102625-64-9

Usage

Chemical Properties

Beige Solid

Uses

Different sources of media describe the Uses of 102625-64-9 differently. You can refer to the following data:
1. A metabolite of Pantoprazole, an antiulcerative, gastric pump inhibitor
2. A metabolite of Pantoprazole (P183000), an antiulcerative, gastric pump inhibitor.
3. Pantoprazole Sulfide (Pantoprazole EP Impurity B) is a metabolite of Pantoprazole (P183000), an antiulcerative, gastric pump inhibitor.

InChI:InChI=1/C16H15F2N3O3S/c1-22-13-5-6-19-12(14(13)23-2)8-25-16-20-10-4-3-9(24-15(17)18)7-11(10)21-16/h3-7,15H,8H2,1-2H3,(H,20,21)

Upstream product

• 97963-62-7 5-(difluoromethoxy)-2-mercapto-1H-benzimidazole 
• 72830-09-2 2-Chloromethyl-3,4-dimethoxy-pyridine; hydrochloride 
• 15931-25-6 3-methoxy-2-methyl-4-nitropyridine 1-oxide 
• 76015-11-7 3-methoxy-2-methylpyridin-4(1H)-one 
• 35392-65-5 3-methoxy-2-methylpyridine 1-oxide 
• 169905-10-6 2-(chloromethyl)-3,4-dimethoxypyridine 
• 86604-75-3 2-(chloromethyl)-4-methoxy-3,5-dimethylpyridine hydrochloride 
• 577-71-9 3,4-dinitophenol 
• 172282-50-7 4-(difluoromethoxy)benzene-1,2-diamine 
• 102625-99-0 2-acetoxymethyl-3,4-dimethoxypyridine 
• 72830-07-0 3,4-dimethoxy-2-methylpyridine N-oxide ? 
• 72830-08-1 2-hydroxymethyl-3,4-dimethoxypyridine 
• 122307-41-9 4-chloro-3-methoxy-2-methylpyridine N-oxide 
• 107512-34-5 4-Chloro-3-methoxy-2-methyl-pyridine 

Downstream Products

• 102625-70-7 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridyl)methyl]sulfinyl]-1H-benzimidazole 
• 142678-35-1 5‐(difluoromethoxy)‐2‐[(3,4‐dimethoxy‐2‐pyridyl)methylsulfinyl]‐1H‐benzimidazole 
• 953787-55-8 5-(difluoromethoxy)-2-[(3,4-dimethoxypyridin-2-yl-1-oxide)methylsulfonyl]-1H-benzoimidazole 
• 138786-67-1 pantoprazole sodium 
• 142706-18-1 ((R)-6-(difluoromethoxy)-2-[(3,4-dimethoxypyridin-2-yl)methylsulfinyl]-1H-benzo[d]imidazole) 

Relevant academic research and scientific papers

An improved and single-pot process for the production of pantoprazole substantially free from sulfone impurity

Pantoprazole (1), a substituted benzimidazole derivative, is an irreversible proton pump inhibitor, essentially used for the prevention and treatment of gastric acid-related diseases. The process for its preparation generally suffers from the drawback of producing a potential sulfone impurity (5). The present work details a report of the journey towards the development of a simple, single-pot process for the production of pantoprazole, substantially free from sulfone impurity (5). The detailed study of the different parameters affecting the purity and yield of the compound has been presented.

Application of continuous flow micromixing reactor technology for synthesis of benzimidazole drugs

Synthesis of pharmaceutically active compounds by employing continuous flow micromixing reactor technology is an interesting research area. In this article we describe the synthesis of benzimidazole core drugs, such as lansoprazole (1a), pantaprazole (1b), and rabeprazole (1c) by using a continuous flow micromixing reactor technology. A key feature of the sulfoxidation includes the decreasing the reaction time from 3 h to ～1 s to minimize the formation of sulfone impurities and improve the yields.

An electronic circular dichroism study for the structurechiroptical relationship of chiral proton pump inhibitors

In this paper, we investigated the electronic circular dichroism (ECD) of proton pump inhibitors (PPIs) using a method of combining experimental spectrum and time-dependent density functional theory (TD-DFT) calculations. In our research, an intriguing helicity-like phenomenon was discovered for the relationship between static dipole moment and ECD curves of different conformers in lansoprazole. The scope and validity of the precious phenomenon have been examined by four PPIs using the same method. Hence, it can be used as a reference to determine and verify the absolute configuration of PPIs-type and PPIs-like chiral sulfoxide.

Preparation of Pantoprazole sodium method and Pantoprazole sodium (by machine translation)

The invention relates to the preparation of Pantoprazole sodium method and pantoprazole sodium. In particular, the invention relates to a method of preparing pantoprazole sodium, comprising the following steps: 1) to 2 - hydroxymethyl - 3, 4 - dimethoxy pyridine (II) as the starting material, in under the action of chloride, the compound of formula III; 2) will be of the formula III compound in the presence of an inorganic base with 5 - difluoro - 2 - mercapto - 1 H - benzimidazole condensation, the compound of formula IV; 3) will be of the formula IV compound is oxidized by an oxidant generating 5 - difluoro - 2 - [(3, 4 - dimethoxy - 2 - pyridyl) methyl] sulfinyl - 1 H - benzimidazole is pantoprazole; 4) the obtained 5 - difluoro - 2 - [(3, 4 - dimethoxy - 2 - pyridyl) methyl] sulfinyl - 1 H - benzimidazole with sodium hydroxide reaction to produce salt that pantoprazole sodium (I); and optionally a 5) the resulting pantoprazole sodium is refined. The method of the invention said product has high purity, and the related impurities such as oxidation impurity, reducing the impurity, decomposition low impurity content. (by machine translation)

Triple Mode of Alkylation with Ethyl Bromodifluoroacetate: N, or O-Difluoromethylation, N-Ethylation and S-(ethoxycarbonyl)difluoromethylation

In this report, we have explored a triple mode of chemical reactivity of ethyl bromodifluoroacetate. Typically, bromodifluoroacetic acid has been used as a difluorocarbene precursor for difluoromethylation of soft nucleophiles. Here we have disclosed nucleophilicity and base dependent divergent chemical reactivity of ethyl bromodifluoroacetate. It furnishes lithium hydroxide and cesium carbonate promoted difluoromethylation of tosyl-protected aniline and electron-deficient phenols respectively. Interestingly, switching the base from lithium hydroxide to 4-N,N-dimethylamino pyridine (DMAP) tosyl-protected anilines afforded the corresponding N-ethylation product. Whereas, highly nucleophilic thiophenols furnished the corresponding S-carboethoxydifluoromethylation product via a rapid SN2 attack to the bromine atom prior to the ester hydrolysis. This mechanistic divergence was established through several control experiments. It was revealed that difluoromethylation reaction proceeds through a tandem in situ ester hydrolysis/decarboxylative-debrominative difluorocarbene formation and subsequent trapping by the soft nucleophile-NHTs or electron-deficient phenolic ?OH groups. In the presence of DMAP the hydrolysis of the ester is perturbed instead a nucleophilic attack at the ethyl moiety provides the N-ethylation product. Hence, besides the development of a practical base-promoted N-difluoromethylation of amines and electron-deficient phenols, divergent reactivity pattern of inexpensive and user-friendly ethyl bromodifluoroacetate has been explored. (Figure presented.).

A pantoprazole sodium production process (by machine translation)

Pantoprazole sodium (Pantoprazole Sodium), chemical name 5 - difluoro - 2 - [[ (3, 4 - dimethoxy - 2 - pyridyl) - methyl] sulfinyl] - 1 H - benzimidazole sodium monohydrate, is the treatment of peptic ulcer and acute gastric mucosal lesion caused by bleeding of a safe, effective drug, to peptic ulcer and reflux esophagitis have very high cure rate. For the injection of the injection by the German hectogram (Byk Gulden) the pharmaceutical Company (now renamed Takeda pharmaceutical companies) lead to the successful development of, for 1994 years 10 months in south Africa listed for the first time, tradenames for pan tuo lOOc. The present invention provides a pantoprazole sodium production process. A specific process comprises the following process: 1, pantoprazole sodium intermediate synthesis of IV; 2, pantoprazole sodium crude synthesis of V; 3, crude refined product. (by machine translation)

A method for preparing divides the request to pull zuozuo the sodium nitrogen oxide impurity

The present invention discloses a preparation method for a pantoprazole sodium oxynitride impurity. The preparation method comprises the following steps: 2-chloromethyl-3,4-dimethoxypyridine hydrochloride is used as a raw material to react with 5-difluoromethoxy-2-mercapto-1H-benzimidazole and produce 5-difluoromethoxy-2-{[(3,4-dimethoxy-2-pyridyl)methyl]sulphur}-1H-benzimidazole; then in a presence of hydrogen peroxide and acetic acid, with copper hydroxyphosphate as a catalyst, oxidation is performed to obtain an oxynitride product of the pantoprazole; and finally a sodium salt is obtained by a reaction with sodium hydroxide, and pantoprazole sodium oxynitride impurity is obtained. According to the preparation method, no extreme reaction condition is needed, and raw materials are easy to obtain; the oxidant is capable of selective oxidations, which can not only oxidate pyridine ring, but also can oxidate thioether to sulfoxide, and by controlling the dosage of the catalyst, i.e., copper hydroxyphosphate, a peroxidation is less likely to occur (oxidate thioether to sulphone); and a post-treatment is simple and easy in operation, and the resulting product is high in purity and high in yield.

A method for preparing divides the request to pull zuozuo the sodium sulphone nitrogen oxide impurity

The invention discloses a method for preparing a pantoprazole sodium sulfone-nitrogen oxidized impurity. The method comprises the steps: enabling 2-chloromethyl-3,4-dimethoxy pyridine hydrochloride, which serves as a raw material, to react with 5-difluoromethoxy-2-mercapto-1H-benzimidazole so as to produce 5-difluoromethoxy-2-{[(3,4-dimethoxy-2-pyridyl)methyl]sulfo}-1H-benzimidazole; then, oxidizing 5-difluoromethoxy-2-{[(3,4-dimethoxy-2-pyridyl)methyl]sulfo}-1H-benzimidazole in the presence of hydrogen peroxide and acetic acid in a manner of using methyl rhenium trioxide as a catalyst, so as to produce a sulfone-nitrogen oxidized product of pantoprazole; and finally, forming a sodium salt by the sulfone-nitrogen oxidized product of pantoprazole and sodium hydroxide, thereby obtaining the pantoprazole sodium sulfone-nitrogen oxidized impurity. According to the method, the hydrogen peroxide-acetic acid system can oxidize a pyridine ring. The oxidizer methyl rhenium trioxide is adopted as the catalyst and can be complexed with hydrogen peroxide so as to produce peroxide of rhenium, oxygen in the peroxide of rhenium can be transferred to thioether needing oxidization, and thioether can be oxidized into sulfone through controlling the usage amount of the catalyst and the reaction temperature, so that the high-yield and high-purity product can be obtained.

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.

Synthesis process of (L)-pantoprazole

The invention discloses a synthesis process of (L)-pantoprazole. The synthesis process comprises the following steps: 1) in the presence of iodine and alkali, 5-(difluoromethoxy)-2-mercapto-1H-benzimidazole and 2-(chloromethyl)-3,4-dimethoxypyridine hydrochloride are subjected to stirring reaction to obtain the pantoprazole thioether as shown in the formula I, and the pantoprazole thioether represented by the formula I shown in the specification and hydrogen peroxide are subjected to oxidation reaction in the presence of (R)-(-)-binaphthol phosphate to obtain the (L)-pantoprazole. The synthesis process is good in stereo selectivity, high in the product yield, mild in the conditions, simple in the steps and easier in after-treatment and purification.