152628-02-9Relevant articles and documents
Novel synthetic approach, spectroscopic characterization and theoretical studies on global and local reactive properties of a bibenzimidazolyl derivative
Prasad, Kollur Shiva,Nayak, Nagaraj,Pillai, Renjith Raveendran,Armakovi?, Stevan,Armakovi?, Sanja J.
, p. 121 - 128 (2017)
Benzimidazole derivatives are of interest because they can exhibit multi-drug like properties and thus finds wide applications in biomedicine. Present work describes a novel route for the synthesis of a benzimidazole derivative, 1,7′-Dimethyl-2′-propyl-1H,3′H-[2,5′]bibenzoimidazolyl (R4) by using dibutyltin dilaurate (DBTDL) as catalyst. The catalyst, DBTDL is commercial and environmentally benign. The molecular structure of R4 was confirmed by FT-IR, 1H, 13C NMR, and mass spectrometry techniques. The detailed reactivity study of R4 encompasses spectroscopic characterization and computational investigations of global and local reactive properties based on the density functional theory (DFT) and time dependent density functional theory (TD-DFT) calculations, and molecular dynamics (MD) and molecular docking (MDoc) simulations. Global reactive properties of the title compound have been investigated by the analysis of frontier molecular orbitals. Local reactive properties have been investigated by the analysis of quantum-molecular descriptors such as molecular electrostatic potential (MEP), average local ionization energy (ALIE) surfaces, and Fukui functions. Bond dissociation energies (BDE) have been calculated in order to determine molecule sites that could be sensitive towards the autoxidation mechanism, while the radial distribution functions have been calculated in order to determine atoms with the significant interactions with water molecules.
Compound based on benzimidazole substituted halogenated phenyl n-butylamidine and preparation method of compound
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, (2021/04/29)
The invention relates to a compound based on benzimidazole substituted halogenated phenyl n-butylamidine as shown in a formula II and a preparation method thereof. According to the method disclosed by the invention, nitrification and polyphosphoric acid cyclization reactions are avoided, and the generation of a large amount of waste acid reaction liquid is avoided from the source.
Compound based on benzimidazole substituted phenyl n-butylamide and preparation method of compound
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, (2021/03/06)
The invention relates to a compound based on benzimidazole substituted phenyl n-butylamide and a preparation method of the compound. According to the method disclosed by the invention, nitrification and polyphosphoric acid cyclization reactions are avoided, and the generation of a large amount of waste acid reaction liquid is avoided from the source. The synthesis method disclosed by the inventionhas the advantages of simplicity, high efficiency, mild conditions, less pollutants and the like, and is suitable for being developed into a green sustainable production process.
Highly Efficient and Practical Synthesis of the Key Intermediate of Telmisartan
Zhao, Jianhong,Xiong, Yicheng,Yang, Wu-Lin,Yang, Fan,Jin, Yu
, p. 1022 - 1027 (2021/04/12)
We reported herein an efficient and practical method to access 1,7′-dimethyl-2′-propyl-2,5′-bi(1H-benzimidazole) 1, a key intermediate for the synthesis of telmisartan. The synthetic route was based on readily available o-methylaniline as the starting material, and the target product 1 was prepared through a six-step process, including amidation, formylation, cyclization, hydrolysis, amidine, and oxidation. The overall yield for the preparation of 1 was 51.5% on the 100 g scale, with a purity of 99.91%. The salient features of this method include economic and easily available starting materials, operational simplicity, and environmentally friendly, which is suitable for the industrial production.
Synthetic method 2 - n-propyl -4 - methyl -6 - (1 -methylbenzimidazole -2 -yl) benzimidazole (by machine translation)
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, (2020/10/04)
The invention relates to the technical field of synthesis of medical intermediates, and discloses a synthesis method of 2 - n-propyl -4 - methyl -6 - (1 -methylbenzimidazole -2 -yl) benzimidazole; S1: a condensation closed loop is obtained; and the reaction temperature is controlled to 3 - and the intermediate IV is N - [-4 - methyl -5 - (40 - 110 °C-methylbenzimidazole) 2 -nitrophenyl]-butylamide; S2: a reduction ring; and the preparation method comprises the following steps: S3: condensation ring-ring synthesis and intermediate IV of -4 -propyl -4 - 1 -6 - methyl 1 - S4 -2 - (-6 -methylbenzimidazol 2 -yl) benzimidazole -2 . 2 - N-propyl -4 - methyl -6 - (1 -methylbenzimidazole -2 -yl) benzimidazole is higher in purity, reduced in impurities and high in yield. (by machine translation)
Preparation method of telmisartan key intermediate
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, (2020/07/28)
The invention discloses a preparation method of a telmisartan key intermediate 2-n-propyl-4-methyl-6-(1 '-methylbenzimidazole-2-yl) benzimidazole, and belongs to the field of pharmaceutical chemicals.According to the preparation method, cheap o-phenylenediamine is used as an initial raw material, acylation with butyryl chloride is carried out to obtain Z-2, chloromethylation is carried out to generate (Z-3), and then the (Z-3) is reacted with hexamethylenetetramine to generate an important intermediate (Z-4) rather than a methyl ester compound of a carboxylic acid generated through saponification in a conventional route 1; nitrifying of compound (Z-4) is carried out to generate a nitro compound (Z-5), palladium on carbon is replaced with iron powder, one-step reaction reduction and cyclization are carried out to obtain a compound (Z-7), and further reaction with N-methyl o-phenylenediamine is carried out to obtain 2-n-propyl-4-methyl-6-(1 '-methylbenzimidazol-2-yl) benzimidazole (bis-imidazole). The method is simple in process, raw materials are easy to obtain, industrial production is easy, the prepared product is high in purity and yield, and the method has very high economic value and application prospects.
An improved synthesis of telmisartan: Via the copper-catalyzed cyclization of o -haloarylamidines
Li, Rui,Shen, Jingshan,Sun, Changliang,Zhang, Junchi,Zhu, Fuqiang
, p. 13717 - 13721 (2020/04/23)
A concise synthetic route was designed for making telmisartan. The key bis-benzimidazole structure was constructed via the copper-catalyzed cyclization of o-haloarylamidines. By adopting this approach, telmisartan was obtained in a 7-step overall yield of 54% starting from commercially available 3-methyl-4-nitrobenzoic acid, and the use of HNO3/H2SO4 for nitration and polyphosphoric acid (PPA) for cyclization in the reported literatures were avoided.
A method for the preparation of telmisartan (by machine translation)
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Paragraph 0028-0035, (2019/02/08)
The invention relates to a kind of telmisartan intermediate 2 - n-propyl - 4 - methyl - 6 - (1' - methylbenzimidazole - 2 - yl) benzimidazole preparation method, which belongs to the field of pharmaceutical chemicals. The method in order to 2 - n-propyl - 4 - methyl - 6 - carboxyl benzimidazole and N - methyl O-phenylene diamine salt as raw materials, such as sulfonic acid in the acidic catalyst and the presence of organic solvent reflux water diversion, a cyclization reaction occurs, after the treatment to obtain 2 - n-propyl - 4 - methyl - 6 - (1' - methylbenzimidazole - 2 - yl) benzimidazole product. The process is simple, easily available raw materials, solvent can be recycled, not only the production cost is reduced, but also the product quality and yield significantly improved, safe operation, small pollution to the environment, and is suitable for large-scale industrial production. (by machine translation)
2-n-propyl-4-methyl-6-(1-methylbenzimidazole-2-yl) benzimidazole preparation method (by machine translation)
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Paragraph 0050-0053, (2017/01/09)
The invention discloses a 2-n-propyl-4-methyl-6-(1-methylbenzimidazole-2-yl) benzimidazole preparation method, comprising the following steps: 1, 2-n-propyl-4-methyl-6-carboxyl benzimidazoly with an acylating agent in 20-40 ° C acidylated obtained under 2-n-propyl-4-methyl-6-Carbamoyl paradichlorbenzene benzimidazole; 2, 2-n-propyl-4-methyl-6-Carbamoyl paradichlorbenzene and imidazole with N-methyl O-phenylenediamine mixing, adding organic alkali in 30-50 ° C after the reaction, the organic acid is added 50-80 ° C lower reaction to obtain 2-n-propyl-4-methyl-6-(1-methylbenzimidazole-2-yl) benzimidazole. The above-mentioned preparation method for the mild reaction conditions, the reaction is one pot reaction process, separation and purification is not required in the middle, after treatment is simple, preparation to obtain 2-n-propyl-4-methyl-6-(1-methylbenzimidazole-2-yl) benzimidazole high purity. (by machine translation)
N-Phenyl indole derivatives as AT1 antagonists with anti-hypertension activities: Design, synthesis and biological evaluation
Zhu, Weibo,Bao, Xiaolu,Ren, He,Da, Yajing,Wu, Dan,Li, Fuming,Yan, Yijia,Wang, Li,Chen, Zhilong
, p. 161 - 178 (2016/04/05)
The design, synthesis, in vitro and in vivo evaluation of 6-substituted benzimidazole with 1, 4-disubsituted or 1, 5-disubsituted indole derivatives as novel angiotensin II receptor antagonists are outlined. Radioligand binding assays showed that several 6-substituted benzimidazole derivatives displayed high affinities binding to the angiotensin II type 1 receptor at the same order of magnitude to telmisartan. The biological evaluation on spontaneously hypertensive rats showed that 2-[4-[[2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole-1-yl]methyl]-1H-indol-1-yl]benzoic acid, 1c, could cause significant decrease on MBP in a dose dependent manner. Its maximal response lowered 53 mmHg of MBP at 5 mg/kg and 64 mmHg of MBP at 10 mg/kg after oral administration, and the significant antihypertensive effect lasted beyond 24 h, which was better than both losartan and telmisartan. A study designed to determine acute toxicity showed that 1c had low acute toxicity with no significant changes in the weight and no obvious untoward reactions. The encouraging results make 1c an effective and durable anti-hypertension drug candidate and deserve further investigation for therapeutic application.
