New Approach for the Synthesis of Pyrido[1,2-a]pyrimidines

Raghunath B Toche,Muddassar A Kazi,Bhausaheb K Ghotekar,Shivaraj P Patil,Madhukar N Jachak

doi:10.3814/2008/434329

Abstract

A novel method was successfully demonstrated towards the synthesis of pyrido[1,2-a]pyrimidines having chloroethyl as an intractable side chain, through dihydrofuranone intermediates. The dihydrofuranone intermediates were synthesized by condensation of 2-aminopyridines with α-acetyl-γ-butyrolactone, which upon cyclization using phosphorus oxychloride or ethanol in sodium ethoxide furnished the pyrido[1,2-a]pyrimidines in good yield.

Highlights

Heterofused pyrimidines exhibit promising antiviral [1], antibacterial [2], anti-AIDS [3], and antinociceptive [4] activities
A novel method was successfully demonstrated towards the synthesis of pyrido[1,2-a]pyrimidines having chloroethyl as an intractable side chain, through dihydrofuranone intermediates
The dihydrofuranone intermediates were synthesized by condensation of 2-aminopyridines with α-acetyl-γ-butyrolactone, which upon cyclization using phosphorus oxychloride or ethanol in sodium ethoxide furnished the pyrido[1,2-a]pyrimidines in good yield

Summary

Introduction

Heterofused pyrimidines exhibit promising antiviral [1], antibacterial [2], anti-AIDS [3], and antinociceptive [4] activities. Resperdone is a derivative of pyrido[1, 2-a]pyrimidines[10, 11] These compounds showed antipsychotic activity [12] were used as α2 antagonists [13,14,15]. They exhibits high affinity for α2adrenoceptor with high selectivity versus the α-receptor and possesses potent in vivo central activity [16, 17], Wamhoff and Korte [18, 19] have reported the synthesis of pyrido[1,2a]pyrimidines by using 2-aminoheterocylic compounds and α-acetyl-γ-butyrolactone by refluxing dioxane or using PPA, and observed the formation of mixture of products. After the successful study of the reactions of α-formy-γ-butyrolactone with 2-aminoheterocyles [20], our interest was sparked to synthesize old compounds by new method with improved yields

Methods

Results

Conclusion