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WO2000027841A1 - Procede de preparation de derives de sulfure - Google Patents

Procede de preparation de derives de sulfure Download PDF

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Publication number
WO2000027841A1
WO2000027841A1 PCT/KR1998/000354 KR9800354W WO0027841A1 WO 2000027841 A1 WO2000027841 A1 WO 2000027841A1 KR 9800354 W KR9800354 W KR 9800354W WO 0027841 A1 WO0027841 A1 WO 0027841A1
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WO
WIPO (PCT)
Prior art keywords
group
carbons
linear
type
branched alkyl
Prior art date
Application number
PCT/KR1998/000354
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English (en)
Inventor
Geun-Jho Lim
Dong-Sung Kim
Nung-Min Yoon
Original Assignee
Dong-A Pharmaceutical Co., 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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Publication date
Application filed by Dong-A Pharmaceutical Co., Ltd. filed Critical Dong-A Pharmaceutical Co., Ltd.
Priority to PCT/KR1998/000354 priority Critical patent/WO2000027841A1/fr
Priority to AU10548/99A priority patent/AU1054899A/en
Publication of WO2000027841A1 publication Critical patent/WO2000027841A1/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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
    • C07D235/28—Sulfur atoms

Definitions

  • the present invention relates to a method of preparing sulfide derivatives, and more particularly, to a method of preparing sulfide derivatives with high yield.
  • Sulfide derivatives are precursors of omeprazole, lansoprazole, pantoprazole, rabeprazole and leminoprazole which have gastric acid secretion inhibition, gastric mucosa protection and antiulcer.
  • the sulflde derivatives preparation are classified into three categories.
  • R is selected from the group consisting of hydrogen; linear or branched alkyl having 1 to 6 carbons; OR 6 ; -O-(CH 2 ) m -OR 7 ; and -NR 8 R 9 , wherein m is an integer of 1 to 6, R 6 is selected from the group consisting of hydrogen; linear or branched alkyl having 1 to 6 carbons; and linear or branched alkyl having 1 to 6 carbons, substituted with 1 to 5 halogen atoms, R 7 is selected from the group consisting of hydrogen; linear or branched alkyl having 1 to 6 carbons; and an usual alcohol protective group, and R 8 and R 9 are same or different and are each selected from the group consisting of hydrogen; and, linear or branched alkyl having 1 to 6 carbons,
  • R 2 and R 3 are same or different and each selected from the group consisting of hydrogen; linear or branched alkyl having 1 to 6 carbons; and OR 6 , and
  • R 4 and R 5 are same or different and each selected from the group consisting of hydrogen; linear or branched alkyl having 1 to 6 carbons; -OR 10 ; and -COOR 6 , wherein R 10 is selected from the group consisting of hydrogen; linear or branched alkyl having 1 to 6 carbons; and methyl group substituted with 1 to 3 halogen atoms.
  • R ⁇ R 2 , R 3 , R 4 and R 5 have the meanings given above and X represents an usual leaving group.
  • R R 2 , R 3 , R 4 and R 5 have the meanings given above and M represents lithium, sodium and potassium, Y represents chlorine, bromine, iodine, methanesulfonyloxy and paratoluenesulfonyloxy, and n is an integer of 0- 1.
  • a method of preparing sulfide derivatives of formula 1 including the steps of reacting a compound of formula 5 with a compound of formula 6 or a hydrochloride salt thereof in the presence of a borohydride-based compound selected from the group consisting of a borohydride exchange resin and (R 11 ) 4 N + BH 4 " (wherein R ⁇ is linear or branched lower alkyl having 1 to 6 carbons) in a solvent.
  • the present invention provides a method of preparing sulfide derivatives of formula 2 including the steps of reacting a compound of formula 5 with a compound of formula 10 or a hydrochloride salt thereof in the presence of a borohydride-based compound selected from the group consisting of a borohydride exchange resin and (R 11 ) 4 N + BH 4 " (wherein R ⁇ is linear or branched lower alkyl having 1 to 6 carbons) in a solvent, [formula 1]
  • R 1 is selected from the group consisting of hydrogen; linear or branched alkyl having 1 to 6 carbons; R 6 ; -O-(CH 2 ) m -OR 7 ; and -NR 8 R 9 , wherein m is an integer of 1 to 6,
  • R 6 is selected from the group consisting of hydrogen; linear or branched alkyl having 1 to 6 carbons; and linear or branched alkyl having 1 to 6 carbons, substituted with 1 to 5 halogen atoms
  • R 7 is selected from the group consisting of hydrogen; linear or branched alkyl having 1 to 6 carbons; and an usual alcohol protective group
  • R 8 and R g are same or different and are each selected from the group consisting of hydrogen; and linear or branched alkyl having 1 to 6 carbons,
  • R 2 and R 3 are same or different and each selected from the group consisting of hydrogen; linear or branched alkyl having 1 to 6 carbons; and OR 6 ,
  • R 4 and R 5 are same or different and each selected from the group consisting of hydrogen; linear or branched alkyl having 1 to 6 carbons; -OR 10 ; and -COOR 6 , wherein R 10 is selected from the group consisting of hydrogen; linear or branched alkyl having 1 to 6 carbons; and methyl group substituted with 1 to 3 halogen atoms, and
  • X represents an usual leaving group.
  • the present invention provides a method of preparing sulfide derivatives in the presence of borohydride-based compound.
  • a compound of formula 5 reacts with a compound of formula 6 or a hydrochloride salt thereof in the presence of a borohydride- based compound selected from the consisting of a borohydride exchange resin or (R 11 ) 4 N + BH 4 " (wherein R ⁇ is linear or branched lower alkyl having 1 to 6 carbons, for example, tetrabuthylammoniumborohydride) in suitable solvent, thereby obtaining sulfide derivatives of formula 1.
  • a compound of formula 10 is used instead of the compound of formula 6, sulflde derivatives of formula 2 may be obtained, [formula 1]
  • R ⁇ is selected from the group consisting of hydrogen; and, linear or branched alkyl having 1 to 6 carbons; OR 6 ; -O-(CH 2 ) m -OR 7 ; and -
  • R 6 is selected from the group consisting of hydrogen; linear or branched alkyl having 1 to 6 carbons; and linear or branched alkyl having 1 to 6 carbons, substituted with 1 to 5 halogen atoms, for example 2,2,2-trifluoroethyl
  • R 7 is selected from the group consisting of hydrogen; linear or branched alkyl having 1 to 6 carbons; and an usual alcohol protective group such as trialkylsilyl, benzyl, methoxyethyl, acethyl and benzyloxycarbonyl, and R 8 and R 9 are same or different and each selected from the group consisting of hydrogen; linear or branched alkyl having 1 to 6 carbons,
  • R 2 and R 3 are same or different and each selected from the group consisting of hydrogen; linear or branched alkyl having 1 to 6 carbons; and OR 6 , R 4 and R 5 are same or different and each selected from the group consisting of hydrogen; linear or branched alkyl having 1 to 6 carbons; -OR 10 ; and -COOR 6 , where R 10 is selected from the group consisting of hydrogen; linear or branched alkyl having 1 to 6 carbons; and methyl group substituted with 1 to 3 halogen atoms, and X represents an usual leaving group such as halogen, for example bromine, chlorine, iodine, lower alkylsulfonyloxy and arylsulfonyloxy.
  • halogen for example bromine, chlorine, iodine, lower alkylsulfonyloxy and arylsulfonyloxy.
  • borohydride-based compound Owing to the use of borohydride-based compound, a pure sulflde derivatives may be obtained without further purification.
  • borohydride exchange resin when borohydride exchange resin is used for the borohydride-based compound, a very pure may be obtained.
  • the borohydride exchange resin is used for the borohydride-based compound because the yield of the product is very high.
  • the borohydride exchange resin is prepared by reacting an amberite IRA 400-X type resin with sodium borohydride (NaBH 4 ) in an aqueous solution according to the conventional method (J. Chem. Soc. Chem. Comm. 1997, 915, U. S. Patent No. 4,107,099).
  • an amberite IRA 416-X type resin For preparing borohydride exchange resin, an amberite IRA 416-X type resin, an amberite IRA 420-X type resin, an amberite IRA 900-X type resin, an amberite IRA 904-X type resin, an amberite IRA 910-X type resin, an amberite CG 400-X type resin, an amberite CG400- ll-X type resin, an amberite IRA 743-X type resin, an amberlyst A-26-X type resin and an amberlyst A-27-X type resin may be used.
  • X is selected from the group consisting of Cl “ , Br, F “ , I “ , CN “ , HO “ , NO 2 " , NaCO 3 ⁇ , " SCN and acetate.
  • the solvent includes linear or branched lower alcohol having 1 to 6 carbons and it is preferred to use methanol as the solvent.
  • the reaction temperature is 0 ° C to reflux temperature of the solvent.
  • the yield of compounds of 1 and 2 is very high and it is not required to perform further process such as extraction and purification after terminating reaction. Furthermore, after terminating reaction, the used resin can be repeatedly used by washing it with diluted hydrochloric acid so that the production cost is reduced.
  • the molecular structure is confirmed by determining Infrared spectrometry, ultraviolet-visible spectrometry, nuclear resonance spectrometry or mass spectrometry and comparing calculated and found values of elemental analysis.
  • 5-methoxy-2-mercaptobenzimidazole (20.28 g, 112.56 mmol)
  • a borohydride exchange resin (BER) prepared by IRA400-CI " type resin (46.58 g, 135.07 mmol)
  • 3,5-dimethyl-4-methoxypyridyl-2-methylchloride (20.86 g, 112,56 mmol) were added to methanol (550 ml) and reflux-shaken for 1 hour.
  • hydrochloride salt thereof instead of 3,5-dimethyl-4-methoxypyridyl-2-methylchloride, instead of 3,5-dimethyl-4-methoxypyridyl-2-methylchloride, hydrochloride salt thereof may be used.
  • Example 12 A sulfide derivative was prepared by the same procedure in Example 1 except that (n-Bu) 4 N + CI " was used. The reaction temperature and times, and the yield are shown in Table 1. [Table 1]
  • IRA 400-CI " type resin (15.75 g, 45.52 mmol), 3-methyl-4-(2,2,2- trifluoroethoxy)pyridyl-2-methylchloride (6.0 g, 25.04 mmol) were added to methanol (200 ml) and reflux-shaken for 50 minutes. In the step, instead of
  • Example 24 A sulfide derivative was prepared by the same procedure in Example 13 except that (n-Bu) 4 N + CI " was used..
  • a product was prepared by the same procedure in Example 1 except that 4-(3-methoxypropoxy)-3-methylpyridyl-2-methylchloride and 2- mercaptobenzimidazole were used.
  • a hydrochloride salt thereof instead of 4-(3- methoxypropoxy)-3-methylpyridyl-2-methylchioride, a hydrochloride salt thereof may be used.
  • Example 27 Preparation of 2-[4-(3-hydroxypropoxy)-3-methyl- 2-pyridyl]methylthio-1 H-benzimidazole A product was prepared by the same procedure in Example 1 except that 4-(3-hydroxypropoxy)3-methyipyridyl-2-methylchloride and 2- mercaptobenzimidazole were used. In the example, instead of 4-(3- hydroxypropoxy)3-methylpyridyl-2-methylchloride, a hydrochloride salt thereof may be used.
  • Example 28 Preparation of 2-[2-(N-isobutyl-N-methylamino)benzyl]thio-1 H-benzimidazole A product was prepared by the same procedure in Example 1 except that 2-(N-isobutyl-N-methylamino)benzylchloride and 2- mercaptobenzimidazole were used. In the example, instead of 2-(N-isobutyl- N-methylamino)benzylchloride, a hydrochloride salt thereof may be used.

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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 concerne un procédé de préparation de dérivés de sulfure. Selon le procédé, une résine d'échange de borohydrure ou (R11)4N+BH4- est utilisée afin d'assurer une production élevée de dérivés de sulfure par le biais d'un procédé d'obtention simple.
PCT/KR1998/000354 1998-11-06 1998-11-06 Procede de preparation de derives de sulfure WO2000027841A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
PCT/KR1998/000354 WO2000027841A1 (fr) 1998-11-06 1998-11-06 Procede de preparation de derives de sulfure
AU10548/99A AU1054899A (en) 1998-11-06 1998-11-06 Method of preparing sulfide derivatives

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/KR1998/000354 WO2000027841A1 (fr) 1998-11-06 1998-11-06 Procede de preparation de derives de sulfure

Publications (1)

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WO2000027841A1 true WO2000027841A1 (fr) 2000-05-18

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008102145A3 (fr) * 2007-02-21 2008-11-13 Cipla Ltd Procédé pour la préparation de ésoméprazole magnésium dihydraté
CN102675285A (zh) * 2012-06-02 2012-09-19 大连理工大学 一种纯水相制备雷贝拉唑钠的方法

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SU509595A1 (ru) * 1974-01-04 1976-04-05 Ордена Трудового Красного Знамениинститут Органического Синтезаан Латвийской Сср Способ получени производныхтетрагидропиридина
US4107099A (en) * 1977-02-10 1978-08-15 Ventron Corporation Borohydride exchange resins and their uses as reducing agents and in preparation of volatile metal hydrides
US4255431A (en) * 1978-04-14 1981-03-10 Aktiebolaget Hassle Gastric acid secretion inhibiting substituted 2-(2-benzimidazolyl)-pyridines, pharmaceutical preparations containing same, and method for inhibiting gastric acid secretion
GB2134523A (en) * 1983-02-11 1984-08-15 Haessle Ab Novel pharmacologically active compounds
US4472409A (en) * 1981-11-05 1984-09-18 Byk Gulden Lomberg Chemische Fabrik Gesellschaft Mit Beschrankter Haftung 2-Pyridylmethyl thio(sulfinyl)benzimidazoles with gastric acid secretion inhibiting effects
GB2163747A (en) * 1984-08-31 1986-03-05 Nippon Chemiphar Co Benzimidazole derivatives
EP0204215A1 (fr) * 1985-05-24 1986-12-10 G.D. Searle & Co. [(1H-benzimidazol-yl-2-sulfonyl)méthyl]-2-benzèneamines
KR900001164B1 (ko) * 1987-07-09 1990-02-27 주식회사 삼양사 테트라 하이드로 퓨란의 회수 및 정제방법

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SU509595A1 (ru) * 1974-01-04 1976-04-05 Ордена Трудового Красного Знамениинститут Органического Синтезаан Латвийской Сср Способ получени производныхтетрагидропиридина
US4107099A (en) * 1977-02-10 1978-08-15 Ventron Corporation Borohydride exchange resins and their uses as reducing agents and in preparation of volatile metal hydrides
US4255431A (en) * 1978-04-14 1981-03-10 Aktiebolaget Hassle Gastric acid secretion inhibiting substituted 2-(2-benzimidazolyl)-pyridines, pharmaceutical preparations containing same, and method for inhibiting gastric acid secretion
US4472409A (en) * 1981-11-05 1984-09-18 Byk Gulden Lomberg Chemische Fabrik Gesellschaft Mit Beschrankter Haftung 2-Pyridylmethyl thio(sulfinyl)benzimidazoles with gastric acid secretion inhibiting effects
GB2134523A (en) * 1983-02-11 1984-08-15 Haessle Ab Novel pharmacologically active compounds
GB2163747A (en) * 1984-08-31 1986-03-05 Nippon Chemiphar Co Benzimidazole derivatives
EP0204215A1 (fr) * 1985-05-24 1986-12-10 G.D. Searle & Co. [(1H-benzimidazol-yl-2-sulfonyl)méthyl]-2-benzèneamines
KR900001164B1 (ko) * 1987-07-09 1990-02-27 주식회사 삼양사 테트라 하이드로 퓨란의 회수 및 정제방법

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008102145A3 (fr) * 2007-02-21 2008-11-13 Cipla Ltd Procédé pour la préparation de ésoméprazole magnésium dihydraté
JP2010519284A (ja) * 2007-02-21 2010-06-03 シプラ・リミテッド エソメプラゾールマグネシウム二水和物の調製方法
US8394963B2 (en) 2007-02-21 2013-03-12 Cipla Limited Process for the preparation of esomeprazole magnesium dihydrate
KR101522865B1 (ko) * 2007-02-21 2015-05-26 시플라 리미티드 에소메프라졸 마그네슘 2수화물의 형태 a의 제조방법
CN102675285A (zh) * 2012-06-02 2012-09-19 大连理工大学 一种纯水相制备雷贝拉唑钠的方法

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