- An efficient asymmetric approach to the R-enantiomer impurity of esomeprazole
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Esomeprazole {(S)-5-methoxy-2-[(4-methoxy-3, 5-dimethyl-2-pyridinylmethyl) sulfinyl]-1H-benzimidazole} is a proton pump inhibitor used as an antiulcer drug. Its R-enantiomer 3 was synthesized with high enantioselectivity by asymmetric oxidation of prochiral sulfide 2 using the oxaziridinium salt 4. Product 3, useful as a reference for the quality control of esomeprazole, was characterized by 1H and 13C NMR, IR, and HRMS. The enantiomeric excess was determined by HPLC.
- Zhou, Guobin,Guan, Yueqing
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Read Online
- Asymmetric Bio-oxidation Using Resting Cells of Rhodococcus rhodochrous ATCC 4276 Mutant QZ-3 for Preparation of (S)-Omeprazole in a Chloroform–Water Biphasic System Using Response Surface Methodology
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(S)-Omeprazole is a very effective anti-ulcer medicine that is difficult to be prepared using whole cells at elevated substrate concentrations. In the chloroform–water biphasic system, resting cells of the mutant QZ-3 of Rhodococcus rhodochrous (R. rhodochrous) ATCC 4276 were used to catalyze the bio-oxidation of omeprazole sulfide for preparation of (S)-omeprazole. Using response surface methodology (RSM), the reaction was optimized to work at a substrate concentration of 180?mM and a cell concentration of 100?g/L. The optimal yield of (S)-omeprazole obtained was 92.9% with enantiomeric excess (ee) (> 99%), and no sulfone by-product was detected under the optimal working conditions; reaction temperature 37?°C, pH 7.3 and reaction time, 43?h. A quadratic polynomial model was established, which predicts the experimental data with very high accuracy (R2 = 0.9990). The chloroform–water biphasic system may contribute to the significant improvement in substrate tolerance because almost all substrates are partitioned in the organic phase (water solubility of omeprazole sulfide is only about 0.5?mg/mL), resulting in little damage and inhibition to cells by substrates. The mutant QZ-3 of R. rhodochrous ATCC 4276 exhibited high enantioselectivity, activity and substrate and product tolerance. The aerated flask provides enough oxygen for a high concentration of cells. Accordingly, bio-oxidation is thus more promising for efficient preparation of chiral sulfoxides.
- Zhang, Yuanyuan,Lv, Kuiying,Deng, Yashan,Li, Huiling,Wang, Zhiyong,Li, Depeng,Gao, Xin,Wang, Fanye
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p. 2928 - 2938
(2021/02/01)
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- Method for preparing chiral sulfoxide drugs in water phase
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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.
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Paragraph 0039-0049
(2020/09/09)
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- Tartaric acid ester compound as well as preparation method and applications thereof
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The invention discloses a compound shown in formula (I), wherein R1 and R2 are independently selected from optionally substituted C1-6 alkyl, optionally substituted C3-8 cycloalkyl, optionally substituted C6-14 aryl and optionally substituted -(CH2)m-C3-8 cycloalkyl or -(CH2)n Ar; and Ar denotes the optionally substituted C6-14 aryl. The compound can be used for preparing prazole drugs during thetitanium-catalyzed asymmetric oxidation of pyrazole sulfides. (img file='DDA0001401304200000011.TIF' wi='669' he='551'/).
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Paragraph 0101-0106
(2019/03/29)
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- Enzymatic kinetic resolution of chiral sulfoxides-an enantiocomplementary approach
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A new enzymatic assay for the preparation of chiral sulfoxides that is enantiocomplementary to the known (S)-enantiomer-reducing activity of methionine sulfoxide reductase A (MsrA) is described. To this end, we have utilized the enzyme DMSO reductase (DmsABC), recently discovered by us being highly upregulated in stationary phase E. coli bacteria.
- Nosek, Vladimír,Mí?ek, Ji?í
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supporting information
p. 10480 - 10483
(2019/09/07)
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- Method for producing proton pump inhibitor compound having optical activity
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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.
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Page/Page column 12; 13
(2019/06/15)
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- A catalytic asymmetric oxidizing thioether preparation of chiral pharmaceutical method
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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.
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Paragraph 0038-0044
(2020/02/07)
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- Oxidative kinetic resolution of heterocyclic sulfoxides with a porphyrin-inspired manganese complex by hydrogen peroxide
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We have successfully reported here the low loading porphyrin-inspired high-valent manganese (IV)-oxo complex was applied in oxidative kinetic resolution (OKR) of racemic heterocyclic sulfoxides using the environmentally benign hydrogen peroxide for the first time. This approach allows for rapid OKR (0.5 h) of a variety of racemic sulfoxides (including pyridine, pyrimidine, pyrazine, thiazole, benzothiazole, thiophene) in excellent enantioselectivity (up to > 99% ee), simultaneously generating the corresponding sulfones in high yield (up to 80%). The catalytic system also showed an unexceptionable chemoselectivity for the sulfoxide substrates with hydroxyl groups in which only the sulfoxide group was oxidized. The practical utility of the method has been demonstrated in the OKR of gram-scale sulfoxides.
- Yang, Jinchuang,Wang, Lianyue,Lv, Ying,Li, Ning,An, Yue,Gao, Shuang
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supporting information
p. 156 - 159
(2017/12/15)
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- Baeyer-Villiger Monooxygenase-Mediated Synthesis of Esomeprazole As an Alternative for Kagan Sulfoxidation
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A wild-type Baeyer-Villiger monooxygenase was engineered to overcome numerous liabilities in order to mediate a commercial oxidation of pyrmetazole to esomeprazole, using air as the terminal oxidant in an almost exclusively aqueous reaction matrix. The developed enzyme and process compares favorably to the incumbent Kagan inspired chemocatalytic oxidation, as esomeprazole was isolated in 87% yield, in >99% purity, with an enantiomeric excess of >99%.
- Bong, Yong Koy,Song, Shiwei,Nazor, Jovana,Vogel, Michael,Widegren, Magnus,Smith, Derek,Collier, Steven J.,Wilson, Rob,Palanivel,Narayanaswamy, Karthik,Mijts, Ben,Clay, Michael D.,Fong, Ryan,Colbeck, Jeff,Appaswami, Amritha,Muley, Sheela,Zhu, Jun,Zhang, Xiyun,Liang, Jack,Entwistle, David
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supporting information
p. 7453 - 7458
(2018/07/29)
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- Esomeprazole as well as preparation method and application thereof
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The invention discloses esomeprazole as well as a preparation method and application thereof, relates to the technical field of medicines and aims to solve the technical problems that the existing preparation method of esomeprazole is low in economy and cannot meet the requirements of energy economization, consumption reduction, green and environment protection. The preparation method of the esomeprazole comprises a step of selectively oxidizing prochiral thioether ufiprazole into esomeprazole with cooperation of catalysts, oxidants, organic solvents and pH regulators under the action of functional chiral ionic liquid taking (D)-(-)-tartaric acid as anion. After the functional chiral ionic liquid taking (D)-(-)-tartaric acid as anion is added, the dissoluvability of the prochiral sulfide ufiprazole used as the raw material is obviously improved; the higher raw material utilization rate and selectivity can be ensured. The method has the advantages of simple step, easy operation, low consumption of solvents and low raw material dissolving temperature, so that the method is low in energy consumption, can meet the requirements of energy economization, consumption reduction, green and environment protection, and is suitable for large-scale industrial production.
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Paragraph 0077; 0078; 0081; 0084; 0087; 0090; 0093
(2018/01/11)
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- Ultrafast chiral separations for high throughput enantiopurity analysis
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Recent developments in fast chromatographic enantioseparations now make high throughput analysis of enantiopurity on the order of a few seconds achievable. Nevertheless, routine chromatographic determinations of enantiopurity to support stereochemical investigations in pharmaceutical research and development, synthetic chemistry and bioanalysis are still typically performed on the 5-20 min timescale, with many practitioners believing that sub-minute enantioseparations are not representative of the molecules encountered in day to day research. In this study we develop ultrafast chromatographic enantioseparations for a variety of pharmaceutically-related drugs and intermediates, showing that sub-minute resolutions are now possible in the vast majority of cases by both supercritical fluid chromatography (SFC) and reversed phase liquid chromatography (RP-LC). Examples are provided illustrating how such methods can be routinely developed and used for ultrafast high throughput analysis to support enantioselective synthesis investigations.
- Barhate, Chandan L.,Joyce, Leo A.,Makarov, Alexey A.,Zawatzky, Kerstin,Bernardoni, Frank,Schafer, Wes A.,Armstrong, Daniel W.,Welch, Christopher J.,Regalado, Erik L.
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supporting information
p. 509 - 512
(2017/01/13)
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- Ti-Salan catalyzed asymmetric sulfoxidation of pyridylmethylthiobenzimidazoles to optically pure proton pump inhibitors
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The asymmetric sulfoxidation of two pyridylmethylthiobenzimidazoles to anti-ulcer drugs of the PPI family (S)-omeprazole and (R)-lansoprazole with hydrogen peroxide, mediated by a series of chiral titanium(IV) salan complexes is reported. High sulfoxide yields (up to?>95%) and enantioselectivities (up to 94% ee) have been achieved. The introduction of electron-withdrawing substituents leads to less active and less enantioselective catalysts. Like for the previously reported Ti-salalen catalyzed sulfoxidations, the temperature dependence of the sulfoxidation enantioselectivity in the presence of Ti-salan complexes is nonmonotonic, demonstrating isoinversion behavior with decreasing temperature. The oxidation is likely rate-limited by the formation of the active (presumably peroxotitanium(IV)) species, followed by a faster oxygen transfer to the substrate.
- Talsi, Evgenii P.,Bryliakov, Konstantin P.
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- An efficient silica supported Chitosan@vanadium catalyst for asymmetric sulfoxidation and its application in the synthesis of esomeprazole
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A new type of silica supported Chitosan@vanadium complex was used as a highly active heterogeneous catalyst for asymmetric oxidation of aryl alkyl sulfides. With the economic aqueous H2O2(30%) as the oxidant, the oxidation products were obtained in high yields (up to 95%) with good enantioselectivities (up to 68% ee). It is noted that the marketed drug Nexium (first proton-pump inhibitor, esomeprazole) could be synthesized easily by the newly developed asymmetric sulfoxidation reaction. In addition, the highly active catalyst can be reused five times without losing its catalytic activity.
- Shen, Chao,Qiao, Jun,Zhao, Linwei,Zheng, Kai,Jin, Jianzhong,Zhang, Pengfei
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p. 114 - 118
(2017/01/25)
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- Aqueous two-phase system chiral separation Prazole compound
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The invention discloses a new method for chiral resolution and racemization of a prazole compound, and particularly an aqueous two-phase resolution system is adopted. An aqueous phase contains a hydrophilic chiral resolving agent and the prazole compound, and the other phase contains an alcohol soluble chiral resolving agent; after the two phases are mixed, the pH is adjusted to neutral, and the prazole compound is resolved into optical-pure chiral compounds under the actions of the two chiral resolving agents. When a phase-separating salt is added into the system, the system can become two separable phases respectively containing two different chiral isomers.
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Paragraph 0013
(2016/12/01)
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- A method for preparing of ammonium salts of esomeprazole
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The invention relates to a synthesis method for preparing esomeprazole. The required protection method comprises the step that: Ufiprazole is subjected to asymmetric oxidation by using a mild and cheap oxidant in the existence of N substituted 1-amino-2-indanol ligand and a complex catalyst formed by titanium, so that an optical pure or esomeprazole-enriched product can be obtained.
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Paragraph 0028; 0029
(2017/02/24)
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- Method for realizing asymmetric oxidation reaction of thioether under aqueous-phase catalysis of chiral Salen Ti complex catalyst based on temperature-sensitive type ionic liquid
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The invention discloses a method for realizing an asymmetric oxidation reaction of thioether under aqueous-phase catalysis of a chiral Salen Ti complex catalyst based on a temperature-sensitive type ionic liquid. According to the method, a chiral thioether compound and hydrogen peroxide are subjected to an asymmetric oxidation reaction under the catalytic action of the chiral Salen Ti complex catalyst based on the temperature-sensitive type ionic liquid in a water medium, and a chiral sulfoxide compound is obtained; the chiral Salen Ti complex catalyst based on the temperature-sensitive type ionic liquid also contains a chiral Salen Ti complex catalyst unit and a temperature-sensitive material unit. Compared with a conventional chiral Salen Ti catalyst, the catalyst has good water solubility, can be subjected to a catalytic reaction in the water medium and is easily recycled; the catalyst is applicable to the aqueous-phase catalytic oxidation reaction of chiral thioether and has the characteristics of high catalysis efficiency and good chiral sulfoxide selectivity.
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Paragraph 0087-0089; 0090
(2017/02/24)
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- Synthesis of prazole compounds
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The present disclosure relates to non-naturally occurring monooxygenase polypeptides useful for preparing prazole compounds, polynucleotides encoding the polypeptides, and methods of using the polypeptides.
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Page/Page column 50-52
(2016/02/03)
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- Catalytic Asymmetric Synthesis of Esomeprazole by a Titanium Complex with a Hexa-aza-triphenolic Macrocycle Ligand
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An efficient synthesis of esomeprazole via catalytic asymmetric oxidation of 1H-benzimidazolyl pyridinylmethyl sulfide by a titanium complex with a hexa-aza-triphenolic macrocycle ligand is described. Esomeprazole was prepared with 99.6% ee, which meets the high requirement of the European Pharmacopeia on enantiomeric purity.
- Song, Weiguo,Dong, Liangjun,Zhou, Yuhan,Fu, Yongqiang,Xu, Wenfang
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- Enantioselective oxidation of sulfides with H2O2 catalyzed by a pre-formed manganese complex
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A facile and environmentally friendly method is presented for the asymmetric oxidation of sulfides with H2O2, utilizing a pre-formed manganese complex. Just in the presence of a low catalytic amount of carboxylic acid (CA), a variety of sulfide substrates, including aryl alkyl, aryl benzyl and cyclic sulfides, reacted to form chiral sulfoxides in high yields (up to 95%) and excellent enantioselectivities (>99% ee) under mild conditions. Moreover, the practical utility of the method has been demonstrated by the synthesis of esomeprazole and albendazole sulfoxide (ABZO).
- Dai, Wen,Li, Guosong,Wang, Lianyue,Chen, Bo,Shang, Sensen,Lv, Ying,Gao, Shuang
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p. 46545 - 46554
(2014/12/10)
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- Asymmetric oxidation catalysis by a porphyrin-inspired manganese complex: Highly enantioselective sulfoxidation with a wide substrate scope
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The first genuinely promising porphyrin-inspired manganese-catalyzed asymmetric sulfoxidation method using hydrogen peroxide has been successfully developed, allowing for rapidly oxidizing (0.5-1.0 h) a wide variety of sulfides in high yields with excellent enantioselectivities (up to >99% ee).
- Dai, Wen,Li, Jun,Chen, Bo,Li, Guosong,Lv, Ying,Wang, Lianyue,Gao, Shuang
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supporting information
p. 5658 - 5661
(2013/12/04)
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- Catalytic asymmetric oxidation of 1H-benzimidazolyl pyridinylmethyl sulfides with cumene hydroperoxide catalyzed by a titanium complex with (S,S)-N,N′-dibenzyl tartramide ligand
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A chiral titanium complex, formed in situ from Ti(Oi-Pr)4, (S,S)-N,N′-dibenzyl tartramide and water was found to serve as an efficient catalyst for the asymmetric oxidations of 1H-benzimidazolyl pyridinylmethyl sulfides with cumene hydroperoxide (CHP) in the absence of a base. Several proton pump inhibitors (PPIs), such as esomeprazole, lansoprazole, rabeprazole and pantoprazole were obtained in high yield (up to 92%) and excellent enantiomeric excess (up to 96%).
- Che, Guoyong,Xiang, Jing,Tian, Tian,Huang, Qingfei,Cun, Linfeng,Liao, Jian,Wang, Qiwei,Zhu, Jin,Deng, Jingen
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experimental part
p. 457 - 460
(2012/07/28)
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- A METHOD OF MANUFACTURING (S)-5-METHOXY-2-[[(4-METHOXY-3,5-DIMETHYL-2- PYRIMIDINYL)METHYL]SULFINYL]-1H-BENZIMIDAZOLE USING A CHIRAL COMPLEX WITH MANDELIC ACID
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The invention deals with a new manufacturing method of (S)-5-methoxy-2-[[(4-methoxy- 3,5-dimethyl-2-pyridinyl)methyl]sulphinyl]-1H-benzimidazole of formula (I) and its salts of general formula (II), wherein the sulfide of general formula (III) is oxidized by hydroperoxides on a catalyst consisting of a chiral metallic complex containing ligands constituted by chiral functional derivatives of mandelic acid.
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Page/Page column 13; 14
(2011/10/13)
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- Process for preparation of esomeprazole sodium of high chemical purity and new forms of esomeprazole sodium
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A process for preparing esomeprazole sodium comprises the steps of providing a solution of esomeprazole sodium in a solvent constituted mainly of methanol or only of methanol; and carrying out precipitation or crystallisation of esomeprazole sodium from said solution. Esomeprazole sodium is preferably obtained from pure form of neutral racemate through chiral chromatography using methanol-based mobile phase, and a subsequent reaction with sodium source. Novel crystal and semicrystal forms of esomeprazole sodium can be provided repeatedly and in physically stable and highly pure form.
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Page/Page column 9
(2010/01/29)
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- OPTICAL PURIFICATION OF ESOMEPRAZOLE
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The present invention relates to process for optical purification of esomeprazole or a salt thereof. Thus, esomeprazole sodium having 20 to 1 % R-omeprazole by weight of the sum of the contents of esomeprazole and R-omeprazole is precipitated from a solvent selected from an alcohol or a mixture of alcohols and the precipitated solid is collected to obtain optically pure esomeprazole sodium.
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Page/Page column 6
(2010/07/10)
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- PROCESS FOR THE PREPARATION OF ENANTIOMERICALLY ENRICHED PROTON PUMP INHIBITORS
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The invention discloses a process for the preparation of compounds having structures typical for proton pump inhibitors in enantiomerically enriched form by using particular metal catalysts in an enantioselective oxidation step. Also disclosed are useful further processes and pure intermediate and subsequently final products.
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Page/Page column 31
(2010/04/30)
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- A METHOD FOR THE MANUFACTURE OF (S) -5-METHOXY-2- [ [ (4-METHOXY-3, 5-DIMETHYL-2-PYRIMIDINYL) METHYL] SULFINYL] -IH-BENZ IMIDAZOLE USING A CHIRAL COMPLEX WITH LACTIC ACID
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The invention deals with a new method of manufacturing (S)-5-methoxy-2-[[(4- methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole of formula (I) and its salts of general formula (II), wherein the sulfide of general formula (III) is oxidized with hydroperoxides on a catalyst consisting of a chiral metallic complex containing ligands constituted by chiral functional derivatives of lactic acid.
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Page/Page column 14
(2010/09/03)
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- IMPROVED PREPARING METHOD OF (S)-OMEPRAZOLE FROM OMEPRAZOLE RACEMATE USING OPTICAL RESOLUTION AGENT
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The present invention relates to an improved preparing method of (S)-omeprazole from omeprazole racemate. In an exemplary embodiment, the preparing method according to the present invention comprises the steps of: a) reacting omeprazole racemate with optically active diethyl-D-tartrate and a titanium compound in an alcohol solvent to prepare an omeprazole racemic complex; b) reacting the omeprazole racemic complex with 1.5-3.0 molar equivalents of (S)-(+)-mandelic acid as optical resolution agent to prepare an optically active (S)-omeprazole complex; and c) dissociating the optically active (S)-omeprazole complex with a basic solution to prepare an (S)-omeprazole free base or reacting the (S)- omeprazole free base with a metal salt to transfer to a metal salt or a metal salt hydrate of (S)- omeprazole. With optical purity of 99.0 %ee or better, the (S)-omeprazole, the metal salt thereof or the hydrate thereof prepared in accordance with the present invention is useful as a medicinal material.
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Page/Page column 19-20
(2009/12/27)
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- PROCESS FOR OPTICALLY ACTIVE SULFOXIDE COMPOUNDS
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The present invention discloses novel processes for preparing optically active sulphoxide compounds of formula I by asymmetric oxidation of prochiral sulphide compounds of Formula II. More particularly, the invention discloses processes for preparation of optically active proton pump Inhibitors (PPIs) or their optically active precursor (=intermediate) compounds (Formula I) that can be converted into pharmaceutically useful PPIs.
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Page/Page column 19
(2009/06/27)
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- Catalytic asymmetric oxidation of heteroaromatic sulfides with tert-butyl hydroperoxide catalyzed by a titanium complex with a new chiral 1,2-diphenylethane-1,2-diol ligand
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Heteroaromatic sulfoxides, especially 1H-benzimidazolyl pyridinylmethyl sulfoxides, usually used as the blockbuster gastric proton pump inhibitors (PPIs), have been prepared highly enantioselectivily by catalytic asymmetric oxidation of sulfides attached to nitrogen-containing heterocyles with tert-butyl hydroperoxide in the presence of a chiral titanium complex, formed in situ from Ti(iPrO)4, chiral 1,2-diphenylethane-1,2-diol 3c and water. The chiral sufoxides were obtained in high yield (97%) with excellent enantiomeric excess (up to 98%).
- Jiang, Biao,Zhao, Xiao-Long,Dong, Jia-Jia,Wang, Wan-Jun
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experimental part
p. 987 - 991
(2009/07/19)
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- Synthesis of optically active omeprazole by catalysis with vanadyl complexes with chiral Schiff bases
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A new method for the preparation of optically active omeprazole, consisting in asymmetric oxidation of the corresponding sulfide with the use of vanadyl complexes with chiral Schiff bases as the catalysts has been elaborated. The best results of the oxidation were achieved by the use of the combination VO(acac)2-2-[{(1S,2S,3R,5S)-3-hydroxymethyl-2,6,6-trimethyl- bicyclo[3.1.1]hept-2-ylimino}methyl]phenol-N-ethyl-N,N-diisopropylamine.
- Koneva,Khomenko,Kurbakova,Komarova,Korchagina,Volcho,Salakhutdinov,Tolstikov,Tolstikov
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experimental part
p. 1680 - 1685
(2011/04/23)
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- Process for solvent removal from omeprazole salts
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The present invention relates to a process for removing an organic solvent from a salt of omeprazole, in particular a magnesium salt of omeprazole, a composition comprising a salt of omeprazole, in particular a magnesium salt of omeprazole obtainable by such a process, and pharmaceutical compositions comprising said composition or a salt of omeprazole, in particular a magnesium salt of omeprazole, in particular where omeprazole is S-omeprazole..
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Page/Page column 11-12
(2008/12/07)
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- An investigation on key parameters that influence the resolution of omeprazole sodium
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In this document are highlighted systematic studies on factors such as water content, temperature, solvent, and mole ratio of the resolving agents that influence the resolution of omeprazole sodium.
- Reddy, Lekkala Amarnath,Malakondaiah, Golla China,Babu, Karrothu Srihari,Bhattacharya, Apurba,Bandichhor, Rakeshwar,Himabindu, Vimmidi,Reddy, Padi Pratap,Anand, Ramasamy Vijaya
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- Enantioselective Preparation of Benzimidazole Derivatives and Their Salts
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The invention relates to a new process for preparing benzimidazole derivatives having a chiral sulfoxide group in enantiomerically pure form or in a form in which one of the two enantiomers is present in an increased quantity over the other enantiomer. The invention likewise relates to a process for preparing the salts of the individual enantiomers of the benzimidazole derivatives with a chiral sulfoxide group. The invention relates in particular to a process for preparing the S-enantiomer of omeprazole (also known as esomeprazole) and the salts thereof, more particularly the zinc salt of the S-enantiomer of omeprazole. In the new process a prochiral sulfide is oxidized in an organic solvent with an oxidizing agent in the presence of a titanium(IV) complex.
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Page/Page column 5
(2009/01/24)
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- An efficient procedure for the synthesis of Esomeprazole using a titanium complex with two chiral ligands
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A procedure has been proposed for the selective preparation of Esomeprazole via asymmetric oxidation of the corresponding prochiral sulfide in the presence of a catalytic complex derived from titanium(IV) isopropoxide and two different chiral ligands, diethyl d-tartrate and (R)-N,N-dimethyl-1-phenyl-ethanamine.
- Khomenko,Volcho,Komarova,Salakhutdinov
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p. 124 - 127
(2008/12/21)
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- Synthesis of optically active 2,5-dialkylcyclohexane-1,4-diols and their application in the asymmetric oxidation of sulfides
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A simple and efficient approach to obtain optically pure 1,4-diols was established. The asymmetric oxidation of sulfides to sulfoxides with cumyl hydroperoxide in moderate yields and moderate to high enantioselectivities (up to 84%) catalyzed by chiral Ti/ 1,4-diols complexes has been achieved. A 76% ee value was obtained in the asymmetric synthesis of esomeprazole. Georg Thieme Verlag Stuttgart.
- Sun, Jiangtao,Yang, Minghua,Dai, Zhenya,Zhu, Chengjian,Hu, Hongwen
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experimental part
p. 2513 - 2518
(2009/04/11)
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- S-omeprazole magnesium
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The present invention discloses a process for preparing a magnesium salt of S-omeprazole. The S-omeprazole salt preferably has a water content below about 4.8% by weight, a magnesium content of about 3.4-4.0% by weight, calculated on the weight of anhydrous, solvent free S-omeprazole magnesium, and has an optical purity of at least about 85% entantiomeric excess (“e.e.”). In addition, the present invention provides a magnesium salt of S-omeprazole which is substantially free of neutral omeprazole, meaning that the product contains less than about 3% by weight of a-sum of neutral S-omeprazole and neutral omeprazole. Moreover, the S-omeprazole magnesium according to the invention preferably has assay of related substances and degradation products of less than about 0.1 % by weight as determined by high performance liquid chromatography (HPLC).
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Page/Page column 6
(2008/06/13)
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- PROCESS FOR PRODUCING SUBSTITUTED SULPHOXIDES
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A process for preparing substituted sulphoxide using asymmetric oxidation of a pro-chiral sulphide employing a novel enantioselective agent along with oxidizing agents optionally in presence of an organic solvent, wherein said enantioselective agents is chiral transition metal complex or chiral dioxiranes. The chiral ligand used in this process is selected from dicyclohexylidene or diacetonide or substituted or unsubstituted benzylidene derivatives of sugars.
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Page/Page column 9-10
(2008/06/13)
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- A NOVEL STEREOSELECTIVE SYNTHESIS OF BENZIMIDAZOLE SULFOXIDES
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The present invention relates to a process for stereoselective synthesis of substituted sulfoxides either as a single enantiomer or in an enantiomerically enriched form. Thus, 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]thio]-1H-benzimidazole is reacted with (R)-camphorsulfonyl chloride to form a mixture of 1-(R)-camphorsulfonyl-5-(and 6-)methoxy-2-[(3,5-dimethyl-4-methoxy-2-pyridyl)methylthio]-1H-benzimidazole, oxidized to obtain a diastereomeric excess of 1-(R)-camphorsulfonyl-(5- and 6-)-methoxy-2-[(3,5-dimethyl-4-methoxy-2-pyridyl)methyl-(S)-sulfinyl]-1H-benzimidazole over 1-(R)-camphorsulfonyl-(5- and 6-)-methoxy-2-[(3,5-dimethyl-4-methoxy-2-pyridyl)methyl-(R)-sulfinyl]-1H-benzimidazole, the diastereomers are separated by fractional crystallization and the separated 1-(R)-camphorsulfonyl-(5- and 6-)-methoxy-2-[(3,5-dimethyl-4-methoxy-2-pyridyl)methyl-(S)-sulfinyl]-1H-benzimidazole is deprotected to give esomeprazole.
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Page/Page column 21
(2008/06/13)
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- Magnesium-S-omeprazole
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The invention provides magnesium S-omeprazolato compounds according to formula (I): [in-line-formulae][Mg(solva)x(solvb)y][Mg(S-omeprazolato)3]2.(solvc)z??(I), [/in-line-formulae] pharmaceutical compositions and processes of making the same. In formula (I), solva, solvb, and solvc represent solvent molecules where x and y are independently selected from integers 0 to 6, the sum of which is 4 or 6, while z is a positive rational number from 0 to 6. The compounds are useful for the treatment of gastric acid related conditions and the inhibition of gastric acid secretion.
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Page/Page column 10-11
(2008/06/13)
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- A PROCESS FOR PREPARATION OF OPTICALLY PURE OR OPTICALLY ENRICHED SULFOXIDE COMPOUNDS, INCLUDING AMORPHOUS ESOMEPRAZOLE AND SALTS THEREOF
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A process of preparation of optically pure or optically enriched isomers of omeprazole and structurally related sulfoxides is provided. Also provided are an amorphous form of esomeprazole, as well a pharmaceutical composition containing it and a method of using it for treatment of gastric disorders.
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- Resolution of omeprazole by inclusion complexation with a chiral host BINOL
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Both (S)-(-)- and (R)-(+)-enantiomers of omeprazole were directly resolved by inclusion complexation with a chiral host compound (S)-(-)- or (R)-(+)-2,2'-dihydroxy-1,1'-binaphthyl in high enantiomeric excess (>99% e.e.). (C) 2000 Elsevier Science Ltd.
- Deng, Jingen,Chi, Yongxiang,Fu, Fangmin,Cui, Xin,Yu, Kaibai,Zhu, Jin,Jiang, Yaozhong
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p. 1729 - 1732
(2007/10/03)
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