SE441829B - 6-HYDROZONO-pyrido / 2,1-b / quinazolin-11-ones - Google Patents
6-HYDROZONO-pyrido / 2,1-b / quinazolin-11-onesInfo
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- SE441829B SE441829B SE8103940A SE8103940A SE441829B SE 441829 B SE441829 B SE 441829B SE 8103940 A SE8103940 A SE 8103940A SE 8103940 A SE8103940 A SE 8103940A SE 441829 B SE441829 B SE 441829B
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- 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
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Description
sío394u-6 to O 4Û__r 2 en grupp bestående av halogen, alkyl och alkoxi med l~4 kolatomer, fenrloxi, hydroxi, nitro, amino, cyano, kar- boxi,ealkoxikarbonyl med l-4 kolatomer, alkanoyl med l-4 kolatomer, metylendioxi, trifluormetyl, fenyl och dialkyl- amino med 1-4 kolatomer i alkyldelen eller R4 är naftyl: pyridyl, och de streckade linjerna representerar en even- tuell dubbelbindning. Föreningarna framställes genom att (a) ett pyrido[2.l-b/kinazolin-ll~onderivat med den all- männa formeln II där R, Rl, R2, R5 och de streckade linjerna har ovan an~ givna betydelser och Ro är väte eller formyl, omsättes med ett diazoniumsalt med den allmänna formeln n” - n? cl 9 III där Ru representerar en fenylgrupp eventuellt substitue- rad med l-5 inbördes lika eller olika substituenter valda ur en grupp bestående av halogen, alkyl med 1-4 kolatomer, alkoxi med 1-4 kolatomer, fenyloxi, hydroxi, nitro, amino oyano, karboxi, alkoxikarbonyl med l-4 kolatomer i alkoxi- delen,alkanoyl med l-4 kolatomer, metylendicxi, trífluor- metyl, fenyl och dialkylamino med l-4 kolatomer i alkyl- gruppen eller naftyl, så att det bildas föreningar med den allmänna formeln I, där R4 represen- terar fenyl eventuellt substituerad med 1-3 inbördes lika eller olika substituenter valda bland följande, näm~ ligen halogen, alkyl med l-ll- kolatorner, alkoxí med l-ll- kolatomer, fenyloxi, hydroxi, nitro, amino, cyano, kar-b- bxi; alkoxikarbonyl med l-4 kolatomer i alkoxidelen, alkanoyl med l-4 kolatomer, metylendioxi, trifluormetyl, fenyl och dialkylamino med 1-4 kolatomer i alkylgruppen; eller naftyl 0Ch R: R1, R2, R3 och de strecka- de linjerna har ovan angivna betydelser, eller "^ *“ ee”\\“*íñíI::“ FM) eeflrêklïv '10 ,...^ “ J! ÄH) Uv' 8103940-6 (b) ett pyrido[?.l-Q/kinazolin-ll-bnderivdt med den all- männa formeln N \\ R7 .R __ /c\/R7 _ a_ H där R, Rl, H2, R5 och de streckade 1in¿erna har ovan an- givna betydelser och R? representerar en alkylgrupp med l-4 kolatomer, omsättes med ett diazoniumsalt med den ovan definierade allmänna formeln III, så att man erhålller före- ningar med den allmänna formeln I, där Ra representerar fenyl eventuellt substituerad med 1-3 inbördes lika eller olika substituenter valda bland följande, nämligen halo- gen,alkyl med l-4 kolatomer,alkoXi med l-4 kolatomer, fenyl~ oxí, hydroxi, nitro, amino, cyano, karboxi, alkoxikar- bonyl med l-4 kolatomer i alkoxidelen, alkanoyl med 1-4 kolatomer, metylendioxí, trlfluormetyl, fenyl och di- _ alkylamino med 1-4 kolatomer i alkylgruppen, eller maf- 1, R2, R3 och de streckade lin- tyl och R, R jerna har ovan angivna betydelser, eller (c) ett pyridolë.l-b7kinazolin-ll-onderivat med den all- männa formeln Rz ' 3 R al I \\ñ/I V R Q R. a group consisting of halogen, alkyl and alkoxy having 1 to 4 carbon atoms, phenyloxy, hydroxy, nitro, amino, cyano, carboxy, alkoxycarbonyl having 1 to 4 carbon atoms, alkanoyl having 1 to 4 carbon atoms, methylenedioxy, trifluoromethyl, phenyl and dialkylamino having 1-4 carbon atoms in the alkyl moiety or R 4 are naphthyl: pyridyl, and the dashed lines represent an optional double bond. The compounds are prepared by (a) a pyrido [2.lb / quinazoline] derivative of the general formula II wherein R, R1, R2, R5 and the dashed lines have the meanings given above and Ro is hydrogen or formyl , is reacted with a diazonium salt of the general formula n ”- n? Cl 9 III where Ru represents a phenyl group optionally substituted with 1-5 identical or different substituents selected from a group consisting of halogen, alkyl of 1-4 carbon atoms, alkoxy of 1-4 carbon atoms, phenyloxy, hydroxy, nitro, amino oyano, carboxy, alkoxycarbonyl having 1-4 carbon atoms in the alkoxy moiety, alkanoyl having 1-4 carbon atoms, methylenedioxy, trifluoromethyl, phenyl and dialkylamino having 1-4 carbon atoms in the alkyl group or naphthyl to form compounds having the general formula I, wherein R 4 represents phenyl optionally substituted with 1-3 mutually identical or different substituents selected from the following, namely halogen, alkyl having 1 - 11 carbon atoms, alkoxy having 1 - 11 carbon atoms, phenyloxy, hydroxy, nitro, amino, cyano, car-b-bxi; alkoxycarbonyl having 1-4 carbon atoms in the alkoxy moiety, alkanoyl having 1-4 carbon atoms, methylenedioxy, trifluoromethyl, phenyl and dialkylamino having 1-4 carbon atoms in the alkyl group; or naphthyl OCh R: R1, R2, R3 and the dashed lines have the meanings given above, or "^ *" ee "\\" * íñíI :: “FM) ee fl reclil '10, ... ^“ J! ÄH Uv '8103940-6 (b) a pyrido [?. LQ / quinazoline-11-bonded derivative of the general formula N \\ R7 .R __ / c \ / R7 _ a_ H where R, R1, H2, R5 and the dashed 1s have the meanings given above and R 2 represents an alkyl group having 1 to 4 carbon atoms, is reacted with a diazonium salt of the above-defined general formula III, to give compounds of the general formula I, wherein Ra represents phenyl optionally substituted with 1-3 mutually identical or different substituents selected from the following, namely halogen, alkyl of 1-4 carbon atoms, alkoxy of 1-4 carbon atoms, phenyloxy, hydroxy, nitro, amino, cyano, carboxy , alkoxycarbonyl having 1-4 carbon atoms in the alkoxy moiety, alkanoyl having 1-4 carbon atoms, methylenedioxy, trifluoromethyl, phenyl and dialkylamino having 1-4 carbon atoms in the alkyl group, or maf- 1, R2, R3 and the dashed lines. tyl and R, R jerna has the meanings given above, or (c) a pyridolyl-b7quinazoline-11-derivative of the general formula Rz '3 R al I \\ ñ / I V R Q R.
RB där R, Rl, RQ, R5 och de streckade linjerna har ovan an- givna betydelser och R8 representerar väte eller halogen och R9 halogen, omsättes med ett hydrazinderivat med den allmänna formeln 4 R\N H - NH VI 8103940-6 \|': ' 'U 40, där R4 har ovan angiven betydelse, varpå, om så önskas, en så erhållen förening med den allmänna formeln I och innehållande en syragrupp omvandlas med en bas till ett salt eller en förening I omvandlas med en syra till ett syraadditionssalt, eller en förening med den allmänna formeln I frigöres ur ett salt därav bildat med en syra eller en bas. I Det under (a) här ovan angivna förfarandet, dvs. om- sättning av föreningen II med diazoniumsaltet III, genom- föres enligt Parmerter: Org. Reactions, lO, p, l-142 (l959); Phillips: Org. Reactions 10, p. 143-178 (1959)).RB where R, R1, RQ, R5 and the dashed lines have the meanings given above and R8 represents hydrogen or halogen and R9 halogen is reacted with a hydrazine derivative of the general formula 4 R \ NH - NH VI 8103940-6 \ | ' U 40, where R 4 is as defined above, whereupon, if desired, a compound of the general formula I thus obtained containing an acid group is converted with a base into a salt or a compound I is converted with an acid into an acid addition salt. , or a compound of general formula I is liberated from a salt thereof formed with an acid or a base. In the procedure specified under (a) above, i.e. reaction of the compound II with the diazonium salt III, is carried out according to Parmerter: Org. Reactions, 10, p, l-142 (l959); Phillips: Org. Reactions 10, pp. 143-178 (1959)).
Enligt en töredragen utföringsform.genomfördes reak- tionen vid en temperatur under 5000, företrädesvis mellan -10 och +20°C. Komponenterna kan tillföras genom att man tillsätter en given förening II till en lösning av dia- zoniumsaltet III eller omvänt. Komponenterna kan före- trädesvis användas i ekvimolara mängder, men en av kompo- nenterna kan eventuellt användas i ett ringa överskott.According to a preferred embodiment, the reaction was carried out at a temperature below 5000, preferably between -10 and + 20 ° C. The components can be added by adding a given compound II to a solution of the diazonium salt III or vice versa. The components can preferably be used in equimolar amounts, but one of the components can possibly be used in a small excess.
Reaktionen kan lämpligen genomföras i vattenhaltigt medium, om så önskas i närvaro av ett med vatten blandbart, inert, organiskt lösningsmedel.The reaction may conveniently be carried out in aqueous medium, if desired in the presence of a water-miscible, inert organic solvent.
Som inert organiskt lösningsmedel kan man använda alkankarboxylsyror, företrädesvis ättikeyra, propion- syra, syraamider, företrädesvis N,N-dimetyl-formamid, alkoholer, företrädesvis metanol, etanol, propanol, iso- propanol, ketoner, såsom aceton, metyletylketon, aroma- tiska baser, företrädesvis pyridin. Reaktionen kan lämp- ligen genomföras i närvaro av ett syrabindande medel.As the inert organic solvent one can use alkane carboxylic acids, preferably acetic acid, propionic acid, acid amides, preferably N, N-dimethylformamide, alcohols, preferably methanol, ethanol, propanol, isopropanol, ketones such as acetone, methyl ethyl ketone, aromatic bases, preferably pyridine. The reaction may conveniently be carried out in the presence of an acid scavenger.
Som syrabindande-medel användes alkalimetallalkanoat, företrädesvis natriumacetat, kaliumacetat eller alkali- metallhydroxider, företrädesvis natriurahydroxíd, kalium- hydroxid eller alkalimetallkarbonat, företrädesvis na- triumkarbonat, kaliumkarbonat, natriumbikarbonat etc.As acid-binding agents, alkali metal alkanoate, preferably sodium acetate, potassium acetate or alkali metal hydroxides, preferably sodium hydroxide, potassium hydroxide or alkali metal carbonate, preferably sodium carbonate, potassium carbonate, sodium bicarbonate, etc. are used.
Vid det under (b) här ovan angivna förfarandet om- sättes föreningen IV med ett diazoniumsalt III. En före- dragen utföringsform genomföras på sätt som ovan an- gives beträffande'det'unda=(a) angivna förfarandet.In the process indicated under (b) above, compound IV is reacted with a diazonium salt III. A preferred embodiment is carried out in the manner indicated above with respect to the'unda'unda = (a) specified procedure.
Vid det under (c) här ovan angivna förfarandet om- sättes föreningen V med en hydrazin_med formeln VI. Som förening V kan man lämpligen använda en föreninå V, där Q.In the process indicated under (c) above, compound V is reacted with a hydrazine of formula VI. As compound V it is convenient to use a compound V, where Q.
?O *am i) 8103940-6 R8 och H9 representerar klor eller brom. Föreningarna V och VI omsättes lämpligen i närvaro av ett inert lös~ ningsmedel. Som inert lösningsmedel kan man använda alka~ noler företrädesvis metanol, etanol, propanol, isopropa~ noler etc. alkankarboxylsyror, företrädesvis ättiksyra, propionsyra, syraamider, såsom N,N-dimetylformnmid, aromatiska baser, företrädesvis pyridin. De uppräknads lösningsmedlen kan eventuellt sammanblandas med vatten, varpå reaktionen genomfördes i en blandning av vatten och ett med vatten icke blandbart organiskt lösningsmedel. Om så önskas kan man använda ett syrabindande medel. Som syrabindande medel kan man använda de substanser som uppräknats här ovan i samband med det under (a) angivna förfarandet. Ett överskott på hydrazinen VI kan också tjäna som syrabindande medel. Enligt en föredragen ut- föringsform av sättet kan man använda 1-8 mol, i synner- het 2,5-4,5 mol hydrazin VI per en mol av föreningen V.? O * am i) 8103940-6 R8 and H9 represent chlorine or bromine. Compounds V and VI are conveniently reacted in the presence of an inert solvent. As the inert solvent one can use alkanols preferably methanol, ethanol, propanol, isopropanols etc. alkanecarboxylic acids, preferably acetic acid, propionic acid, acid amides such as N, N-dimethylformamide, aromatic bases, preferably pyridine. The solvents listed can optionally be mixed with water, whereupon the reaction is carried out in a mixture of water and a water-immiscible organic solvent. If desired, an acid scavenger can be used. As acid-binding agents, the substances listed above can be used in connection with the process indicated under (a). An excess of hydrazine VI can also serve as an acid scavenger. According to a preferred embodiment of the process, 1-8 moles, in particular 2.5-4.5 moles of hydrazine VI can be used per one mole of the compound V.
Reaktionen kan genomföras vid en temperatur mellan O och l50°G och när man använder ett lösningsmedel genomfördes reaktionen lämpligen vid lösningsmedlets eller lösnings~ medelsblandningens kokpunkt. Reaktionstiden kan variera mellan 50 minuter och 10 timmar allt efter vilka reaktions- komponenter som omsättes. Föreningarna I som erhålles under de under Ca), (b) eller (c) här ovan beskrivna förfarandena utfatter ur reaktionsblandningen eller också utfaller de vid utspädning med vatten och kan av- filtreras, avcentrifugeras eller isoleras på annat lämp- ligt sätt.The reaction can be carried out at a temperature between 0 DEG and 150 DEG C. and when using a solvent, the reaction is conveniently carried out at the boiling point of the solvent or solvent mixture. The reaction time can vary between 50 minutes and 10 hours depending on the reactants being reacted. The compounds I obtained during the processes described under Ca), (b) or (c) above are extracted from the reaction mixture or they precipitate on dilution with water and can be filtered off, centrifuged or isolated in another suitable manner.
Föreningarna I bildar salter med organiska och oor- ganiska syror, sålunda kan man exempelvis framställa hydroklorider, hydrobromider, sulfat, fosfat, perklorat, maleat, acetat etc.The compounds I form salts with organic and inorganic acids, thus, for example, hydrochlorides, hydrobromides, sulphates, phosphates, perchlorate, maleate, acetate, etc. can be prepared.
Föreningarna I, som innehåller minst en karboxyl- grupp bildar salter med baser, såsom alkalimetallsalter, exempelvis natrium- eller kaliumsalter, salter av alkalis- ka jordartsmetaller, såsom kalcium- eller magnesiumsalter, eller salter av tertiära aminer, såsom trietylaminsalter eller etanolaminsalter etc.Compounds I, which contain at least one carboxyl group, form salts with bases, such as alkali metal salts, for example sodium or potassium salts, salts of alkaline earth metals, such as calcium or magnesium salts, or salts of tertiary amines, such as triethylamine salts or ethanolamine salts, etc.
Uppfinningen innefattar också framställning av op- tiska och geometríska isomerer och tautomerer av före- Pülo" ÛUAL/ïïy -š C 8103940-6 ß . ^ _ . -"_ N ” 7 nlngarna. Optlska lsomerer upptrauer nar R) i formeln I representerar någon av de angivna grupperna med undan» tag av väte. De gebmetriska isomerernas struktur framgår av följande allmänna formler 3 - R Ra (f RI // R N\ 4 1 f R N H / och 2 R 0 Rg R-l I R H Rflr/ "_ H Strukturen hos möjliga tautomerer framgår av tionsschema A.The invention also encompasses the preparation of optical and geometric isomers and tautomers of the precursors of the C8103940-6 β. Optical isomers occur when R) in formula I represents one of the groups indicated with the exception of hydrogen. The structure of the geometric isomers is given by the following general formulas 3 - R Ra (f RI // R N \ 4 1 f R N H / and 2 R 0 Rg R-1 I R H R fl r / "_ H The structure of possible tautomers is shown in Scheme A.
IA IB reak- ?Ü \N W 'GJ \.J“| #0 I 8103940-6 Reaktionsschema A 3 En förening med den allmänna focmoïr I kan frigöras ur sina salter med en syra eller en bas på i och för si¿ känt sätt. a En erhållen förening I kan omvandlas till ett syra- additionesalt genom omsättning med en organisk eller o- organisk syra. Saltbildningen kan genomföras på i och för sig känt sätt och innefattar omsättning av föreningen I med en motsvarande syra i molar ekvivalent mängd eller i överskott i närvaro av ett inert organiskt lösnings- medel.IA IB reak-? Ü \ N W 'GJ \ .J “| # 0 I 8103940-6 Reaction Scheme A 3 A compound of the general form I can be liberated from its salts with an acid or a base in a manner known per se. A obtained compound I can be converted into an acid addition salt by reaction with an organic or inorganic acid. The salt formation can be carried out in a manner known per se and comprises reacting the compound I with a corresponding acid in molar equivalent amount or in excess in the presence of an inert organic solvent.
Föreningar I innehållande en karboxylgrnpp kan om- vandlas till salter genom omsättning med en lämplig bas, alkelmetallhydroxid, hydroxid av alkalisk jordartsmetall eller organisk amin på i och för sig känt sätt.Compounds I containing a carboxyl group can be converted into salts by reaction with a suitable base, alkali metal hydroxide, hydroxide of alkaline earth metal or organic amine in a manner known per se.
De flesta av utgàngsmaterialen är kända. Utgångs~ materialen med de allmänna formlerna II, IV och V be- skrives i Kokai Tokyo Koho 78 150 435 och BE-PS 849 542 och 84? Oll och DE~PS 2 812 585 och 2 812 586, Hosby: Heterocyclic Systems with bridgehead nitrogen atom, Vol. 2, p. ll55-ll59, Interscience Publishers, Inc.Most of the starting materials are known. The starting materials of the general formulas II, IV and V are described in Kokai Tokyo Koho 78 150 435 and BE-PS 849 542 and 84? Oll and DE ~ PS 2 812 585 and 2 812 586, Hosby: Heterocyclic Systems with bridgehead nitrogen atom, Vol. 2, pp. Ll55-ll59, Interscience Publishers, Inc.
New York, 1961, Him. Geterocycl. Soed. 1976, l564-1569, 8105940-6 '/\ .lv H.) a x ß.) nn 1,10 1979, 684-691 eller kan framställas på sätt som beskriven i ovan nämnda artiklar.New York, 1961, Him. Geterocycl. Soed. 1976, l564-1569, 8105940-6 '/ \ .lv H.) a x ß.) Nn 1,10 1979, 684-691 or can be prepared in the manner described in the above-mentioned articles.
Föreningarna I är mellanprodukter för rutekarpin- alkaloider och rutekarpinanaloger.Compounds I are intermediates for rutecarpine alkaloids and rutinecarpine analogues.
Ytterligare detaljer beträffande uppfinningen fram- går av följande icke begränsande exempel.Further details regarding the invention appear from the following non-limiting examples.
Exempel l-22 - - 0,1 mol anilinderivat blandades med 5 ml 28 % (volym/ vikt) saltsyralösníng i utspädning 1:1 och blandningen kyldes till -5°C.En lösning av 0,69 g (0,0l mol) natrium- nitrit i 5 ml vatten tillsattes långsamt och droppvis under oavbruten omrörning och kylning. Reaktionsbland- ningen omrördes därefter i 50 minuter vid en temperatur mellan -5 och OOC, varpå reaktionsblandningens pH in- justerades pâ 4 genom tillsats av natriumacetat. Bland- ningen utspäddes med 5 ml isättika och en lösning av 2,0 g (0,0l mol) ll-oxo-6,7,8,9-tetrahydro-1lH-pyrido- /2.1-a/kinazolin i 10 ml av en 50 volymprocentig ättik- syra tillsattes droppvis. Reaktionsblandningen omrördes i 5 timmar vid en temperatur mellan -5 och 000. Bland- ningen fick därefter stå över natten i kylskåp. De ut- fällda kristallerna avfiltrerades och tvättades med vat- ten och man erhöll 6-fenylhydrazon-ll-oxo-6,?,8,Q-tetra- hydro-llH-pyrido[É.l-b/kinazolin, som, om så erfordades, renades genom omkristallisation i n-propanol. Det fram- ställda produkterna är sammanställda i tabell l.Example 1-22 - 0.1 mol of aniline derivative was mixed with 5 ml of 28% (v / v) hydrochloric acid solution in dilution 1: 1 and the mixture was cooled to -5 ° C. A solution of 0.69 g (0.0l mol) Sodium nitrite in 5 ml of water was added slowly and dropwise with continuous stirring and cooling. The reaction mixture was then stirred for 50 minutes at a temperature between -5 and 0 ° C, after which the pH of the reaction mixture was adjusted to 4 by the addition of sodium acetate. The mixture was diluted with 5 ml of glacial acetic acid and a solution of 2.0 g (0.01 mol) of 11-oxo-6,7,8,9-tetrahydro-11H-pyrido [2,1-a] quinazoline in 10 ml of a 50% by volume acetic acid was added dropwise. The reaction mixture was stirred for 5 hours at a temperature between -5 and 000. The mixture was then allowed to stand overnight in a refrigerator. The precipitated crystals were filtered off and washed with water to give 6-phenylhydrazone-11-oxo-6,8,8-Q-tetrahydro-11H-pyrido [ε] /binazoline, which, if required , was purified by recrystallization from n-propanol. The products produced are summarized in Table 1.
Exempel 2§-24 Man förfor på sätt som angives i exemplen l-22 med den ändringen, att man som utgângsmaterial använde ll- oxo-I,2,5,4,6,7,8,9-oktahydro-llH-pyridojë.l-Qfkinazolin i stället- far il-om-e,7,8,94:etrahyaro-lln-pyriaogë.1- Q/kinazolin.Example 2§-24 The procedure set forth in Examples 1-22 was modified with the change that the starting material used was 11-oxo-I, 2,5,4,6,7,8,9-octahydro-11H-pyrido .l-Qfkinazoline instead- far il-om-e, 7,8,94: etrahyaro-lln-pyriaogë.1- Q / quinazoline.
De framställda föreningarna är sammanställda i tabell 2. 8103940-6 I. mans b.5420 _ wm.mH mw.v mw.om oß.mH ow.w mm.ow Ho~o«z>HImHo Im \@\o0m- II|oI|w I I I I mfl mH.mH.wß.v mm.mm ~<.«H mm.« ~ß.mm HooHImfio vw o Hmw II|@z|v I I I Holm IH ImN.wH mm.m mm.mm ßH.wH m~.m ßm.v~ mm.< mm.oß mm.vH ww.w ßm.oß on=nwvw .I I I I wfi ow.«H Im.« mm.oß mm.«~ s=nmrH I I I I HH mw.ßH mw.m «m.Hß Im.ßH mm.m ßm.H> ovzw~ImHu mß o@wm~|mmH II mI|m I I I od w>.<fl mß.m wo.mm .mo.m~ m>.m mo.mm ~Hoo Hß.wH wm.v mw.wH mm.v mm.mm mm.wH w<.« Hw.mw HoowzmHIw~u mm o°mwH|HmH II|Hu|m I I I I ß ßo. mm. ~m.«H mw.m v~.mm Hw.«H wm.m Hv.wm Imo«zmHImHo Im ommufifomfl II|Im|< .I I I I I ww.>~ ow.m mH.~ß mm.ßH mm.m ßm.Hß o m~.wH ßw.w Ho. w~.wH ß~.m ßm.@ß H«.mH m~.m mo.Hß owzmHIm~o om o° II ...I u* za II ua. vm. mm Nm .HI I ßwflflßm mhflmfiåvmfluflmfimm Mm..¶...m_~._.u~%flw~m _ R . fiflfim H flfimsnom mflflwfiflflm .mmm I . m mnhnvm ...Pflmäw flmø .nos mflwflmnmm 1895 I¿\\wm H Hflwpma É I o nu. 0 Nm 8TÛ394Û-6 H~.mH w~.míNß.mw ßm.mH mw.m ~m.mm mowzowmomu mm Apvooomm gm : I omznm o@z|~fl Nm ~m.mH om.< w~.~m wd.m~ Hefiw mm.~m Hu:.omzm~:mHo Nm . ooßflw .;m|zu|< z : _: I . HN Hm.oN wm.v ~m.mm mw.o~ ~>.< «ß.mm Hu:.omzmH:ßAo mw Uommfl H>uflL>@|m : = : z ow ~m. ~o.mH mv-w mm.Qw .Hw.mH m<.w m~.om Houowzmfizwflo om oomvw _;m|m|v _: = :_ =. QH wm.mH mH.« «o.wm mH.mH wH.w >H.mm fluwomzmflxßfio mm ñpvooomm Lmuwoznv I = : :H ßfl om.wH m~.m.oH.~m oH.mfl w~.m mm.Hm fluwowzmfirmflu um nommm ;L|ou:|v I I : I wfl zæ š o m z* .ä o vu nu m .Hm m ¶ pwnøsm _ pmqxwnmm fiwsnofl , pxøøm H.nH@ano« wflnmefifiw =fl@m mhfimfiå Mmflnwmäm .wnhnufifi ...ßfimëm flwu vwa wnwflonæm ...Smfim . . .m .mfimnmmå .mwrHoH P00 WALÉY 6 y _ 0 W 0/ 4 0 l 9 A. s PU 4II o Û 8 . .2 86 mmåm. .BLS Så mßåß owzwwzmflu mm oQmmH-om." m.. »fïm z _.. _._ vw BJJ Så 39mm 3.2 nmå oïoß owzomxmfiu mm oomowumow .É _.. _.. z z nu l _ . . l z z u z _ z o . m wm mm wm Hm m »mcnsm .Éfiwnwm .Ršnom wfiwp »Musa _ H mšæë mfifimmw mä, _ »ämsw WWMEMMW MMMMWMNM Läww m Swêå m w _.=_._\ QS z z m . \ Hm m 8103940-6 12 \."\ .N \J'! Exemgel 25 ,8 g (0¿0Z mal) 6,6~dibrom-5,7,8,9~tetrahydro-ll~oxo~ llH-pyridofë.5-Qfkinazolín-och 15,0 g (0,l2 mol) fenyl~ hydrazin upphettades i l2O ml etanol i 4 timmar. De ut- fällda kristallerna avfiltrerades efter kylning. Efter in- dunstning av moderluten utföll ytterligare kristaller. Denna avfiltrcrades och tvättades med en ringa mängd alkohol, Den kombinerade, avfiltrerade produkten suspenderades i l50 ml vatten innehållande 8,4 g (0,06 mol) natriumacetat, -varpå den avfiltrerades och tvättades med vatten. kan erhöll 3,4 g (81%) 6-fenylhydrazono-6,?,8,9~tetrahydro-ll-oxo- llH-Qyrido[ä.l-bzkinazolin, som efter omkristallisation i isopropanol hade smältpunkt 177-17900. Den gav vid samman- blandning med produkten enligt exempel 1 ingen smältnunkta- depression. G Exemgel 26 ,74 g (0,01 mol) 6,6-dibrom-9-metyl-ll-oxo-6,7,8,9- tetrahyaro-113-pyriao/2.1-aíkinazolin och 4,52 g (o,o4 mol) fenylhydrazin upphettades i 40 ml etanol i 10 timmar.The compounds prepared are summarized in Table 2. 8103940-6 I. mans b.5420 _ wm.mH mw.v mw.om oß.mH ow.w mm.ow Ho ~ o «z> HImHo Im \ @ \ o0m- II | oI | w IIII m fl mH.mH.wß.v mm.mm ~ <. «H mm.« ~ Ss.mm HooHIm fi o vw o Hmw II | @z | v III Holm IH ImN.wH mm.m mm. mm ßH.wH m ~ .m ßm.v ~ mm. <mm.oß mm.vH ww.w ßm.oß on = nwvw .IIII w fi ow. «H Im.« mm.oß mm. «~ s = nmrH IIII HH mw.ßH mw.m «m.Hß Im.ßH mm.m ßm.H> ovzw ~ ImHu mß o @ wm ~ | mmH II mI | m III od w>. <Fl mß.m wo.mm. mo.m ~ m> .m mo.mm ~ Hoo Hß.wH wm.v mw.wH mm.v mm.mm mm.wH w <. «Hw.mw HoowzmHIw ~ u mm o ° mwH | HmH II | Hu | m IIII ß ßo. mm. ~ m. «H mw.mv ~ .mm Hw.« H wm.m Hv.wm Imo «zmHImHo Im ommu fi fom fl II | Im | <.IIIII ww.> ~ ow.m mH. ~ ß mm.ßH mm.m ßm.Hß om ~ .wH ßw.w Ho. w ~ .wH ß ~ .m ßm. @ ß H «.mH m ~ .m mo.Hß owzmHIm ~ o om o ° II ... I u * za II ua. vm. mm Nm .HI I ßw flfl ßm mh fl m fi åvm fl u fl m fi mm Mm..¶ ... m_ ~ ._. u ~% fl w ~ m _ R. H m H flfi msnom m flfl w fiflfl m .mmm I. m mnhnvm ... P fl mäw fl mø .nos m fl w fl mnmm 1895 I¿ \\ wm H H fl wpma É I o nu. 0 Nm 8TÛ394Û-6 H ~ .mH w ~ .míNß.mw ßm.mH mw.m ~ m.mm mowzowmomu mm Apvooomm gm: I omznm o @ z | ~ fl Nm ~ m.mH om. <W ~. ~ m wd.m ~ He fi w mm. ~ m Hu: .omzm ~: mHo Nm. ooß fl w.; m | zu | <z: _: I. HN Hm.oN wm.v ~ m.mm mw.o ~ ~>. <«Ss.mm Hu: .omzmH: ßAo mw Uomm fl H> u fl L> @ | m: =: z ow ~ m. ~ o.mH mv-w mm.Qw .Hw.mH m <.w m ~ .om Houowzm fi zw fl o om oomvw _; m | m | v _: =: _ =. QH wm.mH mH. «« O.wm mH.mH wH.w> H.mm fl uwomzm fl xß fi o mm ñpvooomm Lmuwoznv I =:: H ß fl om.wH m ~ .m.oH. ~ M oH.m fl w ~ .m mm.Hm fl uwowzm fi rm fl u um nommm; L | ou: | v II: I w fl zæ š omz * .ä o vu nu m .Hm m ¶ pwnøsm _ pmqxwnmm fi wsno fl, pxøøm H.nH@ano «w fl nme fifi w = fl @ m mm mh fi m .wnhnu fifi ... ß fi mëm fl wu vwa wnw fl onæm ... Sm fi m. . .m .m fi mnmmå .mwrHoH P00 WALÉY 6 y _ 0 W 0/4 0 l 9 A. s PU 4II o Û 8. .2 86 mmåm. .BLS Så mßåß owzwwzm fl u mm oQmmH-om. "M ..» fïm z _ .. _._ vw BJJ Så 39mm 3.2 nmå oïoß owzomxm fi u mm oomowumow .É _ .. _ .. zz nu l _.. Lzzuz _ zo . m wm mm wm Hm m »mcnsm .É fi wnwm .Ršnom w fi wp» Musa _ H mšæë m fifi mmw mä, _ »ämsw WWMEMMW MMMMWMNM Läww m Swêå mw _. = _._ \ QS zzm. \ Hm m 8103940-6. "\ .N \ J '! Example gel 25, 8 g (0Z2 mal) 6,6-dibromo-5,7,8,9-tetrahydro-11-oxo-11H-pyridophe-5-quinazoline and 15.0 g (0.2 mol) phenyl-hydrazine was heated in 120 ml of ethanol for 4 hours. The precipitated crystals were filtered off after cooling. After evaporation of the mother liquor, additional crystals precipitated. This was filtered off and washed with a small amount of alcohol. The combined, filtered product was suspended in 150 ml of water containing 8.4 g (0.06 mol) of sodium acetate, whereupon it was filtered off and washed with water. can be obtained 3.4 g (81%) of 6-phenylhydrazono-6, 8,9-tetrahydro-11-oxo-11H-Qyrido [α] b-quinazoline, which after recrystallization from isopropanol had a melting point of 177-17900. When mixed with the product of Example 1, it did not give a melting point depression. G Example gel 26, 74 g (0.01 mol) of 6,6-dibromo-9-methyl-11-oxo-6,7,8,9-tetrahyaro-113-pyrrolo [2,1-a] quinazoline and 4.52 g (o (4 mol) of phenylhydrazine was heated in 40 ml of ethanol for 10 hours.
De utfällda kristallerna avfiltrerades efter kylning. Den filtrerade produkten suspenderades i 100 ml vatten inne- hållande 2,?2 g (0,02 mol) natriumacetat, filtrerades och tvättades med vatten. Man erhöll 2,4 g (75%) orangefärgad 6-fenylhydrazono-9-metyl-ll-oxo-E,?,8,9-tetrahydro-llH- pyrido[É.l-Qfkinazolin, som efter omkrístallisation i etanol hade smältpunkt l85~l87°G.The precipitated crystals were filtered off after cooling. The filtered product was suspended in 100 ml of water containing 2.2 g (0.02 mol) of sodium acetate, filtered and washed with water. 2.4 g (75%) of orange-6-phenylhydrazono-9-methyl-11-oxo-E, 8,9-tetrahydro-11H-pyrido [ε] -quinazoline were obtained, which had a melting point after recrystallization from ethanol. l85 ~ l87 ° G.
Analys -. % C % H % H Beräknat för 0l9Hl8H4O 71,67 .5,69 _ l7,59 Funnet: 5 71,62 5,58 l?,55 Exemnel 22 2,?9 5 (0,0l mol 6-brom-ll-oxo-6,?,8,9-tetrahydro- 11H-pyriaojë.1-Q/kinazolin och 2,15 g (o,o2 moi) fenyl- hydrazin upphettades i 50 ml etanol i 6 timmar vid 8000.Analysis -. % C% H% H Calculated for 19 H 18 H 4 O 71.67 .5.69 - 17.59 Found: 5 71.62 5.58 l?, 55 Example 22 2.9 5 (0.0l mol 6-bromo-11 -oxo-6,8,8,9-tetrahydro-11H-pyrrolo [1,1-quinazoline] and 2.15 g (0.8 mole) of phenylhydrazine were heated in 50 ml of ethanol for 6 hours at 8000.
Etanolen koncentrerades därefter till en tredjedel av sin volym och blandningen fick kristallisera i en islåda. De utfällda gula kristallerna avfiltrerades och tvättades med etanol och vatten. Man erhöll 2,1 g (69%) 6-fenyl-hyåra- zono-ll-oxo-6,7,8,9-tetrahydro-pyridojë.l-Qfkinazolin, som efter omkristallisation i isopropanol hade smältnunkt 179- ' 18000. Produkten gav vid sammanblandning-med produkten '7enligt'exempel l eller É5 ingen smëltpunktsdepression.The ethanol was then concentrated to one third of its volume and the mixture was allowed to crystallize in an ice box. The precipitated yellow crystals were filtered off and washed with ethanol and water. 2.1 g (69%) of 6-phenyl-hyrazone-11-oxo-6,7,8,9-tetrahydro-pyridoyl-quinaquinazoline were obtained, which after recrystallization from isopropanol had a melting point of 179-18000. When mixed with the product '7 according to Example 1 or É5, the product did not give a melting point depression.
Poonii* o lwAuTv \}'ï r-J \_n Ä) ' .Fl <3 8103940-6 Analys - % C I 5 J % L Beräknat för Cl8HlöN¿0 71,05 5,29 l8,“l Funnet: ?0,88 5,25 16,58 Exempel 28 s o,95 g (o,9 ml, o,o1 mel) aniiin leaves 1 5 ml 38 % (volym/vikt) saltsyra i utspädning 1:1 och lösningen kyl- des till -500. En lösning av 0,65 5 (0,fi1 mol) natrium- nitrit i 5 ml vatten tilleattes droppvis under oavbruten kylning och omrörning. Reaktionsblandningen omrördes i 50 minuter vid en temperátur mellan -5 och 000, varpå lösningens pH injusterades på 4 genom tillsats av natrium~ aeetat, varpå lösningen utspäddes med_l0 ml ättiksyra.Poonii * o lwAuTv \} 'ï rJ \ _n Ä)' .Fl <3 8103940-6 Analysis -% CI 5 J% L Calculated for Cl8HlöN¿0 71.05 5.29 l8, “l Found:? 0.88 5.25 16.58 Example 28 so, 95 g (0.9 ml, 0.1 ml flour) aniiin leaves 1 5 ml 38% (v / v) hydrochloric acid in dilution 1: 1 and the solution was cooled to -500. A solution of 0.65 (0.1 mol) of sodium nitrite in 5 ml of water was added dropwise with continuous cooling and stirring. The reaction mixture was stirred for 50 minutes at a temperature between -5 and 000, after which the pH of the solution was adjusted to 4 by the addition of sodium acetate, after which the solution was diluted with 10 ml of acetic acid.
Till lösningen av diazoniumsaltet sattes långsamt och droppvis vid -500 en lösning av 2,55 5 9-(dimetylamino- metylen)-ll- oxo-6,7,8,9-tetrahydro~llH-pyrido[É.1-of kinazolin i 25 ml dimetylformamid. Reaktionsblandningen omrördes vid OOC i 5 timmar, varpå den fick stå över nat- ten i en islåda. ßlandningen utspäddes därefter med vat- ten och de utfällda kristallerna avfiltrerades och tvätta- dee med vatten. man erhöll ?,ßl 5 (ßëfi) fi-fenyl-hydra- zono-6,7,8,9-tetrahydro-11-oxo-llfl-pyríüo/É.l-b/kinezo- lin, som efter omkristallisation i isopropanol hade on smältpunkt av 182-l8#°C. Produkten gav vid sammanblnnd- ning med produkten enligt exempel 1 ingen smältpunkts- depression.To the solution of the diazonium salt was added slowly and dropwise at -500 a solution of 2,55 9- (dimethylaminomethylene) -11-oxo-6,7,8,9-tetrahydro-11H-pyrido [.1.1-of quinazoline in 25 ml of dimethylformamide. The reaction mixture was stirred at 0 ° C for 5 hours, after which it was allowed to stand overnight in an ice box. The landing was then diluted with water and the precipitated crystals were filtered off and washed with water. There was obtained?, ßl 5 (ßë fi) fi-phenyl-hydrazono-6,7,8,9-tetrahydro-11-oxo-11-pyriol / É.lb / quinezoline, which after recrystallization from isopropanol had on melting point of 182-188 ° C. The product did not give melting point depression when mixed with the product of Example 1.
Analys - r _ % 0 % H m N Beräknat för Cl8Hl6N40" 71,05 5,29 18,41 Funnet: 70,95 5,24 18,55 Exemgel 2? 0,95 g (0,0l mol) anilin löstes i 5 ml av en (volym/vikt) saltsyrn i utspädning Lïl och det hela kyl- des till -500. En lösning av 0,59 g (Û,Ol mel) natrium- nitrit i 5 ml vatten tillsattes droppvis under oavbruten 58% omrörning och kylning. Reaktioneblandningen omršrdev i en halv timme vid en temperatur mellan -500 och OÛC, varpå lösningens pH injusterades på 4 genom tillsats av na- triumaoetat. Lösningen utspäddes med 10 ml ättiksyra. till reaktioneblandningen sattes långaamt och droppvis en lösning av 2,28 3 (0,0l mol) ö-formy"-ll-oxo-í,?,8,9- tetrahydro-11H-pyridojë.1-Qjkinazolin i 50 ml ättikeyra. 8103940-6 _ 14 'Jl elle" Blandningen omrördes i l timme vid en temperatur under 000 oeh_lösningen fick därefter stå i kylskåpet. De ut- - fällda kristallerna avfiltrerades och tvättades med vatten och man erhöll 5,1 g (91%) e-fenyl~hyarazono-e,?,s,9- tetrahydro-ll-oxo-llH-pyrido/É_1-Q/kinazolin-hydroklorid med smältpunkt 25500.Analysis - r% 0% H m N Calculated for C 18 H 16 N 4 O 71.05 5.29 18.41 Found: 70.95 5.24 18.55 Example gel 2? 0.95 g (0.01 mol) of aniline was dissolved in 5 ml of one (v / v) hydrochloric acid in dilution L11 and the whole was cooled to -500. A solution of 0.59 g (Û, Ol flour) of sodium nitrite in 5 ml of water was added dropwise with continuous 58% stirring. The reaction mixture was stirred for half an hour at a temperature between -500 DEG C. and 0 DEG C., after which the pH of the solution was adjusted to 4 by the addition of sodium acetate, the solution was diluted with 10 ml of acetic acid and the reaction mixture was slowly added dropwise. 3 (0,01 mol) of β-formyl "-11-oxo-1,8,9-tetrahydro-11H-pyrido [1,1] quinazoline in 50 ml of acetic acid. The mixture was stirred for 1 hour at a temperature below 000 DEG C. The solution was then allowed to stand in the refrigerator. The precipitated crystals were filtered off and washed with water to give 5.1 g (91%) of e-phenyl. Hyarazono-e,?, s, 9-tetrahydro-11-oxo-11H-pyrido [ε] -1-quinazoline hydrochloride, m.p. 25,500.
Analyr - % C % E % N % Cl Beräknat för Cl8Hl7N4OCl 55,50 5,04 16,48 10,16 Funnet: 65,44 4,98 l&,59 10,11 Exempel §O-fifi lDet i exemplen 1-22 beskrivna förfarandet upprepades med andra utgångsmaterial. Sålunda användes i exempel 50 som pyrido[É.l-bfkinazolinderivat 2,5,4-trimetoxi-ll-oxo- 6,7,8,9¥tetrahydro-llH-pyridozä.l-bfkinazolin; i exempel 31 ll-oxo~6,7,8,9-tetrahydro-llH-pyrido[2.l-Qfkinaáolin- 2-karboxylsjra; i exempel 52 etyl-ll-oxo-6,7,8,9-tetra- hydro-llH~pyrido[2,l-Qfkinazolin-2-karboxylat och i exem- pel 55 ll-oxo-6,7,8,9-tetrahydro-1lH-pyridojë.lebfkina-4 zolin, och man erhöll 6-fenylhydrazono-ll~oxo-G,?,8,9- tecrahyaro-llfi-pyriao/2.1-hïkinazølin enligt tabell 5.Analysis -% C% E% N% Cl Calculated for Cl8H17N4OCl 55.50 5.04 16.48 10.16 Found: 65.44 4.98 l & .59 10.11 Example §O- fifi lIt in examples 1-22 described procedure was repeated with other starting materials. Thus, in Example 50, the pyrido [1,1-b] quinazoline derivative 2,5,4-trimethoxy-11-oxo-6,7,8,9 g of tetrahydro-11H-pyridoza.1-b] quinazoline was used; in Example 31 11-oxo-6,7,8,9-tetrahydro-11H-pyrido [2,1-quinaquinoline-2-carboxylic acid; in Example 52 ethyl 11-oxo-6,7,8,9-tetrahydro-11H-pyrido [2,1-f] quinazoline-2-carboxylate and in Example 55 11-oxo-6,7,8, 9-Tetrahydro-11H-pyridoylphequina-4zoline, and 6-phenylhydrazono-11-oxo-G, 8,9-tecrahyaro-11-pyriao-2,1-hikinazoline was obtained according to Table 5.
Produkterna omkristalliserades i n-propanol.The products were recrystallized from n-propanol.
Exempel 24-44 Man förfor på sätt som angiven i exemplen 23-24 och använde som utgångsmaterial ll-oxo-l,2,5,4,6,7,8,9~okta~ hydro-l1H-pyridojë.l-Qfkinazoliner, varigenom man erhöll 6-fenyl-hydrazono-4-oxo-l,2,5,4,6,7,8,9-oktahydro-llH- pyrido/2.1-bfkinazoliner enligt tabell 4. I I exemplen 42 och 45 suspenderades de kristaller som utföll ur diazokopplingsreaktionsblandningen i en % (volym/vikt) natriumhydroxidlösning och den vattenhal- tiga lösningen urskakades med kloroform. Klbroformlös- ningen torkades över vattenfritt natriumsulfat, indunsta- des och återstoden omkristalliserades.Examples 24-44 The procedure was as described in Examples 23-24 and the starting material used was 11-oxo-1,2,5,4,6,7,8,9-octa-hydro-11H-pyridoyl-1-quinaquinolines. to give 6-phenyl-hydrazono-4-oxo-1,2,5,4,6,7,8,9-octahydro-11H-pyrido [2,1-b] quinazolines according to Table 4. In Examples 42 and 45, the crystals which precipitated from the diazo coupling reaction mixture in a% (v / v) sodium hydroxide solution and the aqueous solution were shaken out with chloroform. The chloroform solution was dried over anhydrous sodium sulfate, evaporated and the residue was recrystallized.
Exempel 4§ 0,46 g (0,005 mol) anilin löstes i 5 ml 56% (volym/ vikt) saltsyra i utspädning lzl och lösningen kyldeš till -500. En lösning av 0,35 g (0,005 mol) natriumnitrit i ml vatten tillsattes droppvis. Reaktionsblandningen om- prördes i en halv timme vid en temperatur mellan -5 och OOC, varpå lösningens-pH injuseterades på 4 genom tillsats fïilñííx* auALgïví ~+--- ¿...A \_"I % 8103940-6 av natriumacetat. Till reaktíonsblandningen sattes lång- samt och droppvis en lösning av 1,23 g (0,005 mol) 6-formyl~ ll-oxo-l,2,5,4,6,7,8,9-oktahydro-11H-pyrido/É,1-Q/kinazolin i 15 ml av en 75% (volym/vikt) ättiksyra och lösningen om- rördes i 5 timmar vid en temperatur under 000. Därefter fick blandningen stå över natten i kylskåp och utspïddes med 50 ml vatten. De utfällda kristallerna avfiltrerades och tvättades med vatten och manerhöll 1,5 g (75%) 6~fenyl~ hydrazono-ll-oxo-1,2,3,4,6,?,8,9-oktahydro-ll-pyridojë.l-Q/ kinazolin~hydroklorid med smältpunkt 24?-24406.Example 4 § 0.46 g (0.005 mol) of aniline was dissolved in 5 ml of 56% (v / v) hydrochloric acid in dilution lzl and the solution cooled to -500. A solution of 0.35 g (0.005 mol) of sodium nitrite in ml of water was added dropwise. The reaction mixture was stirred for half an hour at a temperature between -5 DEG C. and 0 DEG C., after which the pH of the solution was injected at 4 by the addition of sodium acetate in% 8103940-6% sodium chloride. To the reaction mixture was added slowly and dropwise a solution of 1.23 g (0.005 mol) of 6-formyl-11-oxo-1,2,5,4,6,7,8,9-octahydro-11H-pyrido [E] , 1-Q / quinazoline in 15 ml of a 75% (v / v) acetic acid and the solution was stirred for 5 hours at a temperature below 000. The mixture was then allowed to stand overnight in a refrigerator and diluted with 50 ml of water. The crystals were filtered off and washed with water to give 1.5 g (75%) of 6-phenyl-hydrazono-11-oxo-1,2,3,4,6,,8,8,9-octahydro-11-pyridoyl. quinazoline hydrochloride, m.p. 24 DEG-244406.
Analys - % 0 % H % N % 01 Beräknat för clgfizšnuøcl 65,59 4,46 1;,c1 9,36 Funnet= 53,21 :,2s t 15,75 9,65 16 8103940-6 mtfi mwå mNZB ßmå.. moå moåm nowzowzflwo .mm . oošw ...fiïoooflïw I z _._ . 1 _ .mm wwiå 9.6 8.3 3.3 wmå 00.2 . nowzomzflwu . mm ooflou . .i _ _.. _.. z »mooulm .mn 4.0.2 mwtv 3.3 8.2 Nmå.. duåmm noqzmfixmflu . om Töooßm .É I z z :oounw Jm mwåå 36 moåö 3.3 36 ååw. wowzwuzflwu .R oïråmfi .E _._ mzonw Eànm 251m .om z .I u.. z. I Q _ . . fwm mm .~m. Hm m. vmnflsm ßmfimmnmm . flwëfiou & uxnßm H flflmfinow mfinmëflflm . Hmm _ mhfiæflfl Mmwnwmëm muhnßß Infimaw _ , flmø wms mflwfiwnæm lflmwm .. . _ . . . m Såwa, m :z\w H nflmflnou øma mnfldmnmm 2 .m 8103940-6 17 m«.ßH mß.m Hm.oß ßn.ßH ~m.m m~.oß owz-ImHu .mm oow II @z|ß I I I .vw ß~.wH m~.m ow.mm ~m.wH mH.m mn.mm ~HuowzoNImHu mm oomwwußww Im|Hoflu|m.n @z|m I I I .ne uv.>H ~m.w nm.oß nm.ß~ ~@.m mß.o~ owzmwImwu mm øomfiw II @:|w I I I .ww ~ß.«H ow.w mH.wß wo.mH om.m ßH.<ß o I I 0 HH oømßfifißfl H>I»IIm=|~ @:|m I I I .fiw um.mH mm.m mv.mm om.m~ mm.m wH.mm ~o nu.mH ~m.ß mm.Hß mm.mw@m«.ß ßm.Hß ø ~>.mH mm.w ßH.Hß m.mH .H.ß o<.Hß o ßH.ßH wm.m nm.oß wn.ßH @m.m wß.oß o«z-ImHu mw oowounmow II|uz|v I I I I .ßm oU.ßH m~.mH ßH.w ~m.mH Hm.m -.mm vm.wH mm.m mo.nm ~uowzmflI@Hu mn uoouu II|Hu|w . I I I I .«n.Analysis -% 0% H% N% 01 Calculated for clg fi zšnuøcl 65.59 4.46 1;, c1 9.36 Found = 53.21: .2s t 15.75 9.65 16 8103940-6 mt w mwå mNZB ßmå. .moå moåm nowzowz fl wo .mm. oošw ... fi ïooo fl ïw I z _._. 1 _ .mm wwiå 9.6 8.3 3.3 wmå 00.2. nowzomz fl wu. mm oo fl ou. .i _ _ .. _ .. z »mooulm .mn 4.0.2 mwtv 3.3 8.2 Nmå .. duåmm noqzm fi xm fl u. om Töooßm .É I z z: oounw Jm mwåå 36 moåö 3.3 36 ååw. wowzwuz fl wu .R oïråm fi .E _._ mzonw Eànm 251m .om z .I u .. z. I Q _. . fwm mm. ~ m. Hm m. Vmn fl sm ßm fi mmnmm. ë wë fi ou & uxnßm H flfl m fi now m fi nmë flfl m. Hmm _ mh fi æ flfl Mmwnwmëm muhnßß In fi maw _, fl mø wms m fl w fi wnæm l fl mwm ... _. . . m Såwa, m: z \ w H n fl m fl nou øma mn fl dmnmm 2 .m 8103940-6 17 m «.ßH mß.m Hm.oß ßn.ßH ~ mm m ~ .oß owz-ImHu .mm oow II @z | ß III .vw ß ~ .wH m ~ .m ow.mm ~ m.wH mH.m mn.mm ~ HuowzoNImHu mm oomwwußww Im | Ho fl u | mn @z | m III .ne uv.> H ~ mw nm.oß nm. ß ~ ~ @ .m mß.o ~ owzmwImwu mm øom fi w II @: | w III .ww ~ ß. «H ow.w mH.wß wo.mH om.m ßH. <ß o II 0 HH oømß fifi ß fl H> I »IIm = | ~ @: | m III .fi w um.mH mm.m mv.mm om.m ~ mm.m wH.mm ~ o nu.mH ~ m.ß mm.Hß mm.mw@m«. ß ßm.Hß ø ~> .mH mm.w ßH.Hß m.mH .H.ß o <.Hß o ßH.ßH wm.m nm.oß wn.ßH @mm wß.oß o «z-ImHu mw oowounmow II | uz | v IIII .ßm oU.ßH m ~ .mH ßH.w ~ m.mH Hm.m -.mm vm.wH mm.m mo.nm ~ uowzm fl I @ Hu mn uoouu II | Hu | w. I I I I. «N.
I I .u z I o Im , nu ~m Hu I uwnmøm vmfimnwm .nøflnom & ännu. H nfioanom .wflnmafiflm .Hmm mhdmflå. xmwnwnam mpmøbb Ivfimflm nmfl .uwfl wnwnonww lsæwm _ vu _ I fiflmpma Iñ\\\ H Qfiwsnow maa mnwnwnmm. _: m IL W POOR m QUALITYI I .u z I o Im, nu ~ m Hu I uwnmøm vm fi mnwm .nø fl nom & yet. H n fi oanom .w fl nma fifl m .Hmm mhdm fl å. xmwnwnam mpmøbb Iv fi m fl m nm fl .uw fl wnwnonww lsæwm _ vu _ I fifl mpma Iñ \\\ H Q fi wsnow maa mnwnwnmm. _: m IL W POOR m QUALITY
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU801559A HU183173B (en) | 1980-06-24 | 1980-06-24 | Process for producing 6-hydrazono-pyrido-aracket-2,1-b-bracket closed-quinazolin-11-ones |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SE8103940L SE8103940L (en) | 1981-12-25 |
| SE441829B true SE441829B (en) | 1985-11-11 |
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ID=10955013
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SE8103940A SE441829B (en) | 1980-06-24 | 1981-06-23 | 6-HYDROZONO-pyrido / 2,1-b / quinazolin-11-ones |
Country Status (25)
| Country | Link |
|---|---|
| JP (1) | JPS5738781A (en) |
| AT (1) | AT379393B (en) |
| AU (1) | AU544360B2 (en) |
| BE (1) | BE889339A (en) |
| CA (1) | CA1167842A (en) |
| CH (1) | CH648312A5 (en) |
| CS (1) | CS296285A2 (en) |
| DD (1) | DD160060A5 (en) |
| DE (1) | DE3124577A1 (en) |
| DK (1) | DK277281A (en) |
| ES (1) | ES8203370A1 (en) |
| FI (1) | FI70897C (en) |
| FR (1) | FR2485534A1 (en) |
| GB (1) | GB2080291B (en) |
| GR (1) | GR74608B (en) |
| HU (1) | HU183173B (en) |
| IL (1) | IL63061A (en) |
| IT (1) | IT1144814B (en) |
| NL (1) | NL8102935A (en) |
| NO (1) | NO157142C (en) |
| PL (2) | PL129635B1 (en) |
| PT (1) | PT73248B (en) |
| SE (1) | SE441829B (en) |
| SU (2) | SU1192614A3 (en) |
| YU (1) | YU42722B (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ194196A (en) * | 1979-07-17 | 1983-07-15 | Ici Australia Ltd | -(quinoxalin-2-yl(oxy or thio) phen (oxy or ylthio)-alkanoic acid derivatives or precursors |
| AT377586B (en) * | 1981-06-30 | 1985-04-10 | Erba Farmitalia | METHOD FOR PRODUCING SUBSTITUTED PYRROLO- (2,1-B) -QUINAZOLINES AND PYRIDO (2,1-B) -QUINAZOLINES |
| JPS5987269A (en) * | 1982-11-12 | 1984-05-19 | Nissan Motor Co Ltd | Fuel injection valve |
| JPS61126367A (en) * | 1984-11-24 | 1986-06-13 | Mitsubishi Heavy Ind Ltd | Fuel injection device |
| JPS61129457A (en) * | 1984-11-27 | 1986-06-17 | Mitsubishi Heavy Ind Ltd | Multi-fuel-valve injector |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU178496B (en) * | 1977-12-29 | 1982-05-28 | Chinoin Gyogyszer Es Vegyeszet | Process for preparing 6,7,8,9-tetrahydro-4h-pyrido/1,2-a/pyrimidine derivatives with antiallergic activity |
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1980
- 1980-06-24 HU HU801559A patent/HU183173B/en not_active IP Right Cessation
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1981
- 1981-06-09 IL IL63061A patent/IL63061A/en unknown
- 1981-06-18 NL NL8102935A patent/NL8102935A/en not_active Application Discontinuation
- 1981-06-18 CS CS852962A patent/CS296285A2/en unknown
- 1981-06-22 GR GR65305A patent/GR74608B/el unknown
- 1981-06-22 FR FR8112209A patent/FR2485534A1/en active Granted
- 1981-06-22 ES ES503266A patent/ES8203370A1/en not_active Expired
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- 1981-06-23 PL PL1981235214A patent/PL129635B1/en unknown
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- 1981-06-23 SU SU813301195A patent/SU1192614A3/en active
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- 1981-06-23 DE DE19813124577 patent/DE3124577A1/en not_active Withdrawn
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- 1981-06-23 AU AU72081/81A patent/AU544360B2/en not_active Ceased
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- 1981-06-23 BE BE0/205178A patent/BE889339A/en not_active IP Right Cessation
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1982
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