Matthew E. Voss

Preparation of 9,9-Disubstituted 4,5-Diazafluorenes Useful as Cognitive Enhancers

A novel synthesis of symmetric and nonsymmetric 9,9-disubstituted 4,5-diazafluorenes has been developed. These compounds have activity in both an in vitro acetylcholine release assay and in vivo rodent models of learning and memory. Preparation of these compounds involves a unique aldol condensation between 4,5-diazafluoren-9-one (4) and 4-picoline. Reduction of aldol product 5 (5-(4-pyridinylmethylene)-5H-cyclopenta[2,1-b:3,4-b‘]dipyridine) provides monoalkylated diazafluorene 6 (5-(4-pyridinylmethyl)-5H-cyclopenta[2,1-b:3,4-b‘]dipyridine) which proved to be a key intermediate for synthesis of nonsymmetric analogs.