ACRIDONE DERIVATIVES AND METHOD OF PREPARATION OF 8-HYDROXY IMIDAZOACRIDINONE DERIVATIVES

摘要

A process of preparing a compound of formula (I), wherein R<1> and R<2> are alkyl groups of 1 to 4 carbon atoms and n is from 2 to 5, comprises reacting a 1-chloro-7-(protected hydroxy)-4-nitroacridin-9(10H)-one of formula (IV-P), wherein A is a hydroxy-protecting group removable by reduction, with an omega -(dialkyl-amino)alkylamine of formula: NH2-(CH2)nNR<1>R<2>, in which n, R<1> and R<2> are as defined above, to produce a 7-(protected hydroxy)-4-nitro-1-[[ omega -(dialkylamino)alkyl]amino]acridin-9(10H)-one(III-P), reducing the compound (III-P) at a temperature of from 15 to 50 DEG C with a hydrogen gas or with formate ions, in the presence of a palladium catalyst and formic acid, removing substantially all the residual palladium and heating the remaining reaction mixture to effect cyclisation to the corresponding compound of formula (I). If desired, after removal of the palladium, the intermediate 7-hydroxy-4-N-formyl-1-[[ omega -(dialkylamino)alkyl]amino]acridin-9(10H)-one can be isolated and subsequently cyclised by heating. Such compounds have anti-neoplastic activity.