DK143402B - Analogifremgangsmaade til fremstilling af astriazino-(5,6-c)-kinolinderivater - Google Patents
Analogifremgangsmaade til fremstilling af astriazino-(5,6-c)-kinolinderivater Download PDFInfo
- Publication number
- DK143402B DK143402B DK245073AA DK245073A DK143402B DK 143402 B DK143402 B DK 143402B DK 245073A A DK245073A A DK 245073AA DK 245073 A DK245073 A DK 245073A DK 143402 B DK143402 B DK 143402B
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- DK
- Denmark
- Prior art keywords
- triazino
- quinoline
- nitroquinoline
- general formula
- carbon atoms
- Prior art date
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- 238000000034 method Methods 0.000 title claims description 8
- 238000002360 preparation method Methods 0.000 title claims description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical class N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 title description 7
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- ZRFUZDDJSQVQBY-UHFFFAOYSA-N 4-chloro-3-nitroquinoline Chemical compound C1=CC=CC2=C(Cl)C([N+](=O)[O-])=CN=C21 ZRFUZDDJSQVQBY-UHFFFAOYSA-N 0.000 claims description 5
- -1 hydroxy, amino Chemical group 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- ARFYZKAYDRJATN-UHFFFAOYSA-N [1,2,4]triazino[5,6-c]quinoline Chemical class C1=NN=C2C3=CC=CC=C3N=CC2=N1 ARFYZKAYDRJATN-UHFFFAOYSA-N 0.000 claims description 2
- 150000004820 halides Chemical class 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 125000003884 phenylalkyl group Chemical group 0.000 claims 1
- 125000004076 pyridyl group Chemical group 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 238000003756 stirring Methods 0.000 description 4
- 206010030113 Oedema Diseases 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 235000010418 carrageenan Nutrition 0.000 description 2
- 229920001525 carrageenan Polymers 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- DERASAFMHXNKGC-UHFFFAOYSA-N (3-nitroquinolin-2-yl)hydrazine Chemical compound C1=CC=C2C=C([N+]([O-])=O)C(NN)=NC2=C1 DERASAFMHXNKGC-UHFFFAOYSA-N 0.000 description 1
- SKRZKNWOHLTARM-UHFFFAOYSA-N (3-nitroquinolin-4-yl)hydrazine Chemical compound C1=CC=C2C(NN)=C([N+]([O-])=O)C=NC2=C1 SKRZKNWOHLTARM-UHFFFAOYSA-N 0.000 description 1
- FPTCVTJCJMVIDV-UHFFFAOYSA-N 2-phenylacetohydrazide Chemical compound NNC(=O)CC1=CC=CC=C1 FPTCVTJCJMVIDV-UHFFFAOYSA-N 0.000 description 1
- 150000005014 3-aminoquinolines Chemical class 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- WARCRYXKINZHGQ-UHFFFAOYSA-N benzohydrazide Chemical compound NNC(=O)C1=CC=CC=C1 WARCRYXKINZHGQ-UHFFFAOYSA-N 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000006501 nitrophenyl group Chemical group 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960002895 phenylbutazone Drugs 0.000 description 1
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
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
- C07D215/38—Nitrogen atoms
- C07D215/42—Nitrogen atoms attached in position 4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Quinoline Compounds (AREA)
Description
'tiA
ns) DANMARK
^ (12) FREMLÆGGELSESSKRIFT (n> 143^+02 B
DIREKTORATET FOR PATENT- OG VAREMÆRKEVÆSENET
(21) Ansøgning nr. 2450/73 (51) IntCI.* C 07 D 471/04 (22) Indleveringsdag 4. maj 1973 (24) Løbedag 4. maj 1973 (41) Aim. tilgængelig 6. nov. 1973 (44) Fremlagt 17· aug. 1981 (86) International ansøgning nr. - (86) International indleveringsdag - (85) Videreførelsesdag - (62) Stamansøgning nr. -
(30) Prioritet 5- maj 1972, EE 2022, HU
(71) Ansøger EG YT GYOGYSZERVEGYESZETI GYåR, Budapest X, HU.
(72) Opfinder Edit Berenyi, HU: Laezlo Pallos, HU: Lujza E. Petoecz, HU: Peter Goeroeg, HU: Zoltan Budai, HU: ra. fl.
(74) Fuldmægtig Kontor for Industriel Eneret v. Svend Schønning.
(54) Analogifremgangsmåde til fremstil« ling af as-triazino-(5,β-c)-kino« linderivater.
Den foreliggende opfindelse angår en analogifremgangs-måde til fremstilling af hidtil ukendte as-triazino- [5,6-c]-kinolinderivater med den almene formel R2
I I
1 N
R -N*^ X-R
_ i N 1 2 1 A3 40 2 1 2 hvor R, R og R har de i kravets indledning angivne betydninger, eller salte deraf. De omhandlede forbindelser udviser betændelseshæmmende virkning.
Fremgangsmåden ifølge opfindelsen er ejendommelig ved at man omsætter a) 4—ldor-3-nitrolcinolin med et learboxylsyrehydrazid med den almene formel
R3- CO - NH - NH2 II
eller b) 4-hydrazino-3-nitrolcinolin med et syrehalogenid med den almene formel R3- CO - X Ila i hvilke formler R3 har den ovenfor for R angivne betydning eller betyder en med en nitrogruppe substitueret fenylgruppe og X er et halogenatom, reducerer det vundne 4-acylhydrazino-3-ni-trokinolin med den almene formel /NH 3
NH XC0-R
i. N02
©qT
3 hvor R har den ovenfor angivne betydning, ringslutter det dannede 4-acylhydrazino-3-aminolcinolin med den almene formel
NH
NH^ ^CO-R IV
hvor R har den ovenfor angivne betydning, 3 143402 i surt medium til det tilsvarende l,2-dihydro-as-triazino-^5,6-c7-kinolin og isolerer dette i form af et salt deraf eller om ønsket oxyderer det tildet tilsvarende as-triazino~/5,6-c7-kinolin og om ønsket omdanner dette til et salt deraf.
Ved en foretrukken udførelsesform for fremgangsmåden ifølge den foreliggende opfindelse omsættes 4-klor-3-nitrokinolin og karboxylsyrehydrazid i ækvimolære mængder i alkoholisk medium, hvorved der vindes hydrokloridet af 4-acylhydrazino-3-nitrokinolin. Dette hydroklorid er let hydrolyserbart. Men det kan også foregå således at 4-klor~3-nitrokinolin omsættes med et overskud af karboxyl-syrehydrazidet hvorved forbindelsen med den almene formel III vindes i baseform. Acylhydrazinonitrokinolinet kan både i form af basen og i form af et salt deraf omdannes til det tilsvarende 3-amino-kinolinderivat med godt udbytte ved katalytisk hydrogenering i op-løsningsmiddelmediet. Ved denne hydrogenering vil en nitrofenylgrup-pe R samtidigt reduceres til en aminofenylgruppe.
Ringslutningsreaktionen af 3-aminoforbindelsen sker ved behandling med syre, som f.eks. med saltsyre eller polyfosforsyre.
Ved uiførelse af ringslutningen i saltsurt ætylalkohol vindes hydrokloridet af det 3-substituerede l,2-dihydro~as-triazino-/5,6-c7-kinolin, som for størstedelens vedkommende udskilles fra reaktionsblandingen. Hydrokloridet af dihydro-forbindelsen kan om ønsket oxyderes til den aromatiske ringforbindelse, hvilket hensigtsmæssigt foregår i alkalisk medium i nærværelse af hexacyanoferrationer.
Forbindelserne med den almene formel I, der ved farmakologiske undersøgelser viser betændelseshæmmende virkning, kan alene eller sammen med andre biologisk aktive og/eller virkningsforøgende midler indarbejdes i farmaceutiske præparater under anvendelse af de i farmacien anvendelige hjælpestoffer.
Den betændelseshæmmende virkning undersøgtes efter Winters metode (j. Pharmacol. Exp. Ther., 141, 369, 1963) ved karragenin-ødem-prøve på hanrotter med en vægt på 150-180g, idet der i rotterne plantart og subkutant blev indgivet 0,1 ml karrageninsuspension i bagbenet. Det dannede ødem måltes med plethysmometer. De værdier (udbredelse af ødem) der måltes ved oral indgift af de under afprøvning værende stoffer er i den følgende tabel angivet i procent udtrykt i forhold til kontrolværdien.
4 143402
Tabel.
Forbindelse Dosis Hæmning LD
mg/kg * 50 3-f enyl-1,2-diiiydro-as- triazino-/5,6-c7-kinolin 200,00 23,3 3000 400,00 31,8 3-£enyl-as~triazino- /5,6-c7-kinolin 200,00 15,7 3000 400,00 20,3 3-(3',4', 5,-trimeto:xy-£enyl)- as-triazino-/5,6-c7-kinolin 200,00 33,8 3000 3-(3',4'-dimetoxy£enyl)-as- triazino-/5,6-c7-kinolin 200,00 38,6 3000 3-benzyl-as-triazino-75,6-cJ- kinolin 200,00 32,6 3000 3_(4»-pyridyl)-as-triazino- /5,6-c/-kinolin 20,00 12,9 " 40,0 34,1 1000 80,0 56,2 as-triazino-/5,6-c7~kinolin 0,87 24,3 1,75 32,8 90 3,5 43,5
Acetylsalicylsyre 180,0 39,0 1500
Fenylbutazon 30,0 33,0 90,0 45,0 1000
Indomethacin 3,0 30,0 9,0 44,0 24,3
Fremgangsmåden ifølge den foreliggende opfindelse forklares nærmere i det følgende ved hjælp af nogle eksempler.
5 143402
Eksempel 1.
4-β-Benzhydrazino~3-nitrokinolin.
13,6 g (0,1 mol) benzoesyrehydrazid opløses i 200 ml ætylalkohol. Til opløsningen sættes under omrøring 20,8 g (0,1 mol) 4-klor-3-nitrokinolin, idet temperaturen holdes ved 30-40°C. Den fremkomne mørkerøde suspension ændrer sin farve videre mod gul.
Efter 3 timers omrøring frafiltreres de vundne bleggule krystaller.
Der vindes 31,6 g (92%) 4-P'-benzhydrazino-3'-nitrokinolin-hydro-klorid med smp. 244-246°C.
Det vundne salt suspenderes i 10 gange så meget vand og basen frigøres med den ækvivalente mængde Na^O^. Den vundne 4-3-benz-hydrazino-3-nitrokinolin-base har mørkebordeauxrød farve og smelter ved 2Q2-203°C (nitrobenzen).
Eksempel 2.
4-β-fenylacetylhydraz ino-3-nitrokinolin.
30,0 (0,2 mol) fenyleddikesyrehydrazid opløses i den ti-dobbelte mængde ætylalkohol og under omrøring tilsættes 20,8 g (0,1 mol) 4-klor-3-nitrokinolin. Der omrøres yderligere i 2 timer ved stuetemperatur hvorefter det vundne 4-8-fenylacetylhydrazino-3-nitrokinolin frafiltreres. Der vindes 30,6 g (96%) produkt med smp. 199-200°C.
På samme måde som beskrevet i eksempel 1 og 2 fremstilles følgende forbindelser: 4H3-Formylhydrazino-3-nitrokinolin; smp. 190-191°C, 4-P-Acetylhydrazino-3-nitrokinolin; smp. 194-195°C, 4-β-Niko t insyrehydraz ino-3-n i trokinolin; smp. 243°C, 4-p-Salicylsyrehydrazino-3-nitrokinolin; smp. 206-208°C, 4-P-(p-Nitrobenzhydrazino)-3-nitrokinolin; smp. 230-231°C, 4-β-(3',4',5'-Trimetoxybenzhydrazino)-3-nitrokinolin; smp. 213-215°C, 4-β-(3’,4'-Dimetoxyfenacetylhydrazino)-3-nitrokinolin, smp, 168-1?0°C, 4-8-(p-brombenzhydrazino)-3-nitrokinolin; smp. 219-221°C.
6 143402
Eksempel 3.
2,04 g (0,01 mol) 4-hydrazino-3-nitrokinolin opløses i 20 ml pyridin og under omrøring tildryppes der til opløsningen 1,4 g (0,01 mol) benzoylklorid. Reaktionsblandingen koges i en time, afkøles derpå og udhældes i vand. Egenskaberne ved det vundne 4_β„benzhydrazino-3-nitrokinolin stemmer overens med egenskaberne ved det ifølge eksempel 1 vundne produkt.
Eksempel 4· 3-Amino-4-P-benzhydraz inokinolin.
6,2 g (0,02 mol) 4-P~benzhydrazino-3-nitrokinolin hydrogeneres i ætanolisk medium i nærværelse af en palladiumkatalysator. Efter afsluttet hydrogenoptagelse inddampes opløsningen. Der vindes 4,6 g (83%) S-amino-4-β-benzhydrazinokinolin med smp. 292-293°C.
Eksempel 5.
3-Fenyl-l,2-dihydro-as-triazino-/5,6-c7-kinolin-hydroklorid.
5,6 g (0,02 mol) 3-amino-4-β-benzhydrazino-kino1in koges i en time i 50 ml 20%s alkoholisk saltsyre. Der vindes 5,9 g (98%) 3-fenyl-1,2-dihydro-as-triazino-/5,6-c7-kinolin-hydroklorid i form af mørklilla farvede krystaller med smp. 197-198°C.
På analog måde fremstilles følgende forbindelser: l,2-Dihydro-as-triazino-/5,6-c7-kinolin,HCl; smp. 2δ5-2δ7°0, 3-Metyl-l,2-dihydro-as-triazino-/5,6-c7-kinolin,HC1; smp. 301-303°C, 3-(p-Hydroxyfenyl)-l,2-dihydro-as-triazino-/5,6-c7-kinolin,HC1; smp. 312-313°C, 3-(p-Aminofenyl)-1,2-dihydro-as-triazino-/5,6-c7-kinolin,HC1; smp. 308-310°C, 3-Benzyl-1,2-dihydro-as-triazino-/5,6-c7-kinolin,HC1; smp. 296-298°C, 3-(4'-pyridyl)-!,2-dihydro-as-triazino-75,6-c7-kinolin,HC1; smp. 308-310°C, 3-Fenyl-l,2-dihydro-as-triazino-/5,6-c7-kinolin,HBr; smp. 309-311°C.
Eksempel 6.
7 143402 6,0 g (0,02 mol) 3-fenyl-l,2-dihydro-as-triazino-^5,6-c7-kinolin- hydroklorid sættes ved 0° til en opløsning af 13,2 g (0,04 mol) K3/Fe(CN)g_7i 100 ml vand som i forvejen er indstillet til en pH-værdi på 9 med koncentreret ammoniumhydroxyd. Reaktionsblandingen omrøres i 3 timer ved 0°C og filtreres derpå. Der vindes 5,0 g {31%) 3-fenyl-as-triazino-75,6-c7-kinolin med smp. 203-204°0 (c2h5oh/chci3).
På lignende måde vindes følgende forbindelser: as-Triazino-^/5,6-c7-kinolin; smp. 162-164°C, 3-Metyl-as-triazino-/5,6-c7-kinolin; smp. 137-138°C, S-Ætyl-as-triazino-^^-^-kinolin; smp. 106-108°C, 3_(4'_pyridyl)-as-triazino-75,6-c7-kinolin; smp. 213-214°C, 3-Benzyl-as-triazino-75,6-c7-kinolin; smp. 150-152°C, 3-(3»,4»-Dimetoxybenzyl)-as-triazino-(/5,6-c7^kinolin; smp. 150-151°C, 3—(3T,4',5'-Trimetoxyfenyl)-as-triazino-/5,6-c7-kinolin; smp. 182-183°C, 3-(2'-Hydroxyfenyl)-as-triazino-r/5,6-c7-kinolin; smp. 246°C, 3_(4»_Aminofenyl)-as-triazino-75,6-c7-kinolin; smp.268-270,'C, 3_(4«_Bromfenyl)-as-triazino-/5,6-c7-kinolin; smp. 245-247°C.
Claims (1)
- 8 143402 Analogifremgangsmåde til fremstilling af as-triazino-[5,6-c]-kinolinderivater med den almene formel R2 i R-ir N|-R (6igf’ hvor R er et hydrogenatom, en allcylgruppe med 1-4 kulstof atomer, en pyridylgruppe eller en fenylgruppe der eventuelt er substitueret med 1-3 substituenter valgt blandt halogen, hydroxy, amino, alkoxy med 1-4 kulstofatomer eller eventuelt med 2 metoxygrupper substitueret fenylalkyl med op til 4 kulstof atomer i alkylkæden, og R”*" 2 og R er hydrogen eller tilsammen udgør en kemisk binding, eller salte af disse forbindelser, kendetegnet ved at man omsætter a) 4-lclor-3-nitrokinolin med et learboxylsyrehydrazid med den almene formel R1- CO - NH - NH2 ii eller b) 4-hydrazino-3-nitrolcinolin med et syrehalogenid med den almene formel 3 R - CO - X Ila i hvilke formler R har den ovenfor for R angivne betydning eller betyder en med en nitrogruppe substitueret fenylgruppe og X er et halogenatom, reducerer det vundne 4-acylhydrazino-3-nitrokinolin med den almene formel
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HUEE002022 | 1972-05-05 | ||
| HUEE2022A HU165678B (da) | 1972-05-05 | 1972-05-05 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DK143402B true DK143402B (da) | 1981-08-17 |
| DK143402C DK143402C (da) | 1981-12-21 |
Family
ID=10995440
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK245073A DK143402C (da) | 1972-05-05 | 1973-05-04 | Analogifremgangsmaade til fremstilling af as-triazino-(5,6-c)-kinolinderivater |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US3873543A (da) |
| JP (1) | JPS523958B2 (da) |
| AT (1) | AT323747B (da) |
| CA (1) | CA963469A (da) |
| CH (1) | CH583234A5 (da) |
| CS (1) | CS174880B2 (da) |
| DD (1) | DD106843A5 (da) |
| DE (1) | DE2322486C2 (da) |
| DK (1) | DK143402C (da) |
| FR (1) | FR2183839B1 (da) |
| GB (1) | GB1401164A (da) |
| HU (1) | HU165678B (da) |
| NL (1) | NL165740C (da) |
| PL (1) | PL85373B1 (da) |
| SE (1) | SE416470B (da) |
| YU (1) | YU36373B (da) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3919219A (en) * | 1974-11-04 | 1975-11-11 | Dow Chemical Co | 6-Pyridyl-tetrahydro-1,2,4-triazinoquinazolines |
| US3919216A (en) * | 1974-11-04 | 1975-11-11 | Dow Chemical Co | 6-(Alkyl)-3,4,6,7-tetrahydro-1,2,4-triazinoquinazolines |
| US3922274A (en) * | 1974-11-04 | 1975-11-25 | Dow Chemical Co | Dihydro-1,2,4-triazinoquinazolines |
| US3919220A (en) * | 1974-11-04 | 1975-11-11 | Dow Chemical Co | 6-(Phenyl and substituted phenyl)tetrahydro-1,2,4-triazinoquinazolines |
| US3919215A (en) * | 1974-11-04 | 1975-11-11 | Dow Chemical Co | 3-(2-Acylaminophenyl)-1,2,4-triazines |
| HU181689B (en) * | 1980-04-18 | 1983-11-28 | Egyt Gyogyszervegyeszeti Gyar | Process for producing new dihydro-as-triazino-square bracket-5,6-c-square bracket closed-quinoline derivatives |
| WO2024094150A1 (en) * | 2022-11-04 | 2024-05-10 | Insilico Medicine Ip Limited | Nlrp3 inflammasome inhibitors and uses thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR1449778A (fr) * | 1965-06-28 | 1966-05-06 | Nouveaux dérivés pyridotriaziniques utilisables comme stabilisants pour émulsions photographiques et procédé pour leur préparation | |
| US3597427A (en) * | 1969-01-13 | 1971-08-03 | American Cyanamid Co | 1,2-dihydropyrido(3,4-e)-as-triazines |
| US3721670A (en) * | 1971-04-05 | 1973-03-20 | Morton Norwich Products Inc | 3-substituted-as-triazino(5,6-c)quinolines |
-
1972
- 1972-05-05 HU HUEE2022A patent/HU165678B/hu not_active IP Right Cessation
-
1973
- 1973-04-25 GB GB1975973A patent/GB1401164A/en not_active Expired
- 1973-05-02 AT AT384773A patent/AT323747B/de not_active IP Right Cessation
- 1973-05-03 DD DD170598A patent/DD106843A5/xx unknown
- 1973-05-03 CH CH628373A patent/CH583234A5/xx not_active IP Right Cessation
- 1973-05-04 DK DK245073A patent/DK143402C/da not_active IP Right Cessation
- 1973-05-04 DE DE2322486A patent/DE2322486C2/de not_active Expired
- 1973-05-04 CS CS3186A patent/CS174880B2/cs unknown
- 1973-05-04 PL PL1973162338A patent/PL85373B1/pl unknown
- 1973-05-04 NL NL7306283.A patent/NL165740C/xx not_active IP Right Cessation
- 1973-05-04 YU YU11830/73A patent/YU36373B/xx unknown
- 1973-05-04 CA CA170,479A patent/CA963469A/en not_active Expired
- 1973-05-04 FR FR7316235A patent/FR2183839B1/fr not_active Expired
- 1973-05-04 JP JP48050227A patent/JPS523958B2/ja not_active Expired
- 1973-05-04 SE SE7306320A patent/SE416470B/xx unknown
- 1973-05-07 US US357722A patent/US3873543A/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| HU165678B (da) | 1974-10-28 |
| AT323747B (de) | 1975-07-25 |
| DD106843A5 (da) | 1974-07-05 |
| YU118373A (en) | 1981-11-13 |
| NL7306283A (da) | 1973-11-07 |
| CS174880B2 (da) | 1977-04-29 |
| CA963469A (en) | 1975-02-25 |
| PL85373B1 (en) | 1976-04-30 |
| NL165740C (nl) | 1981-05-15 |
| US3873543A (en) | 1975-03-25 |
| SE416470B (sv) | 1981-01-05 |
| YU36373B (en) | 1983-06-30 |
| CH583234A5 (da) | 1976-12-31 |
| FR2183839A1 (da) | 1973-12-21 |
| DE2322486A1 (de) | 1973-11-15 |
| FR2183839B1 (da) | 1976-10-22 |
| JPS4947394A (da) | 1974-05-08 |
| DE2322486C2 (de) | 1982-06-03 |
| NL165740B (nl) | 1980-12-15 |
| DK143402C (da) | 1981-12-21 |
| JPS523958B2 (da) | 1977-01-31 |
| GB1401164A (en) | 1975-07-16 |
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| Date | Code | Title | Description |
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| PBP | Patent lapsed |