Microwave-Assisted Three-Component Synthesis of 7-Aryl-2-alkylthio-4,7-dihydro-1,2,4-triazolo[1,5-a]-pyrimidine-6-carboxamides and Their Selective Reduction

Abstract

Multicomponent reactions (MCRs) and microwave-assisted organic synthesis (MAOS) have been used as key methods for the synthesis of fused dihydropyrimidine derivatives. The three-component condensation of 3-amino-5-alkylthio-1,2,4-triazoles with aromatic aldehydes and acetoacetamides under microwave irradiation was developed as a rapid and efficient solution-phase method for the high-yielding preparation of 7-aryl-2-alkylthio-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine-6-carboxamide libraries. In addition, the selective reduction of the formed dihydrotriazolopyrimidines to trans-trans-2-alkylthio-7-aryl-4,5,6,7-tetrahydro-1,2,4-triazolo[1,5-a]pyrimidine-6-carboxamides was established. The described synthetic protocols provide rapid access to novel and diversely substituted dihydroazolopyrimidine libraries.

Syntheses and some features of five new cyclohexane-1,3-dicarboxylates with multiple stereogenic centers

“…The singlepot multicomponent coupling reactions (MCRs) have proved to be one of the most powerful and efficient methods for the preparation of bioactive compounds due to their atom economy, simple experimentation, and high yields of the products [1][2][3]. Such reactions offer a wide range of possibilities for the efficient construction of highly complex molecules in a single procedural step, usually avoiding the complicate purification operations and allowing savings of both solvents and reagents.…”

Synthesis and Evaluation of 1,2,4-Triazolo[1,5-a]pyrimidines as Antibacterial Agents Against Enterococcus faecium

“…Subsequently, equal amounts of derivatives I , II , and III were heated in DMF for roughly 15–20 min (with a temperature of 130–160 °C), which yielded the desired compounds after the work up. This three-component Biginelli-like heterocyclization method 25,26 afforded the rapid and efficient synthesis of a focused library of these compounds, using commercially available reagents. In light of the essentially single-pot reactions that led to these molecules, only the final compounds have been characterized in this report.…”

“…26 Equimolar mixtures of compounds I , II , and III (0.80–2.0 mmol) were heated in 0.30–0.50 mL of DMF within the temperature range of 130–160 °C for 15–20 min. After cooling, acetone (10–25 mL) was added to the solution.…”

Heterocycles as Key Substrates in Multicomponent Reactions: The Fast Lane towards Molecular Complexity

“…This approach allowed the preparation of complex and functionalized bicyclic systems in one step (Scheme 14). [29] MCRs based on Michael addition processes have been mastered by Rodriguezs group and displayed a high synthetic versatility. [30] The participation of transient heterocycles, formed in the course of the reaction cascade, has recently enabled access to novel scaffolds, including bridged structures (Scheme 15).…”