the drug meets the required standards and provides the desired therapeutic effects without causing adverse side effects.

Upstream product

• 1403474-75-8 ethyl 2-ethoxy-1-((2'-(N'-((ethoxycarbonyl)oxy)carbamimidoyl)[biphenyl]-4-yl)methyl)-1H-benzoimidazole-7-carboxylate 
• 1397836-41-7 ethyl 2-ethoxy-1-((2′-(N′-hydroxycarbamimidoyl)biphenyl-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylate 
• 530-62-1 1,1'-carbonyldiimidazole 
• 105-58-8 Diethyl carbonate 
• 139481-41-7 ethyl 1-[(2'-cyano-[1,1']-biphenyl-4-yl)methyl]-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate 
• 1397836-41-7 2-ethoxy-3-[[2'-(N-hydroxycarbamimidoyl)biphenyl-4-yl]methyl]benzimidazole-4-carboxylic acid ethyl ester 

Downstream Products

• 863031-21-4 Azilsartan medoxomil 
• 147403-03-0 azilsartan 

Relevant articles and documents

Azilsartan synthesis process

The invention provides an azilsartan synthesis process which is characterized by comprising the following steps: dissolving hydroxylamine hydrochloride into dimethyl sulfoxide, adding sodium bicarbonate at 20-25 DEG C, increasing the temperature to 45-55 DEG C, performing stirring for 45-60 minutes, further adding AQST-SM, increasing the temperature to 80-85 DEG C, and performing a temperature-keeping reaction for 20-22 hours so as to obtain AQST-1; dissolving the AQST-1 into tetrahydrofuran, dropping DBU (diazabicyclo) at 20-25 DEG C, further adding carbonyl diazole, and performing a reactionfor 1.5-2.5 hours at 20-25 DEG C so as to obtain AQST-3; mixing the AQST-3 with a sodium hydroxide solution, increasing the temperature to 70-75 DEG C, and performing a temperature-keeping reaction for 1-2 hours so as to obtain a crude product of AQST; and adding methanol into the crude product of AQST, increasing the temperature to 60-65 DEG C, performing pulping for 45-50 minutes, reducing thetemperature to the room temperature, performing filtering, bleaching filter cakes by using methanol, performing suction filtration till dryness, and performing vacuum drying, so as to obtain an AQST product. By adopting the azilsartan synthesis process provided by the invention, the AQST product is prepared, the yield is high, the content of AQST is high, the content of impurities is low, the quality of the AQST product is remarkably improved, and the azilsartan synthesis process is well applied to production of high-quality azilsartan tablets.

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%.

Novel preparation method of azilsartan

The invention relates to a novel preparation method of azilsartan with relatively high yield and relatively high purity. A multi-refining or column chromatography method is not needed, in addition, the final yield reduction can not be caused. According to the preparation route provided by the application, the contents of an impurity A and an impurity B can be effectively reduced, the refining frequency is reduced, and the yield is also increased.

A PROCESS FOR PREPARING HIGHLY PURE AZILSARTAN

The present invention relates to a process for preparing 1-[[2'-(2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)[ 1,1'-biphenyl]-4-yl]methyl] -2-ethoxy-1H-benzimidazole-7-carboxylic acid of formula (I) (azilsartan). The invention also relates to preparation of new solid forms of intermediates that make it possible to obtain azilsartan with a high purity over 99.7% (HPLC) and to their characterization.

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.

A arab League Qi Shatan crystal A and its preparation method

The invention relates to 1-[[2'-(4,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)- [1,1'-biphenyl]-4-yl]methyl]-2-ethoxy-1H-benzimidazole-7-carboxylate, that is, Azilsartan of crystal form A, and a preparation method thereof. The Azilsartan prepared in the invention has small particle sizes, can be used in preparation production after direct sieving without a crushing technology, has a low content of relevant substances, and is suitable for the industrial production.

A METHOD OF PREPARING A HIGHLY PURE POTASSIUM SALT OF AZILSARTAN MEDOXOMIL

A method of preparing the potassium salt of azilsartan medoxomil of formula I, in which a solvate of azilsartan medoxomil of formula II with a solvent selected from the group that consists of dimethyl acetamide or N-methyl pyrrolidone or their mixtures with other solvents is prepared, or re-crystallized from dimethyl acetamide or N-methyl pyrrolidine or their mixtures with other solvents, and, in the next step, converted to the potassium salt using a potassium source in a suitable solvent.

Improved process for azilsartan medoxomil: A new angiotensin receptor blocker

An improved process for the active pharmaceutical ingredient of a new angiotensin II AT1 receptor antagonist, azilsartan medoxomil, has been developed. The results include reinvestigation of the described process as well as its novel modifications. This new process includes transformation of the CN group into amidoxime moiety by aqueous hydroxylamine, its cyclization into the corresponding oxadiazole by treatment with dialkyl carbonates, and the following hydrolysis of the ester and transformation into the medoxomil ester. Several thus far undocumented side products were identified, and some of them were synthesized and duly characterized as potential impurities. Formation and control of possible critical impurities are described.

A METHOD OF PREPARING 2-ETHOXY-1-((2'-(5-OXO-4,5-DIHYDRO-1,2,4-OXADIAZOL-3-YL)BIPHENYL- 4-YL)METHYL)-1H-BENZO[D]IMIDAZOLE-7-CARBOXYLATES AND CONVERSION THEREOF TO AZILSARTAN

A method of preparing alkyl 2-ethoxy-1-((2'-(5-oxo-4,5-dihydro- 1,2,4-oxadiazol-3- yl)biphenyl-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylates of the general formula I, wherein R is either a branched or unbranched C1-C4 alkyl, ArCH2, Ar2CH, or Ar3C, wherein Ar is a substituted or unsubstituted phenyl, in which an alkyl 2-ethoxy-1 -((2'- ((hydroxyamino)iminomethyl)biphenyl-4-yl)methyl)- 1H-benzo[d]imidazole-7-carboxylate of the general formula V is reacted with a cyclization agent in a solvent in the presence of suitable bases. (I) (V)