Patent GB-1021524-A (GB)
Title: Derivatives of acridan
IPC: C07D219/06
Filed: 1963-06-06
Abstract: The invention comprises compounds of the formula <FORM:1021524/C2/1> wherein R1 represents a hydrogen atom or a methyl group; R2 represents a hydrogen atom, a halogen atom with an atomic weight of less than 80, a lower alkyl, lower alkoxy, trifluoromethyl, trifluoromethyl sulphonyl, dimethylsulphamoyl or alkylthio group; R3 represents a lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl-lower alkyl, phenyl or phenyl-lower alkyl group and Z represents a di-lower alkylamino, mono - lower alkylamino, N - pyrrolidinyl, N - piperidinyl, N1 - lower alkyl-N - piperazinyl, N1 - hydroxy alkyl - N-piperazinyl or N1 - benzyloxy alkyl - N - piperazinyl group, where lower alkyl and lower alkoxy groups have 1-4 carbon atoms, alkylene portions of substituted alkylpiperazinyl radicals have 2-4 carbon atoms and cycloalkyl, lower alkenyl and lower alkynyl groups have 3-6 carbon atoms.  Compounds of the Formula I may be prepared by reacting an acridone of the formula <FORM:1021524/C2/2> with a compound of the formula ZCH2CH(R1)CH2MgX where X represents a halogen atom and Z represents a di - lower alkylamino, N - pyrrolidinyl, N - piperidinyl, N1 - lower alkyl - N-piperazinyl or N1 - benzyloxy alkyl - N-piperazinyl. 9-Hydroxy-9-(N1-hydroxy alkyl-N-piperazinyl) alkyl derivatives of the Formula I are prepared by debenzylation of the corresponding N-benzyloxyalkyl derivatives.  Compounds of the Formula I when Z represents a mono-lower alkylamino group are prepared by reacting the acridone with a methoxy propyl magnesium halide, reacting the resulting 9-hydroxy - 9 - methoxypropylacridan with hydrobromic acid to give a product which is treated with a mono-lower alkylamine to give the hydrobromide of the 9-mono lower alkylamino-propylideneacridan which on treatment with a base gives the desired compound 9-Hydroxy-9-[3 - (4 - hydroxy alkyl - 1 - piperazinyl) alkyl]-acridans of the Formula I may be prepared by hydrolysis of the corresponding 9-[3-(4-benzyloxyalkyl - 1 - piperazinyl) alkylidene] acridan which is made by dehydration of the corresponding 9-hydroxy acridan.  Acridones of the Formula II may be prepared by treating the appropriately substituted diphenylamine - 2 - carboxylic acid with a cyclizing agent.  When phosphorus oxychloride is used as cyclizing agent, the product is 9-chloro acridine which is converted to the 9-[N-(p - toluenesulphonyl)hydrazino] derivative which is treated with an alkali metal hydroxide to give the required acridone.  2 - Benzyloxyethyl - p - toluenesulphonate, prepared by the reaction of 2-benzyloxy ethanol and p-toluenesulphonyl chloride, is reacted with N - ethoxycarbonylpiperazine to give 1-benzyloxyethyl - 4 - ethoxycarbonylpiperazine which on hydrolysis gives N-benzyloxyethylpiperazine which is treated with 3-bromopropanol to give 1-benzyloxyethyl-4-(3-hydroxypropyl) piperazine.  This compound with thionyl chloride gives 1-benzyloxyethyl-4-(3-chloropropyl) piperazine.  N - Methyl ecridones are prepared by the reaction of methyl iodide on the appropriate acridone.  2 - (4 - R2 - phenylamino) benzoic acids, where R2 is as defined above are prepared by the reaction of the appropriate 1-bromo-4-R2-benzene with N-acetylanthranilic acid, or the appropriate 4-R2-aniline with o-chlorobenzoic acid.