Synthesis of 6H-Pyrrolo[2,3,4-gh]perimidines from naphthalene-1,4,8-triamine

Abstract

The importance of indole derivatives as biologically active compounds is difficult to overestimate. Benzo[c,d]indoles are not an exception; for example, efficient inhibitors of thymidylate synthase were found among compounds of this series [1]. The present communication describes the synthesis of fused benzo[c,d]indole derivatives, 6H-pyrrolo[2,3,4-gh]perimidines IVa–IVc, from naphthalene-1,4,8-triamine (I) and 1,3,5-triazines IIa–IIc. We previously showed that 1,3,5-triazine in polyphosphoric acid (PPA) acts as efficient formylating and acylating agent [2–5], in particular toward naphthylamines [5]. Therefore, it may be expected that the use of 1,3,5-triazine should ensure convenient synthesis of pyrroloperimidines IVa–IVc. In fact, by heating triamine I with triazines IIa–IIc in PPA first at 80–90°C and then at 130–140°C we obtained the corresponding pyrroloperimidines IVa–IVc in 38–48% yield. The reaction is likely to involve intermediate formation of aminoperimidines IIIa–IIIc. Unlike the known procedure [6], the proposed method requires no preliminary preparation and acylation of perimidines. Furthermore, the key step in the known procedure [6] is the Schmidt reaction utilizing sodium azide in acid medium, and there exists a risk of evolution of toxic and explosive hydrazoic acid. The procedure proposed by us is free from the said disadvantage.