The solid phase synthesis of trisubstituted 1,4-diazabicyclo[4.3.0]nonan-2-one scaffolds: On bead monitoring of heterocycle forming reactions using 15N NMR

Article abstract of DOI:10.1016/S0040-4039(97)10375-6

Several representative 3,4,8-trisubstituted 1,4-diazabicyclo[3.4.0]nonan-2-ones have been prepared employing solid phase methodologies. Elaboration of a 4-hydroxyproline derivative with an ¹⁵N-amino acid derivative allowed convenient monitoring of the reaction sequence on solid support by gel-phase ¹⁵N NMR. An intramolecular Mitsunobu cyclization provided the desired heterocycle, which could be further functionalized at the 4-position. This synthetic method is facile, general, and suitable for the construction of large libraries of compounds for biological assays.