Direct Access to New Gem-Difluorinated Pyrido[1,2-a]Pyrimidine-2-one Systems

Mohamed Abarbri

doi:10.26717/bjstr.2019.16.002859

Abstract

The pyrido[1,2-a]pyrimidine core is of great pharmaceutical importance due to its potent and significant biological activities

Highlights

The pyrido[1,2-a]pyrimidine core is of great pharmaceutical importance due to its potent and significant biological activities as an anti-inflammatory,[1] antiallergic,[2] analgesic,[3] and anticancer agent (3-5 antifolate),[4] and its anti-aggressive activities.[5]
The Harriman group investigated the reactivity of the fluorinated alkyne ethyl 4,4,4-trifluorobut-2-ynoate with the 2-aminopyridine that led to the formation of 4-(trifluoromethyl)-2H-pyrido[1,2-a]pyrimidin2-one as the sole product with an excellent yield[10] (Scheme 2)
Our investigation started by exploring the cycloaddition reaction between two different 2-aminopyridines and gem-difluorinated alkynes

Summary

Introduction

The pyrido[1,2-a]pyrimidine core is of great pharmaceutical importance due to its potent and significant biological activities as an anti-inflammatory,[1] antiallergic,[2] analgesic,[3] and anticancer agent (3-5 antifolate),[4] and its anti-aggressive activities.[5] there are two types of position isomers within the same family; pyrido[1,2-a]pyrimidin-2-ones and pyrido[1,2-a] pyrimidin-4-ones (Figure 1) They are associated in the synthesis of broad range of biologically active heterocycles such as antiulcerative agents,[6] tranquilizers and antipsychotic drugs (Pirenperone),[7] inhibitors of polyhydroxylase, or inhibitors of dihydrofolate reductase in humans (hDHFR)[8] (Figure 1). The Harriman group investigated the reactivity of the fluorinated alkyne ethyl 4,4,4-trifluorobut-2-ynoate with the 2-aminopyridine that led to the formation of 4-(trifluoromethyl)-2H-pyrido[1,2-a]pyrimidin2-one as the sole product with an excellent yield[10] (Scheme 2)

Methods

Results

Conclusion