WO2007066202A1 - Procede de fabrication de 2-(2-pyridylmethyl)-sulfinyl-1h-benzimidazoles - Google Patents

Procede de fabrication de 2-(2-pyridylmethyl)-sulfinyl-1h-benzimidazoles Download PDF

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Publication number
WO2007066202A1
WO2007066202A1 PCT/IB2006/003482 IB2006003482W WO2007066202A1 WO 2007066202 A1 WO2007066202 A1 WO 2007066202A1 IB 2006003482 W IB2006003482 W IB 2006003482W WO 2007066202 A1 WO2007066202 A1 WO 2007066202A1
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WIPO (PCT)
Prior art keywords
formula
oxidation
substituted
derivatives
alkoxy
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PCT/IB2006/003482
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English (en)
Inventor
Reguri Buchi Reddy
Gudaparthi Om Prakash
Gutta Madhusudhan
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Inogent Laboratories Private Limited
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Publication of WO2007066202A1 publication Critical patent/WO2007066202A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • the present invention relates to an improved process for the preparation of substituted 2-(2-pyridylmethyl)-sulfinyl-lH-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 with relatively high purity and pharmaceutically acceptable salt, hydrate and solvate thereof.
  • Rj and R 3 are selected from the group consisting of hydrogen, methyl or C 1 - 4 alkoxy
  • R 2 is selected from the group consisting of substituted or unsubstituted C 1-4 alkoxy
  • R 4 is selected from the group consisting of hydrogen or substituted or unsubstituted C,- 4 alkoxy.
  • Ri R 2 R 3 & R 4 are as defined above.
  • a number of compounds of industrial interest in particular Pharmaceuticals for human or veterinary use, contain a sulfinyl or sulfonyi group. Their synthesis usually comprises an oxidation step wherein a thioether intermediate (-S-) is transformed into a sulfinyl (-SO-) compound.
  • S-S- thioether intermediate
  • -SO- sulfinyl
  • Different oxidizing agents are available for this oxidation, such as those described by S. Uemura in "Comprehensive Organic Synthesis", chapter 6.2, edited B. M. Trost and J. Fleming, Pergamon Press (1991). Nevertheless, only some of these oxidizing agents are suitable for industrial application, due to the facts that they are not easily available on the market, environmentally unsafe and their poor chemical selectivity.
  • hydrogen peroxide and sodium hypochlorite arc usually preferred, as they are commercially available in large amounts and at low cost, Moreover, the oxidation of organic compounds with hydrogen peroxide is very often carried out in the presence of catalysts based on transition metals, such as tungsten, titanium, vanadium and molybdenum. The removal of these catalysts from the reaction product is recognizably troublesome, as it requires additional purification steps with consequent increase in production costs and decrease in yield.
  • the oxidizing power of sodium hypochlorite is not sufficient to obtain sulfonyi derivatives. Moreover, in most cases the oxidation of thioethers with sodium hypochlorite is not sufficiently selective and leads to undesired byproducts.
  • a known medicament that contains a sulfinyl group is modafmil, i.e. 2- [(diphenylmcthyl)sulfmyl]acetamide.
  • modafmil i.e. 2- [(diphenylmcthyl)sulfmyl]acetamide.
  • intermediate 2- [(diphenylmethyl)thio] acetic acid or 2-[(diphenylmethyl) thio]acetamide is oxidized with hydrogen peroxide to give 2-[(diphenylmethyl) sulfmyl]acetic acid, or 2-[(diphenylmethyl)sulfmyl]acetamide, respectively.
  • This oxidation usually performed with 110 volumes hydrogen peroxide. involves safety problems.
  • sulindac i.e. (Z)-5-fluoro-2- metfayl- l-[[4-(methyl ⁇ ulflnyI)phenyl]niethytene]-lH-indcne-3-acetic acid
  • prazoles i.e. [[(pyridyl)methyl]sulfmyl]benzimidazole derivatives, which are known anti-secretory agents.
  • Benzimidazole derivatives of general formula (I) are produced from their corresponding sulphides by oxidation with an oxidising agent exemplified by m-chloroperbenzoic acid, petacetic acid, trifluoroperacetic acid, permaleic acid, sodium bromite, sodiumhypochlorite, hydrogen peroxide or other reagents as described in a number of patents.
  • an oxidising agent exemplified by m-chloroperbenzoic acid, petacetic acid, trifluoroperacetic acid, permaleic acid, sodium bromite, sodiumhypochlorite, hydrogen peroxide or other reagents as described in a number of patents.
  • Oxidizing agents previously disclosed in the art for the oxidation of the sulfide compound include iodosobenzene (Spanish Patent No. 539,793 (1985)), iodosomethylbenzene (Spanish Patent No. 540,147 (1985)), m-chloroperbenzoic acid (US Patent No. 4,628,098 (1986) and 4,255,431 (1981)), peroxyacetic acid (WO 98/09962 (1998)), sodium hypochlorite (EP 268,956 (198S)) , sodium periodate (Spanish Patent No. 550,070 (1985)) and the like.
  • the main objective of the present invention is to provide an improved process for the preparation of substituted 2-(2-pyridylmethyl)-sulfinyl-lH- benzirnidazoles the formula (I) or its pharmaceutically acceptable salts.
  • Yet another objective of the present invention is to develop a simple and commercially viable process for the preparation of substituted 2-(2- pyridylmethyl)-siulfinyl-lH-benzimidazoles derivatives of the formula (I) using the compound of formula (IT).
  • Yet another objective of the present invention to provide an improved process for oxidation of (2- [[[3-methyl-4- (2, 2, 2-trifluoro-ethoxy)-2-pyridinyl] methyl] thio] IH- benzimidazole to the corresponding (2- ([[3-methyl-4- (2, 2,2- trifluoro-ethoxy)-2- pyridinyl] methylj-sulfinyl] IH-benzimidazole (lansoprazole), preferably using an inexpensive and readily available reagent.
  • Still another objective of the present invention is to provide an improved process for oxidation of ((5-(difruoromethoxy)-2-[[(3, 4-dimethoxy-2-pyridinyl) methyl] thio] IH-benzimidazole, to the corresponding ((5-(difluoromethoxy)-2-[ [(3 ? 4-dimethoxy-2-pyridmyl)methyl]-sulfmyl]lH-ben2imidazole (pantoprazole), preferably using an inexpensive and readily available reagent.
  • Yet another objective of the present invention is to provide an improved process for oxidation of (2- [[[4- (3-methoxy-propoxy) 3-methyl-2-pyridmyl] methyl]-thio]-lH- benzimidazole, to the corresponding (2- [[[4- (3-methoxy- propoxy) 3-methyl-2- pyridinyl] methyl]-sulfinyl]-lH-benzimidazole (rabeprazole), preferably using an inexpensive and readily available reagent.
  • Yet another objective of the present invention is to use Peroxyacetic acid or its derivatives at a pH around 5-7 using alkaline Sodium Carbonate solution to produce benzimidazole derivatives with higher purity and remarkably reduced process impurities.
  • Yet another objective of the invention is to carryout the process of oxidation in a single or bi phase reaction medium using organic solvents selected from alcohols such as methanol, ethanol, isopropylalcohol (EPA) and the like or chlorinated solvents like chloroform, dichloromethane (DCM) and the like or ethers such as Isopropylether, diethylether and cyclic ethers such as tetrahydrof ⁇ ran, dioxane, or water and the like or mixtures thereof.
  • organic solvents selected from alcohols such as methanol, ethanol, isopropylalcohol (EPA) and the like or chlorinated solvents like chloroform, dichloromethane (DCM) and the like or ethers such as Isopropylether, diethylether and cyclic ethers such as tetrahydrof ⁇ ran, dioxane, or water and the like or mixtures thereof.
  • the present invention provides a process for the preparation of substituted 2-(2-pyridylmethyl)-sulfmyI-lH-benzimidazoles derivatives of the formula (D in good yield with relatively high purity and pharmaceutically acceptable salt, hydrate and solvate thereof.
  • R 1 and R 3 are selected from the group consisting of hydrogen, methyl or Cr 4 alkoxy.
  • R 2 is selected from the group consisting of substituted or unsubstituted C w alkoxy
  • R 4 is selected from the group consisting of hydrogen or substituted or unsubstituted C 1 - 4 alkoxy
  • the present invention provides an efficient and industrially feasible process for preparing various substituted 2-(2-pyridylmethyl)-sulfmyl-lH- benzimidazoles derivatives in good yield with relatively high purity and pharmaceutically acceptable salt, hydrate and solvate thereof.
  • the peroxyacetic acid or its derivatives used is selected from peroxyacetic acid (PAA), substituted peroxyaceticacids such as fluoroperoxyacetic acid, and the like or mixture thereof.
  • PAA peroxyacetic acid
  • substituted peroxyaceticacids such as fluoroperoxyacetic acid
  • oxidation of sulfide (II) is carried out with Peroxyacetic acid or its derivatives at a pH around 5-7 using aqueous sodium carbonate solution during oxidation process.
  • the purpose of using peroxyacetic acid along with aqueous sodium carbonate is to eliminate or minimize the impurities such as sulphone and N-oxide that are formed in the final product.
  • organic solvents selected from alcohols such as methanol, ethanol, isopropylalcohol (IPA) and the like, or chlorinated solvents like chloroform, dichloromethane (DCM) and the like or ethers such as Isopropylether, diethylether and cyclic ethers such as tetrahydrofuran, dioxane, or water and the like or mixtures thereof.
  • alcohols such as methanol, ethanol, isopropylalcohol (IPA) and the like
  • chlorinated solvents like chloroform, dichloromethane (DCM) and the like
  • ethers such as Isopropylether, diethylether and cyclic ethers such as tetrahydrofuran, dioxane, or water and the like or mixtures thereof.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne un procédé amélioré de fabrication de 2-(2-pyridylméthyl)-sulfinyl-1H-benzimidazoles substitués ou de leurs dérivés, lesdits composés étant utiles pour la fabrication d’un médicament tel qu’un inhibiteur de sécrétion gastrique acide ou un agent anti-ulcère, ou d’un intermédiaire pour la fabrication de médicaments, avec un bon rendement et une pureté élevée. La présente invention concerne plus particulièrement un procédé de fabrication d’un composé de sulfoxyde de formule (I) avec un bon rendement et une pureté relativement élevée, ainsi que d’un sel, un hydrate et un solvate pharmaceutiquement acceptables de ce composé. (I) dans laquelle R1 et R3 sont choisis parmi l’hydrogène, le méthyle ou les alcoxy en C1-4, R2 est choisi parmi les alcoxy en C1-4 substitués ou non substitués, R4 est choisi parmi l’hydrogène et les alcoxy en C1-4 substitués ou non substitués. Le procédé comprend une étape d’oxydation d’un composé de sulfure de formule (II) avec de l’acide peroxyacétique ou ses dérivés, à un pH compris entre 5 et 7 en utilisant une solution aqueuse de carbonate de sodium. (II) dans laquelle R1 R2 R3 et R4 sont tels que définis précédemment.
PCT/IB2006/003482 2005-12-06 2006-11-23 Procede de fabrication de 2-(2-pyridylmethyl)-sulfinyl-1h-benzimidazoles WO2007066202A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN1786/CHE/2005 2005-12-06
IN1786CH2005 2005-12-06

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7683177B2 (en) 2003-06-10 2010-03-23 Teva Pharmaceutical Industries Ltd Process for preparing 2-[(pyridinyl)methyl]sulfinyl-substituted benzimidazoles and novel chlorinated derivatives of pantoprazole
CN109354587A (zh) * 2018-10-18 2019-02-19 成都天台山制药有限公司 泮托拉唑钠的制备方法和泮托拉唑钠

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998009962A1 (fr) * 1996-09-09 1998-03-12 Slovakofarma, A.S. Procede de preparation d'omeprazole
WO2000009497A1 (fr) * 1998-08-11 2000-02-24 Merck & Co., Inc. Procede ameliore de preparation, d'isolation et de purification de l'omeprazole et compositions d'omeprazole

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998009962A1 (fr) * 1996-09-09 1998-03-12 Slovakofarma, A.S. Procede de preparation d'omeprazole
WO2000009497A1 (fr) * 1998-08-11 2000-02-24 Merck & Co., Inc. Procede ameliore de preparation, d'isolation et de purification de l'omeprazole et compositions d'omeprazole

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7683177B2 (en) 2003-06-10 2010-03-23 Teva Pharmaceutical Industries Ltd Process for preparing 2-[(pyridinyl)methyl]sulfinyl-substituted benzimidazoles and novel chlorinated derivatives of pantoprazole
CN109354587A (zh) * 2018-10-18 2019-02-19 成都天台山制药有限公司 泮托拉唑钠的制备方法和泮托拉唑钠
CN109354587B (zh) * 2018-10-18 2020-09-18 成都天台山制药有限公司 泮托拉唑钠的制备方法和泮托拉唑钠

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