Synthesis of Novel N-Heterocyclic Compounds Containing 1,2,3-Triazole Ring System via Domino, “Click” and RDA Reactions

Abstract

An uncomplicated, high-yielding synthetic route has been developed to constitute complicated heterocycles, applying domino, click and retro-Diels–Alder (RDA) reaction sequences. Starting from 2-aminocarboxamides, a new set of isoindolo[2,1-a]quinazolinones was synthesized with domino ring closure. A click reaction was performed to create the 1,2,3-triazole heterocyclic ring, followed by an RDA reaction resulting in dihydropyrimido[2,1-a]isoindole-2,6-diones. The absolute configuration, concluded by the norbornene structure that served as a chiral source, remained constant throughout the transformations. The structure of the synthesized compounds was examined by 1H and 13C Nuclear Magnetic Resonance (NMR) methods.

Synthesis and biological evaluation of the new ring system benzo[f]pyrimido[1,2-d][1,2,3]triazolo[1,5-a][1,4]diazepine and its cycloalkane and cycloalkene condensed analogues

“…Alicyclic N-Boc-protected propargyl amides (AE)-3, (AE)-4, (AE)-9, and (AE)-10 were prepared according to a previous procedure, starting from the corresponding Boc-protected amino acids (AE)-1, (AE)-2, (AE)-7, and (AE)-8, using a mixture of N,N 0 -diisopropylcarbodiimide (DIC) and hydroxybenzotriazole (HOBt) in tetrahydrofuran. 22,24 The other starting materials, 2-azidobenzaldehyde derivatives, were obtained by the addition of sodium azide to 2-nitrobenzaldehydes in hexamethylphosphoramide (HMPA) following the procedure already described in the literature. 25 Aerwards, the free amide bases, prepared by an acidic deprotection of amides (AE)-3, (AE)-4, (AE)-9, and (AE)-10 were reacted further without purication.…”

“…3). 22 Most of the compounds elicited negligible growth inhibiting action against the utilized cancer cells. None of the substances elicited >10% inhibition on ovarian (A2780) cancer cells.…”

“…[7][8][9] Furthermore, various biologically active compounds containing a triazole-fused 1,4-benzodiazepine unit, such as protease inhibitors, 10 alprazolam, 11 estazolam, 12 and triazolam, 13 continuously attract the attention of organic and medicinal chemists due to their medicinal potential. [14][15][16] Following our studies on diastereoselective, two-component multi-functional domino ring-closure reactions and our project for the synthesis of novel N-heterocycles with the focus on the biological potential of fused quinazolinones and triazoles, [17][18][19][20][21][22] herein we report our study with respect to the diastereoselectivity of a onepot, two-step cascade synthesis procedure of quinazolinotriazolobenzodiazepines described by Guggenheim et al 23 and the synthesis of a new series of alicyclic derivatives.…”

Triazole analogues as potential pharmacological agents: a brief review

“…Azolic derivatives such as thiazole, triazole, oxadiazole, and thiadiazole are pharmacologically active compounds and, due to their effective use in medicinal chemistry, have been intensely studied for various biological activities [ 3 ].…”

Synthesis of Alicyclic 2-Methylenethiazolo[2,3-b]quinazolinone Derivatives via Base-Promoted Cascade Reactions

“…20 Although the biological properties of thiazolo[2,3-b]quinazolinones have stimulated the development of a large number of synthetic methods to construct and decorate this moiety, there are fewer synthetic approaches towards the corresponding cyclic and alicyclic derivatives. Hence, in conjunction with our ongoing research on the study and modification of alicyclic -amino propargylamide deriva-tives through domino reaction procedures, 21,22 our present work is directed towards the syntheses of alicyclic 2-methylene-substituted thiazolo [2,3-b]quinazolinones. The synthetic process involves base-promoted cascade reactions of alicyclic -amino propargylamides or alicyclic ethyl 2-isothiocyanatocarboxylates, followed by investigations on retro-Diels-Alder (RDA) reactions of the norbornene derivatives.…”