528560-93-2

Basic information

• Product Name: EXECUTE STANDARD
• Synonyms: EXECUTE STANDARD;Intermediate of Telmisartan A;1'-yl)methyl]-, methyl ester;4'-[(1,4'-dimethyl-2'-propyl[2,6'-bi-1H-benzimidazol]-;4'-[(1,4'-Dimethyl-2'-propyl[2,6'-bi-1H-benzimidazole]-1'-yl)methyl]-1,1'-biphenyl-2-carboxylic acid methyl ester;Telmisartan methyl ester;[1,1'-Biphenyl]-2-carboxylicacid, 4'-[(1,4'-diMethyl-2'-propyl[2,6'-bi-1H-benziMidazol]-1'-yl)Methyl]-,Methyl ester;4'-[(1,4'-DiMethyl-2'-propyl[2,6'-bi-1H-benziMidazol]-1'-yl)Methyl]-[1,1'-biphenyl]-2-carboxylic Acid Methyl Ester
• CAS NO: 528560-93-2
• Molecular Formula: C₃₄H₃₂N₄O₂
• Molecular Weight: 528.653
• Product Categories: Intermediate of Telmisartan;INTERMEDIATESOF;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 528560-93-2.mol

Chemical Properties

• Melting Point: 170-175 ºC
• Boiling Point: 771.187 °C at 760 mmHg
• Flash Point: 420.199 °C
• Appearance: /
• Density: 1.20
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.646
• Storage Temp.: Refrigerator
• Solubility: Chloroform (Slightly), Methanol (Slightly, Sonicated)
• PKA: 5.00±0.10(Predicted)
• CAS DataBase Reference: EXECUTE STANDARD(CAS DataBase Reference)
• NIST Chemistry Reference: EXECUTE STANDARD(528560-93-2)
• EPA Substance Registry System: EXECUTE STANDARD(528560-93-2)

Safety Data

• Hazardous Substances Data: 528560-93-2(Hazardous Substances Data)

Usage

Chemical Properties

Pale Yellow Solid

InChI:InChI=1/C34H32N4O2/c1-5-10-31-36-32-22(2)19-25(33-35-28-13-8-9-14-29(28)37(33)3)20-30(32)38(31)21-23-15-17-24(18-16-23)26-11-6-7-12-27(26)34(39)40-4/h6-9,11-20H,5,10,21H2,1-4H3

Upstream product

• 114772-38-2 Methyl 4'-(bromomethyl)biphenyl-2-carboxylate 
• 152628-02-9 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole 
• 17103-26-3 methyl 4'-bromo-[1,1'-biphenyl]-2-carboxylate 
• 1190092-27-3 methyl 4'-((6-formyl-4-methyl-2-n-propyl-1H-benzimidazol-1-yl)methyl)biphenyl-2-carboxylate 
• 612-28-2 2-nitro-N-methylaniline 
• 887583-89-3 1,4'-dimethyl-2'-propyl-1H,1'H-2,5'-dibenzimidazole 
• 152628-03-0 4-methyl-2-n-propyl-1H-benzimidazole-6-carboxylic acid 
• 152628-01-8 4-butyrylamino-3-methyl-5-nitro-benzoic acid methyl ester 
• 152628-00-7 4-methyl-2-propyl-1H-benzimidazole-6-carboxylic acid methyl ester 
• 1345840-14-3 C₁₅H₁₃N₃O₃ 
• 1345840-21-2 2-(4-methoxy-3-methyl-5-nitrophenyl)-1-methyl-1H-benzimidazole 
• 1345840-05-2 2-methyl-4-(1-methyl-1H-benzimidazol-2-yl)-6-nitrobenzenamine 
• 15174-69-3 4-hydroxy-3-methyl-benzaldehyde 
• 54674-91-8 4-hydroxy-3-methyl-5-nitrobenzaldehyde 

Downstream Products

• 884330-05-6 4'-(1,4'-dimethyl-2'-propyl-1H-[2,5']dibenzimidazolyl-3'-ylmethyl)biphenyl-2-carboxylic acid methyl ester hydrochloride 
• 960356-44-9 4'-[[2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)-benzimidazol-1-yl]-methyl]-biphenyl-2-carboxylic acid ammonium salt 
• 515815-47-1 telmisartan sodium 
• 144701-48-4 telmisatran 

Relevant articles and documents

Preparation method of telmisartan

The invention relates to a preparation method of telmisartan. According to the preparation method, 3-methyl-4-n-butylamide benzoic acid is used as a raw material, an intermediate (1) is prepared through cyaniding, nitration, reduction, ring closing and other reactions, the intermediate (1) and 4 '-bromomethyl biphenyl-2-methyl formate are subjected to condensation to generate an intermediate (2), the intermediate (2) and N-methyl o-phenylenediamine are subjected to condensation to prepare an intermediate (3), and finally the telmisartan is prepared through hydrolysis. The invention develops a new preparation method of telmisartan. The raw material 3-methyl-4-n-butyrylamide benzoic acid adopted by the method is easy to obtain and low in price; the method is mild in reaction condition, easy to operate and high in yield, the cyanation reaction avoids the use of toxic cyanide, the environmental pollution is small, and the method is suitable for industrial production.

Imidazotetrazines as Weighable Diazomethane Surrogates for Esterifications and Cyclopropanations

Diazomethane is one of the most versatile reagents in organic synthesis, but its utility is limited by its hazardous nature. Although alternative methods exist to perform the unique chemistry of diazomethane, these suffer from diminished reactivity and/or correspondingly harsher conditions. Herein, we describe the repurposing of imidazotetrazines (such as temozolomide, TMZ, the standard of care for glioblastoma) for use as synthetic precursors of alkyl diazonium reagents. TMZ was employed to conduct esterifications and metal-catalyzed cyclopropanations, and results show that methyl ester formation from a wide variety of substrates is especially efficient and operationally simple. TMZ is a commercially available solid that is non-explosive and non-toxic, and should find broad utility as a replacement for diazomethane.

MANUFACTURING METHOD OF BIPHENYL-2-CARBOXYLIC ACID METHYL ESTER

PROBLEM TO BE SOLVED: To provide a manufacturing method of 4'-{[4-methyl-6-(1-methyl-1H-benzimidazole-2-yl)-2-propyl-1H-benzimidazole-1-yl]methyl}biphenyl-2-carboxylic acid methyl ester, capable of improving yield and quality, and enhancing efficiency of workability in an industrial scale. SOLUTION: There is provided a manufacturing method of 4'-{[4-methyl-6-(1-methyl-1H-benzimidazole-2-yl)-2-propyl-1H-benzimidazole-1-yl]methyl}biphenyl-2-carboxylic acid methyl ester by adding water to a reaction mixture containing an organic polar solvent and 4'-{[4-methyl-6-(1-methyl-1H-benzimidazole-2-yl)-2-propyl-1H-benzimidazole-1-yl]methyl}biphenyl-2-carboxylic acid methyl ester generated by mixing a mixture obtained by adding 2-n-propyl-4-methyl-6-(1'-methylbenzimidazole-2-yl)benzimidazole and a base to an organic polar solvent, and 4'-bromomethyl biphenyl-2-carboxylic acid methyl ester, to crystallize the methyl ester. SELECTED DRAWING: None COPYRIGHT: (C)2019,JPOandINPIT

Method for preparing telmisartan and intermediates thereof

Disclosed is a telmisartan preparation method, characterized in that: 2-n-propyl-4-methyl-6-(1-methyl benzimidazole-2-yl) benzimidazole (compound I) and 4'-halomethyl diphenyl-2-substituted compound (compound II) conduct a nucleophilic substitution reaction to obtain a compound III; when R is COOH, the compound III is telmisartan; and when R is COOR' or CN, the compound III can be hydrolyzed to obtain telmisartan.

METHOD FOR PRODUCING AMMONIUM SALT OF TELMISARTAN

PROBLEM TO BE SOLVED: To provide a method for producing an ammonium salt of telmisartan effective as a hypotensive agent with high purity. SOLUTION: The method for producing an ammonium salt of telmisartan comprises a dissolution step of dissolving a crude body of telmisartan by adding, in a mixed solvent of water, a 2-12C alcohol and ethyl acetate, ammonia in an amount of 2.0 to 30.0 mol based on 1 mol of the telmisartan at 0 to 30°C to form an ammonium salt of telmisartan and a crystallization step of depositing the ammonium salt of telmisartan from the solution produced in the dissolution step at 0 to 30°C and achieves reduction of specific impurities C and D. SELECTED DRAWING: None COPYRIGHT: (C)2016,JPOandINPIT

A Novel Method for Preparing of Telmisartan

The present invention relates to a method for preparing telmisartan used as an angiotensin-II receptor blocker (ARB)-based hypertension medicine and telmisartan prepared by the method. According to the method of the present invention, a condensation reaction for obtaining an intermediate during a telmisartan preparing procedure is conducted in a solvent containing an ionic liquid, thereby significantly shortening the reaction time by 1-2 hours compared with the conventional method; and a hydrolysis reaction of the intermediate for preparing telmisartan is conducted by controlling the ratio of water containing a hydroxyl group, thereby significantly improving filtering efficiency, the process rate, and process convenience and obtaining high-purity and high-yield telmisartan without further purification.

Telmisartan alkyl ester (by machine translation)

PROBLEM TO BE SOLVED: To provide a method for stably and efficiently producing a high quality telmisartan alkyl ester. SOLUTION: The method for producing the telmisartan alkyl ester comprises mixing 2-n-propyl-4-methyl-6-(1'-methylbenzimidazol-2-yl)benzimidazole with a polar aprotic solvent and a base, and then sequentially adding an alkyl 4'-bromomethylbiphenyl-2-carboxylate solution thereto. Thus, the telmisartan alkyl ester little containing impurities can efficiently be produced. COPYRIGHT: (C)2011,JPO&INPIT

Highly practical and cost-efficient synthesis of telmisartan: An antihypertensive drug

A novel and cost-efficient strategy for synthesis of an antihypertensive drug telmisartan, a substituted bis-benzimidazole derivative, is described. The key strategy is the construction of bis-benzimidazole 4 by reductive cyclization of o-nitroanilines 11 with butyl aldehyde and cyclocondensation of aromatic aldehydes 9 with o-phenylenediamine, then N-alkylation is allowed to give the target compound telmisartan after hydrolysis. The simple operation and workup procedure, along with the low production costs, make it suitable for industrial production and will benefits those with cardiovascular disease.

AN IMPROVED PROCESS FOR THE PREPARATION OF TELMISARTAN

Methyl-4-(butyramido)-3-methyl-5-nitrobenzoate is treated with sulphur containing reducing agent to give methyl-4-methyl-2-propyl-lH-benzimidazole-6-carboxylate, which is further hydrolyzed to the corresponding acid, 2-n-propyl-4-methyl-6- carboxy benzimidazole. The critical intermediate l,4'-dimethyl-2'-propyl-lH,3'H- 2,6'-bisbenzimidazol (DMPBB) is prepared by treating the above acid with N- mehtyl-o-phenylenediamine dihydrochloride under acidic conditions. Reaction of 4'-halomethylbiphenyl-2-carboxylic acid alkyl ester with DMPBB in presence of base to give Telmisartan ester which is further converted to Telmisartan of Formula (I).

AN IMPROVED PROCESS FOR PREPARING TELMISARTAN

The present invention relates to an improved process for preparing telmisartan from 4-methyl-6-(1-methyl-1H-benzimidazole-2-yl)-2-propyl-1H-benzimidazole and 2-[4-(bromomethyl)phenyl] benzoate by using condensation reaction and hydrolysis reaction wherein the condensation reaction is performed to prepare an intermediate by using mixed solvent of dimethyl sulfoxide and isopropanol as reaction solvent using dimethyl sulfoxide of 0.5~1.5 times and isopropanol of 1.5~4.5 times on the basis of the usage of 4-methyl-6-(1-methyl-1H-benzimidazole-2-yl)-2-prophyl-1H-benzimidazole and the hydrolysis reaction is performed to cause the reaction in mixed solvent of methanol of 7~9 times and purified water of 5~7 times on the basis of the intermediate. The process for preparing telmisartan according to the present invention provides a simple preparing process for mass production and improves a manufacturing yield with high purity by eliminating an additional process for removing an inorganic salt as a byproduct due to a base used in the condensation reaction and the hydrolysis reaction.