114772-54-2Relevant articles and documents
An efficient, commercially viable, and safe process for preparation of losartan potassium, an angiotensin II receptor antagonist
Madasu, Suri Babu,Vekariya,Koteswaramma, Ch,Islam, Aminul,Sanasi, Paul Douglas,Korupolu, Raghu Babu
, p. 2025 - 2030 (2012)
An efficient, commercially viable and safe process for the preparation of losartan potassium, an antihypertensive drug substance, with an overall yield of 55.5% and ～99.9% purity (including five chemical reactions and two recrystallizations) and meeting all other regulatory requirements is described. Formation and control of all the possible impurities are also described.
Synthesis, characterization and in vitro screening on bacterial, fungal and malarial strain of piprazinyl cyano biphenyl based compounds
Malani, Mahesh H.,Dholakiya, Bharat Z.
, p. 16 - 23 (2013)
A series of eight 4′-[4-(3-substituted phenyl-acryloyl)-piprazin-1- ylmethyl]-biphenyl-2-carbonitrile were synthesized using 4′-Bromomethyl- biphenyl-2-carbonitrile and 4-Acetyl piprazine as a starting material. Furthermore, there has been some additional work done investigating effects of these derivatives on biological activities on bacterial, fungal and malarial strain. Synthesized compounds were characterized using FTIR, 1H NMR and 13C NMR spectrometry. These compounds shows good antimalarial, antibacterial and antifungal activity. In fact some compounds are more potent than standard drug quinine and Ampicillin some are with comparable activity with Ampicillin and quinine.
Bacterial Peptide deformylase inhibition of cyano substituted biaryl analogs: Synthesis, in vitro biological evaluation, molecular docking study and in silico ADME prediction
Khan, Firoz A. Kalam,Patil, Rajendra H.,Shinde, Devanand B.,Sangshetti, Jaiprakash N.
, p. 3456 - 3463 (2016)
Herein, we report the synthesis and screening of cyano substituted biaryl analogs 5(a–m) as Peptide deformylase (PDF) enzyme inhibitors. The compounds 5a (IC50value?=?13.16?μM), 5d (IC50value?=?15.66?μM) and 5j (IC50value?=?19.16?μM) had shown good PDF inhibition activity. The compounds 5a (MIC range?=?11.00–15.83?μg/mL), 5b (MIC range?=?23.75–28.50?μg/mL) and 5j (MIC range?=?7.66–16.91?μg/mL) had also shown potent antibacterial activity when compared with ciprofloxacin (MIC range?=?25–50?μg/mL). Thus, the active derivatives were not only potent PDF inhibitors but also efficient antibacterial agents. In order to gain more insight on the binding mode of the compounds with PDF, the synthesized compounds 5(a–m) were docked against PDF enzyme of Escherichia coli and compounds exhibited good binding properties. In silico ADME properties of synthesized compounds were also analyzed and showed potential to develop as good oral drug candidates.
A high-throughput process for valsartan
Beutler, Ulrich,Boehm, Matthias,Fuenfschilling, Peter C.,Heinz, Thomas,Mutz, Jean-Paul,Onken, Ulrich,Mueller, Martin,Zaugg, Werner
, p. 892 - 898 (2007)
With the redesign of three chemical steps, the throughput of the valsartan manufacturing process could be significantly increased, and with the substitution of chlorobenzene with cyclohexane in the bromination of 4′-methyl-biphenyl-2-carbonitrile (6) to 4′bromomethyl-biphenyl-2- carbonitrile (5), halogenated solvents are no longer used in the whole valsartan production process. The alkylation of (S)-2-amino-3-methyl-butyric acid benzyl ester (8) with 4′-bromomethyl-biphenyl-2-carbonitrile (5), and the acylation of(S)-2-[(2′-cyano-biphenyl-4-ylmethyl)-amino]-3-methyl-butyric acid benzyl ester (4) to (S)-2-[(2′-cyano-biphenyl-4-ylmethyl)-pentanoyl- amino]-3-methyl-butyric acid benzyl ester (3) were thoroughly modified. In the acylation of 4 to 3, N-ethyldiisopro-pylamine was replaced by aqueous sodium hydroxide by using the conditions of the Schotten-Baumann reaction, leading to a better quality of intermediate 3. In the alkylation of 8 with 5, N-ethyldiisopropylamine was indirectly replaced by aqueous sodium hydroxide. The reaction runs under homogenous conditions with (S)-2-amino-3-methyl-butyric acid benzyl ester (8) acting as acceptor for hydrobromic acid; recycling of 8 is performed by extraction with aqueous sodium hydroxide.
Readily Reconfigurable Continuous-Stirred Tank Photochemical Reactor Platform
Blacker, A. John,Francis, Daniel,Kapur, Nikil,Marsden, Stephen P.
supporting information, (2022/01/12)
A new modular photochemical continuous stirred-tank reactor (CSTR) design is described, based upon the development of light-source units that can be fitted to the previously described fReactor CSTR platform. In addition to use in homogeneous photochemical reactions (e.g., photoredox-catalyzed hydroamination), these units are especially well suited to handling multiphasic mixtures, exemplified here in solid-liquid (Wohl-Ziegler bromination) and gas-liquid (photocatalytic oxidative decarboxylation) reactions. The use of slurries as input feeds allows for the intensification of photochemical brominations, while the modular nature of the system facilitates the simple integration of downstream reaction steps, exemplified here in a continuous synthesis of an intermediate for the antihypertensive drug valsartan.
Photocatalytic continuous bromination method
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Paragraph 0070-0071, (2021/04/03)
The invention provides a photocatalytic continuous bromination method. The method comprises the following steps: carrying out a first-stage photocatalytic continuous bromination reaction on a materialcontaining an aromatic substrate with a structural general formula I and a bromination reagent in a first continuous illumination reactor to form a first continuous system; overflowing the obtained first continuous system into a second continuous illumination reactor for a second-stage photocatalytic continuous bromination reaction to form a second continuous system; and purifying the second continuous system, wherein the structural general formula I is shown in the specification, R is selected from any one of carboxyl, ester group, NO2, CN, C1 to C8 alkyl and alkoxy, and R1 is C1 to C8 alkyl; n is 1 or 2; X is N or C, and the bromination reagent is Nbromo succinimide or dibromohydantoin. According to the bromination reagent, the selectivity of a product is improved, so the yield of the product is improved; the photocatalytic continuous bromination reaction of the two stages effectively relieves the reaction heat accumulation, and enhances the yield of the target product.
Preparation method of bromoilsartan soluble in 1,2 - dichloroethane (by machine translation)
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Paragraph 0036-0054, (2020/07/12)
The invention discloses a preparation method of brominated sartan biphenyl dissolved 1,2 - dichloroethane, and belongs to the technical field of pharmaceutical chemical engineering. The method uses methylbiphenyl as a raw material, 1,2 - dichloroethane as a solvent, and a brominated reagent, dibromohydantoin, N - bromosuccinimide or sodium bromide and sodium bromate. 2 - Cyano -4 ’ - bromomethylbiphenyl synthesized by the method is good in purity, high in yield, simple in reaction system, low in toxicity, high in atom conversion rate and suitable for industrial application in the field of biological medicine. (by machine translation)
Preparation method of bromo-sartan biphenyl based on hydrogen peroxide-hydrobromic acid system
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Paragraph 0036-0056, (2020/07/15)
The invention discloses a preparation method of bromo-sartan biphenyl based on a hydrogen peroxide-hydrobromic acid system, and belongs to the technical field of pharmaceutical chemicals. The invention discloses a method for preparing substituent-containing bromo-sartan biphenyl by using a flowing photochemical method. According to the method, methyl biphenyl is used as a raw material, hydrobromicacid is used as a bromination reagent, hydrogen peroxide is used as an oxidation reagent, acetonitrile or ethyl acetate is used as a solvent, and after the raw material, the bromination reagent and the oxidation reagent are respectively mixed with the solvent, the mixture flows into a pipeline through an injection pipe, is mixed through a mixer, enters a constant-temperature water bath reactor and undergoes a reaction through illumination. The 2-cyano-4'-bromomethylbiphenyl synthesized by the method is good in purity, high in yield, simple in a reaction system, low in toxicity and high in atom conversion rate, is suitable for industrial application in the field of biological medicines, can be suitable for an automatic continuous production process, and conforms to the development conceptsof green chemical industry, high efficiency and economy.
High-temperature preparation method of 4'-bromomethyl-2-cyanobiphenyl based on bromine
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Paragraph 0038-0058, (2020/07/12)
The invention discloses a high-temperature preparation method of 4'-bromomethyl-2-cyanobiphenyl based on bromine, belongs to the technical field of pharmaceutical chemicals, and particularly disclosesa method for preparing substituent-containing 4'-bromomethyl-2-cyanobiphenyl by using a flowing photochemical method. An oxidant and a radical initiator are not needed; and methyl biphenyl is used asa raw material, bromine is used as a bromination reagent, ethyl acetate, glacial acetic acid or N,N-dimethylformamide is used as a solvent, and after the raw material and the bromination reagent arerespectively mixed with the solvent, the obtained mixtures flow into a pipeline through injection pipes, and are mixed by a mixer, and then the obtained mixture enters a constant-temperature water bath reactor and is subjected to a reaction through illumination. The 4'-bromomethyl-2-cyanobiphenyl synthesized by the method is good in purity, high in yield, simple in reaction system and low in toxicity, is suitable for industrial application in the field of biological medicines, can be suitable for an automatic continuous production process, and conforms to the development concepts of green chemical industry, high efficiency and economy.
Continuous flow method for synthesizing p-bromo-methyl biphenyl carbonitrile and reaction device thereof
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Paragraph 0035; 0056-0086, (2020/12/05)
The invention discloses a continuous flow method for synthesizing p-bromo-methyl biphenyl carbonitrile and a reaction device for synthesizing p-bromo-methyl biphenyl carbonitrile. P-methyl biphenyl carbonitrile is used as a raw material; bromine generated by oxidizing hydrobromic acid through hydrogen peroxide is used as a bromination reagent; materials are continuously input into an efficient mixer through a metering pump to be mixed and then enter a pipeline reactor; and temperature control and illumination on reactants in the pipeline reactor are carried out to complete bromination reaction, quenching of a reaction liquid in the pipeline reactor is carried out, continuous liquid separation, and drying, concentration and recrystallization purification on the obtained organic phase are carried out to obtain the pure p-bromo-methyl biphenyl carbonitrile product. The bromination reaction has the advantages of high bromine atom utilization rate, fewer byproducts and fewer solid wastes, and conforms to the concept of green chemistry; the continuous flow synthesis method has the advantages of good safety, convenience in intelligent control, short reaction time, high post-treatment efficiency and the like, and has industrial production and application values.
