Efficient synthesis of (5-oxo-6,7-dihydro-4H-[1,2,4]triazolo-[1,5-a]pyrimidin-6-yl)acetanilides based on the recyclization of N-arylitaconimides with 3-amino[1,2,4]triazoles

Abstract

A convenient method for the synthesis of 2-(2-R-5-oxo-6,7-dihydro-4H-[1,2,4]triazolo-[1,5-a] pyrimidin-6-yl)acetanilides based on the regioselective domino reaction of N-arylitaconimides with substituted 3-aminotriazoles was proposed. Presumably, the reaction pathway includes the conjugated aza-addition of the endo-nucleophilic center of triazole to imide, followed by the recyclization of the intermediate to triazolo [1,5-a]pyrimidine.

Efficient Synthesis of Tetrahydropyrazolo[1,5-a]pyrimidines Based on the Recyclization of N-Arylitaconimides with Aminopyrazoles

“…Previous studies indicated that preferred conditions for the recyclization of itaconimides with heterocyclic binucleophiles involve boiling the reagents in isopropyl alcohol in the presence of acetic acid. 19 We found that the interaction of N-substituted 5-aminopyrazoles with itaconimides, when boiling the reagents in a mixture of different solvents with acetic acid in a 20:1 ratio, selectively produces the previously described pyrazolo[3,4- b ]pyridines 3a – l . Meanwhile, the recyclization of itaconimides with 4-substituted-2,5-aminopyrazoles under the same conditions yields new derivatives of pyrazolo[1,5- a ]pyrimidine 4a – k (Scheme 1 ).…”

“…Previous studies indicated that preferred conditions for the recyclization of itaconimides with heterocyclic binucleophiles involve boiling the reagents in isopropyl alcohol in the presence of acetic acid. 19 We found that the interaction of N-substituted 5-aminopyrazoles with itaconimides, when boiling the reagents in a mixture of different solvents with acetic acid in a 20:1 ratio, selectively produces the previously described pyrazolo [3,4-b]pyridines 3a-l. Mean-while, the recyclization of itaconimides with 4-substituted-2,5-aminopyrazoles under the same conditions yields new derivatives of pyrazolo [1,5-a]pyrimidine 4a-k (Scheme 1). However, unlike the analogous recyclization of maleimides, 16 in the case of unsubstituted aminopyrazole (R 1 , R 2 = H), no evidence of an alternative product 3a-l was observed under any conditions (boiling in mixtures with varying ratios of acetic acid to isopropyl alcohol, methanol, xylene, dimethylformamide, or in pure acetic acid).…”

“…Itaconimides, considered promising analogues of maleimides, generate C3-synthons upon recyclization. The recyclization of N -arylitaconimides can occur under the influence of both C,N- and N,N-binucleophiles, forming condensed systems containing both pyridine 18 and pyrimidine 19 cycles. In this work, an efficient one-step synthesis of pyrazolo[1,5- b ]pyrimidines is proposed based on the recyclization of N -arylitaconimides with aminopyrazoles.…”

“…ence of both C,N-and N,N-binucleophiles, forming condensed systems containing both pyridine 18 and pyrimidine 19 cycles. In this work, an efficient one-step synthesis of pyrazolo [1,5-b]pyrimidines is proposed based on the recyclization of N-arylitaconimides with aminopyrazoles.…”

“…Previously, it was demonstrated that heterocyclization reactions of N-arylitaconimides with dinucleophilic reagents, including heterocyclic dinucleophiles, typically commence with a Michael-type addition. [18][19][20][21] In our case, we also hypothesize that in the initial stage, aminopyrazole can attach to the activated double bond of itaconimide, forming linearly linked adducts A, B, C corresponding to attacks on the multiple bond by the electrophilic centers of C-4, N-1, or N-2 of the pyrazole cycle (Scheme 1). An alternative intermediate, C, incapable of further cyclization, evidently does not form in this system, as it would accumulate in the reaction mass and undoubtedly be detected during the initial examination of the reaction mixture using TLC.…”