Patent EP-0062844-A1 (EP)
Inventor: COHNEN ERICH DR DIPL-CHEM
IPC: A61K31/435
Filed: 1982-04-01
Abstract: 1. Claims for the Contracting States : BE, CH, DE, FR, GB, IT, LI, NL, SE Substituted benzo[de]isoquinolines of the general formula I see diagramm : EP0062844,P17,F1  in which R**1 and R**2 , which can be identical or different, denote a hydrogen or halogen atom or an alkoxy group having 1 to 4 carbon atoms, or R**1 and R**2 together denote the ethylene group, Z denotes oxygen, sulphur, the methylene group or the group N-R**5 , and either R**3 and R**4 together denote the group -(CH2 )n - wherein n can be the number 2 or 3, R**5 being hydrogen (compounds A), or, if Z is the group N-R**5 , R**3 , R**4 and R**5 , which can be identical or different, denote a hydrogen atom or an alkyl group having 1 to 4 carbon atoms (compounds B), and also acid addition salts thereof. 1. Claim for the Contracting State : AT Process for the preparation of new substituted benzo[de]isoquinolines of the general formula I  see diagramm : EP0062844,P20,F3  in which R**1 and R**2 , which can be identical or different, denote a hydrogen or halogen atom or an alkoxy group having 1 to 4 carbon atoms, or R**1 and R**2 together denote the ethylene group, Z denotes oxygen, sulphur, the methylene group or the group N-R**5 , and either R**3 and R**4 together denote the group -(CH2 )n - wherein n can be the number 2 or 3 and R**5 being hydrogen (compounds A), or, if Z is the group N-R**5 , R**3 , R**4 and R**5 , which can be identical or different, denote a hydrogen atom or an alkyl group having 1 to 4 carbon atoms (compounds B), and also acid addition salts thereof, characterised in that, in order to prepare compounds (A) of the general formula I wherein Z denotes an oxygen or sulphur atom, compounds of the general formula II  see diagramm : EP0062844,P21,F1  in which R**1 and R**2 have the meaning indicated above, are reacted with halogenoalkyl isocyanates or halogenoalkyl isothiocyanates of the general formula III Z=C=N-(CH2 )n -Y in which Z is an oxygen or sulphur atom and n has the abovementioned meaning and Y is a chlorine, bromine or iodine atom, and the initially formed compounds of the general formula IV  see diagramm : EP0062844,P21,F2 in which R**1 , R**2 , Z, n and Y have the meaning indicated, are cyclised to give compounds of the formula I and, if desired, an acid addition salt is prepared therefrom, and, in order to prepare compounds (A) of the general formula I wherein Z denotes the methylene group, compounds of the general formula II  see diagramm : EP0062844,P21,F3  in which R**1 and R**2 have the meaning indicated above, are reacted with iminoethers of the general formula V  see diagramm : EP0062844,P21,F4  in which n has the above meaning and R**6 is a lower alkyl group, and, if desired, an acid addition salt is prepared from the resulting compounds of the formula I, and, in order to prepare compounds (A) of the general formula I wherein Z denotes the imino group, compounds of the general formula II  see diagramm : EP0062844,P22,F1  in which R**1 and R**2 have the meaning indicated above, are reacted with benzoyl isothiocyanate to give the corresponding benzoyl thioureas, and the latter are converted, by elimination of the benzoyl radical, into the corresponding thioureas, which are converted by alkylation into the S-alkylisothiuronium salts of the general formula VI  see diagramm : EP0062844,P22,F2  in which R**7 denotes a lower alkyl group and A denotes an anion, and R**1 and R**2 have the meaning indicated above, and these compounds are reacted with 1,2-diaminoethane or 1,3-diaminopropane, and, if desired, an acid addition salt is prepared from the resulting compounds of the formula I, and, in order to prepared compounds (B), compounds of the general formula II  see diagramm : EP0062844,P22,F3 in which R**1 and R**2 have the meaning indicated above, are reacted with cyanamides, and, if desired, an acid addition salt is prepared from the resulting compounds of the formula I, and, in order to prepare compounds (B), compounds of the general formula II  see diagramm : EP0062844,P22,F4  in which R**1 and R**2 have the meaning indicated above, are reacted with aliphatic isothiocyanates to give thiosemicarbazides of the general formula VII  see diagramm : EP0062844,P23,F1  in which R**1 , R**2 and R**3 have the meaning indicated above, these thiosemicarbazides are subjected to an S-methylation with methyl iodide, and the resulting reaction products are then reacted with ammonia or primary or secondary amines, and, if desired, an acid addition salt is prepared from the resulting compounds of the formula I, and, in order to prepare compounds (B), compounds of the general formula II  see diagramm : EP0062844,P23,F2 in which R**1 and R**2 have the meaning indicated above, are reacted with benzoyl isothiocyanate to give thiosemicarbazides of the general formula VIII  see diagramm : EP0062844,P23,F3  in which R**1 and R**2 have the meaning indicated, which are converted, by reaction with amines of the general formula HNR**4 R**5 in which R**4 and R**5 have the meaning indicated above, into the compounds of the general formula IX  see diagramm : EP0062844,P23,F4  in which R**1 , R**2 , R**4 and R**5 have the meaning indicated, and the benzoyl group is then split off, and if desired, an acid addition salt is prepared from the resulting compounds of the formula I.