Unexpected Sodium Methoxide-catalyzed Rearrangement of 6-Amino-5-aroyl-1,3-dimethyluracils to Form Novel Cinnamoamides

Abstract

A synthetic access to novel cinnamoamides 6 was discovered by chance and explored following a two-step route. Compounds 3 were available from 6-amino-1,3-dimethyluracil (1) by acylation using benzoyl chlorides 2 and subsequently converted to 2-cyano-3-(N-methylamino)cinnamic acid methyl amides 6. This sodium methoxide-catalyzed reaction involves ring opening of the pyrimidine ring followed by elimination of CO to form dimethyl carbonate and rearrangement. The application of 6 as potential catecholamine-O-methyl transferase (COMT) inhibitors for the treatment of Parkinson’s disease is discussed.