177795-59-4Relevant academic research and scientific papers
Method for preparing chiral sulfoxide drugs in water phase
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Paragraph 0056-0058, (2020/09/09)
The invention relates to the field of chiral drug preparation, in particular to a method for preparing chiral sulfoxide drugs in a water phase. The method for preparing the chiral sulfoxide drugs in the water phase comprises the following steps: using a hydrogen peroxide solution as oxidant, using a temperature-sensitive ferrocene chiral amino acid titanium complex as a catalyst and using prochiral thioether as a substrate in the pure water phase to perform an asymmetric oxidation reaction to synthesize the chiral sulfoxide drugs. The temperature-sensitive ferrocene chiral amino acid titaniumcomplex catalyst can be utilized to catalyze the asymmetric oxidation reaction of thioether in the pure water phase and has the characteristics of high catalytic efficiency and easy recovery of the catalyst.
Method for producing proton pump inhibitor compound having optical activity
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Page/Page column 16, (2019/06/15)
A highly pure optically active proton pump inhibitor compound can be produced safely and inexpensively in a high yield and enantioselectivity by a method of producing an optically active sulfoxide of Formula 2 or a salt thereof, comprising oxidizing a sulfide of Formula 1 or a salt thereof with hydrogen peroxide using an iron salt in the presence of a chiral ligand of Formula 3; wherein A is CH or N; R1 is hydrogen atom, an alkyl optionally substituted by halogen(s), or an alkoxy optionally substituted by halogen(s); one to three R2 may exist, and each of R2 is independently an alkyl, a dialkylamino, or an alkoxy optionally substituted by halogen(s) or alkoxy(s); each of R3 is independently hydrogen atom, a halogen, cyano or the like; R4 is a tertiary alkyl; and * and ** represent respectively R configuration or S configuration.
Method for preparing benzimidazole proton pump inhibitor
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Paragraph 0042; 0043; 0044; 0046; 0047; 0048; 0078; 0079, (2018/09/08)
The invention provides a novel method for preparing a benzimidazole proton pump inhibitor, and belongs to the field of medicine synthesis. According to the method provided by the invention, a complexformed by using graphene oxide and a transition metal salt is used as a catalyst, and the corresponding benzimidazole proton pump inhibitor is obtained through oxidizing a thioether by an oxidizing agent under an alkaline condition in an organic solvent. The method has the advantages of mild reaction condition, high yield, environmental friendliness, and less impurity, the catalyst can be recycled, and the method is suitable for industrial production.
INHIBITORS OF SARM1 NADase ACTIVITY AND USES THEREOF
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Page/Page column 123, (2018/04/20)
The present disclosure provides compounds useful as inhibitors of SARM1 NADase activity, compositions thereof, and methods of using the same. The present disclosure provides compounds useful for treating a neurodegenerative or neurological disease or disorder, compositions thereof, and methods of using the same.
Rabeprazole analogue preparation method
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Paragraph 0037-0051, (2018/10/27)
The invention discloses a rabeprazole analogue preparation method, and particularly relates to a (R)-rabeprazole preparation method. According to the method, under the co-action of a vanadium metal and a tetradentate organic ligand, a prochiral thioether compound is oxidized with an oxidizing agent to generate (R)-rabeprazole. The method of the present invention has advantages of high enantioselectivity, high product purity and high yield, and is suitable for industrial production.
Synthesis of Esomeprazole and Related Proton Pump Inhibitors through Iron-Catalyzed Enantioselective Sulfoxidation
Nishiguchi, Shigenobu,Izumi, Takuhiro,Kouno, Takayoshi,Sukegawa, Junpei,Ilies, Laurean,Nakamura, Eiichi
, p. 9738 - 9743 (2018/10/09)
We report here an application of iron catalysis for the kilogram scale asymmetric synthesis of a proton pump inhibitor, esomeprazole, in 87% yield and 99.4% ee by catalytic sulfoxidation with hydrogen peroxide using an iron salt/chiral Schiff base in combination with a carboxylate salt. Under similar reaction conditions, other proton pump inhibitors such as (S)-lansoprazole, (S)-rabeprazole, and (S)-pantoprazole, were also synthesized in high yield and ee. A carboxylate additive was crucial for the success of this reaction, and we consider that it coordinates to the active iron species, and it also acts as a hydrogen-bond acceptor to coordinate to the substrate through the imidazole NH.
A catalytic asymmetric oxidizing thioether preparation of chiral pharmaceutical method
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Paragraph 0038-0044; 0053-0055, (2020/02/07)
The invention provides a preparation method of a chiral sulfoxide medicament though catalysis of asymmetric oxidation of sulfides compounds. A chiral complex formed by quadridentate nitrogen organic ligand and metal manganese compound as a catalyst and hydrogen peroxide as an oxidant are used for asymmetric catalytic oxidation of prochiral thioether compound, so as to obtain the corresponding chiral sulfoxide medicament compounds including S-omeprazole, S-lansoprazole, S-pantoprazole, S-rabeprazole, R-Modafinil and R-sulindac. The reaction has the advantages of cleaness, mild reaction conditions, high conversion rate and antipodal selectivity, and shows industrial prospects.
Preparation method for key intermediate rabeprazole thioether
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Paragraph 0024-0025, (2017/07/12)
The invention discloses a preparation method for rabeprazole thioether 2-[[[4-(3- methoxypropoxy)-3-methylpyridin-2-yl] methyl] sulfo]-1H-benzimidazole. By using Mitsunobu reaction, the rabeprazole thioether is prepared from rabeprazole oxhydryl in one-step synthesis way without chlorination reaction. In the reaction process, the high-corrosive chloride agent, such as, thionyl chloride, is not used, so that the violent corrosion of the reaction to the device is obviously reduced, and meanwhile, the reaction yield is obviously increased due to the shortened reaction step. According to the invention, the process is simple, the reaction condition is mild, the corrosion to the device is small, the yield is higher (70%-80%) and the method is suitable for industrial production.
Method for preparing optically-pure Rabeprazole
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Paragraph 0070; 0071; 0072; 0073; 0074, (2017/08/28)
The invention discloses a method for preparing optically-pure Rabeprazole. The method is used for preparing a chiral 2-[[4-(3-methoxypropoxy)-3-methylpyrid-2-yl]methylsulfinyl]-1H-benzimidazole compound (Rabeprazole), which is present in a single-enantiomer form or rich-enantiomer form, in an enantioselective manner. The same effects, i.e., identical enantioselectivity and conversion ratio can be achieved through complexing a tartaric acid diamide ligand and titanium and adding an organic-base additive or not in the presence of water. The invention further provides a method for preparing a sodium salt from the obtained Rabeprazole.
A optically pure and its sodium salt preparation method
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Paragraph 0047; 0048, (2017/08/10)
The invention discloses preparation methods of optically pure rabeprazole and a sodium salt thereof. The preparation method of optically pure rabeprazole specifically comprises the steps of dissolving an S-(-)-rabeprazole or R-(+)-rabeprazole crude product in an organic solvent, extracting by using ammonium hydroxide, removing an organic layer, adjusting a pH value of the ammonium hydroxide extract to be 8.5-10.5 by using acetic acid, extracting by using a ketone type solvent, washing the obtained organic layer by using a buffering solution with the pH value of 9-11, and cooling and crystallizing to obtain optically pure rabeprazole. According to the preparation method of optically pure rabeprazole, the chiral rabeprazole solids can be obtained at lower temperature without being subjected to high-temperature concentration; the obtained chiral rabeprazole has good crystal form, high chemical purity and high chiral purity.
