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

Abstract

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 attempt to form ammonium salts of HZ2 or to N-demethylate position 7 resulted in an unexpected hemiaminal cyclization product 1. The structure was elucidated by an X-ray analysis, the ¹H- and ¹³C-NMR spectra could be fully assigned by means of H,H-COSY, Grad-HSQC-EA and ACCORD-HMBC experiments. The MS 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 different indicating the formation of a carboxylate.