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WO1992000280A1 - Derive de quinoline et production de ce derive - Google Patents

Derive de quinoline et production de ce derive Download PDF

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Publication number
WO1992000280A1
WO1992000280A1 PCT/JP1991/000824 JP9100824W WO9200280A1 WO 1992000280 A1 WO1992000280 A1 WO 1992000280A1 JP 9100824 W JP9100824 W JP 9100824W WO 9200280 A1 WO9200280 A1 WO 9200280A1
Authority
WO
WIPO (PCT)
Prior art keywords
formula
compound
protecting group
present
ice
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
Application number
PCT/JP1991/000824
Other languages
English (en)
Japanese (ja)
Inventor
Masahiko Kitano
Ken-Ichi Nakamura
Tatsuhiko Kashima
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.)
Nippon Shinyaku Co Ltd
Original Assignee
Nippon Shinyaku 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 Nippon Shinyaku Co Ltd filed Critical Nippon Shinyaku Co Ltd
Publication of WO1992000280A1 publication Critical patent/WO1992000280A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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 to ring carbon atoms
    • C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
    • C07D215/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3 with oxygen atoms in position 4
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Definitions

  • the present invention relates to an important intermediate of a quinoline carboxylic acid derivative which has an antibacterial action and is useful as a therapeutic agent for various infectious diseases.
  • the compound according to the present invention can be represented by the following general formula [I].
  • R 1 represents hydrogen or a low alkyl
  • R 3 represents a nitrogen atom protecting group
  • R 3 represents a sulfur atom protecting group.
  • the compound [II] and its derivative synthesized from the compound [I] according to the present invention as described below have excellent antibacterial activity, and can be used for infections caused by gram-negative bacteria, intractable chlorophyll infections, Useful for the treatment of Gram-positive bacterial infections.
  • R 1 represents chromium or lower alkyl
  • R 2 represents a protecting group for a nitrogen atom
  • R 3 represents a protecting group for a sulfur atom
  • R represents hydrogen, alkyl, or fuunyl.
  • the derivative [VI] was generated in an amount of 5 to 20%, and the yield was poor. Furthermore, when [VI] is mixed into the reaction product, there is a technical problem that it is difficult to remove and purify the product.
  • an object of the present invention was to develop a production method which is significantly superior to the existing production method.
  • the gist of the present invention lies in the chemical structure itself represented by the general formula [I].
  • the compound [I] of the present invention is a novel compound.
  • the method of the present invention is a novel production method not described in the literature, and its feature lies in using the compound [ ⁇ ] as a raw material.
  • the lower alkyl represented by R ′ is preferably a straight-chain or a lower alkyl having 1 to 4 carbon atoms, for example, methyl, ethyl, ⁇ -propyl, i Soprovir, ⁇ -butyl, isobutyl, sec-butyl, tert-butyl and the like can be mentioned.
  • examples of the nitrogen-protecting group represented by R 2 include alkoxycarbonyl (eg, methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, isobutyloxycarbonyl, etc.), and acyl (eg, , Holmil, acetyl, chloroethyl cetyl, benzoyl, P-anisyl, etc.), vinylidylylcarbonyl, penzyloxycarbonyl, ryjenyl (eg, allyl, etc.), rylarky (eg, Penzyl, diphenylmethyl), 2,4'-dinitrofuryl and the like can be used.
  • alkoxycarbonyl eg, methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, isobutyloxycarbonyl, etc.
  • acyl eg, Holmil, acetyl, chloroethyl cetyl,
  • examples of the sulfur-protecting group represented by R 3 include alkoxymethyl, substituted benzyl, and 2,4-dinitrophenyl. , Disulfide as a dimer of [ ⁇ ], alkylthiomethyl, substituted carbamoyl, difluoromethyl, triphenylmethyl, picolyl, acetamidomethyl,, ⁇ , ⁇ -trifluoro- a-ylaminoethyl, ⁇ , ⁇ -diethoxykarponylethyl, acyl (eg, acetyl, penzyl), benzoylcarbonylcarbonyl, tetrahydrobiranyl, benzylthiomethyl, isobutoxymethyl, etc. Can be mentioned.
  • protecting groups include, for example, methoxymethyl and methoxypentyl.
  • the compound [I] of the present invention has a protective group which is deprotected, if necessary, and has an excellent antibacterial effect by the methods described in, for example, JP-A-63-107990 and JP-A-11-29468Q. It can lead to a nor- nic carboxylic acid derivative.
  • the method of the present invention according to the method for producing the compound [I] of the present invention can be carried out as follows.
  • This ring closure reaction can be performed by a method known per se.
  • a method using heating a method using an acidic substance, or the like can be used.
  • the heating is carried out by heating to 100 to 300, preferably 110 to 150 "C in a solvent without or in a solvent.
  • the solvent include diph Xnyl ether, liquid paraffin, diethylene glycol.
  • the starting compound [ ⁇ ] will be described later as a reference example, and ⁇ can be produced by a known method (eg, JP-A-57-136588).
  • the target compound [I] thus produced is isolated and purified by a method known per se, for example, concentration, liquid conversion, phase transfer, solvent extraction, crystallization, recrystallization, fractionation, chromatography, etc.
  • a method known per se for example, concentration, liquid conversion, phase transfer, solvent extraction, crystallization, recrystallization, fractionation, chromatography, etc.
  • the extract is washed with 2% hydrochloric acid, washed forever, and dried over magnesium sulfate.
  • the solvent was distilled off under reduced pressure to obtain a light brown residue. Purification by silica gel column chromatography gave 2.64 g of the target compound as colorless crystals.
  • the present invention by using [II] as a raw material, by-products are not generated, the reaction proceeds almost quantitatively, and the target compound can be obtained in an extremely high yield and purity.
  • the raw material for obtaining [I] can be produced at very low cost and at low cost compared to the conventional method. Therefore, the present invention provides an industrially advantageous medium body and is a very useful production method.

Landscapes

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

Abstract

L'invention concerne un intermédiaire de la formule (I) servant à la synthèse d'un composé de la formule (III) ayant une excellente action antibactérienne, ainsi qu'un procédé de production de l'intermédiaire de la formule (I) par la cyclisation d'un composé de la formule (II), où R1 représente hydrogène ou alkyle inférieur, R2 représente un groupe protecteur d'un atome d'hydrogène et R3 représente un groupe protecteur d'un atome de soufre.
PCT/JP1991/000824 1990-06-22 1991-06-20 Derive de quinoline et production de ce derive Ceased WO1992000280A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP16506890 1990-06-22
JP2/165068 1990-06-22

Publications (1)

Publication Number Publication Date
WO1992000280A1 true WO1992000280A1 (fr) 1992-01-09

Family

ID=15805261

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1991/000824 Ceased WO1992000280A1 (fr) 1990-06-22 1991-06-20 Derive de quinoline et production de ce derive

Country Status (1)

Country Link
WO (1) WO1992000280A1 (fr)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS57136588A (en) * 1981-02-18 1982-08-23 Nippon Shinyaku Co Ltd Carboxylic acid derivative
JPS58103393A (ja) * 1981-12-12 1983-06-20 Nippon Shinyaku Co Ltd キノリンカルボン酸誘導体
JPS61143363A (ja) * 1984-12-17 1986-07-01 Kyorin Pharmaceut Co Ltd キノロンカルボン酸誘導体の製造方法
JPS63107990A (ja) * 1986-05-14 1988-05-12 Nippon Shinyaku Co Ltd キノリンカルボン酸誘導体

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS57136588A (en) * 1981-02-18 1982-08-23 Nippon Shinyaku Co Ltd Carboxylic acid derivative
JPS58103393A (ja) * 1981-12-12 1983-06-20 Nippon Shinyaku Co Ltd キノリンカルボン酸誘導体
JPS61143363A (ja) * 1984-12-17 1986-07-01 Kyorin Pharmaceut Co Ltd キノロンカルボン酸誘導体の製造方法
JPS63107990A (ja) * 1986-05-14 1988-05-12 Nippon Shinyaku Co Ltd キノリンカルボン酸誘導体

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