Facile multi-components one-pot synthesis of dipyrazolo[1,5-a: 3',4'-d]pyrimidine as potent bioactive scaffolds

An efficient, three-component, catalyst free synthesis of dipyrazolo[1,5-a:3,4-d]pyramid scaffolds has been carried out using 3-methyl-1H-pyrazol-5(4H)-one (1), 5-amino pyarazole (2a-b) and substituted aromatic aldehydes.
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Facile multi-components one-pot synthesis of dipyrazolo[1,5-a:3,4-d]pyrimidine as potent bioactive scaffolds Current Chemistry Letters 7 (2018) 111–120 Contents lists available at GrowingScience Current Chemistry Letters homepage: www.GrowingScience.comFacile multi-components one-pot synthesis of dipyrazolo[1,5-a:3,4-d]pyrimidineas potent bioactive scaffoldsRavindra M. Gola and Vijaykumar M. Barota*a P. G. Center in Chemistry, Smt. S. M. Panchal Science College Talod, Gujarat, IndiaCHRONICLE ABSTRACT Article history: An efficient, three-component, catalyst free synthesis of dipyrazolo[1,5-a:3,4-d]pyramid Received June 20, 2018 scaffolds has been carried out using 3-methyl-1H-pyrazol-5(4H)-one (1), 5-amino pyarazole Received in revised form (2a-b) and substituted aromatic aldehydes. The reaction underwent cyclocondensation reaction August 27, 2018 in reflux condition with moderate to good (62%–90 %) yields. The twenty newly prepared Accepted October 30, 2018 molecules were analyzed by means of 1H & 13C NMR, Mass, and IR spectroscopies and their Available online activities against the bacterial and fungal strains were screened. Some of tested compounds October 30, 2018 have shown excellent antibacterial activities while another four were found to have good Keywords: antifungal activity. Dipyrazolo[1,5-a:3,4- d]pyrimidine Multi-component reaction Catalyst free Antibacterial Antifungal © 2018 by the authors; licensee Growing Science, Canada.1. IntroductionPyrimidine scaffold is found in several naturally occurring compounds and they make the corestructures of many biologically active scaffolds and much more pharmaceutical industrial materials.1, 2For the most part, significant fused dipyrazoloes is diprazolopyrimidine derivative which acquires arange of biological potent molecules.3 The MCRs (Multi-components reaction) approach is moreconvenient in comparison to conventional synthesis because of flexibility and atom-efficient character.4We used the MCRs for an optimization of a synthesis of dipyrazolo[1,5-a:3,4-d]pyrimidines.Pyrazolopyrimidines have shown different types of pharmacological activities such as antitumor,5, 6anticancer,7 DPP-4 inhibitory activity,8, 9 PDE-4 inhibitory,10, 11 antiproliferative,12 COX-2-inhibitory,13 11β-HSD1 inhibitory,14 antibacterial15, 16 and many others.17 Thus, the synthesis of thesemoieties has been widely accounted in the most recent couple of years.2, 13, 18-20 Despite the potentialutility of previously mentioned synthetic methods, many of them suffer from usage of organic solventand catalysts as well as strong acidic/basic conditions, long reaction times, and low yields of the targetproducts.2* Corresponding author. E-mail address: vijaykumarmbarot@gmail.com (V. M. Barot)© 2018 by the authors; licensee Growing Science, Canadadoi: 10.5267/j.ccl.2018.010.001112 Herein, we report an efficient catalyst free synthesis of these important biologicaly activepyrazolopyrimidines based on cyclocondensation reaction of 3-methyl-1H-pyrazol-5(4H)-one (1), 3-phenyl-1H-pyrazol-5-amine (2a), 3-(4-chlorophenyl)-1H-pyrazol-5-amine (2b) and substitutedaromatic aldehydes (3a-j) run in a reflux condition.2. Results and Discussion2.1 Chemistry Our preliminary study involving the synthesis of 3-methyl-1H-pyrazol-5(4H)-one (1), 3-phenyl-1H-pyrazol-5-amine (2a) and 3-(4-chlorophenyl)-1H-pyrazol-5-amine (2b) were based on earlierreported procedures.11, 21, 22 The catalyst free, one-pot, high yielding condensation reaction of 3-methyl-1H-pyrazol-5(4H)-one (1), 3-(4-substitutedphenyl)-1H-pyrazol-5-amines (2a-b) and aromaticaldehydes (3a-j) was carried out using methanol as a solvent at reflux temperature to furnish desireddipyrazolo[1,5-a:3,4-d]pyrimidine (4a-t) (Scheme 1). H3C H2N H3C R1 N HN N ...