title: Complete structure analysis of OR-1746, a complex product of cyclocondensation of arylhydrazomalononitriles containing clusters of protonated and unprotonated nitrogens, by pulsed-field-gradient heteronuclear NMR.
abstract: OR-1746, or [4-Ethoxy-6-imino-5-[[4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl]hydrazono]-5,6-dihydro-1H-pyrimidin-2-ylidene]-[4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenylazo]-acetonitrile is the product of the cyclocondensation of two molecules of the arylhydrazomalononitrile levosimendan (CAS registry number [141505-33-1]) with ethanol. OR-1746 is a molecule with a complex structure containing clusters of protonated and unprotonated nitrogens. Its structure was only partially elucidated by elemental analysis and by conventional NMR. However, the presence of many unprotonated nitrogen atoms did not allow the unambiguous assignment of the 1H, 13C and 15N NMR spectra with short-range heterocorrelated techniques, or even with traditional long-range 2D experiments. Pulsed-field-gradient heteronuclear multiple bond coherence sequences (PFG 1H-(13)C and PFG 1H-(15)N) were, therefore, used to fully assign the NMR spectra and elucidate the chemical structure of OR-1746. By using these techniques, long-range couplings between protons and carbons or proton and nitrogen atoms as distant as five bonds in the structure were detected without loosing the signals of the protonated heteroatoms. The long range coupling information provided by the novel NMR experiment can be used effectively in the complete structure determination of complex molecules containing clusters of protonated and unprotonated nitrogens.
authors.affiliation: Orion Pharma, Cardiovascular Research and Development, P.O. Box 65, FIN-02101 Espoo, Finland. piero.pollesello@orionpharma.com
authors.forename: Piero
authors.initials: P
authors.lastname: Pollesello
authors.forename: Pentti
authors.initials: P
authors.lastname: Nore
mesh_terms: D002851:Chromatography, High Pressure Liquid; D006835:Hydrazones / Q000032:analysis*; D009682:Magnetic Resonance Spectroscopy; D009584:Nitrogen / Q000737:chemistry; D011724:Pyridazines / Q000032:analysis*; D000077464:Simendan; D013237:Stereoisomerism
chemical_list: C476889:(4-ethoxy-6-imino-5-((4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl)hydrazono)-5,6-dihydro-1H-pyrimidin-2-ylidene)-(4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenylazo)acetonitrile; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan; D009584:Nitrogen