Mg3N2-assisted one-pot synthesis of 1,3-disubstituted imidazo[1,5-a]pyridine.

Suhas G Patil,Sagar T Sankpal,Jagannath S Jadhav

doi:10.1039/c9ra10848c

Suhas G Patil, Sagar T Sankpal + Show 1 more

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https://doi.org/10.1039/c9ra10848c

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Abstract

A novel Mg3N2-assisted one-pot annulation strategy has been developed via cyclo-condensation reaction of 2-pyridyl ketones with alkyl glyoxylates or aldehydes, allowing the formation of imidazo[1,5-a]pyridines exclusively with an exellent yield.

Highlights

The design and synthesis of new azaheterocyclic ring systems are highly necessary in modern drug discovery to achieve speci c drug–receptor interactions.[1,20] Among them, imidazo [1,5-a]pyridine is one of the most important and medicinally fascinating heterocyclic ring systems, which functions as a building block for the synthesis of important bio-conjugates
The synthesized imidazo[1,5a]pyridine-3-carboxylates can be converted into more complex heterocycles via a systematic approach, which is ongoing in our laboratory
Reactions were monitored by thin layer chromatography (TLC) using MERCK precoated silica gel plates

Summary

Introduction

The design and synthesis of new azaheterocyclic ring systems are highly necessary in modern drug discovery to achieve speci c drug–receptor interactions.[1,20] Among them, imidazo [1,5-a]pyridine is one of the most important and medicinally fascinating heterocyclic ring systems, which functions as a building block for the synthesis of important bio-conjugates. The latest reports on the synthesis of imidazo[1,5-a]pyridine present a straightforward way to construct this particular heterocyclic ring system via the decarboxylative cyclic annulation of amines[12] (Fig. 1, eqn (b)) or a-amino acids[13,19] (Fig. 1, eqn (c)) with 2-pyridyl carbonyl compounds Encouraged by these previous achievements and in continuation of our exploits on the development of novel approaches towards biologically active compounds,[14] we hypothesized the development of a rapid, more practical and eco-friendly technique by utilizing a secondary nitrogen source for the shaping of the imidazo[1,5-a]pyridine ring structure (Fig. 1, eqn (d)). The above reaction only resulted in partial conversion under ambient conditions and at high temperatures (Table 1, entries 1–4) This indicates that the incomplete formation of ketoimine may be due to the slow evolution of ammonia or ammonia escaping out. The optimal reaction conditions were achieved using 1a (1 equiv.), Mg3N2 (1 equiv.) and methyl glyoxylate 2a (1 equiv.) in EtOH : water (8 : 2) as the solvent system to obtain the maximum yield of 3a (Table 1, entry 8), and the same combination was chosen for further studies

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