A microwave reactor was used to synthesize a series of novel 3,6-disubstituted or 3-substituted pyrazolo[1,5-a]pyrimidines in a total of 1 hour reaction time over 3 steps. The products were obtained in good to excellent yields (34-92%, ave = 52%) using a straightforward synthesis starting with the reaction of dimethylformamide-dimethylacetal with commercially available aryl acetonitriles (120C, 20 min). This was followed by treatment with H2NNH2 • HBr (120C, 20 min), and then reacted with either 1,1,3,3-tetramethoxypropane or a 2-aryl-substituted malondialdehydes (120C, 20 min). The resulting product was either collected on a sintered glass funnel or purified via column chromatography. The compounds were screened for anti-cancer activity against A2780 Ovarian and/or MCF7 breast cancer cell lines in vitro. The most active compounds were the 3-(4-(trifluoromethyl)phenyl)-6-[4-(2-(piperidin-1-yl)ethoxy]phenyl analogue and the 3-(2-fluorophenyl)-6-[4-(2-(4-methylpiperzin-1-yl)ethoxy]phenyl analogue, exhibiting EC50 values of 0.84 and 0.52 M respectively, which is 2-3 times more potent than Dorsomorphin. Several of the derivatives also showed promising activities against several viruses of emerging concern, including HBV, MERS Coronavirus, Zika, and Ebola. Use of a microwave reactor to synthesize N’-aryl/(alkyl) substituted N-[(4-hydroxy-6-phenyl)pyrimidin-2-yl]guanidines or N-[(4-hydroxy-6-trifluoromethyl)pyrimidin-2-yl]guanidines from the corresponding cyanamides with alkyl/aryl amines was achieved in good to excellent yields (39-96%, ave = 62%) in 10 minutes at 120C using only 1 equivalent of amine. Work-up was exceptionally simple, and involved collecting precipitated solids on a sintered glass funnel and washing with cold 2-propanol. Products were obtained in analytically pure form and required approximately 1 hour to prepare, start to finish. Compounds in this series showed early promise as potential inhibitors of A2780 Ovarian cancer, in vitro.

Nos travaux de thèse portent sur la mise au point de nouvelles méthodes de synthèse permettant l'accès de façon rapide et efficace à différents dérivés pyrazolo[1,5-a]pyrimidiniques diversement fonctionnalisés.La première partie de ce travail concerne l'étude et l'application de la condensation de la pyran-2-one avec les 5(3)-amino-3(5)-arylpyrazoles que ce soit par chauffage classique ou sous irradiation micro-onde. Par la suite, un nouveau procédé d'(hétéro)arylation pallado-catalysé direct régiosélectif a été mis à profit pour élaborer des pyrazolo[1,5-a]pyrimidines fonctionnalisées tant en position 3 que sur le méthyle situé sur le sommet 7 de la 5,7-diméthylpyrazolo[1,5-a]pyrimidine.Le dernier volet de ce mémoire a été consacré à la préparation des entités pyrazolo[1,5-a]pyrimidiniques substituées en position 7 par des motifs benzyliques et ce, via une procédure " one-pot ", sous irradiation micro-onde, constituée d'une réaction d'arylation directe pallado-catalysée suivie d'une saponification-décarboxylation.