- Method for preparing dexlansoprazole through catalysis of hexadentate ligand
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The invention belongs to the technical field of chemical engineering, and particularly provides a method for preparing dexlansoprazole through catalysis of a hexadentate ligand. Under the catalysis ofa complex formed by a Ti(O-iPr)4 catalyst and a self-made hexadentate ligand, lansoprazole thioether is subjected to asymmetric oxidation, and dextral lansoprazole is obtained. The hexadentate ligandused in the method is simple to prepare and high in yield, and the complex formed by the hexadentate ligand and the Ti(O-iPr)4 catalyst is high in catalytic efficiency and high in enantiomeric excessvalue.
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Paragraph 0037; 0039-0040; 0042-0043; 0045; 0055; 0057
(2020/05/30)
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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 0050-0052
(2020/09/09)
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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 15; 16
(2019/06/15)
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- Synthesis of Esomeprazole and Related Proton Pump Inhibitors through Iron-Catalyzed Enantioselective Sulfoxidation
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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.
- Nishiguchi, Shigenobu,Izumi, Takuhiro,Kouno, Takayoshi,Sukegawa, Junpei,Ilies, Laurean,Nakamura, Eiichi
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p. 9738 - 9743
(2018/10/09)
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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; 0047-0049
(2020/02/07)
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- Enantioselective Separation over a Chiral Biphenol-Based Metal-Organic Framework
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A chiral porous 3D metal-organic framework (MOF) is constructed from an enantiopure carboxylate ligand of 1,1′-biphenol, which can be utilized as adsorbent for the separation of aromatic alcohols and sulfoxides with enantioselectivity of up to 99.4%. Single-crystal X-ray diffraction analysis reveals the binding sites and host-guest interactions clearly, providing microscopic insight into the origin of the enantiosorption in the framework.
- Abbas, Anees,Wang, Zhao-Xi,Li, Zijian,Jiang, Hong,Liu, Yan,Cui, Yong
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supporting information
p. 8697 - 8700
(2018/08/17)
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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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- ION PAIR CATALYSIS OF TUNGSTATE AND MOLYBDATE
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D The present invention relates to ion pair catalysts (I) comprising the cationic bisguanidinium ligand (A) and diperoxomolybdate anion (B). The present invention also relates to ion pair catalysts (III) comprising the cationic bisguanidinium ligand (C) and peroxotungstate anion (D). It further relates to the use of the said catalysts in the manufacture of enantiomerically enriched sulfoxides.
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Page/Page column 56
(2017/10/30)
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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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- Enantioselective Sulfoxidation Catalyzed by a Bisguanidinium Diphosphatobisperoxotungstate Ion Pair
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The first enantioselective tungstate-catalyzed oxidation reaction is presented. High enantioselectivities were achieved for a variety of drug-like phenyl and heterocyclic sulfides under mild conditions with H2O2, a cheap and environmentally friendly oxidant. Synthetic utility was demonstrated through the preparation of (S)-Lansoprazole, a commercial proton-pump inhibitor. The active ion-pair catalyst was identified to be bisguanidinium diphosphatobisperoxotungstate using Raman spectroscopy and computational studies.
- Ye, Xinyi,Moeljadi, Adhitya Mangala Putra,Chin, Kek Foo,Hirao, Hajime,Zong, Lili,Tan, Choon-Hong
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supporting information
p. 7101 - 7105
(2016/07/06)
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- Suitable for industrial production [...] processing method of the (by machine translation)
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The invention relates to a method for processing of Iansoprazole, the temperature in the reaction end directly after precipitation of crude product, then according to the needs of the different crystal forms in accordance with the needs of the preparing fine. The method is simple, the operation step is short, required time is short, the reactor can be loaded with the reaction, the utilization rate of equipment is high. Pure height of the high product yield, the yield of 89 wt % or more, by high performance liquid chromatographic detection, the content of the presence of sulphide with sulphone low, other analogues do not exist, the chiral purity 99% ee the above. Re-crystallization purification of the crude product, the total yield is up to 80 wt % or more. (by machine translation)
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Paragraph 0023-0025
(2017/02/09)
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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 94-96
(2016/02/03)
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- An electronic circular dichroism study for the structurechiroptical relationship of chiral proton pump inhibitors
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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.
- Zhou, Zhixu,Li, Linwei,Yan, Ning,Du, Lei,Sun, Changshan,Sun, Tiemin
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supporting information
p. 110 - 112
(2016/03/01)
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- D-tartaric acid monoester monoamide compound
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The invention relates to a D-tartaric acid monoester monoamide compound, capable of serving as a ligand to catalytically synthesize R type chirality proton pump inhibitors such as Dexlansoprazole. A synthesis method comprises the steps of dissolving a compound II and the D-tartaric acid monoester monoamide compound into an organic solvent, and heating to react, thus obtaining the R type chirality proton pump inhibitors such as the Dexlansoprazole. The method has higher yield and e.e value.
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Paragraph 0177-0184
(2017/01/17)
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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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- OPTICAL RESOLUTION OF SUBSTITUTED 2-(2- PYRIDINYLMETHYLSULPHINYL)-1H-BENZIMIDAZOLES
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The present invention relates to process for preparation of optical resolution of substituted 2-(2-pyridinylmethylsulphinyl)-1H-benzimidazoles either as a single enantiomer or in an enantiomerically enriched form. Thus, for example, R-1,1'-binaphtyl- 2-2'-diyl hydrogen phosphate was reacted with 2-[[[3-methyl-4-(2,2,2-trifluoro-ethoxy)- 2-pyridinyl]methyl]sulfinyl]-1H-benzimidazole (Lansoprazole) in a mixture of benzene and cyclohexane to obtain diasteremeric complexes. The diasteremeric complexes were subjected to fractional crystallization to obtain R-2-[[[3-methyl-4-(2,2,2-trifluoro- ethoxy)-2-pyridinyl]methyl]sulfinyl]-1H-benzimidazole.R-1,1'-binaphthyl-2-2'-diyl hydrogen phosphate. The separated isomer was treated with sodium bicarbonate in a mixture of ethyl acetate and water to obtain R-2-[[[3-methyl-4-(2,2,2-trifluoro-ethoxy)-2- pyridinyl]methyl]sulfinyl]-1H-benzimidazole (dexlansoprazole).
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Page/Page column 19
(2011/04/26)
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- PROCESS FOR THE PREPARATION OF PROTON PUMP INHIBITORS
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The present invention relates to novel and improved processes for the preparation of Proton Pump Inhibitors such as 2-[(R)-[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]sulfinyl]-1H-benzimidazole and pharmaceutically acceptable salts thereof.
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Page/Page column 12
(2010/09/17)
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- Two-dimensional chromatography method applied to the enantiomeric determination of lansoprazole in human plasma by direct sample injection
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A two-dimensional HPLC method based on the direct injection of biological samples has been developed and validated for the determination of lansoprazole enantiomers in human plasma. The lansoprazole enantiomers were extracted from the biological matrix using an octyl restricted access media bovine serum albumin column (C8 RAM BSA) and the enantioseparation was performed on an amylose tris(3,5-dimethoxyphenylcarbamate) chiral column using acetonitrile:water (35:65 v/v) and UV detection at 285 nm. Analysis time was 25 min with no time spent on sample preparation. The method was applied to the analysis of the plasma samples obtained from nine Brazilian volunteers who received a 30 mg oral dose of racemic lansoprazole and was able to quantify the enantiomers of lansoprazole in the clinical samples analyzed.
- Gomes, Ricardo F.,Cassiano, Neila M.,Pedrazzoli Jr.,Cass, Quezia B.
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experimental part
p. 35 - 41
(2010/09/05)
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- PROCESS FOR THE PREPARATION OF DEXLANSOPRAZOLE
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Process for the preparation of (R)-2-[[[3-methyl-4(2,2,2-trifluoroethoxy)-2-piridyl]methyl]sulfinyl]benzimidazole (Dexlansoprazole) and new intermediates useful in its preparation.
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Page/Page column 3
(2010/06/13)
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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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- PROCESS FOR PREPARING SULFOXIDE COMPOUNDS
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Disclosed are a process for preparing a chiral sulfoxide compound of general formula I as a single enantiomer or in an enantiomerically enriched form, and S-(-)-levo-omeprazole, S-(-)-levo-pantoprazole and S-(-)-le vo-lansoprazole prepared thereby. Formula (I) omeprazole: R 1=CH 3, R 2=OCH 3, R 3=CH 3, R 4= R 6= R 7=H, R 5=OCH 3 lansoprazole: R 1=H, R 2=OCH 2CF 3, R 3=CH 3, R 4= R 5= R 6= R 7=H pantoprazole: R 1=H, R2=OCH 3, R 3=OCH 3, R 4= R 6= R 7=H, R 5=OCHF 2
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Page/Page column 40
(2009/10/22)
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- A PROCESS OF SULFOXIDATION OF BIOLOGICALLY ACTIVE COMPOUNDS
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The present invention relates to a new process for the preparation of sulfoxides, preferably stereoselective preparation of substituted or unsubstituted chiral sulfinyl derivatives 2-(2- pyridylmethyl) sulfinyl-l H-benzimidazole by oxidation with oxaziridine in presence of suitable solvent and base.
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Page/Page column 18
(2009/01/24)
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- Process for the crystallization of (r)-or (s)-lansoprazole
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The present invention relates to a production method of a crystal of (R)-lansoprazole or (S)-lansoprazole, which includes crystallization at a temperature of about 0° C. to about 35° C. from a C1-4 alkyl acetate solution containing (R)-lansoprazole or (S)-lansoprazole at a concentration of about 0.1 g/mL to about 0.5 g/mL and the like. According to the production method of the present invention, a crystal of (R)-lansoprazole or (S)-lansoprazole superior in preservation stability can be produced efficiently on an industrial large scale.
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- Crystals of benzimidazole compounds
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Crystals of (S)-2[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]sulfinyl]-1H-benzimidazole or salts thereof, useful as excellent antiulcer drugs.
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- WO3-30% H2O2-cinchona alkaloids: A new heterogeneous catalytic system for the asymmetric oxidation of sulfides and the kinetic resolution of racemic sulfoxides
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WO3-catalyzed asymmetric oxidation of thioethers and kinetic resolution of sulfoxides with 30% aq. H2O2 in the presence of cinchona alkaloids under heterogeneous conditions affords chiral sulfoxides in high yields with moderate to good enantioselectivities.
- Thakur, Vinay V.,Sudalai
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p. 407 - 410
(2007/10/03)
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