Synthesis of highly functionalised 5-membered ring fused pyrimidine derivatives using an isocyanide-based one-pot, three component reaction

Synthesis of 6-Membered-Ring Fused Thiazine-Dicarboxylates and Thiazole-Pyrimidines via One-Pot Three-Component Reactions

“…Depending on the nature of the fivemembered ring, in certain cases such as for thiol 6, we observed that there was competition between the three-component reaction (to give 7) and the two-component reaction (to give 8). For the latter, DMAD 2 reacts directly with the five-membered ring, as shown in Scheme 1 for 1H-1,2,4-triazole-5-thiol 6, to give methyl 7-oxo-7H-[1, 2,4]triazolo [5,1b][1,3]thiazine-5-carboxylate 8 [19]. We found that the most successful three-component reactions involved five-membered rings containing more acidic protons.…”

“…We went on to investigate the direct reaction of various five-membered ring substrates with electron deficient alkynes (DMAD/DEtAD). This study was started when we noticed the presence of co-products resulting from direct reaction of DMAD with some of the five-membered rings when we were attempting three-component reactions including an isocyanide [19]. Crank and co-workers [33] previously reported the reaction of 4-methylthiazol-2-amine 11 with DMAD 2 to afford Diels-Alder adduct 12, methyl 3-methyl-7-oxo-7H-thiazolo[3,2-a]pyrimidine-5-carboxylate 13 and product 14, resulting from reaction with two moles of DMAD (Scheme 3).…”

Synthesis of Hexahydroquinoline-3-carboxamide Derivatives and Their HIV-1 Antiviral Activity

“…Of particular interest is the disruption of interactions between HIV-1-proteins and host proteins. [1][2][3][4][5][6] Computational modelling was used as a strategy to identify scaffolds as the starting point to derive small molecules that could possibly disrupt interactions between HIV-1 integrase (HIV-1-IN) and host lens epithelium-derived growth factor (LEDGF/p75) proteins. Virtual screening of the ChemBridge Diverset library of compounds (consisting of 20,000 diverse and unique drug-like structures) was performed using Schrödinger Maestro 11.2 software.…”

A Multifield Study on Dimethyl Acetylenedicarboxylate: A Reagent Able to Build a New Cycle on Diaminoimidazoles

“…For example, it was found that N , N - and N , S -dinucleophiles, such as amino- and mercaptotriazoles 2a and 2b , respectively [ 21 , 22 ], by interaction with DMAD in dichloromethane, led to the formation of 4,7-dihydro-s-triazolo[1,5-a]pyrimidinones 4a , [1,2,4]triazolo[5,1-b][1,3]thiazinones 4b and dihydro[1,2,4]triazolo[4,3- a ]pyrimidinones 4c with high antibacterial activity [ 23 , 24 ] ( Scheme 1 ). In a first step, an addition ofDMAD at the multiple bond by the amino or mercapto group of the starting triazole occurs, then an intramolecular cyclization on the NH fragment due to the “far” ester group happens.…”