Synthesis of bis(indole)-1,2,4-triazinones

A facile method for the synthesis of paraand meta-substituted bis(indole)-1,2,4-triazinones is presented. Our approach to access these triazinones involves a cyclocondensation reaction between amidrazone and ketoester functionalities. The structures of these interesting compounds were established unambiguously by X-ray crystallography. 2005 Elsevier Ltd. All rights reserved. Over the past several decades, the search for natural products in marine environments has led to the discovery of a number of biologically active bis(indole) alkaloids. These compounds, as well as many unnatural analogs, have shown promise as leads for the development of novel cancer therapies. In conjunction with an ongoing research program involving the synthesis of bis(indole) natural products, in 2002 we reported a simple method for the preparation of bis(indole)pyrazinone 1 via the cyclocondensation of ketoaldehyde 2 with aminoamide 3 (Scheme 1). We then wondered if a similar approach involving the cyclization of amidrazones (5) and ketoesters (6) could be used to prepare 0040-4039/$ see front matter 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2005.01.162