Synthesis of Symmetrical Dinitro- and Diamino-Substituted Troger's Base Analogues

This report describes a new synthetic approach to symmetrical diamino-substituted Troger's base analogues, allowing the synthesis of 1,7-, and 4,10-diamino derivatives with no additional substituents and of 3,9-diamino derivative with methyl groups in the 1-, 4-, 7- and 10-positions. The synthesis uses regioselective nitration of dihalo-substituted- or tetrahalo-substituted Troger's bases followed either by hydrogenation of the nitro functions accompanied by removal of halogen atoms or alternatively by chemoselective reduction of nitro groups to obtain the dihalo-diamino-substituted Troger's base analogues. The 2,8-diamino derivatives, not accessible by this approach, can be prepared by BuchwaldHartwig amination of the 2,8-dibromo-substituted Troger's bases.