Synthesis of pyrrolo[2,1-f][1,2,4]triazin-4(3H)-ones: Rearrangement of pyrrolo[1,2-d][1,3,4]oxadiazines and regioselective intramolecular cyclization of 1,2-biscarbamoyl-substituted 1H-pyrroles

Abstract

SummaryPyrrolo[2,1-f][1,2,4]triazin-4(3H)-ones 12 have been easily prepared via nucleophile-induced rearrangement of pyrrolooxadiazines 11 and regioselective intramolecular cyclization of 1,2-biscarbamoyl-substituted 1H-pyrroles 10. In this work, we demonstrated that the described synthetic approaches can be considered to be more facile and practical than previously reported procedures.

Pyrrolotriazinone as an Underexplored Scaffold in Drug Discovery

“…The starting material, substituted pyrrole-2-carboxylic acid, is first converted into an amide based on conventional peptide coupling methodologies or via amidation of the corresponding acyl chloride. Then, the pyrrole is converted into 1-amino-pyrrole (with in situ generated chloramine under phase transfer condition) that is further acylated and the corresponding product is cyclized under oxidative conditions thanks to PPh 3 /Br 2 into the title compound according to Scheme 1 [8]. Due to the growing interest in biological applications of pyrrolotriazinones, new synthetic strategies should be explored in the future in order to offer a quicker access to more complex analogs, a highly challenging task for organic chemists.…”

Synthetic strategies for pyrrolo[2,1-f][1,2,4]triazine: the parent moiety of antiviral drug remdesivir

“…A practical synthesis of pyrrolo[2,1- f ][1,2,4]triazin-4(3 H )-ones has been proposed via rearrangement of pyrrolo-[1,2- d ][1,3,4]oxadiazines. 25 The methodology involved synthesis of pyrrole-2-carboxamides 62 from 3-chloro-1 H -pyrrole-2-carboxylic acid ( 61 ) (Scheme 14 ). Treating pyrroles 62 with NH 4 Cl, Aliquat 336, and NaClO afforded 1-aminopyrroles 63 .…”