Synthesis of 1-Amino-1-aryl-1,2-dihydropyrrolo[3,4-c]pyridin-3-one Derivatives by the Reaction of 4-Lithiopyridine-3-carbonitrile with Aromatic Tertiary Amides

Abstract

A one-pot procedure for the preparation of 1-amino-1-aryl-1,2-dihydropyrrolo[3,4-c]pyridin-3-one derivatives from pyridine3-carbonitrile and aromatic tertiary amides has been developed. Thus, the reaction of 4-lithiopyridine-3-carbonitrile, generated by the treatment of pyridine-3carbonitrile with lithium 2,2,6,6-tetramethylpiperidide (LTMP), with aromatic tertiary amides in THF at –78 C yields the pyrrolopyridinone derivatives in moderate yields. In the course of our study on the development of new methods for the preparation of heterocyclic compounds, we became in need of 2-aroylpyridine-3-carbonitriles. So we attempted the reaction of 4-lithiopyridine-3-carbonitrile with N-methoxy-N-methylbenzamide. However, we were surprised to find that this reaction resulted in the formation of 1-methoxy(methyl)amino-1-phenyl-1,2-dihydropyrrolo[3,4-c]pyridin-3-one. Herein, we wish to report the results of our study on the reaction of lithiopyridinecarbonitriles with aromatic tertiary amides, which offer a simple synthetic method for 1-amino-1-aryl-1,2-dihydropyrrolo[3,4-c]pyridin-3-one derivatives. The 1,2-dihydropyrrolo[3,4-c]pyridine-3-one structure has been reported to be involved in the naturally occurring isoniazid–NAD(P) adducts. 1,2-Dihydropyrrolo[3,4-c]pyridine-3-one derivatives have been mainly prepared by the reduction of pyrrolo[3,4-c]pyridine-1,3-diones. Recently, a method based on microwave-assisted intramolecular hetero-Diels-Alder cycloaddition of acetylenic pyrimidines has been reported. However, there have been no reports on the synthesis of this heterocyclic derivatives carrying an amino group at the 1-position. First, the reaction of 4-lithiopyridine-3-carbonitrile with N-methoxy-N-methylbenzamide was examined under conditions illustrated in Scheme 1. Thus, the 4-position of pyridine-3-carbonitrile (1) was lithiated HETEROCYCLES, Vol. 85, No. 1, 2012 165