WO1990006922A1 - 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
WO1990006922A1
WO1990006922A1 PCT/HU1989/000063 HU8900063W WO9006922A1 WO 1990006922 A1 WO1990006922 A1 WO 1990006922A1 HU 8900063 W HU8900063 W HU 8900063W WO 9006922 A1 WO9006922 A1 WO 9006922A1
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WO
WIPO (PCT)
Prior art keywords
general formula
process according
compound
hydrogen
compounds
Prior art date
Application number
PCT/HU1989/000063
Other languages
English (en)
French (fr)
Inventor
István HERMECZ
Géza KERESZTURI
Lelle Vasvári
ágnes Horváth
Mária BALOGH
Péter RITLI
Judit Sipos
Anikó PAJOR
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
Publication date
Application filed by Chinoin Gyógyszer és Vegyészeti Termékek Gyára Rt. filed Critical Chinoin Gyógyszer és Vegyészeti Termékek Gyára Rt.
Priority to GB9018360A priority Critical patent/GB2245562B/en
Priority to KR1019900701858A priority patent/KR0146335B1/ko
Publication of WO1990006922A1 publication Critical patent/WO1990006922A1/en
Priority to SU904830873A priority patent/RU2044734C1/ru

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
    • C07F5/02—Boron compounds
    • C07F5/022—Boron compounds without C-boron linkages

Definitions

  • This invention relates to a new process for the preparation of 1- (optionally halo-substituted) -ethyl-7- (3, 4, 5-substituted piperazine)-6 , 8-difluoro-4-oxo-l , 4-dihydro-quinoline-3-carboxylic acid derivatives of the general Formula I
  • R 1 and R 3 stand for hydrogen or C 1-4 alkyl
  • R 2 stands for C 1-4 alkyl
  • R 4 , R 5 and R 6 stand for hydrogen or halogen.
  • R 4 , R 5 and R 6 stand for hydrogen or halogen.
  • the advantage of the process of the present invention is that it enables the preparation of the compounds of the general Formula I in a simple manner, with very high yields and in a short reaction time.
  • the boron derivatives of the general Formula IV are new compounds.
  • the boron derivative of the general Formula IV is converted into the desired quinoline-3--carboxylic acid of the general Formula I without isolation.
  • the boron derivatives of the general Formula II can be reacted with the amine of the general Formula III if desired in the presence of an inert organic solvent and an acid binding agent.
  • inert organic solvent preferably an acid amide
  • a ketone e.g. 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
  • a nitrile e.g. acetonitrile
  • halogenated organic solvents e.g. chloroform, dichloroethane
  • an organic or inorganic base may be used.
  • organic bases trialkyl amines (e.g. triethyl amine, tributyl amine), cyclic amines (e.g. pyridine,
  • the boron derivative of the general Formula II and the amine of the general Formula III can be reacted at a temperature between 10 and 200 °C, depending on the solvent used.
  • reaction time may vary between 0,1-10 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 compounds of the general Formula IV precipitates from the reaction mixture e.g. on cooling and can be separated e.g. by filtration or centrifuging, if desired.
  • Basic hydrolysis may be preferably carried out by heating, with the aid of a hydroxide or carbonate of an alkali metal or an alkaline earth metal hydroxide, used as aqueous solution.
  • organic amines e.g. triethyl
  • amine may also be applied in the hydrolysis step.
  • Acidic hydrolysis may preferably be accomplished by using an aqueous mineral acid.
  • One may preferably proceed by hydrolysing a compound of the general Formula IV by heating with an aqueous solution of hydrochloric acid, hydrogen bromide,
  • an organic acid e.g. acetic acid, propionic acid, etc.
  • Hydrolysis of the compounds of the general Formula IV may also be carried out in aqueous medium in the presence of a watermiscible organic solvent.
  • a watermiscible organic solvent e.g. alcohols (e.g. methanol, ethanol), a ketone (e.g. acetone), an ether (e.g.
  • dioxane an acid amide (e.g. dimethyl formamide), a sulfoxide (e.g. dimethyl sulfoxide), or pyridine may be used.
  • acid amide e.g. dimethyl formamide
  • sulfoxide e.g. dimethyl sulfoxide
  • pyridine e.g. pyridine
  • the quinoline-3-carboxylic acid of the general Formula I thus obtained may be isolated e.g. adjusting the pH value of the aqueous solution to a suitable value and separating the precipitated crystals e.g. by filtration or centrifuging or by liophylizing the aqueous reaction mixture.
  • the compounds of the general Formula I can be converted into pharmaceutically 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.
  • 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
  • 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-ethyl-6,7,8-trifluoro-4-oxo-1,4-dihydro -quinoline-3-carboxylic acid (GB patent specification
  • boron derivative e.g. with a compound of the general Formula V ;
  • Example 1 319 g of (1-ethyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylate-O 3 , O 4 )-difluoro-boron are reacted with 50,1 g of 2-methyl-piperazine in 150 ml of dimethyl sulfoxide. Thus 30,6 g of 1-ethyl-6,8-difluoro-1,4-dihydro-4-oxo-7-(3-methyl-piperazino)- -quinoline-3-carboxylic acid are obtained.
  • M.P. is 238-240 oC
  • Example 1 39,9 g of (1-ethyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylate-O 3 , O 4 )-bis-(acetato-O)-boron are reacted with 50,1 g of 2-methyl--piperazine in 150 ml of dimethyl sulfoxide. Thus 30,2 g of 1-ethyl-6,8-difluoro-1,4-dihydro-4-oxo-7-(3-methyl-piperazino)-quinoline-3-carboxylic acid are obtained.
  • Example 1 42 7 g of (1-ethyl-6,7,8-tri- fluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylate-O 3 , O 4 )-bis- (propionato-O)-boron are reacted with 50,1 g of 2-methyl- piperazine.
  • 287 g of 1-ethyl-6,8-difluoro-1,4-dihydro -4-oxo-7-(3-methyl-piperazino)-quinolin-3-carboxylic acid are obtained.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Communicable Diseases (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Oncology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Quinoline Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
PCT/HU1989/000063 1988-12-22 1989-12-15 Process for the preparation of quinoline carboxylic acid derivatives WO1990006922A1 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
GB9018360A GB2245562B (en) 1988-12-22 1989-12-15 Process for the preparation of quinoline carboxylic acid derivatives
KR1019900701858A KR0146335B1 (ko) 1988-12-22 1989-12-15 퀴놀린 카르복실산 유도체의 제조방법
SU904830873A RU2044734C1 (ru) 1988-12-22 1990-08-21 Способ получения хинолинкарбоновой кислоты или ее фармацевтически приемлемых солей и соединение

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
HU886560A HU203746B (en) 1988-12-22 1988-12-22 Process for producing quinoline-carboxylic acid derivatives
HU6560/88 1988-12-22

Publications (1)

Publication Number Publication Date
WO1990006922A1 true WO1990006922A1 (en) 1990-06-28

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ID=10971814

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/HU1989/000063 WO1990006922A1 (en) 1988-12-22 1989-12-15 Process for the preparation of quinoline carboxylic acid derivatives

Country Status (11)

Country Link
JP (1) JP2825641B2 (ko)
KR (1) KR0146335B1 (ko)
CN (1) CN1031190C (ko)
AT (1) AT397385B (ko)
AU (1) AU622256B2 (ko)
FR (1) FR2640974B1 (ko)
GB (1) GB2245562B (ko)
HU (1) HU203746B (ko)
IL (1) IL92821A0 (ko)
WO (1) WO1990006922A1 (ko)
YU (1) YU47215B (ko)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GR960100116A (el) * 1995-04-12 1996-12-31 Quimica Sintetica S.A. Μεθοδος παρασκευης 1-κυκλοπροπυλο-6-φλουορο-1,4-διυδρο-7-[(1s,4s)-5-μεθυλο-2,5-διαζαβικυκλο[2.2.1]-επτ-2-υλο] -4-οξο-3-κουινολινοκαρβοξυλικο οξυ και αλατα αυτων.

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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.
NZ260530A (en) * 1994-05-16 1997-06-24 Nigel Paul Maynard Organoborate complexes of divalent metal; use as timber treament agents

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4550167A (en) * 1983-05-23 1985-10-29 Ethyl Corporation Preparation of 1-alkyl-1,4-dihydro-4-oxo-7-(4-pyridyl)-3-quinoline carboxylic acid
JPS6165882A (ja) * 1984-09-06 1986-04-04 Hokuriku Seiyaku Co Ltd １−エチル−６，８−ジフルオロ−１，４−ジヒドロ−４−オキソ−７−ピペラジニルキノリン−３−カルボン酸エステル誘導体、及びその製造法
JPS6185381A (ja) * 1984-10-04 1986-04-30 Hokuriku Seiyaku Co Ltd １−エチル−６，８−ジフルオロ−１，４−ジヒドロ−４−オキソ−７−ピペラジニルキノリン−３−カルボン酸誘導体の製造法
WO1987003586A1 (en) * 1985-12-09 1987-06-18 Chinoin Gyógyszer és Vegyészeti Termékek Gyára Rt. Process for the preparation of 1-methylamino-quinoline-carboxylic acid derivatives
JPS6419069A (en) * 1987-07-14 1989-01-23 Dainippon Pharmaceutical Co Production of polyhalogenoquinoline derivative

Family Cites Families (5)

* 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
JPS6078986A (ja) * 1983-10-07 1985-05-04 Dai Ichi Seiyaku Co Ltd オキサジン誘導体の製法
CA1306750C (en) * 1985-12-09 1992-08-25 Istvan Hermecz Process for the preparation of quinoline carboxylic acide
US4738800A (en) * 1986-03-26 1988-04-19 Ciba-Geigy Corporation Process for the preparation of 1,4-diamino-2,3-dicyanoanthraquinones
HU198709B (en) * 1987-04-08 1989-11-28 Chinoin Gyogyszer Es Vegyeszet Process for producing quinoline-carboxylic acid derivatives

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4550167A (en) * 1983-05-23 1985-10-29 Ethyl Corporation Preparation of 1-alkyl-1,4-dihydro-4-oxo-7-(4-pyridyl)-3-quinoline carboxylic acid
JPS6165882A (ja) * 1984-09-06 1986-04-04 Hokuriku Seiyaku Co Ltd １−エチル−６，８−ジフルオロ−１，４−ジヒドロ−４−オキソ−７−ピペラジニルキノリン−３−カルボン酸エステル誘導体、及びその製造法
JPS6185381A (ja) * 1984-10-04 1986-04-30 Hokuriku Seiyaku Co Ltd １−エチル−６，８−ジフルオロ−１，４−ジヒドロ−４−オキソ−７−ピペラジニルキノリン−３−カルボン酸誘導体の製造法
WO1987003586A1 (en) * 1985-12-09 1987-06-18 Chinoin Gyógyszer és Vegyészeti Termékek Gyára Rt. Process for the preparation of 1-methylamino-quinoline-carboxylic acid derivatives
JPS6419069A (en) * 1987-07-14 1989-01-23 Dainippon Pharmaceutical Co Production of polyhalogenoquinoline derivative

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GR960100116A (el) * 1995-04-12 1996-12-31 Quimica Sintetica S.A. Μεθοδος παρασκευης 1-κυκλοπροπυλο-6-φλουορο-1,4-διυδρο-7-[(1s,4s)-5-μεθυλο-2,5-διαζαβικυκλο[2.2.1]-επτ-2-υλο] -4-οξο-3-κουινολινοκαρβοξυλικο οξυ και αλατα αυτων.

Also Published As

Publication number Publication date
GB2245562B (en) 1992-12-23
ATA902489A (de) 1993-08-15
AU622256B2 (en) 1992-04-02
HUT52086A (en) 1990-06-28
AU4748090A (en) 1990-07-10
HU203746B (en) 1991-09-30
AT397385B (de) 1994-03-25
FR2640974A1 (ko) 1990-06-29
IL92821A0 (en) 1990-09-17
CN1031190C (zh) 1996-03-06
YU47215B (sh) 1995-01-31
CN1043712A (zh) 1990-07-11
FR2640974B1 (ko) 1994-02-18
JP2825641B2 (ja) 1998-11-18
KR0146335B1 (ko) 1998-08-17
JPH03502803A (ja) 1991-06-27
KR910700245A (ko) 1991-03-14
YU243789A (en) 1991-02-28
GB2245562A (en) 1992-01-08
GB9018360D0 (en) 1990-10-24

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