Synthesis of a New Scaffold: the 7H,8H-Pyrimido[1,6-b]pyridazin-6,8-dione Nucleus

Abstract

This paper describes a modified method of preparation of a number of α-aryl-α-(pyridazin-3-yl)-acetonitriles via the C-arylation reaction of the corresponding carbanions of phenylacetonitriles using 3-chloropyridazine derivatives. KOH and DMSO were used in the deprotonation process, which made the reaction very simple and safe to perform. Nitriles were obtained in the hydrolysis reaction to the corresponding α-aryl-α-(pyridazin-3-yl)-acetamide derivatives, which were next subjected to cyclization to afford the final products. A number of new derivatives of 7H,8H-pyrimido[1,6-b]pyridazin-6,8-dione were synthesized in the cyclocondensation reaction of respective α-aryl-α-(pyridazin-3-yl)-acetamides with diethyl carbonate in the presence of EtONa. The structure and composition of the new compounds were confirmed by IR, 1 H-and 13 C-NMR analyses and by elemental C, H and N analysis.

Organic Superbases in Annulation with Propargylic Alcohols: Straightforward Synthesis of the Functionalized Oxazolopyrrolohexahydropyrimidine and Oxazolohexahydropyrimidoazepine Scaffolds

“…Reactions of DBN and DBU with methyl perfluoro‐2‐alkynoates (CH 2 Cl 2 , 20–25 °C, 30 min)[5b], [5c] or methyl propiolate (CH 2 Cl 2 , 42 °C, time not indicated)[5d] also yielded condensed tricyclic derivatives. Such tricycles are structurally related to important natural products (e.g., strychnine, vindoline, eudistomidins H and I, vincadifformine,, cinachyramine, and the like) and have gained pharmaceutical interest owing to their hexahydropyrimidine moiety, which is present in some alkaloids (verbamethine and verbametrine) and compounds with various biological activities (anticancer, anti‐inflammatory, analgesic,[13a], [13b] antibiotic,[12b] antianginal, anxiolytic, and antidepressant).…”