4H‐Pyrido[1,2‐a]pyrimidin‐4‐one, biologically important fused heterocyclic scaffold: Synthesis and functionalization

Abstract

4H‐pyrido[1,2‐a]pyrimidin‐4‐one and their derivatives are highly bioactive and multipurpose heterocyclic motifs, having application in drugs, natural products, agrochemical, material science, and organic synthesis. The C‐H functionalization of basic core structure of heterocycles have become indispensable tools that have continually increased the importance in the pharmaceutical industry for the synthesis of various useful heterocyclic molecules and their derivatives. In this review, we have provided a summary of various routes to synthesize 4H‐pyrido[1,2‐a]pyrimidin‐4‐one derivatives along with various derivatization methods such as via cross‐coupling, C‐H functionalization through arylation, alkenylation, sulfenylation, selenylation, phosphonation etc. taking into account the synthetic potentiality and significant influence of this scaffold in drug discovery.

Synthesis of Fused Imidazoles and Pyrimidinones from 2‐Aminoazines

“…Pyridin-2-amine (1 a, Figure 1) and aza derivatives, such as pyrimidin-2-amine (1 b, Figure 1), pyrimidin-4-amine (1 c, Figure 1), pyrazin-2-amine (1 d, Figure 1), pyridazin-3-amine (1 e, Figure 1), and 1,2,4-triazin-3-amine (1 f, Figure 1) play crucial roles as intermediates in medicinal and industrial chemistry. [1][2][3][4] The amine group and aromatic nitrogen in 2-aminoazines have basic and nucleophilic properties, enabling reaction with electrophiles to form fused imidazoles and pyrimidinones. These compounds exhibit a wide range of pharmaceutical and biological activities that encompass anti-tumor, [5] anti-fungal, [6] anti-viral, [7] anti-tubercular, [8] and anti-inflammatory [9] properties.…”

“…Pyridin‐2‐amine ( 1 a , Figure 1) and aza derivatives, such as pyrimidin‐2‐amine ( 1 b , Figure 1), pyrimidin‐4‐amine ( 1 c , Figure 1), pyrazin‐2‐amine ( 1 d , Figure 1), pyridazin‐3‐amine ( 1 e , Figure 1), and 1,2,4‐triazin‐3‐amine ( 1 f , Figure 1) play crucial roles as intermediates in medicinal and industrial chemistry [1–4] . The amine group and aromatic nitrogen in 2‐aminoazines have basic and nucleophilic properties, enabling reaction with electrophiles to form fused imidazoles and pyrimidinones.…”

A New Efficient One‐Pot Three‐Component Synthesis of Diverse Pyrido[1,2‐a]pyrimidines

“…Pyrido[1,2‐ a ]pyrimidines have great potential for the new drugs design, [1] since their structure combines two important motifs that are present in a variety of natural compounds, including vital ones. The pyridine core is the basis of alkaloids, [2] and the pyrimidine backbone is contained in pyrimidine and purine bases of nucleic acids [3] .…”

Supporting Electrolyte‐Free Electrochemical Oxidative C−H Sulfonylation and Thiocyanation of Fused Pyrimidin‐4‐Ones in an All‐Green Electrolytic System

“…Fused pyrimidin‐4‐ones or their derivatives are important molecular scaffolds found in natural products and drugs with various biological activities, making their C−H functionalization a significant area of research [12] . However, many of these approaches require expensive transition‐metal catalysts, [13] stoichiometric quantities of oxidants, [14] photoredox catalysts, [15] and harsh reaction conditions, [12d] resulting in increased reagent waste. Recently, the C3‐functionalization of 4 H ‐pyrido‐[1,2‐ a ]‐pyrimidin‐4‐ones through electrochemical anodic coupling reactions has been described in the literature (Scheme 1b).…”