WO2006019151A1 - Procédé pour la fabrication d’un dérivé de benzimidazole - Google Patents

Procédé pour la fabrication d’un dérivé de benzimidazole Download PDF

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Publication number
WO2006019151A1
WO2006019151A1 PCT/JP2005/015123 JP2005015123W WO2006019151A1 WO 2006019151 A1 WO2006019151 A1 WO 2006019151A1 JP 2005015123 W JP2005015123 W JP 2005015123W WO 2006019151 A1 WO2006019151 A1 WO 2006019151A1
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WIPO (PCT)
Prior art keywords
group
water
added
dichloromethane
methoxypropoxy
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
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PCT/JP2005/015123
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English (en)
Japanese (ja)
Inventor
Kiyoshi Ozawa
Hideyuki Kosumi
Satoshi Takeda
Toshiaki Kurose
Kazukata Murakami
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
JUZEN CHEMICAL Corp
Eisai Co Ltd
Eisai R&D Management Co Ltd
Original Assignee
JUZEN CHEMICAL Corp
Eisai Co Ltd
Eisai R&D Management Co Ltd
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Filing date
Publication date
Application filed by JUZEN CHEMICAL Corp, Eisai Co Ltd, Eisai R&D Management Co Ltd filed Critical JUZEN CHEMICAL Corp
Priority to JP2006531865A priority Critical patent/JP4987477B2/ja
Publication of WO2006019151A1 publication Critical patent/WO2006019151A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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 a method for producing 2-[(pyridine-2-yl) methylsulfiel] 1H-benzimidazole derivatives useful as intermediates for the production of pharmaceuticals such as gastric acid secretion inhibitors and anti-ulcer agents. .
  • the present invention also relates to a method for recovering a raw material compound, that is, a 2-[(pyridin-2-yl) methylthio] 1H-benzimidazole derivative, in the above production method.
  • Patent Document 1 International Patent Publication Pamphlet WO03Z008406
  • An object of the present invention is to suppress the formation of 2-[(pyridine-2-yl) methylsulfol] 1H benzimidazole derivative, while maintaining 2-[(pyridine-2-yl) methylthio] 1H-benzimidazole. It is an object to provide a method for efficiently converting a derivative into a 2-[(pyridine 2-yl) methylsulfinyl] — 1H-benzimidazole derivative. Means for solving the problem
  • the present invention provides:
  • R1 and R2 are the same or different and each represents a hydrogen atom, a methoxy group or a difluoromethoxy group, R3 represents a methyl group or a methoxy group, R4 represents a methoxy group, 2, 2, 2 trifluoro group) And represents a roethoxy group or a 3-methoxypropoxy group, and R5 represents a hydrogen atom or a methyl group.
  • the oxidant used in the operation (1) has an equivalent amount of 0.4 to 0.7 with respect to the compound of the formula (Y), [1] to [3]
  • R1 and R2 are hydrogen atoms, R3 is a methyl group, R4 is a 3-methoxypropyloxy group, and R5 is hydrogen,
  • R1 is a methoxy group
  • R2 is a hydrogen atom
  • R3 is a methyl group
  • R5 is a methyl group
  • R1 is a difluoromethoxy group
  • R2 is a hydrogen atom
  • R3 is a methoxy group
  • R4 force methoxy group
  • R5 is a hydrogen atom
  • R1 and R2 are hydrogen atoms, R3 is a methyl group, R4 is a 2,2,2-trifluoroethyl ethoxy group, and R5 is a hydrogen atom, any of [1] to [11]
  • the present invention also provides:
  • R1 and R2 are the same or different and each represents a hydrogen atom, a methoxy group or a difluoromethoxy group, R3 represents a methyl group or a methoxy group, R4 represents a methoxy group, 2, 2, 2-trifluoro) Represents an ethoxy group or a 3-methoxypropoxy group, and R5 represents a hydrogen atom or a methyl group.
  • the organic solvent power immiscible with water is dichloromethane, the recovery method according to any one of [14] to [17],
  • Alkaline aqueous solution power A sodium hydroxide aqueous solution or a potassium hydroxide aqueous solution, [14] to [19], the recovery method according to any one of
  • R1 and R2 are hydrogen atoms, R3 is a methyl group, R4 is a 3-methoxypropyloxy group, and R5 is hydrogen, (2) Rl is a methoxy group, R2 is a hydrogen atom, R3 is a methyl group, R4 carboxy group, and R5 is a methyl group,
  • R1 is a difluoromethoxy group
  • R2 is a hydrogen atom
  • R3 is a methoxy group
  • R4 force methoxy group
  • R5 is a hydrogen atom
  • R1 and R2 are hydrogen atoms, R3 is a methyl group, R4 is a 2,2,2-trifluoroethyl ethoxy group, and R5 is a hydrogen atom, any one of [14] to [20]
  • a recovery method according to claim 1 is a hydrogen atom, any one of [14] to [20]
  • R1 and R2 are hydrogen atoms, R3 is a methyl group, R4 is a methoxypropoxy group, and R5 is hydrogen,
  • R1 is a difluoromethoxy group
  • R2 is a hydrogen atom
  • R3 is a methoxy group
  • R5 is a hydrogen atom
  • R1 and R2 are hydrogen atoms
  • R3 is a methyl group
  • R4 is a 2,2,2-trifluoroethyloxy group
  • R5 is a hydrogen atom.
  • the salt of the compound (X) is not particularly limited as long as it forms a salt with the compound (X) and is pharmacologically acceptable.
  • the inorganic base salt include sodium salts, Alkali metal salts such as potassium salts, alkaline earth metal salts such as calcium salts and magnesium salts, aluminum salts, and ammonium salts can be mentioned.
  • organic base salts include jetylamine salts, diethanolamine salts, isopropyl salts. Examples include amine salts, sec-butylamine salts, cyclopentylamine salts, medalamine salts, N, N, and dibenzylethylenediamine salts.
  • the structural formula of a compound may represent a certain isomer for convenience.
  • the present invention includes isomers and isomer mixtures such as all optical isomers generated in the structure of the compound, and is not limited to the description of the formula for convenience, and may be any one isomer or mixture. Therefore, the compound of the present invention may have an asymmetric sulfoxide group in the molecule, and there may be an optically active form and a racemic form. However, the present invention is not limited to these and includes both. It is.
  • the compound (Y) can be efficiently converted to the compound (X) while suppressing the formation of the compound.
  • the compound (X) is useful as a method for producing a 2-[(pyridine-2-yl) methylsulfiel] 1H-benzimidazole derivative.
  • the raw material compound can be dissolved to some extent and the reaction is not inhibited.
  • halogenated hydrocarbons such as chloroform, dichloromethane, carbon tetrachloride and dichloroethane, or aromatic hydrocarbons such as benzene, toluene and xylene, Esters such as methyl acetate, ethyl acetate, dimethyl carbonate, and jetyl carbonate, aliphatic hydrocarbons such as pentane, hexane, and heptane Selected solvent and alcohol such as methanol and ethanol From the kind A mixed solvent consisting of one selected solvent can be used, and more preferably, toluene, xylene, methyl acetate, ethyl acetate, isopropyl acetate, dimethyl carbonate, dimethyl
  • the oxidizing agent used in the operation of (1) and / or (3) is hydrogen peroxide, peracetic acid, t-ptylnoide mouth peroxide, peroxygen peroxide.
  • 1S is preferably m-chloroperbenzoic acid.
  • the amount of the oxidizing agent used in the operation (1) is preferably less than 1 equivalent relative to the raw material compound (Y). More preferably, it is 0.3, 0.8, and more preferably 0.8 equivalent, and particularly preferably, 0.4, 0.7, and 0.7 equivalent.
  • the amount of the oxidizing agent used in the operation (3) is preferably 1 equivalent to the raw material compound ( ⁇ ) contained in the organic layer ( ⁇ 2).
  • the equivalent is less, more preferably 0.3 to 0.8 equivalent, particularly preferably 0.4 to 0.7 equivalent.
  • the reaction temperature varies depending on the solvent, the raw material compound, the acidifying agent, etc., and is usually -50 to 0 ° C, preferably -30 to -10. ° C.
  • the reaction time varies depending on the solvent, the raw material compound, the oxidizing agent, the reaction temperature, and the like. Usually, the reaction time is 30 minutes to 6 hours, and preferably 1 or less. 2 hours.
  • the alkaline aqueous solution used in the operation (2) can produce a state having a ⁇ of 11.5 or more, and is usually used in this field.
  • a sodium hydroxide aqueous solution or a potassium hydroxide aqueous solution is preferable, and a sodium hydroxide aqueous solution is particularly preferable.
  • the pH in the operation (2) is preferably 11.5 or more, and more preferably pH 13 or more.
  • Isolation of compound (X) can be performed, for example, as follows.
  • Operation (4) An aqueous alkali solution is added to the reaction mixture obtained in operation (3), and the mixture is shaken or stirred at pH 13 or higher, and then allowed to stand to separate the organic layer (A2) and aqueous layer (B2).
  • Operation (6) After adding an organic solvent (eg, halogenated hydrocarbons such as black mouth form, dichloromethane, carbon tetrachloride, dichloroethane, especially dichloromethane) to the aqueous layer (B3), vigorously stirring or shaking vigorously The organic layer was separated to obtain an aqueous layer (B4),
  • an organic solvent eg, halogenated hydrocarbons such as black mouth form, dichloromethane, carbon tetrachloride, dichloroethane, especially dichloromethane
  • Operation (8) Add the same organic solvent to the aqueous layer (B5), stir vigorously or shake vigorously and leave to stand to obtain the organic layer (A4), which is combined with the organic layer (A3), and Add water or sodium bicarbonate water, vigorously stir or shake vigorously, and then leave to stand to remove the aqueous layer, concentrate the organic layer (A5), about 1 equivalent of hydroxide in the organic layer (A5). It is obtained by adding an alkali metal hydroxide such as sodium salt and concentrating.
  • an alkali metal hydroxide such as sodium salt and concentrating.
  • the recrystallization method it does not react with the target compound !, and a single solvent or a plurality of mixed solvents can be used. Specifically, first, the target compound is dissolved in one or more solvents that do not react with the target compound at room temperature or under heating. The target compound can be crystallized from the mixture by allowing the mixture to cool with ice water or at room temperature.
  • optical isomer obtained for the compound (1) according to the present invention can be obtained by a conventional separation means such as recrystallization, diastereomer salt method, enzyme resolution method, various chromatography (eg, thin layer chromatography). , Column chromatography, gas chromatography, etc.) can be purified and isolated.
  • a conventional separation means such as recrystallization, diastereomer salt method, enzyme resolution method, various chromatography (eg, thin layer chromatography). , Column chromatography, gas chromatography, etc.) can be purified and isolated.
  • mcpba Metaclochrome perbenzoic acid
  • HPLC High performance liquid chromatography.
  • the separated dichloromethane layer was washed twice with 5 Oml of water, the obtained dichloromethane layer was cooled, and 4.51 g (18.3 mmol) of mcpba (70.2% purity) was again not allowed to exceed 15 ° C. I added little by little.
  • sodium hydroxide aqueous solution (3.36 g of sodium hydroxide sodium was dissolved in 63 ml of water) was added, and the mixture was allowed to stand with stirring to separate the aqueous layer (aqueous layer-2).
  • Aqueous layer-1 and aqueous layer-2 were combined and washed twice with 67 ml of dichloromethane.
  • the separated dichloromethane layer was washed twice with 5 Oml of water, the obtained dichloromethane layer was cooled, and 4.3 g (17.6 mmol) of mcpba (70.2% purity) was again added. The internal temperature did not exceed 15 ° C. I added little by little. Subsequently, sodium hydroxide aqueous solution (3.36 g of sodium hydroxide sodium was dissolved in 63 ml of water) was added and the mixture was allowed to stand with stirring to separate the aqueous layer (aqueous layer-2). Aqueous layer-1 and aqueous layer-2 were combined and washed twice with 67 ml of dichloromethane.
  • the separated dichloromethane layer was washed twice with 5 Oml of water, the obtained dichloromethane layer was cooled, and 3.79 g (15.4 mmol) of mcpba (70.2% purity) was again not allowed to exceed 15 ° C. I added little by little.
  • sodium hydroxide aqueous solution (3.36 g of sodium hydroxide sodium was dissolved in 63 ml of water) was added, and the mixture was allowed to stand with stirring to separate the aqueous layer (aqueous layer-2).
  • Aqueous layer-1 and aqueous layer-2 were combined and washed twice with 67 ml of dichloromethane.
  • the separated dichloromethane layer was washed twice with 5 Oml of water, the resulting dichloromethane layer was cooled, and 3.61 g (14.7 mmol) of mcpba (70.2% purity) was added again with an internal temperature not exceeding 15 ° C. I added little by little. Then water Aqueous sodium hydroxide (3.36 g of sodium hydroxide was dissolved in 63 ml of water) was added and the mixture was allowed to stand with stirring to separate the aqueous layer (aqueous layer-2). Aqueous layer-1 and aqueous layer-2 were combined and washed twice with 67 ml of dichloromethane.
  • the separated dichloromethane layer was washed twice with 5 Oml of water, the obtained dichloromethane layer was cooled, and 4.3 g (17.6 mmol) of mcpba (70.2% purity) was added again with an internal temperature not exceeding 15 ° C. I added little by little.
  • sodium hydroxide aqueous solution (3.36 g of sodium hydroxide sodium was dissolved in 63 ml of water) was added, and the mixture was allowed to stand with stirring to separate the aqueous layer (aqueous layer-2).
  • Aqueous layer-1 and aqueous layer-2 were combined and washed twice with 67 ml of dichloromethane.
  • Ammonium acetate aqueous solution (ammonium acetate 17. Og dissolved in 132 ml of water) was added, followed by extraction twice with 66 ml of dichloromethane. The dichloromethane layer was washed twice with 85 ml of water, concentrated under reduced pressure, crystallized with 277 ml of acetone, filtered, and crude 2 — [ ⁇ 4 -— (3-methoxypropoxy) —3-methylpyridine-2-yl ⁇ Methylsulfiel] 1H benzimidazole 15.92 g was obtained. Dissolve the crude product in 23 lml of acetone, cool the resulting crystals after filtration, and recrystallize them.
  • the separated dichloromethane layer was washed twice with 5 Oml of water, the obtained dichloromethane layer was cooled, and 4.3 g (17.6 mmol) of mcpba (70.2% purity) was added again with an internal temperature not exceeding 15 ° C. I added little by little.
  • sodium hydroxide aqueous solution (3.36 g of sodium hydroxide sodium was dissolved in 63 ml of water) was added, and the mixture was left to stir to separate the aqueous layer (aqueous layer-2).
  • Aqueous layer-1 and aqueous layer-2 were combined and washed twice with 67 ml of dichloromethane.
  • the separated dichloromethane layer was washed twice with 5 Oml of water, the obtained dichloromethane layer was cooled, and 3.79 g (15.4 mmol) of mcpba (70.2% purity) was again not allowed to exceed 15 ° C. I added little by little.
  • sodium hydroxide aqueous solution (3.36 g of sodium hydroxide sodium was dissolved in 63 ml of water) was added, and the mixture was allowed to stand with stirring to separate the aqueous layer (aqueous layer-2).
  • Aqueous layer-1 and aqueous layer-2 were combined and washed twice with 67 ml of dichloromethane.
  • the separated dichloromethane layer was washed twice with 5 Oml of water, the obtained dichloromethane layer was cooled, and 4.51 g (18.3 mmol) of mcpba (70.2% purity) was again not allowed to exceed 15 ° C. I added little by little.
  • sodium hydroxide aqueous solution (3.36 g of sodium hydroxide sodium was dissolved in 63 ml of water) was added, and the mixture was left to stir to separate the aqueous layer (aqueous layer-2).
  • Aqueous layer-1 and aqueous layer-2 were combined and washed twice with 67 ml of dichloromethane.
  • Ammonium acetate aqueous solution (ammonium acetate 17.
  • the separated dichloromethane layer was washed twice with 5 Oml of water, the obtained dichloromethane layer was cooled, and 4.3 g (17.6 mmol) of mcpba (70.2% purity) was added again with an internal temperature not exceeding 15 ° C. I added little by little.
  • sodium hydroxide aqueous solution (2.35 g of sodium hydroxide sodium was dissolved in 63 ml of water) was added, and the mixture was allowed to stand with stirring to separate the aqueous layer (aqueous layer-2).
  • Aqueous layer-1 and aqueous layer-2 were combined and washed twice with 67 ml of dichloromethane.
  • the separated dichloromethane layer was washed twice with 50 ml of water, the obtained dichloromethane layer was cooled, and 4.33 g (17.6 mmol) of mcpba (70.2% purity) was again added. I added little by little so that there was no.
  • sodium hydroxide aqueous solution (4.70 g of sodium hydroxide sodium was dissolved in 63 ml of water) was added, and the mixture was left to stir to separate the aqueous layer (aqueous layer-2).
  • Aqueous layer-1 and aqueous layer-2 were combined and washed twice with 67 ml of dichloromethane.
  • the separated dichloromethane layer was washed twice with 50 ml of water, the obtained dichloromethane layer was cooled, and 3.79 g (15.4 mmol) of mcpba (70.2% purity) was added again. The internal temperature did not exceed 15 ° C. I added little by little.
  • sodium hydroxide aqueous solution (2.35 g of sodium hydroxide sodium was dissolved in 63 ml of water) was added, and the mixture was left to stir to separate the aqueous layer (aqueous layer-2).
  • Aqueous layer—1 and aqueous layer—2 combined, 67 ml dichloromethane And washed twice.
  • the separated dichloromethane layer was washed twice with 5 Oml of water, the obtained dichloromethane layer was cooled, and 4.33 g (17.6 mmol) of mcpba (70.2% purity) was added again, the internal temperature did not exceed 15 ° C. I added little by little.
  • sodium hydroxide aqueous solution (3.36 g of sodium hydroxide sodium was dissolved in 63 ml of water) was added, and the mixture was allowed to stand with stirring to separate the aqueous layer (aqueous layer-2).
  • Aqueous layer-1 and aqueous layer-2 were combined and washed twice with 67 ml of dichloromethane.
  • the separated dichloromethane layer was washed twice with 5 Oml of water, the obtained dichloromethane layer was cooled, and 4.3 g (17.6 mmol) of mcpba (70.2% purity) was added again with an internal temperature not exceeding 15 ° C. I added little by little.
  • sodium hydroxide aqueous solution (3.36 g of sodium hydroxide sodium was dissolved in 63 ml of water) was added, and the mixture was allowed to stand with stirring to separate the aqueous layer (aqueous layer-2).
  • Aqueous layer-1 and aqueous layer-2 were combined and washed twice with 67 ml of dichloromethane.
  • the separated dichloromethane layer was washed twice with 50 ml of water, and the resulting dichloromethane layer was cooled, and 41.24 g of dichloromethane and 4.39 g (17.8 mmol) of mcpba (70% purity) were added to 24-26. Slowly added at 5 ° C. Then, sodium hydroxide aqueous solution (3.36 g of sodium hydroxide sodium was dissolved in 30 g of water) and 34 g of water were added, and the mixture was allowed to stand with stirring to separate the aqueous layer (aqueous layer-2). Water layer 1 and aqueous layer 2 were combined and washed twice with 89 g of dichloromethane.
  • the separated dichloromethane layer was washed with 220 ml of water, the resulting dichloromethane layer was cooled, dichloromethane 77 ml and mcpba (70% purity) 13.8 g (56. Ommol) 30-30. A little bit at C Then, sodium hydroxide aqueous solution (10.2 g of sodium hydroxide sodium was dissolved in 92 ml of water) and 11 ml of water were added, and the mixture was allowed to stand with stirring to separate the aqueous layer (aqueous layer-2).
  • the separated dichloromethane layer was washed with 100 ml of water, the obtained dichloromethane layer was cooled, and 25 ml of dichloromethane and 5.5 g (22.3 mmol) of mcpba (22.3 mmol) were added little by little at 30 to 25 ° C. .
  • sodium hydroxide aqueous solution (3.9 g of sodium hydroxide sodium was dissolved in 35 ml of water) and 54 ml of water were added, and the mixture was left to stir to separate the aqueous layer (aqueous layer-3).
  • Aqueous layer 1, aqueous layer 2 and aqueous layer 3 were combined and washed twice with 240 ml of dichloromethane.
  • Ammonium acetate aqueous solution (87 g of ammonium acetate dissolved in 467 ml of water) was added and extracted twice with 240 ml of dichloromethane.
  • the dichloromethane layer was washed twice with 350 ml of water, concentrated under reduced pressure, 980 ml of warm acetone was added and dissolved, 207 ml of cold acetone was added thereto, crystallized and filtered.

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

Abstract

L'invention décrit un procédé pour la fabrication efficace du composé (X) suivant, qui est utile en tant qu’intermédiaire de médicaments, à partir du composé (Y) suivant, tout en inhibant la génération de sous-produits. Le procédé, qui sert à la fabrication d’un composé de formule (X): (X) (où R1 et R2 sont les mêmes ou sont différents et chacun représente un hydrogène, méthoxy ou difluorométhoxy; R3 représente un méthyle ou méthoxy; R4 représente un méthoxy, 2,2,2-trifluoroéthoxy, ou 3-méthoxypropoxy; et R5 représente un hydrogène ou méthyle), se caractérise du fait qu’il comprend les opérations suivantes: ajout d’un agent oxydant à un composé de la formule (Y): (Y) dans un solvant organique non miscible à l’eau et mise en réaction des ingrédients pour obtenir un mélange réactionnel; ajout d’une solution aqueuse alcaline au mélange réactionnel obtenu, secousse ou agitation du mélange résultant à un pH de 13,0 ou plus, puis repos du mélange et, de ce fait, séparation en une couche organique (A1) et une couche aqueuse (B1); et ajout d’un agent oxydant à la couche organique (A1) obtenue et mise en réaction du mélange.
PCT/JP2005/015123 2004-08-20 2005-08-19 Procédé pour la fabrication d’un dérivé de benzimidazole Ceased WO2006019151A1 (fr)

Priority Applications (1)

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JP2006531865A JP4987477B2 (ja) 2004-08-20 2005-08-19 ベンズイミダゾール誘導体の製造方法

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JP2004-240357 2004-08-20
JP2004240357 2004-08-20

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WO2006019151A1 true WO2006019151A1 (fr) 2006-02-23

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Cited By (1)

* 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

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH1171370A (ja) * 1997-06-26 1999-03-16 Eisai Co Ltd ピリジン誘導体の製造法
JPH11124376A (ja) * 1997-08-12 1999-05-11 Jack Edward Baldwin 有機化合物の合成
WO2003008406A1 (fr) * 2001-07-16 2003-01-30 Janssen Pharmaceutica N.V. Procede ameliore de preparation de composes de type benzimidazole

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH1171370A (ja) * 1997-06-26 1999-03-16 Eisai Co Ltd ピリジン誘導体の製造法
JPH11124376A (ja) * 1997-08-12 1999-05-11 Jack Edward Baldwin 有機化合物の合成
WO2003008406A1 (fr) * 2001-07-16 2003-01-30 Janssen Pharmaceutica N.V. Procede ameliore de preparation de composes de type benzimidazole

Cited By (1)

* 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

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JP4987477B2 (ja) 2012-07-25

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