SYNTHESIS OF YDROXY-6,9-DIFLUOROBENZ[G]ISOQUINOLINE-5,10-DIONES AND CONVERSIONS TO (AMINOALKYL)AMINO]-BENZ[G]ISOQUINOLINE-5,10-DIONES

Synthetic procedures have been developed which lead to hydroxy-6,9-dif luorobenz[g]isoquinoline-5,10-dione (4a) and its 3-methyl analogue 4b. Attempts to displace the fluorides from 4a with N,N-dimethylethylened iamine were unsuccessful. Analogue 4a on treatment with N-(t-butoxycar bonyl)ethylene diamine led to 15, formed from addition of the nucleoph ilic amine to C-3. On the other hand, analogue 4b, on treatment with N ,N-dimethylethylenediamine led to the anticipated difluoride displacem ent product 3c. The protection of the hydroxy group of 4a by benzylati on with phenyldiazomethane led to 4c which on treatment with N-(t-buto xycarbonyl)ethylene diamine or N,N-dimethylethylenediamine led to the corresponding 6,9-bis-substituted analogues 18a and 18b, respectively. Reductive debenzylations of 18a and 18b by hydrogenation over Pearlma n's catalyst also effected partial reductions of the quinone. However, air oxidation of the over reduced products led to 3a and 3b, respecti vely. Treatment of 3a with hydrogen chloride gas led to the hydrochlor ide salt of 3d. Addition of O-p-Methoxybenzyl-N,N'-diisopropylurea to 4a led to the p-methoxybenzyl analogue 4d. Treatment of 4d with N,N-di methylethylene diamine or N-(t-butoxycarbonyl)ethylene diamine led to displacements of the fluorides to yield 18c and 18d, respectively. Dep rotection of 18c to 3b was accomplished using methanesulfonic acid. Tr eatment of 18d with trifluoroacetic acid followed by addition of malei c acid led to dimaleate salt of 3d.