Synthesis of Fluoroalkylated Dihydroazolo[1,5-a]pyrimidines and Their Ring-Chain Isomerism

Synthesis of pyrimido[1,2-a]benzimidazoles from ethyl 2-ethoxymethylidene-3-oxo-3-(polyfluoroalkyl)propionates

“…We have found that, unlike transformations described previously [16,17], reactions of esters Ia-Ic with benzimidazol-2-amine under analogous conditions (boiling 1,4-dioxane) were not selective. Almost in each case, we isolated four kinds of products, IIa-IIc, IIIa-IIIc, IVb, IVc, and Va-Vc (Scheme 1).…”

“…This path of reactions with binucleophiles is typical of esters I; analogous pattern was observed in reactions of I with other aminoazoles [16,17]. The presence of an electron-withdrawing polyfluoroalkyl group is likely to hamper elimination of water, thus stabilizing heterocycles IIa-IIc possessing a hemiaminal fragment.…”

“…1 Hz), which is typical of CF 3 group attached to an sp 3 -hybridized carbon atom. In the 19 F NMR spectra of compounds IIb and IIc we also observed signals from fluorine atoms in the α-CF 2 groups neighboring to a quaternary carbon atom: δ F ~37.82 (IIb), 44.92 ppm (IIc) [16,19].…”

“…We previously showed that esters like I react with 1,2,4-triazol-3-amine, pyrazol-5-amines, and imidazol-5-amines in boiling 1,4-dioxane to give the corresponding dihydroazolo [1,5-a]pyrimidines as a result of regioselective cyclization at the ethoxymethylidene (C 3 ) and fluoroacyl fragments (C 2 ) [16,17]. We have found that, unlike transformations described previously [16,17], reactions of esters Ia-Ic with benzimidazol-2-amine under analogous conditions (boiling 1,4-dioxane) were not selective.…”

One-step synthesis of alkyl 2-chloropyrimido[1,2-a]benzimidazole-3-carboxylates under catalyst-free: combined experimental and computational studies

“…6 Among those heterocycles, the N-based heteroaromatic pyrimido[1,2-a]benzimidazole has been widely applied 7 and functionalized in view of their particular privileged structures 8 and wide spectrum of biological activity. 9 In fact, almost all the reported pyrimido[1,2-a]benzimidazoles, known as effective pharmacophores possess antibiotic 10 and anti-arrhythmic 11 activity, substance p receptor-binding activity, 12 as well as promising antineoplastic activity, 13 are highly substituted by various effective groups inherited from the reaction precursors. For instance, Matthew's group 14 utilized pyrimido[1,2-a]benzimidazole structure as a central skeleton to study the treatment of T-cell-mediated autoimmune and inflammatory disorder and organ transplant, and they found that those highly modified derivatives exhibited potent inhibition of lymphocyte specific kinase activity.…”