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

Abstract

Abstract 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 ‐butoxycar‐bonyl)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.