- Synthesis method of lansoprazole
-
The invention discloses a synthesis method of lansoprazole, which comprises the following steps: condensing 2-mercaptobenzimidazole and 2-chloromethyl-3-methyl-4-(2, 2, 2-trifluoroethoxy) pyridine hydrochloride under alkaline conditions, oxidizing by a one-pot method to obtain a lansoprazole crude product, and finally refining to obtain the lansoprazole refined product. The method solves the problems that many three wastes are generated in lansoprazole production, a plurality of refining is needed, and drying deterioration is easily caused; the method is mild in reaction conditions, the total molar yield is 92% or above, the HPLC is 99.9% or above, and the method is suitable for industrial large-scale production.
- -
-
Paragraph 0047-0075
(2021/04/28)
-
- 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.
- Arreguin-Espinosa, Roberto,Calderón-Jaimes, Ernesto,Cuevas-Cruz, Miguel,Gómez-Manzo, Saúl,Hernández-Ochoa, Beatriz,Méndez-Tenorio, Alfonso,Marcial-Quino, Jaime,Ramírez-Nava, Edson Jiovany,Rocha-Ramírez, Luz María,Sánchez-Carrillo, Adrián,Santos-Segura, Araceli
-
-
- Stable high-purity (R)-Lansoprazole, and preparation method thereof
-
The invention provides (R)-Lansoprazole with a purity of 99.5% or higher. The preparation method comprises following steps: a (R)-Lansoprazole crude product is dissolved in a refined solvent system, dissolving and condensation are carried out, and then crystallization, filtering, and impurity removing are carried out to obtain refined (R)-Lansoprazole, wherein in the dissolving preparation process, an alkaline stabilizing agent 1 is added, and in the condensation process, an alkaline stabilizing agent 2 is added, so that the impurity I content of the obtained (R)-Lansoprazole refined product is lower than 0.1%, degradation impurity introduction is controlled preferably, in long term storage process, the obtained product is capable of satisfying medicine purity requirements, the controllability is high, and a quality control problem of (R)-Lansoprazole in industrialized production is solved.
- -
-
Paragraph 0056-0058
(2019/09/14)
-
- Method for preparing lansoprazole
-
The invention belongs to the field of medicinal chemistry and in particular relates to a method for preparing lansoprazole. The method disclosed by the invention comprises the following reaction steps: carrying out an addition reaction on acraldehyde and trifluoroethanol to produce a compound IV, chlorinating 2-mercapto benzimidazole to condense with 3-hydroxy-2-butanone, performing rearrangementto produce a compound VI, performing condensation on the compounds IV and VI and ammonia to produce a compound VII, and further oxidizing the compound VII, thereby obtaining the lansoprazole I. The method disclosed by the invention has the advantages that the reaction does not involve strong acids such as sulfuric acid and nitric acid, and emission of three wastes is reduced while convenience is brought to after-treatment; and the reaction step is short, and the total yield is high and can reach 41-62%. The cost per kilogram is one half that of the conventional process, and cheap and high-quality bulk drugs are provided for the preparation.
- -
-
-
- Preparation method of dexlansoprazole
-
The invention relates to a preparation method of dexlansoprazole. The method includes: preparation of the formula (I) compound into dexlansoprazole by substitution in the presence of a trifluoroethanol metal salt. The method has a simple process, and can acquire high yield and high purity dexlansoprazole without column chromatography, and is very suitable for industrial mass production.
- -
-
Paragraph 0054; 0055; 0056
(2018/08/04)
-
- Method for preparing benzimidazole proton pump inhibitor
-
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.
- -
-
Paragraph 0049; 0050; 0051; 0053; 0054; 0055; 0056-0058
(2018/09/08)
-
- 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 technology of lansoprazole
-
The invention provides a preparation technology of lansoprazole. The preparation technology comprises the following steps that 1, a raw material A 2-mercapto benzimidazole is dissolved into methanol in the presence of alkali, a raw material B 2-chloromethyl-3-methyl-4-(2,2,2,-trifluoroethoxyl)pyridine hydrochloride is added for a reaction, filtering is conducted by adding water, obtained precipitates are washed and dried, and then an intermediate C [[[3-methyl-4-(2,2,2,-trifluoroethoxyl)-2-pyridyl]methyl]sulfydryl]-H-benzimidazole is obtained; the intermediate C is dissolved into ethanol, a mixed solution of hydrogen peroxide, a catalyst and ethanol is added for a reaction, filtering is conducted by adding water, obtained precipitates are washed, and then the lansoprazole is obtained. According to the preparation technology, the yield is increased, the cost is reduced, the production cycle is shortened, and the preparation technology is more suitable for industrialized production.
- -
-
Paragraph 0042
(2017/08/30)
-
- 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%.
- -
-
Paragraph 0032; 0034
(2017/09/02)
-
- 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.
- -
-
Paragraph 0018; 0019; 0020; 0024; 0028; 0029
(2017/10/27)
-
- 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.
- -
-
Paragraph 0032; 0039; 0040; 0044; 0045; 0046-0090
(2017/07/21)
-
- Process for synthesis of Iansoprazole
-
The invention relates to a synthetic process of lansoprazole. The synthetic process comprises the following steps: reacting 2-chloromethyl-3-methyl-4-trifluoroethoxyl pyridine hydrochloride and 2-mercapto-benzimidazole in a sodium carbonate methanol solution and performing after-treatment to obtain off-white solid; oxidizing the off-white solid by using combination of isopropylphenyl hydrogen peroxide and tetraisopropyl titanate, and performing after-treatment to obtain a yellow solid lansoprazole crude product; and purifying the lansoprazole crude product by adopting an organic solvent at 52-56 DEG C to obtain a lansoprazole refined product. According to the synthetic process provided by the invention, the key point is to improve and optimize the purification condition of the lansoprazole crude product in the step 3 so as to ensure that the yield of purification, concentration and drying links in the last step is improved from 90% to 98%, so that the total yield is improved, which is beneficial to industrial large-scale production application.
- -
-
Paragraph 0016-0020
(2016/11/28)
-
- Prepare alkylene sulfonyl-1-H-benzimidazole derivatives
-
The invention relates to a method for preparing a sulfinyl-1-hydrogen-benzimidazole derivative. According to the invention, a 2-(1H-benzimidazole-2-methylmercapto)-4-hydroxy-pyridine derivative expressed in a general formula I is dissolved in a solvent, and under the effect of a catalyst and an additive, a hydrogen peroxide aqueous solution is used as an oxidizing agent for oxidizing reaction, so that the sulfinyl-1-hydrogen-benzimidazole derivative expressed in the general formula II (refer to the Specification) is prepared. The method has the advantages that the operation is simple, a catalyst with the harmful effect on a human body is not used, no pollution to the environment is caused, and the obtained product is higher in yield and purity, so that the method is suitable for industrialization scale production, and has important practical application value.
- -
-
Paragraph 0032; 0033
(2016/11/24)
-
- Asymmetric oxidation synthesis method of zirconium-catalyzed dexlansoprazole
-
The invention discloses an asymmetric oxidation synthesis method of zirconium-catalyzed dexlansoprazole. In an organic solvent, a zirconium catalyst and a ligand of the zirconium catalyst have a complex reaction in the presence of a 4A molecular sieve, then a product is mixed with cumyl hydroperoxide in a certain proportion, and 2-[[[3-methyl-4-(2,2,2 trifluoroethoxy)-2-pyridyl]methyl]thio]-1H-benzimidazole is oxidized at the low temperature for synthesis of the dexlansoprazole. The enantiomer excess value of the dexlansoprazole synthesized with the method is higher than 99.3%, the yield is higher than 82%, and the method is good in process stability and high in enantioselectivity and has the bright industrial production prospect.
- -
-
Paragraph 0028; 0029
(2017/01/02)
-
- 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.
- Reddy, Gunupati Sharathchandra,Reddy, Narra Santosh,Manudhane, Kushal,Rama Krishna, Medisetti Venkata,Ramachandra, Kopparapu Janardana Sarma,Gangula, Srinivas
-
p. 1272 - 1276
(2013/11/06)
-
- PROCESS FOR THE PREPARATION OF 2-PYRIDINYLMETHYLSULFINYL BENZIMIDAZOLES, THEIR ANALOGS AND OPTICALLY ACTIVE ENANTIOMERS
-
The present invention provides a commercially viable, cost effective and energy efficient process for the preparation of 2-pyridinylmethylsulfinyl benzimidazoles, their analogs and optically active enantiomers or pharmaceutically acceptable salts, hydrates or solvates thereof in high purity via application of reactors such as plug flow reactor, microreactor, microfluidic flow reactor, tubular flow reactor, coil-type flow reactor, laminar flow reactor, packed bed reactor, fluidized bed reactor or fixed bed reactor.
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-
Page/Page column 24; 25
(2013/07/31)
-
- OPTICAL RESOLUTION OF SUBSTITUTED 2-(2-PYRIDINYLMETHYLSULPHINYL)-1H-BENZIMIDAZOLES
-
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 7
(2012/08/08)
-
- PROCESS FOR THE PREPARATION OF PROTON PUMP INHIBITORS
-
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.
- -
-
Page/Page column 22
(2010/09/17)
-
- NOVEL COMPOUNDS FOR PRODUCING SUBSTITUTED SULFOXIDES, PROCESS FOR PRODUCING THE SAME AND USE THEREOF
-
Disclosed herein are novel compounds which are useful as intermediates for producing substituted sulfoxide compounds and a process for producing the same. Further disclosed is a process for producing the substituted sulfoxide compounds used as pharmacologically active agents, employing the novel intermediates of the present invention.
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-
Page/Page column 20
(2010/04/27)
-
- 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.).
- Gangula, Srinivas,Elati, Chandrasekhar R.,Neredla, Anitha,Baddam, Sudhakar R.,Neelam, Uday Kumar,Bandichhor, Rakeshwar,Dongamanti, Ashok
-
experimental part
p. 229 - 233
(2010/04/29)
-
- Process for preparing 2-sulfinyl-1H-benzimidazoles
-
The present invention relates to a process for preparing 2-(2-pyridinylmethylsulfinyl)-1H-benzimidazoles by oxidizing a thioether precursor in the presence of trifluoroethanol.
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-
Page/Page column 12
(2009/04/23)
-
- Process For Preparing Crystalline Form A Of Lansoprazole
-
The present invention relates to a process for preparing Crystalline Form A of Lansoprazole. Specifically, the present invention relates to a process for preparing highly pure Crystalline Form A of Lansoprazole in a large scale without any additional conversion step, even by using ethanol in which Crystalline Form B is easily formed.
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-
Page/Page column 2
(2009/01/24)
-
- Method for preparing 2- (2-pyridinylmethylsulfinyl) benzimidazoles
-
The present invention provides a method for preparing an antiulcer agent, 2-(2-pyridinylmethylsulfinyl)benzimidazoles, such as Omeprazole, Lansoprazole, Pantoprazole and Rabeprazole, which includes oxidizing an intermediate having a linkage of methylthio group (—CH2S—) to methylsulfinyl (—CH2S(O)—) in the presence of an oxidation catalyst of an alkali metal salt of tungstate at a temperature of 10-50° C.
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-
Page/Page column 3
(2009/01/24)
-
- SELECTIVE PRODUCTION OF SULPHOXIDES
-
The invention pertains to a process for producing a sulphoxide compound, comprising oxidizing a thioether compound with an ozonide formed from a olefin and ozone, to obtain the corresponding sulphoxide compound, provided that the olefin is not ethene. The ozonide converts thio - ether compounds selectively, unlike its art - known oxidizing counterparts. The milder ozonide does not require manipulation of the stoichiometric amount of available oxidizing agent during the reaction, to prevent the formation of sulphones.
- -
-
Page/Page column 12
(2009/03/07)
-
- PROCESS FOR MANUFACTURING MICROCRYSTALLINE LANSOPRAZOLE FORM I
-
A process for manufacturing crystalline Lansoprazole form I with aparticularly fine particle size comprising the heating of a mixture ofcrystalline Lansoprazole, acetonitrile and water, up to complete conversion,is described, said process beingparticularly advantageous on industrialscale in terms of rapidity, simplicity, yield and purity.
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Page/Page column 16; 18
(2008/12/06)
-
- PROCESS FOR PREPARATION OF LANSOPRAZOLE
-
The present invention provides a process for the preparation of Lansoprazole comprising the steps of oxidizing 2-[[(3-methyl-4-(2,2,2-trifluoroethoxy)pyridinyl]methyl]thio]-lH- benzimidazole with an oxidizing agent, washing the reaction mass with aqueous solution of buffer, alkali bicarbonate and alkali thiosulphate, Isolation of product by cooling to low temperature in presence of water, base, amide or mixture thereof. Slurry/crystallizing from water immiscible organic solvent in presence of water, base, amide or mixture thereof. Slurry the product with sodium bicarbonate solution followed by drying yields Lansoprazole.
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-
Page/Page column 10
(2008/12/07)
-
- A METHOD FOR THE PURIFICATION OF LANSOPRAZOLE
-
The present invention relates to an improved process for the preparation of Lansoprazole of formula (I). More particularly, the present invention relates to a method for the purification of crude Lansoprazole in a solvent in presence of an alkali salt of an organic acid or in presence of an organic base such as piperidine or imidazole.
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-
Page/Page column 5
(2008/06/13)
-
- Synthesis and characterization of metabolites and potential impurities of lansoprazole, an antiulcerative drug
-
Lansoprazole (Prevacid) is an antiulcerative drug used for the treatment of duodenal and gastric ulcers, reflux oesophagitis, and Zollinger-Ellison syndrome. During the bulk synthesis of lansoprazole, we have observed five impurities: lansoprazole N-oxide, lansoprazole sulfone N-oxide, lansoprazole sulfide, lansoprazole sulfone and N-aralkyl lansoprazole. The present work describes the synthesis and characterization of these impurities. Copyright Taylor & Francis Group, LLC.
- Reddy, Ganta Madhusudhan,Mukkanti,Kumar, T. Laxmi,Babu, J. Moses,Reddy, Padi Pratap
-
p. 3477 - 3489
(2008/12/23)
-
- A PROCESS FOR THE PREPARATION OF BENZIMIDAZOLE DERIVATIVES AND THEIR SALTS
-
The present relates to a process for the preparation of 2-(2-pyridylmethyl) sulfinyl-1H-benzimidazole derivatives and their pharmaceutically acceptable salts substantially free from their sulfide and the sulfone impurities.
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-
Page/Page column 28-29
(2008/06/13)
-
- PROCESS FOR PREPARING CRYSTALLINE FORM A OF LANSOPRAZOLE
-
The present invention relates to a process for preparing Crystalline Form A of Lansoprazole. Specifically, the present invention relates to a process for preparing highly pure Crystalline Form A of Lansoprazole in a large scale without any additional conversion step, even by using ethanol in which Crystalline Form B is easily formed.
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-
Page/Page column 8
(2008/06/13)
-
- PROCESS FOR THE PREPARATION OF PYRIDINE COMPOUNDS
-
A process for preparation of a compound of formula (I), both as the isomeric mixture and individual isomers, wherein Q is ═CR8— or ═N—; each R1, R2, R3, R4 is independently selected from hydrogen, halogen, hydroxy; nitro; C1-C6 alkyl optionally substituted with hydroxy; alkylthio C1-C6; C1-C6 alkoxy optionally substituted with halogen or C1-C6 alkoxy; phenyl-C1-C6 alkyl; phenyl-C1-C6 alkoxy; and —N(RaRb) wherein each Ra and Rb is independently hydrogen or C1-C6 alkyl or Ra and Rb, taken together with the nitrogen atom they are linked to, form a saturated heterocyclic ring; and each R5, R6, R7, R8 is independently selected from hydrogen, halogen, hydroxy; C1-C6 alkyl optionally substituted with hydroxy; alkylthio C1-C6; C1-C6 alkoxy optionally substituted with halogen; C1-C6 alkyl-carbonyl, C1-C6 alkoxy-carbonyl, and oxazol-2-yl; comprising converting a compound of formula (IV), to said compound of formula (I), in the presence of a catalyst, if necessary in an organic solvent.
- -
-
Page/Page column 4-5
(2008/06/13)
-
- A process for the preparation of pyridine compounds
-
A process for the preparation of a compound of formula (I) or a salt thereof, both as the isomeric mixture and the individual isomers, wherein Q is =CR8- or =N-; each R1, R2, R3 and R4 is independently selected from hydrogen, halogen, hydroxy; nitro; C1-C6 alkyl optionally substituted with hydroxy; alkylthio C1-C6; C1-C6 alkoxy optionally substituted with halogen or C1-C6 alkoxy; phenyl-C1-C6 alkyl; phenyl-C1-C6 alkoxy; and - N(RaRb) wherein each Ra and Rb is independently hydrogen or C1-C6 alkyl or Ra and Rb, taken together with the nitrogen atom they are linked to, form a saturated heterocyclic ring; and each R5, R6, R7 and R8 is independently selected from hydrogen, halogen, hydroxy; C1-C6 alkyl optionally substituted with hydroxy; alkylthio C1-C6; C1-C6 alkoxy optionally substituted with halogen; C1-C6 alkyl-carbonyl, C1-C6 alkoxy-carbonyl, and oxazol-2-yl; comprising converting a compound of formula (IV), or a salt thereof, wherein Q, R1, R2, R3, R4, R5, R6 and R7 are as defined above, to said compound of formula (I), or a salt thereof, in the presence of a catalyst, if necessary in an organic solvent; and, if desired, converting a compound of formula (I) to a salt thereof to another compound of formula (I); and/or, if desired, resolving an isomeric mixture of a compound of formula (I) in the individual isomers.
- -
-
Page/Page column 6-7
(2008/06/13)
-
- Highly enantioselective oxidation of sulfides to sulfoxides by a new oxaziridinium salt
-
The new oxaziridinium salt 5 (R2 = TBDPS) is an effective reagent for the highly enantioselective oxidation of sulfides to sulfoxides with up to >99% ee and good yields. As such, it represents a new valuable nonmetallic alternative to the existing methods for asymmetric sulfoxidation.
- Del Rio,Wang,Achab,Bohe
-
p. 2265 - 2268
(2008/02/04)
-
- METHOD AND APPARATUS FOR PRODUCING OXIDIZED COMPOUND
-
There is provided a method and an apparatus for producing an oxidized compound, which includes measuring an electric potential of an oxidation reaction solution for producing an oxidized compound by an oxidation reaction, and determining an end point of the oxidation reaction on the basis of a predefined decrease of the electric potential, thereby simply determining the end point of the oxidation reaction to swiftly move on to the next step. For example, the apparatus for producing an oxidized compound has a reactor (1) for carrying out an oxidation reaction; an oxidation reduction potential detection means (5) for detecting the value of an oxidation reduction potential of an oxidation reaction solution in the reactor; and a determination means (6) for monitoring at all time the detected values of the oxidation reduction potential detected by the oxidation reduction potential detection means and determining a point where the amount of an electric potential dropped from a highest electric potential of the oxidation reduction potential reaches the predefined amount of an electric potential, as an end point of the oxidation reaction, in which the apparatus allows to carry out the method of the invention at an industrial production level.
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Page/Page column 15
(2008/06/13)
-
- PROCESS FOR THE PREPARATION OF 2-(2-PYRIDYLMETHYL)-SULFINYL-1H-BENZIMIDAZOLES
-
The present invention relates to an improved process for the preparation of substituted. 2-(2-pyridylmethyl)-sulfinyl-1H-benzimidazoles or its derivatives, which are useful for a medicament such as an inhibitor of gastric acid secretion or an anti-ulcer agent or an intermediate to produce medicaments in good yield and high purity. More particularly, the present invention relates to a process for preparing a sulfoxide compound of the formula (I) in good yield and relatively high purity and pharmaceutically acceptable salt, hydrate and solvate thereof. (I) wherein R1 and R3 are selected from the group consisting of hydrogen, methyl or C1-4 alkoxy, R2 is selected from the group consisting of substituted or unsubstituted C1-4 alkoxy, R4 is selected from the group consisting of hydrogen or substituted or unsubstituted C1-4 alkoxy. Comprising the step of oxidizing a sulfide compound of formula (II) with Peroxyacetic acid or its derivatives necessarily at the pH 5-7 using aqueous sodium carbonate solution. (II) wherein R1 R2 R3 and R4 are as defined above.
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-
Page/Page column 8
(2008/06/13)
-
- PROCESSES FOR THE PREPARATION OF LANSOPRAZOLE
-
The invention relates to processes for the preparation of benzimidazole sulphinyl compounds. More particularly, it relates to the preparation of pure lansoprazole and pharmaceutical compositions that include the pure lansoprazole.
- -
-
Page/Page column 11-12
(2008/06/13)
-
- A PREPARATION METHOD FOR SUBSTITUTED 2-(2-PYRIDYLMETHOYLSULPHINYL)-l-H-BENZIMID AZOLES
-
The invention relates to a process for the preparation of a substituted 2-(2-pyridylmethylsulphinyl)-l-H-benzimidazole involving the reaction of a corresponding 2-(2-pyridylrnethylthio)-l-H-benzirnidazole compound with a hypohalite oxidation agent in the presence of a phase transfer catalyst, wherein the reaction involves a biphasic reaction mixture containing an aqueous and an organic phase. The reaction can immediately succeed the formation of said 2-(2-pyridylmethylthio)-l-H-benzimidazole compound in a one pot synthesis, in order to avoid time-consuming and costly purification steps. Overoxidation, leading to sulphone impurities, is thus avoided and yields improved. Hence, the invention also relates to a substituted 2-(2-pyridylmethylsulphinyl)-l-H-benzimidazole containing less than 0.2 wt% sulphone impurities.
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-
Page/Page column 15 - 17
(2010/11/30)
-
- Process for preparing lansoprazole
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The invention relates to a process for preparing lansoprazole. It is also directed to lansoprazole having a specific surface area and a pharmaceutical composition comprising lansoprazole.
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- METHOD FOR PREPARING 2- (2-PYRIDYLMETHYLSULPHINYL) BENZIMIDAZOLES
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The present invention provides a method for preparing an antiulcer agent, 2-(2-pyridylmethylsulphinyl)benzimidazoles, such as Omeprazole, Lansoprazole and Pantoprazole, which includes oxidizing an intermediate having a linkage of methylthio group (—CH2S—) to methylsulfinyl (—CH2S(O)—) in the presence of an oxidation catalyst of acetyl acetonate of molybdenium (II) [(CH3C(O)CH2C(O)CH2)2Mo].
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- PROCESS FOR THE PREPARATION OF SULPHINYL DERIVATIVES BY OXIDATION OF THE CORRESPONDING SULFIDES
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The present invention relates to a mild and industrially applicable process for preparing sulfinyl derivatives of Formula (II), useful as inhibitors of gastric acid secretion, comprising the selective oxidation of the corresponding sulfides of Formula (I), as represented in scheme (I) and (II) in which said oxidation is performed with hydrogen peroxide in the presence of low amounts of a rhenium compound as catalyst, at a temperature from 0° C to room temperature.
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- Process for the preparation of organic compounds containing a sulfinyl or sulfonyl group in the presence of epsilon-phthalimidoperhexanoic acid
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A process for the oxidation of thioethers to sulfoxides or sulfones or for the oxidation of sulfoxides to sulfones by treatment of thioethers or sulfoxides with an oxidizing amount of ε-phthalimidoperhexanoic acid is particularly useful for the preparation of compounds of industrial interest, in particular pharmaceuticals for human or veterinary use.
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- Process for the preparation of organic compounds containing a sulfinyl or sulfonyl group
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A process for the oxidation of thioethers to sulfoxides or sulfones or for the oxidation of sulfoxides to sulfones by treatment of thioethers or sulfoxides with an oxidizing amount of ε-phthalimidoperhexanoic acid is particularly useful for the preparation of compounds of industrial interest, in particular pharmaceuticals for human or veterinary use.
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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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- A METHOD FOR THE PURIFICATION OF LANSOPRAZOLE
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The present invention provides a method for preparing a substantially pure lansoprazole containing less than about 0.2% (wt/wt) impurities including sulfone/sulfide derivatives. The present invention also provides a process for recrystallizing lansoprazole to obtain a lansoprazole containing less than about 0.1 % (wt/wt) water.
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- BENZIMIDAZOLE COMPOUND, PROCESS FOR PRODUCING THE SAME, AND USE THEREOF
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The present invention relates to a compound represented by the following formula wherein each symbol is as defined in the specification, or a salt thereof, which has superior stability to acid and which is a prodrug of 2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]-1H-benzimidazole. This compound (1) shows a superior anti-ulcer activity, a gastric acid secretion-suppressive action, a mucosa-protecting action, an anti-Helicobacter pylori action and the like in living organisms, (2) shows low toxicity, (3) shows superior stability to acid (which obviates the need to formulate an enteric-coated preparation, thereby lowering the cost, and reduces the size of preparation to facilitate swallowing for patients having difficulty in swallowing), (4) shows faster absorption than enteric-coated preparations (rapid expression of gastric acid secretion-suppressive action), and (5) is sustainable.
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- STABLE LANSOPRAZOLE CONTAINING MORE THAN 500 PPM, UP TO ABOUT 3,000 PPM WATER AND MORE THAN 200 PPM, UP TO ABOUT 5,000 PPM ALCOHOL
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The present invention provides a stable 2-(2-pyridylmethyl) sulfinyl-lH-benzimidazole (lansoprazole) comprising either greater than 500 ppm and not more than about 3,000 ppm water and greater than 200 ppm and not more than about 5,000 ppm alcohol, or both. The present invention provides a method of preparing a stable lansoprozole as well as a pharmaceutical composition containing same. The present invention further provides a method of purifying lansoprazole that is substantially free of sulfone and sulfide derivatives.
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- PREPARATION OF LANSOPRAZOLE AND RELATED COMPOUNDS
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The present invention provides a process for preparing lansoprazole (LNP) (I) and related compounds having a high yield and a low level of impurities by oxidation of corresponding sulfide (compound having formula (II)) with tert-butylhydroperoxide (TBHP), catalyzed by a catalyst vanadium oxytrichloride in an organic solvent selected from the group consisting of a C1-C5 alkanol, decane, nonane, toluene and a mixture of the organic solvent and water, preferably in the presence of a base.
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- Processes for the production of substituted 2-(2-pyridylmethyl) sulfinyl-1H-benzimidazoles
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Improved processes for preparing substituted 2-(2-pyridylmethyl)sulfinyl-1H-benzimidazoles are disclosed.
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- Substituted 2-(2-methyl Pyridylpyrimidine) sulfinylation -1H-dihydrobenzo aminoalkaneimidazole manufacturing method
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Improved processes for preparing substituted 2-(2-pyridylmethyl) sulfinyl- 1H-benzimidazoles are disclosed.
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- PAHARMACEUTICAL PROCESS AND COMPOUNDS PREPARED THEREBY
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The present invention relates to an improved process for the preparation of a sulfinyl compound of formula (I), or a pharmaceutically acceptable salt, hydrate or solvate thereof, from a sulfide compound of formula (II), wherein in both formulae (I) and (II) R1 and R3 are selected from the group consisting of hydrogen, methyl or C1-4alkoxy, R2 is selected from the group consisting of substituted or unsubstituted C1-4alkoxy and R4 is selected from the group consisting of hydrogen or substituted or unsubstituted C1-4alkoxy.
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