This paper describes the synthesis of two amino-quinazolinediones which are potent gyrase/topoisomerase inhibitors anduseful as antibacterial agents. The early scale-up work toprepare a chiral side chain on multigram scale and two differentamino-quinazolinedione cores is detailed. The enabling synthesisfor the side chain employed a previously reported Michaeladdition of MeNO
2 to an enantiomerically enriched
-amino-enoate and a two-step de-oxygenation of a lactam. Key syntheticsteps for core preparation and completion of the amino-quinazolinediones include dianion-promoted cyclization viaintramolecular, nucleophilic aromatic substitution, electrophilicamination, nucleophilic aromatic substitution of the side chainto the core, deprotection and isolation of the hydrochloride saltin acceptable yield.