One-pot synthesis of substituted pyrrolo[3,4-b]pyridine-4,5-diones based on the reaction of N-(1-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-oxo-2-arylethyl)acetamide with amines.

Valeriya G Melekhina,Vasily A Migulin,Arkady A Dudinov,Elizaveta K Melnikova,Boris V Lichitsky,Artem N Fakhrutdinov,Vitaly S Mityanov,Andrey N Komogortsev,Yulia V Nelyubina,Michail M Krayushkin

doi:10.3762/bjoc.15.277

Abstract

The condensation of primary amines with N-(1-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-oxo-2-arylethyl)acetamides was explored. Thus, a previously unknown recyclization of the starting material was observed in acidic ethanol in the presence of an amine, which provided the corresponding dihydropyrrolone derivative as the major reaction product. Based on this transformation, a practical and convenient one-pot synthetic method for substituted pyrrolo[3,4-b]pyridin-5-ones could be devised.

Highlights

Derivatives of pyrrolo[3,4-b]pyridin-5-one are known for their broad-spectrum biological activity [1-3]
One example includes a family of compounds based on this fragment that was tested as dipeptidyl peptidase-4 (DPP4) inhibitors [4-7]
We describe a convenient synthetic method for the preparation of 6-alkyl-2-methyl-7-aryl-6,7-dihydro-1Hpyrrolo[3,4-b]pyridine-4,5-diones 1

Summary

Introduction

Derivatives of pyrrolo[3,4-b]pyridin-5-one are known for their broad-spectrum biological activity [1-3]. Therein, the condensation of N-(1-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-oxo-2arylethyl)acetamides 2 with a diverse range of amines 3 did furnish the desired scaffolds in satisfactory yields and allowed to use a variety of readily available substituted substrates (Scheme 1). Entry 8, the most efficient conditions for the reaction of 2a and 3a were found to be the use of ethanol as solvent as well as equimolar amounts of amine species and acetic acid under reflux.

Results

Conclusion