- Development of a scalable and safe process for the production of 4-chloro-2,3-dimethylpyridine- N -oxide as a key intermediate in the syntheses of proton pump inhibitors
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2-(Pyridin-2-ylmethanesulfinyl)-1H-benzimidazole-based drugs belong to the most prominent and successfully applied proton pump inhibitors. To fulfill the demand for a flexible and safe procedure for the synthesis of early-stage intermediates which are known to possess a strong exothermal decomposition potential, we have developed a high-yielding telescoped procedure for the synthesis of a key intermediate in the synthesis of these drugs. This strategy turned out to be highly reproducible in laboratory as well as on pilot-plant scale. As the starting material, as well as some of the intermediates, shows a highly exothermal decomposition potential, extensive safety investigations were undertaken. The whole process was adapted in a safe and reliable manner based on the outcome of this systematic approach. Considering these precautions, no safety issues were observed, neither in the laboratory nor in the pilot plant.
- Waser, Mario,Obermueller, Roland,Wiegand, John Matthias,Schiek, Wolfgang,Fierz, Hans,Skranc, Wolfgang
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Read Online
- Preparation method of 2-hydroxymethyl-4-(methoxypropoxy)-3-methylpyridine hydrochloride
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The invention relates to a preparation method of 2-hydroxymethyl-4-(methoxypropoxy)-3-methylpyridine hydrochloride. The method comprises the following steps: reacting an initial raw material 2,3-dimethyl-4-chloropyridine-N-oxide hydrochloride with 3-methoxypropanol under a solvent-free condition to obtain 2,3-dimethyl-4-(methoxypropoxy)-pyridine-N-oxide, acetylizing the 2,3-dimethyl-4-(methoxypropoxy)-pyridine-N-oxide, hydrolyzing the acetylized 2,3-dimethyl-4-(methoxypropoxy)-pyridine-N-oxide, and carrying out a salt formation reaction to obtain the 2-hydroxymethyl-4-(methoxypropoxy)-3-methylpyridine hydrochloride. The purity of 2-hydroxymethyl-4-(methoxypropoxy)-3-methylpyridine hydrochloride solid can reach 98% or above, and 2-chloromethyl-4-(methoxypropoxy)-3-methylpyridine obtained after a chlorination reaction of 2-hydroxymethyl-4-(methoxypropoxy)-3-methylpyridine hydrochloride can directly react with 2-mercaptobenzimidazole without a salt formation or purification process in order to prepare rabeprazole thioether; and the solid has good stability, has no strict requirements on transportation or storage conditions, can be stored for a long time, and is suitable for being used as a rabeprazole sodium intermediate.
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Paragraph 0027; 0048
(2017/05/10)
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- Diversified synthesis of novel quinoline and dibenzo thiazepine derivatives using known active intermediates
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The novel drug development to control resisting infections in conventional drug therapy is a need of today. Few antiulcer relative derivatives developed by approaching convergent synthesis. The derivatives synthesized successfully are dibenzo thiazepine-pyridine (SLN11-SLN15) and benzimidazole-hydroquinoline based derivatives (SLN16-SLN20). It involved the coupling through microwave, sonication and conventional techniques at final step. The efficient technology identified as sonication technique basically time and yield. The reported compounds were structural characterized by elemental analysis and spectral studies such as 1H, 13C NMR and MS.
- Sharada,Satyanarayana Reddy,Sammaiah,Sumalatha
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p. 7959 - 7966
(2013/09/23)
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- PROCESS FOR PREPARATION OF PYRIDINYLMETHYLSULPHINYL BENZIMIDAZOLE COMPOUNDS AND PYRIDINE INTERMEDIATES
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Process for preparing 4-chloro-substituted pyridine intermediates of Formula (I), useful for preparation of pyridinylmethylsulphinyl benzimidazole compounds, especially Rabeprazole is disclosed herein. The invention, further describes process for preparation of stable Rabeprazole sodium of high purity in a reproducible and consistent manner.
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Page/Page column 12
(2009/10/22)
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- NEW PRAZOLE COMPOUND AND THE USE THEREOF
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The present invention relates to derivatives of compounds (formula (I) or (II)) and their salts, wherein R1 represents lower alkyl or the lower alkyl substituted by halogen atoms, R2 represents straight-chain or branched-chain alkyl containing 1-4 carbon atoms and R3 represents hydrogen atom or alkali metals such as lithium, sodium, potassium or alkaline-earth metals such as magnesium and calcium. In the present invention, compounds with formula (I) or (II) and their derivatives or salts thereof acceptable in pharmacy and pharmacology can remarkably improve the effectiveness of anti-ulcer in alimentary tract, weakly inhibit gastric acid secretion, reduce the risk of stomach cancer and have excellent bio-availability and other in-vive pharmacokinetic characteristics.
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Page/Page column 5
(2008/06/13)
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- Preparation of substituted pyridine N-oxide compounds
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A process for preparing substituted pyridine N-oxide compounds of the formula in which R1, R2, R3 and R4 are each H, a carboxyl group or a C1-C12-alkyl radical which may contain atoms from the group of N, O and S, or R1 and R2 and/or R3 and R4 together may each form an optionally substituted C4-C20-alkylene radical which may contain atoms from the group of N, O and S, A is benzyl or a (CH2)m group where m may be an integer from 1 to 12, Z1 and Z2 are each independently O or S, and Y is H, a C1-C12-alkyl radical which may optionally contain atoms from the group of N, O and S, a C6-C20-aryl radical or a C5-C20-heterocycle, and the radicals may optionally be substituted, or Z2 and Y together form an optionally substituted ring or ring system, in which case the ring or ring system may contain atoms from the group of N, O and S, from the corresponding 4-halopyridine N-oxide of the formula in which X is chlorine, bromine or iodine, by reacting the compound of the formula (II), in the presence of a phase transfer catalyst and of a base, with a compound of the formula HZ1-A-Z2-Y??(III) in which Z1, Z2, A and Y are each as defined above, at a temperature up to the reflux temperature, to give the corresponding substituted pyridine N-oxide compound of the formula (I), and also a process for preparing the compound of the formula (II).
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- Process to prepare substituted pyridine-N-oxide compounds
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Verfahren zur Herstellung von substituierten Pyridin-N-oxid-verbindungen der Formel in der R1, R2, R3 und R4 H, eine Carboxylgruppe oder ein C1-C12-Alkylrest, der Atome aus der Gruppe N, O, oder S enthalten kann, sein k?nnen, oder R1 und R2 und/oder R3 und R4 gemeinsam einen gegebenenfalls substituierten C4-C20-Alkylenrest bilden k?nnen, der Atome aus der Gruppe N, O, oder S enthalten kann, A Benzyl oder eine Gruppe (CH2)m bedeutet, wobei m eine ganze Zahl von 1 bis 12 sein kann, Z1 und Z2 unabh?ngig voneinander O oder S sind und Y H, einen C1-C12- Alkylrest, der gegebenenfalls Atome aus der Gruppe N, O, oder S enthalten kann, einen C6-C20-Arylrest oder einen C5-C20-Heterocyclus bedeutet, wobei die Reste gegebenenfalls substituiert sein k?nnen, oder Z2 und Y gemeinsam einen gegebenenfalls substituierten Ring bzw. Ringsystem bilden, wobei der Ring oder das Ringsystem Atome aus der Gruppe N, O, oder S enthalten kann, aus dem korrespondierenden 4-Halo-Pyridin-N-oxid der Formel in der X Chlor, Brom oder lod bedeutet, wobei die Verbindung der Formel (II) in Gegenwart eines Phasentransferkatalysators und einer Base mit einer Verbindung der FormelHZ1-A-Z2-Y in der Z1, Z2, A und Y wie oben definiert sind, bei einer Temperatur bis zur Rückflusstemperatur zu der entsprechenden substituierten Pyridin-N-oxid-Verbindung der Formel (I) umgesetzt wird, sowie ein Verfahren zur Herstellung der Verbindung der Formel (II).
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- PYRIDINE DERIVATIVES HAVING ANTI-ULCERATIVE ACTIVITY
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Pyridine derivatives useful for preventing or treating peptic ulcers, pharmaceutical preparations and methods of treating peptic ulcers are described.
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