Synthesis, X-ray analysis and spectroscopic characterization of the hemiaminal cyclization product from 2,4-dipyridine substituted 3,7-diazabicyclo[3.3.1]nonanone 1,5-diesters

The 2,4-dipyridine substituted 3,7-dimethyl-3,7-diazabicyclo[3.3.1]nonan-9- one 1,5-diester, HZ2, is characterized by a high analgesic potency. The att empt to form ammonium salts of HZ2 or to N-demethylate position 7 resulted in an unexpected hemiaminal cyclization product 1. The structure was elucid ated by an X-ray analysis, the H-1- and C-13-NMR spectra could be fully ass igned by means of H,H-COSY, Grad-HSQC-EA and ACCORD-HMBC experiments. The M S spectra of 1 exhibit a ring opening. Interestingly, ESI-MS/MS experiments of HZ2 in aqueous solution showed the formation of a hydrated product. The fragmentation pathways of HZ2 and the hydrated product are rather differen t indicating the formation of a carboxylate.