WO1988010253A1 - Process for the preparation of quinoline carboxylic acid derivatives - Google Patents
Process for the preparation of quinoline carboxylic acid derivatives Download PDFInfo
- 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
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- general formula
- stands
- compound
- hydrogen
- process according
- Prior art date
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.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Quinoline Compounds (AREA)
Abstract
Description
Claims
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1019890700325A KR970005911B1 (en) | 1987-06-24 | 1988-05-20 | Process for preparing quinoline carboxylic acid derivatives |
SU884613512A RU2049783C1 (en) | 1987-06-24 | 1988-05-20 | Method of synthesis of quinoline carboxylic acid derivatives or their pharmaceutically acceptable salts |
FI890723A FI91400C (en) | 1987-06-24 | 1989-02-15 | Process for the preparation of quinoline carboxylic acid derivatives |
DK084089A DK84089D0 (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 |
---|---|---|---|
HU285887A HU200175B (en) | 1987-06-24 | 1987-06-24 | Process for producing quinolinecarboxylic acid derivatives |
HU2858/87 | 1987-06-24 | ||
HU3146/87 | 1987-07-10 | ||
HU873146A HU199822B (en) | 1987-07-10 | 1987-07-10 | Process for production of derivatives of quinoline carbonic acid |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1988010253A1 true WO1988010253A1 (en) | 1988-12-29 |
Family
ID=26317564
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/HU1988/000036 WO1988010253A1 (en) | 1987-06-24 | 1988-05-20 | Process for the preparation of quinoline carboxylic acid derivatives |
Country Status (11)
Country | Link |
---|---|
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) | DK84089D0 (en) |
ES (1) | ES2006994A6 (en) |
FI (1) | FI91400C (en) |
WO (1) | WO1988010253A1 (en) |
YU (1) | YU46570B (en) |
Cited By (7)
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 |
Families Citing this family (4)
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 |
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. |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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 |
-
1988
- 1988-05-20 EP EP88904603A patent/EP0329719A1/en not_active Ceased
- 1988-05-20 WO PCT/HU1988/000036 patent/WO1988010253A1/en not_active Application Discontinuation
- 1988-05-20 JP JP63504328A patent/JP2693988B2/en not_active Expired - Lifetime
- 1988-05-20 KR KR1019890700325A patent/KR970005911B1/en not_active IP Right Cessation
- 1988-06-14 CS CS412388A patent/CS274677B2/en unknown
- 1988-06-21 ES ES8801926A patent/ES2006994A6/en not_active Expired
- 1988-06-23 YU YU121788A patent/YU46570B/en unknown
- 1988-06-23 CA CA000570183A patent/CA1325010C/en not_active Expired - Fee Related
- 1988-06-24 CN CN88103892A patent/CN1025028C/en not_active Expired - Fee Related
-
1989
- 1989-02-15 FI FI890723A patent/FI91400C/en not_active IP Right Cessation
- 1989-02-23 DK DK084089A patent/DK84089D0/en not_active Application Discontinuation
Non-Patent Citations (2)
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)
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 |
Also Published As
Publication number | Publication date |
---|---|
FI91400C (en) | 1994-06-27 |
EP0329719A1 (en) | 1989-08-30 |
FI890723A (en) | 1989-02-15 |
KR970005911B1 (en) | 1997-04-22 |
JP2693988B2 (en) | 1997-12-24 |
FI91400B (en) | 1994-03-15 |
CS412388A2 (en) | 1990-11-14 |
YU121788A (en) | 1989-12-31 |
CN1025028C (en) | 1994-06-15 |
CS274677B2 (en) | 1991-09-15 |
FI890723A0 (en) | 1989-02-15 |
DK84089A (en) | 1989-02-23 |
YU46570B (en) | 1993-11-16 |
CA1325010C (en) | 1993-12-07 |
CN1032166A (en) | 1989-04-05 |
ES2006994A6 (en) | 1989-05-16 |
JPH02500366A (en) | 1990-02-08 |
DK84089D0 (en) | 1989-02-23 |
KR890701564A (en) | 1989-12-21 |
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