EP0329719A1 - Procede pour la preparation de derives d'acide carboxylique de quinoleine - Google Patents

Procede pour la preparation de derives d'acide carboxylique de quinoleine

Info

Publication number
EP0329719A1
EP0329719A1 EP88904603A EP88904603A EP0329719A1 EP 0329719 A1 EP0329719 A1 EP 0329719A1 EP 88904603 A EP88904603 A EP 88904603A EP 88904603 A EP88904603 A EP 88904603A EP 0329719 A1 EP0329719 A1 EP 0329719A1
Authority
EP
European Patent Office
Prior art keywords
general formula
compound
hydrogen
process according
stands
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
EP88904603A
Other languages
German (de)
English (en)
Inventor
István HERMECZ
Géza KERESZTURI
Lelle Vasv Ri
Gnes Horv Th
Mária BALOGH
Péter RITLI
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.)
Chinoin Private Co Ltd
Original Assignee
Chinoin Gyogyszer es Vegyeszeti Termekek Gyara Zrt
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
Priority claimed from HU285887A external-priority patent/HU200175B/hu
Priority claimed from HU873146A external-priority patent/HU199822B/hu
Application filed by Chinoin Gyogyszer es Vegyeszeti Termekek Gyara Zrt filed Critical Chinoin Gyogyszer es Vegyeszeti Termekek Gyara Zrt
Publication of EP0329719A1 publication Critical patent/EP0329719A1/fr
Ceased legal-status Critical Current

Links

Classifications

    • 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

Definitions

  • This invention rel ates to a new process for the preparation of 1-substituted-7-(optionally substituted piperazine )-6-f luoro-8-(optionally fl uoro-substituted)-4-oxo-1 , 4- dihydro-quinoline-3-carboxylic acid derivatives of the general Formula I
  • R 1 stands for phenyl being optionally substituted by 1 or 2 halogen atoms, or a group of the general Formula - -CH 2 CR 6 R 7 R 8 (wherein R 6 , R 7 and R 8 stand for hydrogen or halogen);
  • R 2 stands for piperazlnyl or 4-methyl-piperazinyl;
  • R 3 stands for hydrogen or fluorine.
  • These compounds can be prepared by reacting 1-substituted phenyl-6-fluoro-7-chloro-4- oxo-1,4-dihydro-quinoline-3-carboxylic acid and cyclic amines in the presence of a solvent at a temperature of 100 °C for 20 hours (European patent specification 131839, J . Med. Chem. 1985, 1558., J . Med. Chem. 1987. 504.).
  • acetone methyl ethyl ketone
  • an ether e.g. dioxane, tetrahydrofuran, diethyl ether
  • an ester e.g. ethyl acetate, methyl acetate, ethyl propionate
  • a sulfoxide e.g. dimethyl sulfoxide
  • an alcohol e.g. methanol, ethanol, 1-decanol, butanol
  • an organic or inorganic base may be used. From the group of organic bases trialkyl amines (e.g. triethyl amine, tributyl amine), cyclic amines (e.g. pyridine, 1,5-diazabicyclo/5,4,0/undec-5-ene, 1,5-diazabicyclo/4.3.0/- non-5-ene, 1,4-diazabicyclc/2.2.2/octane) can be mentioned, while as inorganic base preferably hydroxides or carbonates of alkali or alkaline earth metals can be applied.
  • acid binding agent advantageously potassium carbonate, potassium hydrogen carbonate, sodium hydroxide, calcium hydroxide, etc. or an excess of the amine of the general Formula III can be used.
  • the boron derivative of the general Formula II and the amine of the general Formula III can be reacted at a temperature between 0 and 200 °C, depending on the solvent used.
  • the reaction time may vary between half an hour and 10 hours. The reaction time depends on the reaction temperature, too. If the reaction is carried out at higher temperature, the reaction time can be shortened.
  • the above reaction conditions are preferable values and other conditions may be used as well.
  • the compounds of the general Formula IV can be hydrolysed to the desired quinoline-3-carboxylic acids of the general Formula I, after or without isolation, under acidic or basic conditions.
  • the compound of the general Formula IV pre verted into pharmaceu tically acceptable salts thereof in a known manner.
  • acid addition salts can be formed, e.g. salts formed with hydrogen halides, sulfonic acids, sulfuric acid or organic acids.
  • One may form preferably chlorides, bromides, aryl sulfonates, methane sulfonates, maleates, fumarates, benzoates, etc.
  • the compounds of the general Formula I form salts with alkali or alkaline earth metals or other metal ions as well. Accordingly the sodium, potassium, magnesium, silver, copper salts, etc. may be prepared.
  • the compounds of the general Formula I and pharmaceutically acceptable salts thereof can be converted into hydrates (e.g. hemihydrates, trihydrates, etc.) by methods known per se.
  • the starting materials of the general Formula II can be prepared by reacting 1-phenyl-6-fluoro-7-chloro-4-oxo-1,4- dihydro-quinoline-3-carboxylic acid (European patent specification 131.839) or 1-ethyl-6,7,8-trifluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid (GB patent specification 2.057.440) with a boron derivative (e.g. with a compound of the general Formula V
  • R is halogen or an aliphatic acyloxy group containing 2 to 6 carbon atoms or an aromatic acyloxy group containing 7 to 11 carbon atoms
  • fluoroborate in aqueous or in organic medium.
  • Example 2 1.06 g of (1-ethyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylate-0 3 ,0 4 )-bis- (propionato-0)-boron are reacted with 0.64 g of piperazine in 4 ml of dimethyl sulfoxide. A 6 w /v% of aqueous solution of 6.3 ml of sodium hydroxide are added and the reaction mixture is refluxed for an hour. After filtration the pH value is adjusted to 7 with 96 w /v% acetic acid, 10 ml of water are added and the reaction mixture is cooled overnight. The precipitated crystals are filtered, washed with water and dried.
  • Example 3 1.06 g of (1-ethyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylate-0 3 ,0 4 )-bis- (propionato-0)-boron are reacted with 0.75 g of 1-methyl-piperazine. Thus 0.79 g of 1-ethyl-6,8-difluoro-1,4-dihydro-4-oxo- 7-(1-methyl-piperazino)-quinoline-3-carboxylic acid are obtained. M.p. is 239-240 °C.

Abstract

Nouveau procédé pour la préparation de composés de formule générale (I) (où R1 représente un phényle éventuellement substitué par 1 ou 2 atomes d'halogène, ou un groupe de formule générale CH2CR6R7R8 (dans laquelle R6, R7 et R8 représentent un hydrogène ou un halogène); R2 est pipérazinyle ou 4-méthyle-pipérazinyle; R3 est hydrogène ou fluor) et de leurs sels pharmaceutiquement acceptables. Ce procédé consiste à faire réagir un composé de formule générale (II) (dans laquelle R est un halogène ou groupe acyloxy aliphatique contenant de 2 à 6 atomes de carbone ou bien un groupe acyloxy aromatique contenant de 7 à 11 atomes de carbone, R4 est fluor ou chlore) avec un dérivé de pipérazine de formule générale (III) ( où R5 est hydrogène ou méthyle ou bien son sel et à soumettre le composé ainsi obtenu de formule générale (IV) (où R, R1, R2 et R3 ont les notations précitées) à une hydrolyse après ou sans isolation, et si on le désire, à convertir le composé de formule générale (I) ainsi obtenu en son sel ou à libérer ledit composé de son sel. Les composés de formule générale (I) sont des agents antibactériens connus. L'avantage du procédé décrit est qu'il permet d'obtenir les composés désirés de formule générale (I) de manière simple, avec des rendements élevés et un temps de réaction court.
EP88904603A 1987-06-24 1988-05-20 Procede pour la preparation de derives d'acide carboxylique de quinoleine Ceased EP0329719A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
HU285887A HU200175B (en) 1987-06-24 1987-06-24 Process for producing quinolinecarboxylic acid derivatives
HU285887 1987-06-24
HU873146A HU199822B (en) 1987-07-10 1987-07-10 Process for production of derivatives of quinoline carbonic acid
HU314687 1987-07-10

Publications (1)

Publication Number Publication Date
EP0329719A1 true EP0329719A1 (fr) 1989-08-30

Family

ID=26317564

Family Applications (1)

Application Number Title Priority Date Filing Date
EP88904603A Ceased EP0329719A1 (fr) 1987-06-24 1988-05-20 Procede pour la preparation de derives d'acide carboxylique de quinoleine

Country Status (11)

Country Link
EP (1) EP0329719A1 (fr)
JP (1) JP2693988B2 (fr)
KR (1) KR970005911B1 (fr)
CN (1) CN1025028C (fr)
CA (1) CA1325010C (fr)
CS (1) CS274677B2 (fr)
DK (1) DK84089A (fr)
ES (1) ES2006994A6 (fr)
FI (1) FI91400C (fr)
WO (1) WO1988010253A1 (fr)
YU (1) YU46570B (fr)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4562852A (en) * 1984-08-20 1986-01-07 Britt Franklin J Safety valve
US4606367A (en) * 1985-04-04 1986-08-19 Britt Franklin J Apparatus and method for relieving pressure within a high pressure tank
HU198709B (en) * 1987-04-08 1989-11-28 Chinoin Gyogyszer Es Vegyeszet Process for producing quinoline-carboxylic acid derivatives
DE548224T1 (de) * 1990-09-11 1993-10-14 Schering Corp Verfahren zur herstellung von albutero, sowie von arylglyoxal-, acetal-, hemiacetal- und hydrat-zwischenprodukten.
JP3165742B2 (ja) * 1991-07-16 2001-05-14 中外製薬株式会社 キノロンカルボン酸誘導体の製造方法
US5869661A (en) * 1991-07-16 1999-02-09 Chugai Seiyaku Kabushiki Kaisha Method of producing a quinolonecarboxylic acid derivative
ES2049636B1 (es) * 1992-04-15 1994-12-16 Genesis Para La Investigacion Procedimiento para la preparacion de derivados de acidos quinolincarboxilicos.
ES2077490B1 (es) * 1992-11-18 1996-10-16 Marga Investigacion Esteres trimetilsililicos y solvatos de quelatos de acidos quinolin-3-carboxilicos. preparacion y aplicacion al proceso de quinolonas.
ES2092963B1 (es) * 1995-04-12 1997-12-16 Sint Quimica Sa Procedimiento para la preparacion del acido 1-ciclopropil-6-fluoro-1, 4-dihidro-7-(1s,4s)-5-metil-2,5-diazabiciclo(2.2.1) hept-2-il)-4-oxo-3-quinolincarboxilico y sus sales.
ES2095809B1 (es) * 1995-07-27 1997-12-16 Sint Quimica Sa Procedimiento para la preparacion de acidos naftiridin carboxilicos y sus sales.
FR2916446B1 (fr) 2007-05-24 2009-08-21 Biocodex Sa Nouveau procede de synthese de fluoroquinolones

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS59122470A (ja) * 1982-12-27 1984-07-14 Dai Ichi Seiyaku Co Ltd キノリン−３−カルボン酸誘導体の製造法
NZ208470A (en) * 1983-07-18 1988-06-30 Abbott Lab 6-fluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid derivatives and antibacterial compositions containing such

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO8810253A1 *

Also Published As

Publication number Publication date
CN1032166A (zh) 1989-04-05
YU121788A (en) 1989-12-31
KR970005911B1 (ko) 1997-04-22
KR890701564A (ko) 1989-12-21
CN1025028C (zh) 1994-06-15
JP2693988B2 (ja) 1997-12-24
CS412388A2 (en) 1990-11-14
YU46570B (sh) 1993-11-16
FI91400B (fi) 1994-03-15
WO1988010253A1 (fr) 1988-12-29
FI890723A0 (fi) 1989-02-15
JPH02500366A (ja) 1990-02-08
FI890723A (fi) 1989-02-15
DK84089D0 (da) 1989-02-23
FI91400C (fi) 1994-06-27
ES2006994A6 (es) 1989-05-16
CS274677B2 (en) 1991-09-15
CA1325010C (fr) 1993-12-07
DK84089A (da) 1989-02-23

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