A novel synthetic approach to hydroimidazo[1,5-b]pyridazines by the recyclization of itaconimides and HPLC–HRMS monitoring of the reaction pathway

• Dmitry Yu. Vandyshev,
• Khidmet S. Shikhaliev,
• Andrey Yu. Potapov,
• Michael Yu. Krysin,
• Fedor I. Zubkov and
• Lyudmila V. Sapronova

Beilstein J. Org. Chem. 2017, 13, 2561–2568, doi:10.3762/bjoc.13.252

• -addition by the activated C=C double bond and subsequent intramolecular recyclization of the intermediate with the amino group involved. Keywords: cascade reaction; diaminoimidazoles; HPLC–HRESIMS; imidazo[1,5-b]pyridazines; itaconimides; Introduction Among the numerous bicyclic fused imidazole

• ], antitumor agents [9], and are stimulators of guanylate cyclase [10], whereas imidazo[1,5-c]pyrimidines demonstrate anti-infectious effects in the treatment of brucellosis [11], etc. However, the chemistry, medicinal chemistry and pharmacology of imidazo[1,5-b]pyridazines, with the imidazole ring connected

• through the N1–C5 bond of the latter, have been studied to a lesser extent. So, for imidazo[1,5-b]pyridazines, inhibitory activity was found against the viruses of human immunodeficiency HIV-1 [12], influenza [13], and hepatitis C [14]. They also act as stimulators of guanylate cyclase [10], inhibitors of