K. Kobayashi, K. Nakagawa, Taketoshi Kozuki
May 29, 2012
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ChemInform
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