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PROCESS FOR PRODUCING NEW 12-AMINO-PIRIDAZINO/4-COMMA ABOVE,5-COMMA ABOVE:3,4/PYRROLO-ISOQUINOLINES

机译:制备新的12-氨基-吡咯并/ 4-COMMA以上,5-COMMA以上:3,4 /吡咯并异喹啉的过程

摘要

1. Claims for the Contracting States : BE, CH, DE, FR, GB, IT, LI, LU, NL, SE 12-Amino-pyridazino[4',5':3,4]pyrrolo[2,1-a]isoquinolines of general formula I see diagramm : EP0190563,P15,F1 wherein R1 and R2 , which may be identical or different, each represent hydrogen, C3-7 cycloalkyl, C2-5 alkenyl, phenyl (optionally mono- or disubstituted by halogen atoms or methoxy groups), propargyl, a straight-chained or branched, saturated or unsaturated alkyl group with 1 to 5 carbon atoms which may be substituted by hydroxy, alkoxy with 1 to 4 carbon atoms, halogen, NH2 , NH-alkyl with 1 to 2 carbon atoms, N,N-dialkyl with 1 to 2 carbon atoms, NH-acyl with 2 to 4 carbon atoms, cycloalkyl with 3 to 7 carbon atoms, phenyl (optionally substituted by halogen, alkyl with 1 to 2 carbon atoms, alkoxy with 1 to 2 carbon atoms, NH-alkyl with 1 to 2 carbon atoms, N,N-dialkyl with 1 to 2 carbon atoms, NH2 , N-acyl with 2 to 3 carbon atoms), furyl, thienyl, a nitrogen-containing heterocyclic 5- or 6-membered ring which may optionally contain as a further heteroatom an oxygen or sulphur atom (and the ring may optionally be substituted by alkyl with 1 to 4 carbon atoms), or R1 and R2 together with the nitrogen atom represent a 3- to 7-membered ring which may optionally contain as a further heteroatom an oxygen or nitrogen atom [the ring may be optionally substituted by phenyl (C1-4 ) alkyl (this phenyl ring in turn being mono- or disubstituted by halogen atoms or methoxy groups)], or R2 , if R1 represents hydrogen, represents -NH2 , di(C1-2 ) alkylamino, acetonylamino, -NH(C2-3 ) acyl, alkylsulphonyl or alkyloxycarbonyl group with 1 to 3 carbon atoms in the alkyl chain, a isopropylideneimino group see diagramm : EP0190563,P15,F2 or a heterocyclic 5- or 6-membered ring containing a nitrogen atom and optionally containing as a further heteroatom an oxygen, nitrogen or sulphur atom, R3 , R4 and R5 , which may be identical or different, represent hydrogen or alkyl groups with 1 to 4 carbon atoms, R7 and R8 , which may be identical or different, represent hydroxy, alkoxy with 1 to 4 carbon atoms or alkylthio groups with 1 to 4 carbon atoms, and R6 and R9 , which may be identical or different, represent hydrogen, hydroxy, alkoxy with 1 to 4 carbon atoms or alkylthio groups with 1 to 4 carbon atoms or a group see diagramm : EP0190563,P16,F1 wherein R10 represents hydrogen or alkyl with 1 to 4 carbon atoms and R11 represents alkyl with 1 to 4 carbon atoms any such alkyl group being optionally substituted by a hydroxy, methoxy or furfuryl group and physiologically acceptable acid addition salts thereof. 1. Claims for the Contracting State : AT Process for preparing a 12-amino-pyridazino[4',5':3,4]pyrrolo[2,1-a]isoquinoline of general formula see diagramm : EP0190563,P17,F1 wherein R1 and R2 , which may be identical or different, each represent hydrogen, C3-7 cycloalkyl, C2-5 alkenyl, phenyl (optionally mono- or disubstituted by halogen atoms or methoxy groups), propargyl, a straight-chained or branched, saturated or unsaturated alkyl group with 1 to 5 carbon atoms which may be substituted by hydroxy, alkoxy with 1 to 4 carbon atoms, halogen, NH2 , NH-alkyl with 1 to 2 carbon atoms, N,N-dialkyl with 1 to 2 carbon atoms, NH-acyl with 2 to 4 carbon atoms, cycloalkyl with 3 to 7 carbon atoms, phenyl (optionally substituted by halogen, alkyl with 1 to 2 carbon atoms, alkoxy with 1 to 2 carbon atoms, NH-alkyl with 1 to 2 carbon atoms, N,N-dialkyl with 1 to 2 carbon atoms, NH2 , N-acyl with 2 to 3 carbon atoms), furyl, thienyl, a nitrogen-containing heterocyclic 5- or 6-membered ring which may optionally contain as a further heteroatom an oxygen or sulphur atom (and the ring may optionally be substituted by alkyl with 1 to 4 carbon atoms), or R1 and R2 together with the nitrogen atom represent a 3- to 7-membered ring which may optionally contain as a further heteroatom an oxygen or nitrogen atom [the ring may optionally be substituted by phenyl (C1-4 ) alkyl (this phenyl ring in turn being mono- or disubstituted by halogen atoms or methoxy groups)], or R2 , if R1 represents hydrogen, represents -NH2 , di(C1-2 ) alkylamino, acetonylamino, -NH(C2-3 ) acyl, alkylsulphonyl or alkyloxycarbonyl group with 1 to a carbon atoms in the alkyl chain, a isopropylideneimino group see diagramm : EP0190563,P17,F2 or a heterocyclic 5- or 6-membered ring containing a nitrogen atom and optionally containing as a further heteroatom an oxygen, nitrogen or sulphur atom, R3 , R4 and R5 , which may be identical or different, represent hydrogen or alkyl groups with 1 to 4 carbon atoms, R7 and R8 , which may be identical or different, represent hydroxy, alkoxy with 1 to 4 carbon atoms or alkylthio groups with 1 to 4 carbon atoms, and R6 and R9 , which may be identical or different, represent hydrogen, hydroxy, alkoxy with 1 to 4 carbon atoms or alkylthio groups with 1 to 4 carbon atoms or a group see diagramm : EP0190563,P17,F3 wherein R10 represents hydrogen or alkyl with 1 to 4 carbon atoms and R11 represents alkyl with 1 to 4 carbon atoms any such alkyl group being optionally substituted by a hydroxy, methoxy or furfuryl group or a physiologically acceptable acid addition salt thereof, characterised in that a 3,4-dihydro-12-methyl-mercapto- pyridazino[4',5':3,4]pyrrolo[2,1-a]isoquinoline of general formula II see diagramm : EP0190563,P18,F1 wherein the groups R3 , R4 , R5 , R6 , R7 , R8 and R9 are as hereinbefore defined, is reacted with a compound of general formula III see diagramm : EP0190563,P18,F2 wherein R1 and R2 are as hereinbefore defined, and in that a compound thus obtained is optionally converted, in a manner known per se, into a physiologically acceptable acid addition salt.
机译:1.对缔约国的索赔:BE,CH,DE,FR,GB,IT,LI,LU,NL,SE 12-氨基-吡啶并[4',5':3,4]吡咯并[2,1-a通式I的异喹啉见图:EP0190563,P15,F1其中R1和R2可以相同或不同,分别表示氢,C3-7环烷基,C2-5链烯基,苯基(可选地被卤素原子单或双取代)或炔氧基),炔丙基,具有1至5个碳原子的直链或支链,饱和或不饱和烷基,可以被羟基,具有1至4个碳原子的烷氧基取代,卤素,NH 2,具有1至1个碳原子的NH-烷基2个碳原子,具有1-2个碳原子的N,N-二烷基,具有2-4个碳原子的NH-酰基,具有3-7个碳原子的环烷基,苯基(可选被卤素取代,具有1-2个碳原子的烷基,烷氧基具有1-2个碳原子的NH-烷基,具有1-2个碳原子的NH-烷基,具有1-2个碳原子的N,N-二烷基,NH2,具有2-3个碳原子的N-酰基),呋喃基,噻吩基,含氮杂环5或6分子可以任选包含氧或硫原子作为杂原子的环(并且该环可以任选被具有1-4个碳原子的烷基取代),或R1和R2与氮原子一起表示3至7元环,其可任选地包含氧或氮原子作为杂原子[该环可任选地被苯基(C1-4)烷基取代(该苯环又被卤素原子或甲氧基单或二取代)],或如果R 1代表氢,则R 2代表-NH 2,二(C1-2)烷基氨基,丙酮酰基氨基,-NH(C2-3)酰基,烷基磺酰基或烷氧基羰基,在烷基链中具有1-3个碳原子,异丙基亚亚氨基:EP0190563,P15,F2或含有氮原子并任选含有氧,氮或硫原子作为杂原子的5-或6-元杂环,R 3,R 4和R 5可以相同或不同,表示氢或带有1-4个碳的烷基n个原子,R7和R8可以相同或不同,表示羟基,碳数为1至4的烷氧基或碳原子数为1-4的烷硫基,R6和R9可以相同或不同,表示氢,羟基,具有1-4个碳原子的烷氧基或具有1-4个碳原子的烷硫基或一个基团,参见示意图:EP0190563,P16,F1其中R10代表氢或具有1-4个碳原子的烷基,R11代表具有1-4个碳原子的烷基任何此类烷基任选地被羟基,甲氧基或糠基及其生理学上可接受的酸加成盐取代。 1.缔约国的权利要求:AT制备通式为12-氨基-吡啶并[4',5':3,4]吡咯并[2,1-a]异喹啉的方法,参见图:EP0190563,P17,F1 R 1和R 2可以相同或不同,分别代表氢,C 3-7环烷基,C 2-5烯基,苯基(可选被卤素原子或甲氧基单或双取代),炔丙基,直链或支链的饱和或可被羟基取代的不饱和烷基或具有1-5个碳原子的不饱和烷基,具有1-4个碳原子的烷氧基,卤素,NH2,具有1-2个碳原子的NH-烷基,具有1-2个碳原子的N,N-二烷基,碳原子数为2至4的NH-酰基,碳原子数为3至7的环烷基,苯基(可选被卤素取代,碳原子数为1-2的烷基,碳原子数为1-2的烷氧基,碳原子数为1-2的NH-烷基原子,具有1-2个碳原子的N,N-二烷基,NH 2,具有2-3个碳原子的N-酰基),呋喃基,噻吩基,含氮杂环5或6元环可以任选地包含氧或硫原子作为另外的杂原子(并且该环可以任选地被具有1-4个碳原子的烷基取代),或者R 1和R 2与氮原子一起表示3至7元环,其可以任选地包含氧或氮原子作为其他杂原子[该环可以任选地被苯基(C1-4)烷基取代(该苯环又被卤素原子或甲氧基单或二取代)]或R2,如果R1代表氢,代表-NH2,二(C1-2)烷基氨基,丙酮酰基氨基,-NH(C2-3)酰基,烷基磺酰基或烷氧基羰基,在烷基链中具有1个碳原子,异丙叉亚氨基基团见图:EP0190563, P17,F2或含有氮原子并任选含有氧,氮或硫原子作为另外的杂原子的5或6元杂环,R 3,R 4和R 5可以相同或不同,表示氢或烷基具有1-4个碳原子的R7和R 8可以相同或不同,表示羟基,碳原子数为1至4的烷氧基或具有1至4个碳原子的烷硫基,R6和R9可以相同或不同,表示氢,羟基,碳原子数为1至1的烷氧基。 4个碳原子或1至4个碳原子的烷硫基或一个基团,见图:EP0190563,P17其中R10代表氢或具有1-4个碳原子的烷基,R11代表具有1-4个碳原子的烷基,任何这样的烷基任选地被羟基,甲氧基或糠基或其生理学上可接受的酸加成盐取代,通式II的3,4-二氢-12-甲基巯基哒嗪[4',5':3,4]吡咯并[2,1-a]异喹啉见图:EP0190563,P18,F1使R 3,R 4,R 5,R 6,R 7,R 8和R 9如上文所定义,与通式III的化合物反应,参见示意图:EP0190563,P18,F2,其中R 1和R 2如上文所定义,并且因此化合物所获得的产物任选以本身已知的方式转化成生理上可接受的酸加成盐。

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