WO1996037487A1 - Procede de production de derives de thiazolidine - Google Patents

Procede de production de derives de thiazolidine Download PDF

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Publication number
WO1996037487A1
WO1996037487A1 PCT/JP1996/001021 JP9601021W WO9637487A1 WO 1996037487 A1 WO1996037487 A1 WO 1996037487A1 JP 9601021 W JP9601021 W JP 9601021W WO 9637487 A1 WO9637487 A1 WO 9637487A1
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WO
WIPO (PCT)
Prior art keywords
group
formula
thioproline
general formula
reaction
Prior art date
Application number
PCT/JP1996/001021
Other languages
English (en)
Japanese (ja)
Inventor
Katsuo Shinozaki
Masaaki Eta
Original Assignee
Zeria 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.)
Filing date
Publication date
Application filed by Zeria Pharmaceutical Co., Ltd. filed Critical Zeria Pharmaceutical Co., Ltd.
Priority to AU52891/96A priority Critical patent/AU5289196A/en
Publication of WO1996037487A1 publication Critical patent/WO1996037487A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/04—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D277/06—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members 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 to ring carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to an industrially advantageous production method of a thiazolidine derivative useful as a medicine and an intermediate for producing the same.
  • A represents a methylene group or an ethylene group, and n represents an integer of 0 to 5.
  • the thiazolidine derivative (1) can be produced by reacting a reactive derivative of an indane derivative or a tetralin derivative with an L-thioproline alkyl ester to form an N-acyl-L-thioproline alkyl ester, and then adding the ester to water.
  • a method is known in which N-acyl-L-thioproline is decomposed to react with pyrrolidine (Japanese Patent Application Laid-Open No. 2-226557).
  • an object of the present invention is to provide a thiazolidine derivative ( ⁇ ) useful as a medicament. It is to provide an industrially advantageous production method.
  • the present inventors have conducted various studies to overcome the above-mentioned disadvantages of the conventional production method.
  • N the acylation proceeds selectively and hardly causes any side reactions, and it does not adversely affect the subsequent reaction with pyrrolidine, and the reaction can be performed continuously in the same vessel.
  • the present invention is industrially extremely advantageous, and have completed the present invention.
  • the present invention can be represented by the following reaction formula.
  • the present invention provides a compound represented by the general formula (I) wherein a compound represented by the general formula (I) is reacted with L-thioproline to give a compound represented by the general formula (I), and then pyrrolidine is reacted. It is intended to provide a method for producing a thiazolidine derivative represented by the formula (I). Furthermore, the present invention provides a method for producing a compound represented by the general formula (I), which comprises reacting the compound represented by the general formula (I) with L-thioproline.
  • lower means 1 to 4 carbon atoms
  • lower alkoxy group includes, for example, methoxy group, ethoxy group, propoxy group, isopropoquine group, butoxy group, isobutoxy group, sec-butoxy group Tert-butoxy group and the like.
  • A is particularly preferably a methylene group, and n is particularly preferably 1.
  • the compound in which A is a methylene group and n is 1 is (4R) —3- (indane-1-yl) acetyl-4-((1-pyrrolidinylcarbonyl) thiazolidine ( Synonym: 1- [3- (2- (indanylacetyl) -l-thioprolyl] pyrrolidine) is particularly preferred.
  • the reaction of compound (I) with L-thioproline which is the first step of the method of the present invention, can be usually performed in the presence or absence of a base.
  • the solvent used in the reaction may be any solvent that does not affect the reaction, and examples thereof include halogen-based solvents such as methylene chloride, chloroform, 1,2-dichlorobenzene and the like; acetone, methyl ethyl ketone, etc. Dialkyl ketone solvents; polar aprotic solvents such as N, N-dimethylformamide and dimethylsulfoxide; ether solvents such as ether, tetrahydrofuran and dioxane; benzene solvents such as toluene.
  • halogen-based solvent examples include alkaline metal carbonates such as sodium carbonate, sodium hydrogen carbonate, carbon dioxide lime, hydrogen carbonate lime, and the like; alkaline metal water such as sodium hydroxide, hydroxide lime, lithium hydroxide and the like. Oxides; Trialkylamines such as triethylamine and diisopropylethylamine; pyridines such as pyridine, lutidine and 4-dimethylaminopyridine, with trialkylamines being preferred, and Triethylamine is preferred.
  • the reaction can be usually performed at room temperature or under heating.
  • the reaction is carried out using a condensing agent.
  • the condensing agent includes, for example, 11- (3-dimethylaminopropyl) -13-ethylcarbodimidodicyclohexylcarbodiimide.
  • the reaction between compound (H) and pyrrolidine the carboxylic acid of compound (H) is converted into a highly reactive derivative such as carboxylic acid ester, acid halide, or acid anhydride according to a conventional method. , which can be performed by the same operation as in the first step.
  • the first step and the second step can be performed continuously in the same container without isolating and purifying the compound (I), and the method performed continuously is particularly industrially preferable. Good.
  • L-Tioproline (7.32 g) was dissolved in a mixed solution of triethylamine (16.) and methylene chloride (10), and cooled with water. The ⁇ ⁇ solution was added dropwise, and the mixture was stirred at room temperature for 30 minutes. The reaction solution was poured into ice water, stirred and separated, and the organic layer was washed with 1N hydrochloric acid and saturated saline, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, a mixed solution of ethyl acetate and ⁇ -hexane was added to the residue, and the precipitated crystals were collected by filtration to obtain 13.7 g of the title compound ( c yield, 94.0%).
  • the reaction solution was washed sequentially with 1N hydrochloric acid, ⁇ , saturated aqueous sodium bicarbonate, and saturated saline, and dried over anhydrous magnesium sulfate.
  • the solvent was distilled off under reduced pressure, and the residue was mixed with a mixture of ethyl acetate and ⁇ -hexane.
  • the precipitated crystals were collected by filtration to obtain 638 mg of the title compound. Yield 74.1%.
  • a thiazolidine derivative (IE) can be produced in a high yield and a high purity by a simple operation and without using an expensive reagent. It is a multitude.
  • the total yield from compound (I) to compound (IE) is as high as 84% and racemization does not occur. It is most suitable for strategic production.

Landscapes

  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Thiazole And Isothizaole Compounds (AREA)

Abstract

L'invention porte sur un procédé de production de composés (III), bien plus facilement réalisable, plus économique et plus sur que les procédés habituels, selon le type de réaction (I) L-thioproline (II) pyrrolidine (III), où A représente du méthylène ou de l'éthylène, B représente un halogéno, un alcoxy ou un hydroxy inférieurs et n est un nombre entier valant de 0 à 5.
PCT/JP1996/001021 1995-05-23 1996-04-12 Procede de production de derives de thiazolidine WO1996037487A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU52891/96A AU5289196A (en) 1995-05-23 1996-04-12 Process for producing thiazolidine derivatives

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP7146907A JPH08319280A (ja) 1995-05-23 1995-05-23 チアゾリジン誘導体の製造法
JP7/146907 1995-05-23

Publications (1)

Publication Number Publication Date
WO1996037487A1 true WO1996037487A1 (fr) 1996-11-28

Family

ID=15418273

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1996/001021 WO1996037487A1 (fr) 1995-05-23 1996-04-12 Procede de production de derives de thiazolidine

Country Status (3)

Country Link
JP (1) JPH08319280A (fr)
AU (1) AU5289196A (fr)
WO (1) WO1996037487A1 (fr)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH02207070A (ja) * 1989-02-07 1990-08-16 Zeria Pharmaceut Co Ltd アミノ酸イミド誘導体、それを含有する医薬及び該化合物の製造中間体
JPH02262557A (ja) * 1988-12-08 1990-10-25 Zeria Pharmaceut Co Ltd 縮合ベンゼン誘導体、それを含有する医薬及び該化合物の製造中間体
JPH049367A (ja) * 1990-04-26 1992-01-14 Zeria Pharmaceut Co Ltd アリールアルカノイル誘導体，該化合物の製造中間体及びそれらを含有する医薬
WO1995001352A1 (fr) * 1993-06-30 1995-01-12 Zeria Pharmaceutical Co., Ltd. Derive de thiazolidine et medicament le contenant

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH02262557A (ja) * 1988-12-08 1990-10-25 Zeria Pharmaceut Co Ltd 縮合ベンゼン誘導体、それを含有する医薬及び該化合物の製造中間体
JPH02207070A (ja) * 1989-02-07 1990-08-16 Zeria Pharmaceut Co Ltd アミノ酸イミド誘導体、それを含有する医薬及び該化合物の製造中間体
JPH049367A (ja) * 1990-04-26 1992-01-14 Zeria Pharmaceut Co Ltd アリールアルカノイル誘導体，該化合物の製造中間体及びそれらを含有する医薬
WO1995001352A1 (fr) * 1993-06-30 1995-01-12 Zeria Pharmaceutical Co., Ltd. Derive de thiazolidine et medicament le contenant

Also Published As

Publication number Publication date
AU5289196A (en) 1996-12-11
JPH08319280A (ja) 1996-12-03

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