- 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.
- -
-
Paragraph 0027; 0036-0037; 0040; 0049-0050; 0053; 0062-0063
(2021/08/28)
-
- 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.
- Svec, Riley L.,Hergenrother, Paul J.
-
supporting information
p. 1857 - 1862
(2019/12/27)
-
- 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
- -
-
Paragraph 0045-0071
(2019/12/25)
-
- 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.
- -
-
Paragraph 0122-0123
(2017/08/31)
-
- 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
- -
-
Paragraph 0047
(2017/02/23)
-
- 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.
- -
-
Paragraph 0063-0065
(2017/02/23)
-
- 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
- -
-
Paragraph 0042-0044; 0050-0058
(2018/10/31)
-
- 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.
- Wang, Ping,Zheng, Guo-Jun,Wang, Ya-Ping,Wang, Xiang-Jing,Wei, He-Geng,Xiang, Wen-Sheng
-
p. 2509 - 2512
(2012/04/11)
-
- 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.
- -
-
Page/Page column 13
(2011/09/19)
-
- Novel process for the preparation of telmisartan
-
The present invention relates to a novel process for preparing Telmisartan by ester hydrolysis using a silanolate compound.
- -
-
Page/Page column 7
(2011/04/25)
-
- Improved one-pot synthesis of telmisartan
-
Cost-effective and improved one-pot synthesis for telmisartan (1) is described that minimizes the reaction time and gives high-purity material. Copyright Taylor & Francis Group, LLC.
- Rao, Challa Nageswar,Naresh, Tondepu,Satyanarayana, Komati,Reddy, Bojja Ramachandra,Reddy, Ghanta Mahesh
-
experimental part
p. 530 - 534
(2010/04/04)
-
- PROCESS FOR THE PREPARATION OF PURE 4'-[4-METHYL-6-(1-METHYL-2-BENZIMIDAZOLYL)-2-PROPYL-1-BENZIMIDAZOLYL]METHYL]-2-BIPHENYLCARBOXYLIC ACID
-
The present invention relates to the purification of Telmisartan (I) from a mixture of water immiscible solvent and polar aprotic solvent, which results in the Telmisartan with the purity of above 99.5% by HPLC. Further, the precipitation process of the present invention improves flowability of crystallized product, ease of filtration from the crystalline medium, thereby increasing the yield, decreasing the cost and avoiding the drying problems.
- -
-
Page/Page column 6-7
(2010/04/03)
-
- PROCESS FOR PREPARATION OF TELMISARTAN
-
A process for preparation of telmisartan comprises: (i) oxidation of compound of formula (a), wherein R2 is a hydrogen atom or a substituent of formula (b), in which R1 is a protecting group for the carboxyl function, to an aldehyde of formula (c), in which R2 is defined as in the formula (a), and, optionally, (ii) in case R2 in the compound (c) thus obtained is a hydrogen atom, iV-alkylation of the compound (c) with a biphenyl derivative, (iii) treatment of the compound (c) thus obtained with N- methyl- o-nitroaniline in a cyclocondensation reaction, and (iv) cleavage of the protecting group R1.
- -
-
Page/Page column 17-18
(2009/10/30)
-
- An efficient and impurity-free process for telmisartan: An antihypertensive drug
-
Telmisartan (1), a substituted dibenzimidazole derivative, is an antihypertensive drug, essentially used to control blood pressure. An improved, cost-effective, and impurity-free process for telmisartan (1) suitable for large-scale production is described here by addressing various process development issues. The overall yield obtained from this newly developed process is around 50% (over five steps) compared to the literature reported process (21%, over eight steps).
- Reddy, Kikkuru Srirami,Srinivasan, Neti,Reddy, Chinta Raveendra,Kolla, Naveenkumar,Anjaneyulu, Yerremilli,Venkatraman, Sundaram,Bhattacharya, Apurba,Mathad, Vijayavitthal T.
-
-
- PROCESS FOR PREPARING TELMISARTAN
-
Provided are processes for preparing telmisartan alkyl ester and telmisartan using environmentally friendly organic solvents that are easily removed from the reaction mixture, wherein a telmisartan alkyl ester is isolated and hydrolyzed to form telmisartan or the telmisartan is prepared using a synthesis in a single reaction vessel.
- -
-
Page/Page column 15-16
(2008/06/13)
-
- PROCESS FOR PREPARING TELMISARTAN
-
A process for preparing telmisartan and intermediates formed in the process.
- -
-
Page/Page column 32-33
(2008/06/13)
-
- Process for the preparation of angiotensin receptor blockers and intermediates thereof
-
A process for the preparation of a biphenyl-containing compound of general formula I: wherein R1 is a C3-6 carbonyl containing compound; R2 is a substituted or unsubstituted, straight or branched C3-6 alkyl group, or R1 and R2 together with the nitrogen atom to which they are bonded are joined together to form a substituted heterocyclic group selected from the group consisting of substituted or unsubstituted imidazoles, substituted or unsubstituted benzimidazoles and substituted or unsubstituted 1,3-diazaspiro[4,4]non-1-en-4-one; and R3 is a carboxylic acid ester, cyano, a substituted or unsubstituted 1H-tetrazolyl group or a substituted or unsubstituted group which may be converted in vivo into a carboxy group is provided, the process comprising reacting a compound of general formula II: wherein R1 and R2 have the aforestated meanings with a compound of general formula III: wherein Z is a leaving group and R3 has the aforestated meaning in a biphasic solvent system in the presence of a phase transfer catalyst.
- -
-
Page/Page column 5-6
(2008/06/13)
-
- SUBSTANTIALLY PURE MICRONIZED PARTICLES OF TELMISARTAN AND PHARMACEUTICAL COMPOSITIONS CONTAINING SAME
-
The present invention provides micronized particles of substantially pure telmisartan or a pharmaceutically acceptable salt, ester or derivative thereof. Also provided are pharmaceutical compositions containing the micronized particles of substantially pure telmisartan or a pharmaceutically acceptable salt, ester or derivative thereof.
- -
-
Page/Page column 17
(2008/06/13)
-