One-pot synthesis of 1-alkyl- 4,5-dihydro-6H-pyrrolo[1,2-a]- [1,4]benzodiazepin-6-one

Abstract

Annelated derivatives of [1,4]diazepine are well known due to the broad range of their biological activity. We have recently reported a synthesis of derivatives of pyrrolo[1,2-a][1,4]diazepine based on the acidcatalyzed recyclization of N-(5-methyl-2-furyl)-3-aminothieno[2,3-b]pyridinecarboxamides and N-(5-methyl-2-furyl)anthranilamides [1,2]. This method involves the simultaneous formation of diazepine and pyrrole rings. The anthranilamides used in the reaction were obtained by the reduction of the corresponding ortho-nitrobenzamides.In the present work, we present a one-pot synthesis of pyrrolo[1,2 -a][1,4]benzodiazepinones 1a-c directly from o-[N-(5-alkyl-2-furyl)methyl]nitrobenzamides 2a-c.The proposed method involves opening of the furan ring to form a 1,4-diketone and followed by reduction of the nitro group, leading to spontaneous intramolecular cyclization and formation of the pyrrolodiazepine system. R R O N H O R N O O HCl/EtOH R R O N H N O O O R O N H N R O R R SnCl 2 ·2H 2 O, 20°C 2a-c 1a-c 55-65°C -+ 1 1 + -1 1,2 a R = H; R 1 = Me; b R =MeO, R 1 =Me; c R = MeO, R 1 =Et

A Route to (Het)arene-Annulated Pyrrolo[1,2-d][1,4]diazepines via the Expanded Intramolecular Paal–Knorr Reaction: Nitro Group and Furan Ring as Equivalents of Amino Group and 1,4-Diketone

“…Alternatively, the latent form of the amino group (such as nitro or azido functionalities) can be used in combination with the 1,4-diketone moiety or the corresponding furan. Surprisingly, this promising approach is not investigated to date …”