WO2008087665A2 - Procédé de préparation de lansoprazole - Google Patents

Procédé de préparation de lansoprazole Download PDF

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Publication number
WO2008087665A2
WO2008087665A2 PCT/IN2008/000034 IN2008000034W WO2008087665A2 WO 2008087665 A2 WO2008087665 A2 WO 2008087665A2 IN 2008000034 W IN2008000034 W IN 2008000034W WO 2008087665 A2 WO2008087665 A2 WO 2008087665A2
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WO
WIPO (PCT)
Prior art keywords
lansoprazole
solvent
process according
methyl
water
Prior art date
Application number
PCT/IN2008/000034
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English (en)
Other versions
WO2008087665A3 (fr
Inventor
Mohan Bandari
Chandra Ray Purna
Kumar Sethi Madhuresh
Venkata Lakshmi Narayana Chebolu Veera
Ramakrishna Kamatam
Original Assignee
Matrix Laboratories Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Application filed by Matrix Laboratories Ltd filed Critical Matrix Laboratories Ltd
Publication of WO2008087665A2 publication Critical patent/WO2008087665A2/fr
Publication of WO2008087665A3 publication Critical patent/WO2008087665A3/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 Lansoprazole substantially free from its residual impurities & impurities due to over oxidation of the product.
  • a number of substituted 2-(2-pyridylmethyl) sulfinyl-lH-benzimidazole derivatives are reported as gastric proton pump inhibitors. These benzimidazole derivatives include lansoprazole, omeprazole, pantoprazole, and rabeprazole.
  • the Lansoprazole is generally represented by the following chemical formula I
  • lansoprazole having its chemical name (2-[[[3-methyl-4-(2, 2, 2-trifluoro-ethoxy)-2-pyridinyl] methyl] sulfinyl]-lH-benzimidazole.
  • benzimidazole derivatives e.g., omeprazole and pantoprazole
  • lansoprazole can inhibit gastric acid secretion, and thus commonly used as an antiulcer agent.
  • Several methods for preparing Lansoprazole are known. The majority of these methods involve the use of a lansoprazole precursor that contains a thioether group.
  • the thioether group is oxidized in the last step of preparation to form the lansoprazole.
  • These patents ('098 and '333) further describes the oxidation of the thioether group using m-chloroperbenzoic acid, per acid, sodium bromite, sodium hypochlorite, or hydrogen peroxide as the oxidizing agent and the reaction solvent is halogenated hydrocarbon, ether, amide, alcohol, or water.
  • US 6,002,011 describe the crystallization of Lansoprazole from the same ethanol: water system, containing traces of ammonia. This patent discloses a reslurry method in water, which permits to obtain more stable "solvent free” Lansoprazole. This patent fails to disclose the level of purity for Lansoprazole. In addition, the ethanol and water are difficult to eliminate. Even after intensive drying, Lansoprazole still contains solvent and is unstable under storage. US 6,180,652 describe the presence of sulfone derivative. Formation of sulfone derivative brings about the drawback of low yield of the desired sulfoxide.
  • US 6,909,004 describes the method of purifying Lansoprazole, comprising the steps of: a) providing a solution of lansoprazole in a solvent selected from an organic solvent or a mixture of organic solvent and water in the presence of an amine compound; b) combining the provided solution with an acid, and c)isolating the purified Lansoprazole.
  • the amine compound is present in 1:1, mole: mole, ratio relative to the lansoprazole.
  • Solution is in an organic solvent selected from the group consisting of alcohols, acetone, 2-butanone, dimethylformamide and tetrahydrofuran. The alcohol consisting of ethanol, methanol, n-propanol, & iso-propanol.
  • US 7022859 & US 7060837 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.
  • US 2004/010151 disclose a method of preparing crystalline Lansoprazole form A, comprising the steps of: a) preparing a solution of Lansoprazole in a solvent selected from the group consisting of methanol, n-butanol, acetone, methylethylketone, ethyl acetate, dimethyl sulfoxide, dimethylforniamide and their mixtures optionally with water; and b) isolating crystalline Lansoprazole form A.
  • US 2005/020638 describe the process of preparing a stable Lansoprazole, comprising the steps of: a) crystallizing a Lansoprazole from an organic solvent or a mixture of organic solvent and water in the presence of a weak base; and b) isolating a stable Lansoprazole.
  • An amorphous form of Lansoprazole prepared by spray drying method has been described (Farm. Vest. vol. 50, p. 347 (1999)).
  • Curin et al. describe an ethanole solvate form and an ethanole-hydrate form of Lansoprazole (Farm. Vest. vol. 48, pp. 290-291 (1997).
  • crystalline Lansoprazole forms A and B Two lansoprazole polymorphs, designated as crystalline Lansoprazole forms A and B, (Eur. J. Pharm. Sci. vol. 4, p. 182 (1996 Supp). According to Kotar, each of the crystalline Lansoprazole forms A and B exhibits a different DSC curve. In fact, crystalline Lansoprazole form B is unstable and can undergo a solid-solid transition to form crystalline Lansoprazole form A. No XRD data for crystalline Lansoprazole forms A and B, and fails to disclose processes for preparing these crystalline forms. No indication was found in the literature regarding the existence of other crystalline Lansoprazole forms other than the known forms A, B, ethanolate and ethanolate- hydrate.
  • WO 00/78729 is discloses a phenomenon of polymorphism in Lansoprazole.
  • the form I find application as an active ingredient of pharmaceutical compositions.
  • WO 03/082857 disclose a method of preparing crystalline Lansoprazole form A, comprising the steps of: a) preparing a solution of Lansoprazole in a solvent selected from the group consisting of methanol, n-butanol, acetone, methylethylketone, ethyl acetate, dimethyl sulfoxide, dimethylformamide and their mixtures optionally with water; and b) isolating crystalline Lansoprazole form A.
  • WO 2004/046135 describe the process for preparing a stable Lansoprazole compound, comprising the steps of: a) crystallizing a Lansoprazole from an organic solvent or a mixture of organic solvent and water in the presence of an amine; and b) isolating a stable Lansoprazole compound, wherein the stable Lansoprazole compound comprises greater than 500 ppm and not more than about 3,000 ppm water.
  • sulfones of formula (III) due to over-oxidation is almost impossible to avoid and can be kept to a minimum by performing the oxidation reaction at a low temperature and restricting the amount of oxidizing agent.
  • the amount of oxidizing agent is less than 1 molar equivalent of the starting material, i.e. sulfide intermediates of formula (II), which inevitably results in a less than 100% conversion of starting material.
  • the amount of oxidizing agent is a compromise between maximum conversion of starting material, maximum formation of sulfoxides of formula (I) and minimum formation of unwanted sulfones of formula (III).
  • Chlorinating impurities (V) are observed when chlorinating oxidizing agent such as sodium hypochlorite is used for oxidation reaction. Furthermore removal of the sulfones of formula (III) & chlorinating impurities (V) has often proved to be difficult, time-consuming and costly, in particular when high performance chromatography on an industrial scale is needed. Another problem with the benzimidazole-type is very susceptible to degradation when exposed to high temperatures for removal of solvents during distillation.
  • the main object of the present invention is to provide a process for the isolation of (2-[[[3- methyl-4-(2,2,2-trifluoro-ethoxy)-2-pyridinyl]methyl] sulfinyl] - 1 H-benzimidazole from chloroform (water immiscible solvent /halogenated hydrocarbon) layer by avoiding the need for distillation.
  • Another object of the present invention is to provide a process for the isolation of (2-[[[3-methyl- 4-(2,2,2-trifluoro-ethoxy)-2-pyridinyl]methyl] sulfinyl]- 1 H-benzimidazole from chloroform (water immiscible solvent/ halogenated hydrocarbon) layer by cooling in presence of water.
  • Yet another object of the present invention is to provide a commercially feasible, eco-friendly process for the isolation of (2-[[[3-methyl-4-(2, 2, 2-trifluoro-ethoxy)-2-pyridinyl] methyl] sulfinyl] -1 H-benzimidazole from chloroform (water immiscible solvent/ halogenated hydrocarbon) layer by cooling in presence of water & base.
  • Yet another object of the present invention is to provide a process for the isolation of (2-[[[3- methyl-4-(2, 2, 2-trifluoro-ethoxy)-2-pyridinyl]methyl] sulfinyl] -1 H-benzimidazole from chloroform (water immiscible solvent/ halogenated hydrocarbon) layer by cooling in presence of water & base.
  • Yet another object of the present invention is to provide a process for the isolation of (2-[[[3- methyl-4-(2,2,2-trifluoro-ethoxy)-2-pyridinyl]methyl]sulfinyl]-lH-benzimidazole from chloroform (water immiscible solvent/ halogenated hydrocarbon) layer by cooling in presence of water & amide.
  • Yet another object of the present invention is to provide a process for the isolation of (2-[[[3- methyl-4-(2,2,2-trifluoro-ethoxy)-2-pyridinyl]methyl] sulfinyl] - 1 H-benzimidazole from chloroform (water immiscible solvent/ halogenated hydrocarbon) layer by cooling in presence of base.
  • chloroform water immiscible solvent/ halogenated hydrocarbon
  • the process of the present invention comprises of the following steps:
  • the reaction solvent is halogenated hydrocarbon such as dichloromethane, chloroform, carbon tetrachloride, preferably dichloromethane or chloroform.
  • the oxidizing agents used in reaction are such as m-chloroperbenzoic acid/ sodium hypochlorite/ hydrogen peroxide.
  • the resulting product thus obtained may be subjected to terminate oxidation reaction with a conventional method for decomposing excess buffer solution of (pH between 10 -14), organic or inorganic base, aqueous solution of inorganic base, by adding an aqueous solution of sodium thiosulfate of mixture thereof.
  • the layers are separated after washing with aqueous solution of inorganic base & aqueous solution of sodium thiosulfate and finally crystallized by using aqueous solution of chloroform in presence of co-solvent & base.
  • a conventional purification method such as recrystallization by using aqueous solution chloroform in presence of dimethyl amide & base may be used.
  • the crystallisation temperature is between -20°C and 25°C, preferably between -5°C and 20°C.
  • lansoprazole (I) can be obtained by oxidation of 2 [3-methyl- 4- (2, 2, 2-trifluoroethoxy)-2-pyridyl] methylthio-lH-benziniidazole (II) in good yield and high quality.
  • the procedure of the present invention discloses the number of improvements on the previous procedures, such as the following the reagents used are commercially affordable, the pH of the reaction mixture is slightly basic and thus adequate for stability of compounds such as Lansoprazole in a solution, the formation of N-oxide as an impurity is unappreciable or appreciable at negligible amounts, the percentage of sulfone & chlorinating in the produced are low, the oxidized product is isolated by precipitation in the reaction medium by addition of co-solvents, base, amine & amide as mentioned in table -1, The wet precipitate is stirred in a dilute solution of sodium bicarbonate & dried to give pure stable Lansoprazole.
  • Lansoprazole was dissolved in acetone: water (7:3) at pH 10-12 & re-precipitated at pH 7-8 using dil. acetic acid solution. The wet Lansoprazole was slurry washed with sodium bicarbonate solution (0.5%) & dried to get white colour pure compound.
  • Chloroform layer was washed with sodium bicarbonate solution (0.5%; 500 ml) at room temperature. Then N, N-- dimethyl acetamide (1 ml) was slowly added to organic layer and cooled to 0 0 C. Filtered; washed with chilled chloroform (10 ml) & slurried with ethyl acetate (10 ml) followed by sodium bicarbonate solution (0.5%, 50 ml) & dried to get pure Lansoprazole.
  • Chloroform layer was washed with sodium bicarbonate solution (0.5%; 500 ml) at room temperature.
  • Various co-solvents mentioned in Table- 1 were added to organic layer cool slowly to -10 to 10 0 C. Filtered and washed with chilled chloroform (10 ml) followed by sodium bicarbonate solution (0.5%, 100 ml) & dried to get pure Lansoprazole.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

L'invention concerne un procédé de préparation de lansoprazole comprenant les étapes suivantes : oxydation de 2-[[(3-methyl-4-(2,2,2-trifluoroethoxy)pyridinyl]methyl]thio]-lH- benzimidazole au moyen d'un agent d'oxydation, lavage de la masse de réaction au moyen d'une solution aqueuse de tampon, bicarbonate et thiosulphate alcalins, isolation du produit par refroidissement à une basse température en présence d'eau, d'une base, d'un amide ou d'un mélange de ceux-ci. L'invention concerne également une préparation en suspension/cristalline formée à partir d'un solvant organique non miscible dans l'eau en présence d'eau, d'une base, d'un amide ou d'un mélange de ceux-ci. La mise en suspension du produit au moyen d'une solution de bicarbonate de sodium est suivie du séchage de produits secondaires du lansoprazole.
PCT/IN2008/000034 2007-01-18 2008-01-18 Procédé de préparation de lansoprazole WO2008087665A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN103/CHE/2007 2007-01-18
IN103CH2007 2007-01-18

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WO2008087665A2 true WO2008087665A2 (fr) 2008-07-24
WO2008087665A3 WO2008087665A3 (fr) 2011-01-27

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012004802A1 (fr) 2009-07-07 2012-01-12 Council Of Scientific & Industrial Research Processus d'écoulement continu pour la préparation de composés sulfoxyde
CN107964005A (zh) * 2017-11-10 2018-04-27 扬子江药业集团江苏海慈生物药业有限公司 一种兰索拉唑的制备方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4628098A (en) * 1984-08-16 1986-12-09 Takeda Chemical Industries, Ltd. 2-[2-pyridylmethylthio-(sulfinyl)]benzimidazoles
WO2004018454A1 (fr) * 2002-08-21 2004-03-04 Teva Pharmaceutical Industries Ltd. Procede de purification de lansoprazole
US20040049045A1 (en) * 2000-12-01 2004-03-11 Hideo Hashimoto Process for the crystallization of (r)-or (s)-lansoprazole

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4628098A (en) * 1984-08-16 1986-12-09 Takeda Chemical Industries, Ltd. 2-[2-pyridylmethylthio-(sulfinyl)]benzimidazoles
US20040049045A1 (en) * 2000-12-01 2004-03-11 Hideo Hashimoto Process for the crystallization of (r)-or (s)-lansoprazole
WO2004018454A1 (fr) * 2002-08-21 2004-03-04 Teva Pharmaceutical Industries Ltd. Procede de purification de lansoprazole

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012004802A1 (fr) 2009-07-07 2012-01-12 Council Of Scientific & Industrial Research Processus d'écoulement continu pour la préparation de composés sulfoxyde
CN107964005A (zh) * 2017-11-10 2018-04-27 扬子江药业集团江苏海慈生物药业有限公司 一种兰索拉唑的制备方法

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