Pyrazolo[1,5-a]pyrimidines: A Close Look into their Synthesis and Applications

Abstract

Pyrazolo[1,5-a]pyrimidines are fused N-heterocyclic systems of a pyrazole. They are considered as a key structural motif in many vital applications, such as medicinal, pharmaceuticals, pesticides, dyes and pigments. Their synthetic routes have escalated dramatically in the last decades. The current review is a recent synthetic survey of pyrazolo[ 1,5-a]pyrimidines and their applications until recently.

Functional Pyrazolo[1,5-a]pyrimidines: Current Approaches in Synthetic Transformations and Uses As an Antitumor Scaffold

“…Regardless, innovative synthesis methods still emerge that offer creative ways to modify established ones. Notably, the main synthesis route of pyrazolo[1,5-a]pyrimidines allows versatile structural modifications at positions 2, 3, 5, 6, and 7 via the cyclocondensation reaction of 1,3-biselectrophilic compounds with NH-3-aminopyrazoles as 1,3-bisnucleophilic systems ( Figure 1 b) [ 1 , 2 , 3 , 4 , 5 , 6 , 24 , 25 ].…”

“…The synthesis starting from 1,3-dicarbonyl compounds is by far the most employed because it provides high functional group tolerance or enables conditions that are easily accessible while employing cheap commercial reagents. Acid and ethanol are commonly used solvents, while common catalysts include sodium ethoxide and amine-based bases [ 1 , 2 , 3 , 4 , 5 , 26 , 27 , 28 , 29 ]. This synthetic strategy is used to obtain large quantities of starting materials (ranging from mg to even kg) under simple conventional heating conditions.…”

“…This fused pyrazole is a privileged scaffold for combinatorial library design and drug discovery because its great synthetic versatility permits structural modifications throughout its periphery. The PP derivatives synthesis has been widely studied; thus, various reviews related to the obtention and later derivatization steps have been described in the literature [ 2 , 3 , 4 , 5 ], after the first critical review involving this attractive scaffold [ 6 ] ( Figure 1 ).…”

“…These reports should address protocols that aim to minimize synthesis pathways, employ cheap reagents and develop processes that prevent or reduce waste production. Usually, PP derivative synthesis involves the pyrimidine ring construction via the interaction of NH -3-aminopyrazoles with different 1,3-biselectrophilic compounds such as β-dicarbonyls, β-enaminones, β-haloenones, β-ketonitriles, and so on ( Figure 1 b) [ 1 , 2 , 3 , 4 , 5 , 6 ]. Pyrazolo[1,5- a ]pyrimidine scaffold is part of bioactive compounds with exceptional properties like selective protein inhibitor [ 7 ], anticancer [ 8 ], psychopharmacological [ 9 ], among others [ 10 , 11 ].…”

“…Pyrazolo[1,5- a ]pyrimidine scaffold is part of bioactive compounds with exceptional properties like selective protein inhibitor [ 7 ], anticancer [ 8 ], psychopharmacological [ 9 ], among others [ 10 , 11 ]. Furthermore, the biocompatibility and lower toxicity levels of PP derivatives have led them to reach commercial molecules, for instance, Indiplon, Lorediplon, Zaleplon, Dorsomorphin, Reversan, Pyrazophos, Presatovir, and Anagliptin ( Figure 2 ) [ 1 , 2 , 3 , 4 , 5 ]. In recent years, this molecular motif has been a focus of study for promising new applications related to materials sciences [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ], due to its exceptional photophysical properties as an emergent fluorophore [ 15 , 16 , 17 , 18 , 19 , 20 , 21 ].…”