103577-40-8

Basic information

• Product Name: 2-[3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methylthio-1H-benzimidazole
• Synonyms: 2-[[3-Methyl-4-(2,2,2-trifluoroethoxy)pyridine-2-yl]methylthio]-1H-benzoimidazole;2-[3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinylmethylthio]-1H-benzoimidazole;2-[3-Methyl-4-(2,2,2;Lansoprazole Related Compound B (25 mg) (2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-pyridin-2-yl]methyl]sulfanyl]-1H-benzimidazole);2-{[3-Methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]Methyl}-1H-1,3-benzodiazole-1-thiol;2-(((3-Methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl)Methyl)thio)-1H-benzo[d]iMidazole;Lansoprazole related substance C;2-[[[3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]Methyl]thio]-
• CAS NO: 103577-40-8
• Molecular Formula: C₁₆H₁₄F₃N₃OS
• Molecular Weight: 353.36
• EINECS: 1533716-785-6
• Product Categories: Imidazol&Benzimidazole;(intermediate of lansoprazole);Heterocyclic Compounds;Heterocycles;Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals;Lansoprazole
• Mol File: 103577-40-8.mol

Chemical Properties

• Melting Point: 149-150°C
• Boiling Point: 494.9 °C at 760 mmHg
• Flash Point: 253.1 °C
• Appearance: /Crystalline Powder
• Density: 1.41
• Vapor Pressure: 6.2E-10mmHg at 25°C
• Refractive Index: 1.615
• Storage Temp.: -20°C Freezer
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 10.60±0.10(Predicted)
• CAS DataBase Reference: 2-[3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methylthio-1H-benzimidazole(CAS DataBase Reference)
• NIST Chemistry Reference: 2-[3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methylthio-1H-benzimidazole(103577-40-8)
• EPA Substance Registry System: 2-[3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methylthio-1H-benzimidazole(103577-40-8)

Safety Data

• Safety Statements: 24/25
• Hazardous Substances Data: 103577-40-8(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
2-[3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methylthio-1H-benzimidazole is used as an intermediate in the synthesis of various pharmaceutical compounds. Its unique chemical structure allows it to be a valuable building block for the development of new drugs with specific therapeutic properties.
Used in Chemical Research:
In the field of chemical research, 2-[3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methylthio-1H-benzimidazole serves as a subject of study for understanding its reactivity, stability, and potential applications in the synthesis of other complex organic molecules. Researchers may explore its use in the development of new materials, catalysts, or other specialty chemicals.
Used in the Synthesis of Impurities:
2-[3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methylthio-1H-benzimidazole is used as a reference material for the identification and quantification of impurities in the synthesis of related pharmaceutical compounds. Its presence can help ensure the purity and quality of the final product, which is crucial for the safety and efficacy of medications.
Used in the Development of Gastric Pump Inhibitors:
As a metabolite of Lansoprazole, 2-[3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methylthio-1H-benzimidazole is used in the development of gastric pump inhibitors. Lansoprazole is a proton pump inhibitor (PPI) that reduces the production of stomach acid, helping to treat conditions like gastroesophageal reflux disease (GERD), stomach ulcers, and other acid-related disorders. The study of its metabolites, such as 2-[3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methylthio-1H-benzimidazole, can provide insights into the drug's mechanism of action and potential side effects.

InChI:InChI=1/C16H14F3N3OS/c1-10-13(20-7-6-14(10)23-9-16(17,18)19)8-24-15-21-11-4-2-3-5-12(11)22-15/h2-7H,8-9H2,1H3,(H,21,22)

Upstream product

• 103577-45-3 lansoprasole 
• 103577-66-8 2-Hydroxymethyl-3-methyl-4-(2,2,2-trifluoroethoxy)pyridine 
• 75-09-2 dichloromethane 
• 134469-07-1 Benzimidazol-2-thiol 
• 1427321-51-4 2-[[[3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]-methyl]thio]-1H-benzimidazole 2-propanol 
• 37699-43-7 2,3-dimethyl-4-nitropyridine N-oxide 
• 103577-61-3 2,3-dimethyl-4-(2,2,2-trifluoroethoxy)-pyridine N-oxide 
• 128430-66-0 2-(chloromethyl)-3-methyl-4-(2,2,2-trifluoroethoxy)pyridine 

Downstream Products

• 138530-94-6 (R)-lansoprazole 
• 138530-95-7 (S)-lansoprazole 
• 103577-45-3 lansoprasole 
• 131926-99-3 Lansoprazole sulfone 
• 953787-54-7 2-[(3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl-1-oxide)methylsulfonyl]-1H-benzoimidazole 

Relevant articles and documents

A practical one pot synthesis of 2-[2-(pridylmethyl)-thio]-1H-benzimidazoles

A combination of Et3N and pTSCl was found to be far superior than pTSCl or benzene sulfonyl chloride alone in convert ing substituted 2-picoline-N-oxides to the corresponding 2-chloromethylpyridines and has been exploited for the synthesis of a variety of 2-[2-(pyridylmethyl)-thio]-1H-benzimidazoles, key intermediates in the manufacture of H+/K+-ATPase inhibitors in a single pot.

An improved process for the production of lansoprazole: Investigation of key parameters that influence the water content in final API

An improved large-scale synthesis of lansoprazole 1 an anti-ulcer drug is described. The synthesis commences with condensation of 2-mercaptobenzimadazole 3 with 2-chloromethyl-3methyl4-(2,2, 2-trifluoro ethoxy) pyridine hydrochloride 2 using water as a solvent to yield thioether 4. Subsequently, 4 was selectively oxidized to 1 by using sodium hypochlorite, a mild, economic, and eco- friendly oxidizing agent. A systematic investigation of crystallization parameters in the final stage, which enabled us to control the water content in the final API to 0.10%, were also discussed. (As recommended by USP 28 monograph (The United States Pharmacopeia: USP 28: NF 23, 28th rev. of The Pharmacopeia of the U.S., 23rd ed. of The National Formulary; United States Pharmacopeial Convention; Rockville, MD, 2005; p 1110.).

Preparation method of thioether

The preparation method comprises the following steps: (a) reacting a halogenated alkyl pyridine derivative or a salt thereof with 2 -mercaptobenzimidazole derivative in a water-soluble organic solvent under basic conditions. (b) The reaction solution obtained in step (a) was subjected to first devitrification step and second devitrification step, and purified. The prepared thioether is low in water content, uniform in water content and high in thioether purity, facilitates control of the water content of a reaction system in a subsequent thioether asymmetric oxidation reaction, and ensures high selectivity and reproducibility of asymmetric oxidation reaction. In addition, the preparation method of the thioether provided by the invention is simple in process and good in repeatability, and is more conducive to large-scale production.

Electrophilic Chlorine from Chlorosulfonium Salts: A Highly Chemoselective Reduction of Sulfoxides

Herein, we describe a selective late-stage deoxygenation of sulfoxides based on a novel application of chlorosulfonium salts and demonstrate a new process using these species generated in situ from sulfoxides as the source of electrophilic chlorine. The use of highly nucleophilic 1,3,5-trimethoxybenzene (TMB) as the reducing agent is described for the first time and applied in the deoxygenation of simple and functionalized sulfoxides. The method is easy to handle, economic, suitable for gram-scale operations, and readily applied for poly-functionalized molecules, as demonstrated with more than 45 examples, including commercial medicines and analogues. We also report the results of competition experiments that define the more reactive sulfoxide and we present a mechanistic proposal based on substrate and product observations.

Enhanced Antigiardial Effect of Omeprazole Analog Benzimidazole Compounds

Giardiasis is a diarrheal disease that is highly prevalent in developing countries. Several drugs are available for the treatment of this parasitosis; however, failures in drug therapy are common, and have adverse effects and increased resistance of the parasite to the drug, generating the need to find new alternative treatments. In this study, we synthesized a series of 2-mercaptobenzimidazoles that are derivatives of omeprazole, and the chemical structures were confirmed through mass, 1H NMR, and 13C NMR techniques. The in vitro efficacy compounds against Giardia, as well as its effect on the inhibition of triosephosphate isomerase (TPI) recombinant, were investigated, the inactivation assays were performed with 0.2 mg/mL of the enzyme incubating for 2 h at 37 ?C in TE buffer, pH 7.4 with increasing concentrations of the compounds. Among the target compounds, H-BZM2, O2N-BZM7, and O2N-BZM9 had greater antigiardial activity (IC50: 36, 14, and 17 μM on trophozoites), and inhibited the TPI enzyme (K2: 2.3, 3.2, and 2.8 M?1 s?1) respectively, loading alterations on the secondary structure, global stability, and tertiary structure of the TPI protein. Finally, we demonstrated that it had low toxicity on Caco-2 and HT29 cells. This finding makes it an attractive potential starting point for new antigiardial drugs.

Method for preparing high-purity razole intermediate and medicine by using green technology instead of phosgene, thionyl chloride and other toxic and harmful substances

The invention discloses a method for preparing a high-purity razole intermediate and a medicine by using a green technology instead of phosgene, thionyl chloride and other toxic and harmful substances. The preparation method comprises the following steps: dissolving Ph3PO in an organic solvent, placing the obtained solution in a reaction bottle, dropwise adding BTC to form a high-efficiency chloration reagent, carrying out a heat insulation reaction for a period of time after the dropwise addition is finished, dissolving a razole hydroxide in the organic solvent, dropwise adding the obtained solution to the above system, carrying out a heat insulation reaction for a period of time, carrying out suction filtration, and drying the obtained dried reaction product to obtain razole chloride. In the process, the Ph3PO is equivalently regenerated, a mother liquor part is concentrated to precipitate the Ph3PO at a low temperature, and the Ph3PO can be repeatedly used after being washed with a solvent with small polarity. The method has the advantages of few side reactions, high product quality, few "three wastes" pollutions, high atomic economy, and good promotion and application prospect. The invention also provides a relevant razole medicine prepared from the razole chloride obtained through the green technology. The medicine has obviously higher purity than medicines obtained through traditional methods.

Preparation method for dexlansoprazole

The invention discloses a preparation method for dexlansoprazole, belonging to the field of organic synthesis. The method comprises the following steps: (1) carrying out reaction on 2-hydroxymethyl-3-methyl-4-(2,2,2-trifluoro ethyoxyl) pyridine and thionyl chloride, and compounding 2-chloromethyl-3-methyl-4-(2,2,2-trifluoro ethyoxyl) pyridine; (2) putting 2-chloromethyl-3-methyl-4-(2,2,2-trifluoro ethyoxyl) pyridine acquired in the step (1) and 2-sulfydryl-1H-benzimidazole into an aqueous liquid, and then adding a phase transfer catalyst and sodium hydroxide, thereby acquiring 2-[[3-methyl-4-(2,2,2-trifluoro ethyoxyl) pyridine-2-group] methylmercapto]-1H-benzimidazole; (3) taking L-ethyl tartrate as a chiral assistant agent, titanium isopropoxide and diisopropylethylamine as a catalyst and cumyl hydroperoxide as an oxidizing agent and reacting with 2-[[3-methyl-4-(2,2,2-trifluoro ethyoxyl) pyridine-2-group] methylmercapto]-1H-benzimidazole acquired in the step (2) at low temperature, thereby acquiring dexlansoprazole. The preparation method for dexlansoprazole disclosed by the invention is simple and efficient, is capable of obviously shortening the reaction time under the condition of guaranteeing the product yield and is capable of improving the product quality.

Refining method for lansoprazole crude product

The invention discloses a refining method for a lansoprazole crude product. The method includes: firstly dissolving the crude product, performing decoloration, then conducting cooling and filtration to obtain a solid, and subjecting the obtained solid to refrigeration crystallization treatment in a mixed solvent of propylene oxide/tetrahydrocarbon furan/dichloromethane, and carrying out filtering, washing and drying on the obtained crystal so as to obtain a refined lansoprazole product. According to the method, a refined lansoprazole product with extremely high yield and low impurities can be obtained by one treatment, and the prepared refined lansoprazole product does not contain water or solvate of ethanol, has yield up to 83%-88%, purity of not less than 99.76%, and the content of impurities sulfide and sulfone respectively lower than 0.07% and 0.14%.

Preparation method of Dexlansoprazole

The invention discloses a preparation method of Dexlansoprazole. The preparation method comprises: 1, preparing a compound III; 2, preparing crude Dexlansoprazole; and 3, purifying the crude Dexlansoprazole. The method is characterized in that a compound 2 processed with active carbon is added in 1-1.5 h in step 1 to make the reaction completely carried out in order to increase the yield; and isopropyl titanate (IV) or titanium tert-butoxide is added in 10-15 min at 60-65 DEG C to form an enough complex in order to reduce the isomer content and improve the yield and the purity. The method has the advantages of simplicity in operation, high yield and high purity of the above product, and facilitation of commercial production.

Preparation method of (R)-lansoprazole

The invention provides a preparation method of (R)-lansoprazole. Through a condensation reaction and an asymmetric oxidation reaction of thioether, the (R)-lansoprazole is prepared. The preparation method comprises refining a (R)-lansoprazole finished product. In the first reaction step, cheap sodium hydroxide replaces sodium methylate, a reaction temperature is reduced to the room temperature from a return temperature, ethanol is used as a solvent and a high yield of 99.5% is realized. In the second asymmetric oxidation step, a yield is 80% or more. The preparation method has simple processes, is free of multiple complex extraction and separation processes and is suitable for industrial production. In the third step, through reaction condition optimization, a reaction conversion rate is greater than 85% and enantioselectivity is greater than 97%. Through purification, the product quality satisfies the FDA same-type product standards, optical purity and chemical purity are greater than 99.5%, the content of thioether is less than 0.1% and sulphone content is less than 0.1%. The preparation method has stable processes and an industrialization prospect.