NO762489L - - Google Patents

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Publication number
NO762489L
NO762489L NO762489A NO762489A NO762489L NO 762489 L NO762489 L NO 762489L NO 762489 A NO762489 A NO 762489A NO 762489 A NO762489 A NO 762489A NO 762489 L NO762489 L NO 762489L
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carbon atoms
formula
compound
alkyl
stated
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NO762489A
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Norwegian (no)
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G E Hardtmann
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Sandoz Ag
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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
    • C07D215/20—Oxygen atoms
    • C07D215/22—Oxygen atoms attached in position 2 or 4
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pulmonology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Immunology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

Description

Fremgangsmåte for fremstilling av Method of manufacture of

4-hydroksy-3-nitrokinolin-2 (1H)-on-derivater. 4-hydroxy-3-nitroquinolin-2 (1H)-one derivatives.

Foreliggende oppfinnelse vedrorer en fremgangsmåte for fremstilling av 4-hydroksy-3-nitokinolin-2 (1H)-on-derivater med formel I, The present invention relates to a process for the production of 4-hydroxy-3-nitoquinolin-2 (1H)-one derivatives of formula I,

hvori in which

R° betyr hydrogen, alkyl med 1-6 karbonatomer, alkenyl med 3-6 karbonatomer eller alkynyl med 3-6 karbonatomer, hvor den umettede binding i det enkelte tilfelle ikke befinner seg på a-karbonatomet, cykloalkyl med 3-6 karbonatomer, cykloalkylalkyl med 3-6 karbonatomer i cykloalkyldelen og 1-2 karbonatomer i alkyldelen, eller en gruppe R° means hydrogen, alkyl with 1-6 carbon atoms, alkenyl with 3-6 carbon atoms or alkynyl with 3-6 carbon atoms, where the unsaturated bond in the individual case is not located on the α-carbon atom, cycloalkyl with 3-6 carbon atoms, cycloalkylalkyl with 3-6 carbon atoms in the cycloalkyl part and 1-2 carbon atoms in the alkyl part, or a group

hvori in which

Y og Y' uavhengig av hverandre står for hydrogen, halogen, Y and Y' independently of each other stand for hydrogen, halogen,

alkyl med 1-3 karbonatomer, alkoksy med 1-3 karbonatomer eller trifluormetyl og alkyl with 1-3 carbon atoms, alkoxy with 1-3 carbon atoms or trifluoromethyl and

n betyr tallet 0 eller 1, ogn means the number 0 or 1, and

R og R' uavhengig av hverandre står for hydrogen, halogen, alkyl, R and R' independently of each other stand for hydrogen, halogen, alkyl,

med 1-4 karbonatomer, alkoksy med 1-4 karbonatomer, nitro eller trifluormetyl, med den begrensning at bare en av restene R og R' kan bety nitro eller trifluormetyl. with 1-4 carbon atoms, alkoxy with 1-4 carbon atoms, nitro or trifluoromethyl, with the restriction that only one of the radicals R and R' can be nitro or trifluoromethyl.

Halogen betyr fluor, klor eller brom, foretrukket fluor eller klor. Halogen means fluorine, chlorine or bromine, preferably fluorine or chlorine.

Det særegne ved fremgangsmåten i henhold til oppfinnelsen for fremstilling av forbindelsen med formel I er at en forbindelse med formel II, hvori R°, R<1>og R har den ovennevnte betydning, i et inert organisk løsningsmiddel omsettes med det reaksjonsprodukt som dannes ved behandling av en forbindelse med formel III, The peculiarity of the method according to the invention for producing the compound of formula I is that a compound of formula II, in which R°, R<1> and R have the above meaning, is reacted in an inert organic solvent with the reaction product formed by treatment of a compound of formula III,

hvori R'' betyr alkyl med 1-5 karbonatomer, med en sterk base. wherein R'' means alkyl of 1-5 carbon atoms, with a strong base.

Omsetningen i henhold til oppfinnelsen kan skje ved en temperatur på 20 til 200°C. Man arbeider foretrukket i et aprotisk losningsmiddel. I prinsippet arbeides under vannfri betingelser. Foretrukne losningsmidler er f.eks. dimetylacetamid, dimetyl-formamid og tetrahydrofuran, spesielt dimetylacetamid. Man arbeider foretrukket ved en temperatur på 50 til 150°C, vanlig foretrukket til å begynne med ved 50 til 100°C og til slutt ved omtrent 100 til 150°C. Passende molforhold for reaksjonsproduktet som dannes ved behandling av en forbindelse med formel III med en sterk base i forhold til forbindelsen med formel II utgjor omtrent 0,8 : 1 til 2:1, foretrukket omtrent 1:1. Omsetningen varer i 2 til 30 timer, vanlig omtrent 5 til 20 timer. The reaction according to the invention can take place at a temperature of 20 to 200°C. One preferably works in an aprotic solvent. In principle, work is done under water-free conditions. Preferred solvents are e.g. dimethylacetamide, dimethylformamide and tetrahydrofuran, especially dimethylacetamide. One preferably works at a temperature of 50 to 150°C, normally preferred to start at 50 to 100°C and finally at approximately 100 to 150°C. Suitable molar ratios of the reaction product formed by treatment of a compound of formula III with a strong base to the compound of formula II are about 0.8:1 to 2:1, preferably about 1:1. The turnover lasts for 2 to 30 hours, usually about 5 to 20 hours.

Egnede sterke baser er slike som ved avspalting av et proton fra forbindelsene med formel III er i stand til å danne de tilsvarende ioniske forbindelser med formel III A, Suitable strong bases are those which, by removing a proton from the compounds of formula III, are able to form the corresponding ionic compounds of formula III A,

hvori R'<1>har den ovennevnte betydning og M betyr kationet av den sterke base, f.eks. alkalimetallhydrider, butyl-litium og tertiære aminer. Alkalimetallhydrider, f.eks. natrium- og kaliumhydrid er wherein R'<1> has the above meaning and M means the cation of the strong base, e.g. alkali metal hydrides, butyl lithium and tertiary amines. Alkali metal hydrides, e.g. sodium and potassium hydride are

spesielt foretrukket i Egnede molforhold av den sterke base i forhold til forbindelsen med formel III utgjor minst 0,8 : 1, foretrukket 0,9 : i til 1,5 : 1, spesielt 1:1. particularly preferred in Suitable molar ratios of the strong base in relation to the compound of formula III amount to at least 0.8:1, preferably 0.9:1 to 1.5:1, especially 1:1.

For fremstilling av de ioniske forbindelser med formel III A passende temperaturer er omtrent - 100° til + 150°C, foretrukket 10 til 50 C. Man arbeider foretrukket i et organisk losningsmiddel. For dette er f.eks. de losningsmidler som er angitt for fremstilling av forbindelsene med formel I egnet. For the preparation of the ionic compounds of formula III A suitable temperatures are approximately -100° to +150°C, preferably 10 to 50°C. One preferably works in an organic solvent. For this, e.g. the solvents indicated for the preparation of the compounds of formula I are suitable.

Ved en utforelsesform for fremgangsmåten i henhold til oppfinnelsen blandes forbindelsen med formel II og III samtidig med den i det inerte losningsmiddel inneholdte sterke base. Temperaturen er da slik at en ionisk forbindelse med formel III A reagerer direkte med en forbindelse med formel II. In one embodiment of the method according to the invention, the compound of formula II and III is mixed simultaneously with the strong base contained in the inert solvent. The temperature is then such that an ionic compound of formula III A reacts directly with a compound of formula II.

Etter en foretrukket utforelsesform av fremgangsmåten i henhold til oppfinnelsen omsettes en forbindelse med formel III forst for den storste dels vedkommende til den ioniske forbindelse med formel III A, deretter endres reaksjonsbetingelsene slik at omsetningen med en forbindelse med formel II foregår. According to a preferred embodiment of the method according to the invention, a compound of formula III is first reacted for the most part to the ionic compound of formula III A, then the reaction conditions are changed so that the reaction with a compound of formula II takes place.

Etter en spesielt foretrukket utforelsesform for fremgangsmåtenAccording to a particularly preferred embodiment of the method

i henhold til oppfinnelsen omsettes forst i fravær av en forbindelse med formel II en forbindelse med formel III med en sterk base til forbindelsen med formel III A, deretter omsettes den erholdte forbindelse med formel III A med en forbindelse med formel II. according to the invention, in the absence of a compound of formula II, a compound of formula III is first reacted with a strong base to the compound of formula III A, then the obtained compound of formula III A is reacted with a compound of formula II.

Forbindelsene med formel II og III er kjente henholdsvis kan fremstilles etter kjente metoder henholdsvis analogt med i og for seg kjente metoder, ved å gå ut fra kjente utgangsforbindelser. The compounds of formulas II and III are known and can be prepared respectively according to known methods and analogously to methods known per se, by starting from known starting compounds.

Forbindelsen med formel I kan isoleres på kjent måte fra reaksjonsblåndingen, f.eks. ved behandling med en proton-kilde som vandig mineralsyre. The compound of formula I can be isolated in a known manner from the reaction mixture, e.g. by treatment with a proton source such as aqueous mineral acid.

Forbindelsen med formel I kan foreligge i fri form, d.v.s. medThe compound of formula I can be present in free form, i.e. with

fri hydroksygruppe, eller i form av salter med baser. Fra free hydroxy group, or in the form of salts with bases. From

forbindelsen med formel I i fri form lar seg på kjent måte salter fremstille og omvendt. Eksempler på slike salter er natrium-/ kalium- og litium-saltet. Hvis kationet for den ved fremstilling av forbindelsene med formel I anvendte sterke base og kationet i det onskede salt er identiske, kan saltet utvinnes fra reaksjons-blandingen uten isolering av den fri form. the compound of formula I in free form allows salts to be prepared in a known manner and vice versa. Examples of such salts are the sodium/potassium and lithium salt. If the cation of the strong base used in the preparation of the compounds of formula I and the cation of the desired salt are identical, the salt can be recovered from the reaction mixture without isolation of the free form.

Ved fremgangsmåten i henhold til oppfinnelsen fremstilles det også nye 4-hydroksy-3-nitrokinolin-2 (1H)-on-derivater, innenfor rammen av formel I, det vil si forbindelser med formel In, With the method according to the invention, new 4-hydroxy-3-nitroquinolin-2 (1H)-one derivatives are also produced, within the framework of formula I, i.e. compounds of formula In,

hvori R°, Rn og R<n>har den i krav 1 for R°, R og R<1>angitte betydning, med den-begrensning at hvis R° betyr hydrogen, alkyl, fenyl eller benzyl, in which R°, Rn and R<n> have the meaning given in claim 1 for R°, R and R<1>, with the restriction that if R° means hydrogen, alkyl, phenyl or benzyl,

betyr Rntrifluormetyl og Rn hydrogen, halogen, alkyl medmeans Rntrifluoromethyl and Rn hydrogen, halogen, alkyl with

1-4 karbonatomer eller alkoksy med 1-4 karbonatomer, eller R n står for alkoksy med 1-4 karbonatomer og Rn' står for 1-4 carbon atoms or alkoxy with 1-4 carbon atoms, or R n stands for alkoxy with 1-4 carbon atoms and Rn' stands for

hydrogen eller alkoksy med 1-4 karbonatomer.hydrogen or alkoxy with 1-4 carbon atoms.

En gruppe av foretrukne nye forbindelser med formel In består av forbindelsen med formel IA, A group of preferred novel compounds of formula In consists of the compound of formula IA,

hvori in which

R og R<1>har den ovennevnte betydning ogR and R<1> have the above meaning and

R° astår for alkyl med 3-6 karbonatomer eller alkynyl med 3-6 karbonatomer, hvor den umettede binding i det enkelte tilfelle ikke befinner "seg på a-karbonatomet. R° is for alkyl with 3-6 carbon atoms or alkynyl with 3-6 carbon atoms, where the unsaturated bond in the individual case is not located on the α-carbon atom.

Blant forbindelsene med formel I A foretrekkes dem hvori R° stårAmong the compounds of formula I A, those in which R° stands are preferred

Cl Cl

for alkenyl, såvel som de forbindelser hvori R og R' uavhengig av hverandre står for hydrogen, alkyl eller alkoksy. Foretrukket står minst en av restene R og R', spesielt står begge rester R og R' for alkoksy. for alkenyl, as well as the compounds in which R and R' independently of each other stand for hydrogen, alkyl or alkoxy. Preferably, at least one of the residues R and R' stands for, in particular both residues R and R' stand for alkoxy.

En annen gruppe av forbindelser med formel In består av forbindelsen med formel I B, Another group of compounds of formula In consists of the compound of formula I B,

hvori in which

betyr hydrogen, alkyl med 1-6 karbonatomer eller means hydrogen, alkyl with 1-6 carbon atoms or

hvori n har den ovennevnte betydning og where n has the above meaning and

enten R^betyr trifluormetyl og R^ hydrogen, halogen, alkyl med 1-4 karbonatomer eller alkoksy med 1-4 karbonatomer, eller R^betyr alkoksy med 1-4 karbonatomer og R^ betyr hydrogen eller alkoksy med 1-4 karbonatomer. either R^ means trifluoromethyl and R^ hydrogen, halogen, alkyl with 1-4 carbon atoms or alkoxy with 1-4 carbon atoms, or R^ means alkoxy with 1-4 carbon atoms and R^ means hydrogen or alkoxy with 1-4 carbon atoms.

Blant forbindelsene med formel I B foretrekkes dem hvori R^ betyr hydrogen eller alkyl, R^betyr trifluormetyl og R^ betyr hydrogen, og de forbindelser hvori R^ betyr hydrogen eller alkyl, og R^ og begge betyr alkoksy, foretrukket metoksy, foretrukket i 6- og 7-stillingen. Among the compounds of formula I B, preferred are those in which R^ means hydrogen or alkyl, R^ means trifluoromethyl and R^ means hydrogen, and those compounds in which R^ means hydrogen or alkyl, and R^ and both means alkoxy, preferably methoxy, preferred in 6 - and the 7 position.

En del av forbindelsen med formel I B, hvori R^og/eller R^ betyr alkoksy, er beskrevet i det belgiske patentskrift 815.230. Imidlertid kan disse forbindelser ikke fremstilles i henhold til den deri angitte metode. A part of the compound of formula I B, in which R 1 and/or R 2 means alkoxy, is described in the Belgian patent document 815,230. However, these compounds cannot be prepared according to the method stated therein.

En ytterligere gruppe av forbindelsen med formel In består av forbindelsene med formel IC, A further group of the compound of formula In consists of the compounds of formula IC,

hvori in which

R, R' og n har den ovennevnte betydning ogR, R' and n have the above meaning and

Ycbetyr hydrogen, halogen, alkyl med 1-3 karbonatomer, Yc means hydrogen, halogen, alkyl with 1-3 carbon atoms,

alkoksy med 1-3 karbonatomer eller trifluormetyl ogalkoxy with 1-3 carbon atoms or trifluoromethyl and

Y^ betyr halogen, alkyl med 1-3 karbonatomer, alkoksy med Y^ means halogen, alkyl with 1-3 carbon atoms, alkoxy with

1-3 karbonatomer eller trifluormetyl.1-3 carbon atoms or trifluoromethyl.

Blant forbindelsene med formel I C foretrekkes dem hvori n står for tallet 1, Y c står for hydrogen, fluor, eller klor og Y<1>står for halogen eller trifluormetyl, såvel som de forbindelser hvori R og R' uavhengig av hverandre står for hydrogen, alkyl eller alkoksy, idet foretrukket minst en av restene R og R' spesielt begge restene R og R<1>betyr alkoksy, spesielt forbindelsene hvori Yc betyr hydrogen og står i para-stilling. Among the compounds of formula I C, those in which n stands for the number 1, Y c stands for hydrogen, fluorine or chlorine and Y<1> stands for halogen or trifluoromethyl are preferred, as well as those compounds in which R and R' independently of each other stand for hydrogen .

Ennå en ytterligere gruppe av forbindelsen med formel In består av forbindelsene med formel I D, Still a further group of the compound of formula In consists of the compounds of formula I D,

hvori in which

R og R<1>har den ovennevnte betydning ogR and R<1> have the above meaning and

R°j betyr cykloalkyl med 3-6 karbonatomer eller cykloalkyl med 3-6 karbonatomer i cykloalkyldelen og 1-2 karbonatomer i alkyldelen. R°j means cycloalkyl with 3-6 carbon atoms or cycloalkyl with 3-6 carbon atoms in the cycloalkyl part and 1-2 carbon atoms in the alkyl part.

Blant forbindelsen med formel I D foretrekkes dem hvori R° betyr cykloalkyl, såvel som de forbindelser hvori R og R' uavhengig av hverandre står for hydrogen eller alkoksy, idet foretrukket minst en av restene R og R', spesielt begge rester R og R' står for alkoksy. Among the compounds of formula I D, those in which R° means cycloalkyl are preferred, as well as those compounds in which R and R' independently of each other stand for hydrogen or alkoxy, preferably at least one of the residues R and R', especially both residues R and R' for alkoxy.

Forbindelsene med formel I i fri form eller i form av deres farmasoytisk tålbare salter med baser, har interesante farmakodyanamiske egenskaper og kan anvendes som legemidler. The compounds of formula I in free form or in the form of their pharmaceutically acceptable salts with bases have interesting pharmacodynamic properties and can be used as pharmaceuticals.

De har spesielt di^-natrium-kromoglykat (DSOG) -liknende, spesielt histamin-frisettingshemmende virkning. På grunn av denne virkning kan de finne anvendelse som antiallergika, spesielt for behandling av allergisk astma. They have a particularly di^-sodium cromoglycate (DSOG)-like, especially histamine release-inhibiting effect. Because of this effect, they can find use as antiallergic drugs, especially for the treatment of allergic asthma.

Legemidler kan fremstilles på i og for seg kjent måte ved hjelpMedicines can be prepared in a manner known per se by using

av de farmasoytisk vanlige hjelpe- og bærer-substanser. of the pharmaceutical common auxiliary and carrier substances.

Forbindelsene kan tilfores alene eller i passende doseringsform. Preparatformene, f.eks. tabletter eller kapsler, kan fremstilles analogt med kjente metoder. The compounds can be administered alone or in a suitable dosage form. The preparation forms, e.g. tablets or capsules, can be prepared analogously to known methods.

De etterfolgende eksempler skal illustrere oppfinnelsen. Alle temperaturangivelser er i grader Celsius. The following examples shall illustrate the invention. All temperature indications are in degrees Celsius.

Eksempel 1: l-allyl-4-hydroksy-3-nitrokinolin-2 (lH)-onExample 1: 1-allyl-4-hydroxy-3-nitroquinolin-2 (1H)-one

En losning av 7,0 g nitroeddiksyreetylester i 80 ml dimetylacetamid tilsettes porsjonsvis 2,5 g 50% natriumhydrid (vasket med pentan). Hydrogengass utvikles under skumdannelse. Den erholdte losning omrores ved romtemperatur i 30 minutter. Deretter forhoyes temperaturen til 80°C og dråpevis tilsettes 10,7 g N-allylisato-syreanhydrid i 75 ml dimetylacetamid. Karbondioksyd utvikles. Den erholdte losning omrores ved 120°C i 18 timer, dimetylacetamidet fjernes under vakuum, vann tilsettes, den erholdte vandige fase vaskes to ganger med metylenklorid og filtreres. Filtefcatet surgjores med fortynnet saltsyre og den erholdte olje ekstraheres med metylenklorid og torkes. Den i overskriften nevnte forbindelse erholdes (smp. 125-127°C fra eter). A solution of 7.0 g of nitroacetic acid ethyl ester in 80 ml of dimethylacetamide is added in portions to 2.5 g of 50% sodium hydride (washed with pentane). Hydrogen gas is evolved during foaming. The solution obtained is stirred at room temperature for 30 minutes. The temperature is then raised to 80°C and 10.7 g of N-allylic acid anhydride in 75 ml of dimethylacetamide is added dropwise. Carbon dioxide is evolved. The obtained solution is stirred at 120°C for 18 hours, the dimethylacetamide is removed under vacuum, water is added, the aqueous phase obtained is washed twice with methylene chloride and filtered. The filtrate is acidified with dilute hydrochloric acid and the oil obtained is extracted with methylene chloride and dried. The compound mentioned in the title is obtained (m.p. 125-127°C from ether).

Analogt med eksempel 1 erholdes ved å gå ut fra analoge mengder av tilsvarende utgangsforbindelser med formler II og III, folgende forbindelser med formel I: Analogous to example 1, starting from analogous amounts of corresponding starting compounds with formulas II and III, the following compounds with formula I are obtained:

Claims (6)

1. Fremgangsmåte for fremstilling av forbindelser med formel I 1. Process for the preparation of compounds of formula I hvori R° betyr hydrogen, alkyl med 1-6 karbonatomer, alkenyl med 3-6 karbonatomer eller alkynyl med 3-6 karbonatomer, hvor den umettede binding i det enkelte tilfelle ikke befinner seg på oc-karbonatomet, cykloalkyl med 3-6 karbonatomer, cykloalkylalkyl med 3-6 karbonatomer i cykloalkyldelen og 1-2 karbonatomer i alkyldelen, eller betyr en gruppe in which R° means hydrogen, alkyl with 1-6 carbon atoms, alkenyl with 3-6 carbon atoms or alkynyl with 3-6 carbon atoms, where the unsaturated bond in the individual case is not located on the oc-carbon atom, cycloalkyl with 3-6 carbon atoms, cycloalkylalkyl with 3-6 carbon atoms in the cycloalkyl part and 1-2 carbon atoms in the alkyl part, or means a group hvori Y og Y' uavhengig av hverandre står for hydrogen, halogen, alkyl med 1-3 karbonatomer, alkoksy med 1-3 karbonatomer eller trifluormetyl og n betyr tallet 0 eller 1, og R og R <1> uavhengig av hverandre står for hydrogen, halogen, alkyl med 1-4 karbonatomer, alkoksy med 1-4 karbonatomer, nitro eller trifluormetyl, med den begrensning at bare en av restene R og R' betyr nitro eller trifluormetyl, og deres salter, karakterisert ved at en forbindelse med formel II, in which Y and Y' independently of each other stand for hydrogen, halogen, alkyl with 1-3 carbon atoms, alkoxy with 1-3 carbon atoms or trifluoromethyl and n means the number 0 or 1, and R and R<1> independently of each other stand for hydrogen, halogen, alkyl with 1-4 carbon atoms, alkoxy with 1-4 carbon atoms, nitro or trifluoromethyl, with the restriction that only one of the residues R and R' means nitro or trifluoromethyl, and their salts, characterized in that a compound of formula II, hvori R°, R' og R har den ovennevnte betydning, omsettes i et inert organisk losningsmiddel med det reaksjonsprodukt som dannes ved behandling av en forbindelse med formel III, wherein R°, R' and R have the above-mentioned meaning, is reacted in an inert organic solvent with the reaction product formed by treatment of a compound of formula III, hvori R' <1> betyr alkyl med 1-5 karbonatomer, med en sterk base, og de i således erholdte forbindelser ved formel I isoleres i form av fri base eller som salter.wherein R' <1> means alkyl of 1-5 carbon atoms, with a strong base, and the thus obtained compounds of formula I are isolated in the form of free base or as salts. 2. Fremgangsmåte som angitt i krav 1, karakterisert ved at det som sterk base anvendes et alkalimetallhydrid, et butyl-litium, et tertiært amin, natriumhydrid eller kaliumhydrider.2. Method as stated in claim 1, characterized in that an alkali metal hydride, a butyl lithium, a tertiary amine, sodium hydride or potassium hydrides are used as strong base. 3. Fremgangsmåte som angitt i krav 1, karakterisert 'ved at den i krav 1 angitte forbindelse med formel III omsettes med den sterke base i fravær av forbindelsen med formel II og produktet omsettes deretter med forbindelsen med formel II.3. Method as stated in claim 1, characterized in that the compound of formula III stated in claim 1 is reacted with the strong base in the absence of the compound of formula II and the product is then reacted with the compound of formula II. 4. Fremgangsmåte som angitt i krav 1, karakterisert ved at man fremstiller l-allyl-4-hydroksy-3-nitrokinolin-2 (1H)-on.4. Procedure as stated in claim 1, characterized in that 1-allyl-4-hydroxy-3-nitroquinolin-2 (1H)-one is produced. 5. Fremgangsmåte som angitt i krav 1, karakterisert ved at man fremstiller 1-propargyl-6- klor-4-hydroksy-3-nitrokinolin-2 (lH)-on.5. Process as stated in claim 1, characterized in that 1-propargyl-6-chloro-4-hydroxy-3-nitroquinolin-2 (1H)-one is produced. 6. Fremgangsmåte som angitt i krav 1, karakterisert ved at man fremstiller l-metyl-6,6. Method as stated in claim 1, characterized in that l-methyl-6 is produced, 7- dimetoksy-4-hydroksy-3-nitrokinolin-2 (lH)-on.7-dimethoxy-4-hydroxy-3-nitroquinolin-2 (1H)-one.
NO762489A 1975-07-23 1976-07-15 NO762489L (en)

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JPS54130587A (en) * 1978-03-30 1979-10-09 Otsuka Pharmaceut Co Ltd Carbostyryl derivative
IE52656B1 (en) * 1981-04-07 1988-01-06 Shell Int Research Closure device
JPS60101445U (en) * 1983-12-17 1985-07-10 紀伊産業株式会社 sealed container
JPH0621181B2 (en) * 1987-01-12 1994-03-23 テルモ株式会社 Method for producing hydrophilic polyvinylidene fluoride porous membrane
JPH0644827Y2 (en) * 1988-09-20 1994-11-16 エヌオーケー株式会社 cap

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DE1770482A1 (en) * 1968-05-22 1971-11-11 Basf Ag Process for the preparation of 2,4-dioxyquinolines
DE2354145A1 (en) * 1972-11-02 1974-05-16 Sandoz Ag CHINAZOLIN-2 (LH) -ONE AND METHOD FOR MANUFACTURING IT
GB1453863A (en) * 1973-05-19 1976-10-27 Beecham Group Ltd Pharmaceutical compositions comprising nitrocarbostyrils for the treatment of allergic and immunological hypersensitivity

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SE7608151L (en) 1977-01-24
JPS5225781A (en) 1977-02-25
BE844414A (en) 1977-01-24
DK319276A (en) 1977-01-24
PT65391A (en) 1976-08-01
AU1620976A (en) 1978-01-26
DD126769A5 (en) 1977-08-10
ZA764449B (en) 1978-03-29
FR2318633B1 (en) 1978-12-22
PT65391B (en) 1978-04-05
YU181176A (en) 1982-05-31
DE2631317A1 (en) 1977-02-17
FI762046A (en) 1977-01-24
IL50090A0 (en) 1976-09-30
NL7607968A (en) 1977-01-25
ES450060A1 (en) 1977-12-01
FR2318633A1 (en) 1977-02-18
NZ181532A (en) 1978-07-10

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