Synthetic strategies to a telomere-targeted pentacyclic heteroaromatic salt.

Three routes have been explored to synthesise the telomere-targeted agent 3,11-difluoro-6,8,13-trimethyl-8H-quino[4,3,2-kl]acridinium methosulfate . Application of a 6-(2-azidophenyl)phenanthridine precursor gave an entry to the indazolo[2,3-f]phenanthridine ring system not the required quino[4,3,2-kl]acridine. A six step synthesis starting from 2,6-dibromo-4-methylbenzonitrile via a 1-arylacridin-9(10H)-one intermediate, or , gave the required in low overall yield (<10%). The most efficient route entailed the one-pot (five step) conversion of 1,2-dimethyl-6-fluoroquinolinium methosulfate to in 33% yield employing triethylamine as base and nitrobenzene as solvent.