The synthesis of 6,9-bis[(aminoalkyl)amino] substituted benzo[g]quinoxaline-, benzo[g]quinazoline- and benzo[g]phthalazine-5,10- diones via regiospecific displacements

Article abstract of DOI:10.1002/jhet.5570300624

The synthesis of 6,9-difluoro substituted benzo[g]quinoxaline-5,10-diones (3A), benzo[g]quinazoline-5,10-diones (3B) and benzo[g]phthalazine-5,10- diones (3C) have been accomplished. Treatment of 3A, 3B or 3C with diamines or N-(t-butoxycarbonyl)ethylenediamine led to the corresponding 6,9- bis[(aminoalkyl)amino]-substituted analogues related to 2A, 2B and 2C, respectively. The mono-substituted derivatives 4h and 4i could be isolated from displacements commencing from 3A. A competitive ring-opening of the pyrimidine ring of 2C occurred during the reaction with N,N- dimethylethylenediamine. Removal of the BOC-protecting group from 2Ac led to the hydrochloride salt 2Ab. A novel synthetic pathway to 6,9- dihydroxybenzo[g]phthalazine-5,10-dione (21a) was developed. Conversion of 21a to the ditosylate 21b was readily accomplished. Treatment of 21b with N,N-dimethylethylenediamine or N-(t-butoxycarbonyl)ethylenediamine led to 2Ca and 2Cc, respectively. Removal of the BOC-protecting group from 2Cc with trifluoroacetic acid followed by ion-exchange led to the hydrochloride salt 2Cb. Treatment of ditosylate 21b with N-(t-butoxycarbonyl)ethylenediamine also led to the mono-substituted analogue 25a along with a small amount of the O-S cleavage product 25b. Treatment of 25a with N,N- dimethylethylenediamine led to the unsymmetrically substituted derivative 25c which was converted into the trifluoroacetate salt 25d.