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 (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl ester

Base Information

• Chemical Name: 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 (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl ester
• CAS No.: 863031-21-4
• Molecular Formula: C30H24N4O8
• Molecular Weight: 568.543
• Mol file: 863031-21-4.mol

Synonyms:(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl ester of 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;Azilsartan (medoxomil);Azilsartan Medoxomil;Azilsartan kamedoxomil;(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-ethoxy-3-[[4-[2-(5-oxo-2H-1,2,4-oxadiazol-3-yl)phenyl]phenyl]methyl]benzimidazole-4-carboxylate;TAK 491;Azilsartan;[14C]-Azilsartan medoxomil;(5-methyl-2-oxo-1,3-dioxol-4-yl)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;UNII-LL0G25K7I2;azilsartanum medoxomilum;Edarbi;

Chemical Property of 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 (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl ester

Chemical Property:

• PKA: 6.99±0.20(Predicted)
• PSA: 155.59000
• Density: 1.45
• LogP: 4.70520
• Storage Temp.: Refrigerator
• Solubility.: DMSO (Slightly), Methanol (Slightly, Heated, Sonicated)

Purity/Quality:

99% ^*data from raw suppliers

AzilsartanMedoxomil ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: Azilsartan medoxomil (Edarbi), an angiotensin II receptor antagonist, was approved by the U.S. FDA in February 2011 for the treatment of hypertension in adults. The discovery of azilsartan was the result of a medicinal chemistry effort to identify an ARB with a different carboxylic acid isostere than the ones found in the marketed ARBs. Several of the marketed ARBs use a tetrazole group as a carboxylic acid isostere. The medicinal chemistry approach that led to azilsartan involved the replacement of this commonly used tetrazole with a 5-oxo-1,2,4-oxadiazole group. Azilsartan can be synthesized by Suzuki coupling of p-tolyl boronic acid to 2-bromobenzonitrile, followed by bromination of the methyl group. The bromide is displaced to introduce a protected 2-ethoxy-1H-benzo[d] imidazole-7-carboxylate. The cyano group is converted to a hydroxylamidine, followed by reaction with an alkyl-chloroformate and intramolecular cyclization to form the 5-oxo-1,2,4-oxadiazole ring. The acid is then deprotected and converted to a prodrug. The parent, azilsartan has been extensively characterized in vitro and compared with other marketed AT1 antagonists olmesartan, valsartan, telmisartan, irbesartan, and candesartan. Azilsartan was found to be a potent (IC50=2.6 nM), selective, inverse agonist of the AT1 receptor. From washout experiments, azilsartan was found have slow dissociation from the receptor and thus is characterized as an insurmountable antagonist. Azilsartan medoxomil is a prodrug form of azilsartan , a potent and selective angiotensin II receptor 1 (AT1) antagonist. Azilsartan medoxomil (0.1-10 mg/kg) reduces blood pressure and decreases plasminogen activator inhibitor 1 (PAI-1) levels in the plasma, left ventricle, and aortic wall in mice in a dose-dependent manner. It also inhibits the pressor response induced by angiotensin II in normotensive rats (ID50 = 0.12 mg/kg) and reduces blood pressure and improves glucose infusion, a marker of insulin sensitivity, in spontaneously hypertensive rats. Azilsartan medoxomil also has more potent antiproteinuric effects in Wistar fatty rats than olmesartan medoxomil . Formulations containing azilsartan medoxomil have been used in the treatment of hypertension.
• Uses: Azilsartan medoxomil is a long-acting angiotensin II receptor blocker (ARB) that is used to lower hypertension. When Azilsartan medoxomil enters the gastrointestinal tract, it is rapidly converted to its active form, Azilsartan (A926900).

Technology Process of 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 (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl ester

There total 32 articles about 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 (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl ester which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 98.2%

Carbonyldiimidazole (64269-79-0) + (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 (1449029-77-9) → Azilsartan medoxomil (863031-21-4)

Guidance literature:

In dimethyl sulfoxide; at 50 ℃; for 2h;

Reference yield: 95.0%

4-hydroxymethyl-5-methyl-[1,3]dioxol-2-one (91526-18-0) + azilsartan (147403-03-0) → Azilsartan medoxomil (863031-21-4)

Guidance literature:

4-hydroxymethyl-5-methyl-[1,3]dioxol-2-one; azilsartan; With dmap; potassium carbonate; p-toluenesulfonyl chloride; In N,N-dimethyl acetamide; at 10 ℃; for 3h;

In N,N-dimethyl acetamide; pH=5;

In water; acetone; at 35 ℃; for 2h;

Reference yield: 87.0%

(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 (1449029-80-4) → Azilsartan medoxomil (863031-21-4)

Guidance literature:

at 20 - 60 ℃; for 12h; Solvent; Temperature;

upstream raw materials:

4-chloromethyl-5-methyl-1,3-dioxol-2-one

4-hydroxymethyl-5-methyl-[1,3]dioxol-2-one

azilsartan

methyl 1-[(2'-cyanobiphenyl-4-yl)methyl]-2-ethoxy-benzimidazole-7-carboxylate

Downstream raw materials:

(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

(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

azilsartan

Refernces

• 1、 -. "METHOD FOR PREPARING AZILSARTAN WITH ENVIRONMENT-FRIENDLY SOLVENT, AND KEY INTERMEDIATE COMPOUNDS THEREOF". Paragraph 0109-0122. . Retrieved 2021/03/03.
• 2、 -. "arab League Qi Shatan ester or its salt synthetic method and intermediates thereof, and method for synthesizing intermediate (by machine translation)". Paragraph 0075; 0076; 0077; 0078. . Retrieved 2016/10/08.