WO1988010253A1 - Process for the preparation of quinoline carboxylic acid derivatives - Google Patents

Process for the preparation of quinoline carboxylic acid derivatives Download PDF

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Publication number
WO1988010253A1
WO1988010253A1 PCT/HU1988/000036 HU8800036W WO8810253A1 WO 1988010253 A1 WO1988010253 A1 WO 1988010253A1 HU 8800036 W HU8800036 W HU 8800036W WO 8810253 A1 WO8810253 A1 WO 8810253A1
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Prior art keywords
general formula
stands
compound
hydrogen
process according
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PCT/HU1988/000036
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French (fr)
Inventor
István HERMECZ
Géza KERESZTURI
Lelle Vasvári
ágnes Horváth
Mária BALOGH
Péter RITLI
Original Assignee
Chinoin Gyógyszer és Vegyészeti Termékek Gyára Rt.
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
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Priority claimed from HU285887A external-priority patent/HU200175B/en
Priority claimed from HU873146A external-priority patent/HU199822B/en
Application filed by Chinoin Gyógyszer és Vegyészeti Termékek Gyára Rt. filed Critical Chinoin Gyógyszer és Vegyészeti Termékek Gyára Rt.
Priority to SU884613512A priority Critical patent/RU2049783C1/en
Priority to KR1019890700325A priority patent/KR970005911B1/en
Publication of WO1988010253A1 publication Critical patent/WO1988010253A1/en
Priority to FI890723A priority patent/FI91400C/en
Priority to DK084089A priority patent/DK84089A/en
Priority to NO890778A priority patent/NO172743C/en

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    • 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

The invention relates to a new process for the preparation of compounds of general formula (I) (wherein R1 stands for phenyl being optionally substituted by 1 or 2 halogen atoms, or a group of the general formula CH2CR6R7R8 (wherein R6, R7 and R8 stand for hydrogen or halogen); R2 stands for piperazinyl or 4-methyl-piperazinyl; R3 stands for hydrogen or fluorine) and pharmaceutically acceptable salts thereof which comprises reacting a compound of general formula (II) (wherein R stands for halogen or an aliphatic acyloxy group containing 2 to 6 carbon atoms or an aromatic acyloxy group containing 7 to 11 carbon atoms, R4 stands for fluorine or chlorine) with a piperazine derivative of general formula (III) (wherein R5 stands for hydrogen or methyl) or a salt thereof and subjecting the compound of general formula (IV) thus obtained (wherein R, R1, R2 and R3 are as stated above) to hydrolysis after or without isolation and if desired converting the compound of general formula (I) thus obtained into a salt thereof or setting free the same from its salt. The compounds of general formula (I) are known antibacterial agents. The advantage of the process of the present invention is that it makes the desired compounds of general formula (I) available in a simple manner, with high yields and in a short reaction time.

Description

PROCESS FOR THE PREPARATION OF QU INOL INE CARBOXYL IC ACID DERIVATIVES
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
Figure imgf000003_0001
and pharmaceutically acceptable salts thereof.
In the general Formula I R1 stands for phenyl being optionally substituted by 1 or 2 halogen atoms, or a group of the general Formula - -CH2CR6R7R8 (wherein R6, R7 and R8 stand for hydrogen or halogen); R2 stands for piperazlnyl or 4-methyl-piperazinyl; R3 stands for hydrogen or fluorine.
It is known that a group of the 7-sυbstituted- carboxylic derivatives of the general Formula I (wherein R2 stands for piperazinyl, 4-methyl-piperazinyl, R1 stands for a group of the general Formula -CH2CR6R7R8 (wherein R6, R7 and R8 stand for hydrogen or halogen) and R3 stands for fluorine) possesses high antibacterial activity (J.Med. Chem. 1986, 29 , 445; Drugs of Fut. 1984, 9 , 246; 23rd Intersci. Conf. Antimicrob. Agents Chemother. 1983, Abst . 658, 7th Int. Symp. Fut. Trends Chemother. 1986, 86). These compounds can be prepared by reacting 6,7,8-trifluoro-4-cxo-1,4-dihydro-quinoline-3- carboxylic acid and cyclic amines (Belgian patent specification 887874, GB patent specification 2057444, Austrian patent specification 537813 and European patent specification 1064489).
Another group of the 7-substituted-quinoline-3- carboxylic acids of the general Formula I (wherein R1 stands for phenyl optionally substituted by 1 or 2 halogen atoms, R2 stands for piperazinyl or 4-methyl-piperazinyl and R3 stands for hydrogen) has also high antibacterial activity (24th Intersci. Conf. Antimicrob. Agents Chemother, 1984, Abst. 72- 78., Amtimicrob. Agents Chemother. 1987., 619, Antimicrob. Agents Chemother. 1906., 192-208). 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.).
According to the present invention there is provided a new process for the preparation of quinoline-3-carboxylic acid derivatives of the general Formula I (wherein R1 stands for phenyl optionally substituted by 1 or 2 halogen atoms, or a group of the general Formula -CH2CR6R7R8 (wherein R6, R7 and R8 stand for hydrogen cr halogen), R2 stands for piperazinyl, 4-methyl-piperazinyl and R3 stands for hydrogen or fluorine) and pharmaceutically acceptable salts thereof which comprises reacting a compound of the general Formula II
Figure imgf000005_0002
(wherein R stands for halogen, an aliphatic acyloxy group containing 2 to 6 carbon atoms or aromatic acyloxy group containing 7 to 11 carbon atoms, R4 stands for fluorine or chlorine, R1 and R2 are as stated above) with an amine of the general Formula III
Figure imgf000005_0001
(wherein R5 stands for hydrogen or methyl) or a salt thereof and subjecting the compound of the general Formula IV
Figure imgf000006_0001
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) may be used.
As acid binding agent 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. Thus as 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
Figure imgf000008_0001
verted into pharmaceu tically acceptable salts thereof in a known manner. Thus preferably 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.
According to a further aspect of the present invention there are provided new compounds of the general Formula IV (wherein R, R1, R2 and R3 are as stated above).
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
Figure imgf000009_0001
(wherein 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) or with fluoroborate in aqueous or in organic medium.
Further details of the present invention are to be found in the following Examples without limiting the scope of protection to the said Examples.
Example 1
1.59 g of (1-ethyl-6,7,8-trifluoro-1,4-dihydro-4-oxo- quinoline-3-carboxylate-03,04)-difluoro-boron are reacted with 1.29 g of piperazine in 8 ml of dimethyl sulfoxide at 100 °C for 3 hours. A 6 w/v% aqueous solution of 12.6 ml of sodium hydroxide are added and hydrolysis is carried out by heating for 2 hours. The reaction mixture is filtered, the pH value is adjusted to 7 with 96 w/v% acetic acid and diluted with 15 ml of water. The crystalline reaction mixture is cooled overnight and the precipitated crystals are filtered, washed with water and dried. Thus 1.61 g of 1-ethyl-6,8-difluoro-1,4-dihydro-4- oxo-7-piperazino-quinoline-3-carboxylic acid are obtained. M.p. is 234-236 °C.
Analysis for the Formula C 16H 17F2N 3O3 : Calculated: C=56.90% H=5.07% N=12.45% Found: C=56.75% H=5.02% N=12.48%. Example 2
1.95 g of (1-ethyl-6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylate-03,04)-bis(diacetate-0)-boron are reacted with 1.29 g of piperazine in 8 ml of dimethyl sulfoxide at 110 °C for 2 hours. A 3 w/v% aqueous solution of 20 ml of 3 w/v% sodium hydroxide are added. The reaction mixture is re- fluxed for an hour whereupon filtered and the pH value is adjusted to 7 with 96 w/v% acetic acid. After cooling and diluting with 10 ml of water the precipitated crystals are filtered and dried. Thus 1.59 g of ochre coloured 1-ethyl-6,8- difluoro-1,4-dihydro-4-oxo-7-piperazino-quinoline-3-carboxylic acid are obtained. M.p. is 234 °C.
Analysis for the Formula C 16H 17F2N 3O3 : Calculated: C=56.90% H=5.07% N=12.45% Found: C=57.03% H=5.11% N=12.51%.
Example 3
According to Example 2 1.06 g of (1-ethyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylate-03,04)-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.
Figure imgf000012_0001
Example 6
According to Example 3 1.06 g of (1-ethyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylate-03,04)-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.
Analysis for the Formula C17H19F2N3O3 : Calculated: C=58.10% H=5.45% N=11.91% Found: C=57.95% H=5.37% N=11.90%.
Example 7
0.46 g of 1-(4'-fluoro-phenyl)-6-fluoro-7-chloro-1,4- dihydro-4-oxo-quinoline-3-carboxylate-03,04)-bis(acetato-0)- boron are reacted with 0.6 g of N-methyl-piperazine in 5 ml of dimethyl sulfoxide at 110 °C for an hour. 10 ml of 5 w/v%. aqueous sodium hydrogen carbonate solution are added, the reaction mixture is refluxed for 2 hours whereupon the pH value is adjusted to 7 with 96 w/v% acetic acid. The reaction mixture is cooled and the precipitated crystals are filtered and washed with cold water. Thus 3.54 g of 1-(4'-fluorophenyl)-6-fluoro-7-(N-methyl-piperazinyl)-1,4-dihydro-4-oxo- quinoline-3-carboxylic acid are obtained. M.p. is 282-284 °C. The carboxylic acid thus obtained is dissolved in a weak solution of hydrochloride acid under heating, the solution is evaporated in vacuo and thus the hydrochloric salt of 1-(4'- r
: 7
Figure imgf000014_0001

Claims

CLAIMS :
1. Process for the preparation of compounds of the general Formula I
Figure imgf000015_0001
(wherein
R1 stands for phenyl being optionally substituted by 1 or 2 halogen atoms, or a group of the general Formula - CH2CR6R7R8 (wherein R6, R7 and R8 stand for hydrogen or halogen);
R2 stands for piperazinyl or 4-methyl-piperazinyl;
R3 stands for hydrogen or fluorine) and pharmaceutically acceptable salts thereof which comprises reacting a compound of the general Formula II
Figure imgf000016_0001
thus obtained (wherein R, R1, R2 and R3 are as stated above) to hydrolysis after or without isolation and if desired converting the compound of the general Formula I thus obtained into a salt thereof or setting free the same from its salt.
2. Process according to Claim 1 which comprises reacting a compound of the general formula II with an amine of the general Formula III in the presence of an organic solvent, preferably an acid amide, sulfoxide, ketone, alcohol, ether or ester.
3. Process according to Claim 2 which comprises using dimethyl sulfoxide as organic solvent.
4. Process according to Claim 1 which comprises carrying out the reaction of the compounds of the general Formulae II and III in the presence of an acid binding agent.
5. Process according to Claim 4 which comprises using an amine or an excess of the compound of the general Formula VI as acid binding agent.
6. Process according to Claim 1 which comprises carrying out the hydrolysis in acidic medium.
7. Process according to Claim 6 which comprises carrying out the reaction by using an organic or inorganic acid, preferably hydrochloric acid, sulfuric acid or acetic a c i ci .
Figure imgf000018_0001
PCT/HU1988/000036 1987-06-24 1988-05-20 Process for the preparation of quinoline carboxylic acid derivatives WO1988010253A1 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
SU884613512A RU2049783C1 (en) 1987-06-24 1988-05-20 Method of synthesis of quinoline carboxylic acid derivatives or their pharmaceutically acceptable salts
KR1019890700325A KR970005911B1 (en) 1987-06-24 1988-05-20 Process for preparing quinoline carboxylic acid derivatives
FI890723A FI91400C (en) 1987-06-24 1989-02-15 Process for the preparation of quinoline carboxylic acid derivatives
DK084089A DK84089A (en) 1987-06-24 1989-02-23 PROCEDURE AND INTERMEDIATES FOR THE PREPARATION OF QUINOLINE DERIVATIVES AND PHARMACEUTICAL ACCEPTABLE SALTS THEREOF
NO890778A NO172743C (en) 1987-06-24 1989-02-23 PROCEDURE FOR THE PREPARATION OF QUINOLINCARBOXYLIC ACID DERIVATIVES

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
HU2858/87 1987-06-24
HU285887A HU200175B (en) 1987-06-24 1987-06-24 Process for producing quinolinecarboxylic acid derivatives
HU3146/87 1987-07-10
HU873146A HU199822B (en) 1987-07-10 1987-07-10 Process for production of derivatives of quinoline carbonic acid

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

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5091530A (en) * 1987-04-08 1992-02-25 Chinoin Gyogyszer- Es Vegyeszeti Termekek Gyara Rt. Baron chelates of quinoline carboxylic acids
WO1992004314A2 (en) * 1990-09-11 1992-03-19 Schering Corporation Process for preparing albuterol, acetal, hemi-acetal, and hydrates of arylglyoxal intermediates thereof
EP0641782A4 (en) * 1991-07-16 1994-10-17 Chugai Pharmaceutical Co Ltd Process for producing quinolonecarboxylic acid derivative.
ES2077490A1 (en) * 1992-11-18 1995-11-16 Marga Investigacion Trimethyl silicon esters and chelate solvates of quinoline-3-carboxylic acids. Preparation and application to the quinolone process
GR960100116A (en) * 1995-04-12 1996-12-31 Quimica Sintetica S.A. Process for the preparation of 1-cycloprolyl-6-fluoro-1,4- dihydro-7-{(1S,4S)-5-methyl-2,5-diazabicyclo{2,2,1)-hept-2-yl}-4-oxo-3-quinolinocarboxylic acid and the salts.
US5869661A (en) * 1991-07-16 1999-02-09 Chugai Seiyaku Kabushiki Kaisha Method of producing a quinolonecarboxylic acid derivative
EP2138490A1 (en) 2007-05-24 2009-12-30 Biocodex New method for synthesis of fluoroquinolones

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ES2049636B1 (en) * 1992-04-15 1994-12-16 Genesis Para La Investigacion PROCEDURE FOR THE PREPARATION OF QUINOLINCARBOXILIC ACID DERIVATIVES.
ES2095809B1 (en) * 1995-07-27 1997-12-16 Sint Quimica Sa PROCEDURE FOR THE PREPARATION OF NAFTIRIDIN CARBOXYLIC ACIDS AND THEIR SALTS.

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JPS59122470A (en) * 1982-12-27 1984-07-14 Dai Ichi Seiyaku Co Ltd Preparation of quinoline-3-carboxylic acid derivative
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

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Title
CHEMICAL ABSTRACTS, Volume 102, No. 7, issued 1985, February 18 (Columbus, Ohio, USA). Daiichi Seiyaku "1-Ethyl-6-Fluoro-4-oxo-7-(1-Piperazinyl)-1, 4-Dihydroquinoline-3-Carboxylic Acids", see page 605, column 1, the Abstract No. 62 272y. JP, A, 59-122 470 (Daiichi Seiyaku) 14 July 1984. *
CHEMICAL ABSTRACTS, Volume 103, No. 15, issued 1985, October 14 (Columbus, Ohio, USA). Daiichi Seiyaku "Oxazines", see page 730, column 1, the Abstract No. 123 491p. JP, A, 60-78 986 (Daiichi Seiyaku) 04 May 1985. *

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5091530A (en) * 1987-04-08 1992-02-25 Chinoin Gyogyszer- Es Vegyeszeti Termekek Gyara Rt. Baron chelates of quinoline carboxylic acids
WO1992004314A2 (en) * 1990-09-11 1992-03-19 Schering Corporation Process for preparing albuterol, acetal, hemi-acetal, and hydrates of arylglyoxal intermediates thereof
WO1992004314A3 (en) * 1990-09-11 1992-05-29 Schering Corp Process for preparing albuterol, acetal, hemi-acetal, and hydrates of arylglyoxal intermediates thereof
EP0641782A4 (en) * 1991-07-16 1994-10-17 Chugai Pharmaceutical Co Ltd Process for producing quinolonecarboxylic acid derivative.
EP0641782A1 (en) * 1991-07-16 1995-03-08 Chugai Seiyaku Kabushiki Kaisha Process for producing quinolonecarboxylic acid derivative
US5869661A (en) * 1991-07-16 1999-02-09 Chugai Seiyaku Kabushiki Kaisha Method of producing a quinolonecarboxylic acid derivative
ES2077490A1 (en) * 1992-11-18 1995-11-16 Marga Investigacion Trimethyl silicon esters and chelate solvates of quinoline-3-carboxylic acids. Preparation and application to the quinolone process
GR960100116A (en) * 1995-04-12 1996-12-31 Quimica Sintetica S.A. Process for the preparation of 1-cycloprolyl-6-fluoro-1,4- dihydro-7-{(1S,4S)-5-methyl-2,5-diazabicyclo{2,2,1)-hept-2-yl}-4-oxo-3-quinolinocarboxylic acid and the salts.
EP2138490A1 (en) 2007-05-24 2009-12-30 Biocodex New method for synthesis of fluoroquinolones

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YU121788A (en) 1989-12-31
KR970005911B1 (en) 1997-04-22
KR890701564A (en) 1989-12-21
CN1025028C (en) 1994-06-15
JP2693988B2 (en) 1997-12-24
CS412388A2 (en) 1990-11-14
YU46570B (en) 1993-11-16
FI91400B (en) 1994-03-15
FI890723A0 (en) 1989-02-15
JPH02500366A (en) 1990-02-08
FI890723A (en) 1989-02-15
DK84089D0 (en) 1989-02-23
FI91400C (en) 1994-06-27
ES2006994A6 (en) 1989-05-16
CS274677B2 (en) 1991-09-15
EP0329719A1 (en) 1989-08-30
CA1325010C (en) 1993-12-07
DK84089A (en) 1989-02-23

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