De Novo Synthesis of 4-Thio- and 4-Aminopyrrole[3,4-c]pyridines

Significance

The reported chemistry describes the first efficient synthesis of unprecedented 4-amino- and 4-thio-1,3-dioxo-1H-pyrrole[3,4-c]pyridines, via a one-step reaction between a malonamidine or malonthioamide with methyl acetylpyruvate under mildly basic conditions. In the process, a C-C bond and two new C-N bonds are formed. In addition to its efficiency, broad scope, and use of simple starting materials, facile product isolation of sufficient purity for further chemistry may be noted. The method is an­ticipated to be suitable for scale-up reactions designed to prepare large amounts of pyrrolo[3,4c]pyridines for biological testing.