Synthesis of Novel Pyrazine-Substituted 1H-Pyrrole-2-carboxamides and Related Tethered Heterocycles

Abstract

As part of a drug discovery program, 4-pyrazin-2-yl-1H-pyrrole-2-carboxamides were accessed along with a number of bicyclic analogues. Routes to these compounds were largely absent from the scientific literature. The synthesis of a 4-(pyrazin-2-yl)-1H-pyrrole-2-carboxamide and several fused bicyclic analogues all using standard procedures (S_NAr, borylation, C–C cross couplings, hydrolysis, amide bond formation, cyclisation, halogenation, and alkylation) from readily available starting materials is reported. The synthetic sequences range from 4–12 steps per final compound, with yields of isolated intermediates ranging from 20 to ∼100%.

Key words

heterocycle - bicyclic - fused - pyrazine - pyrrole - drug discovery - tethered - core

Publication History

Received: 01 October 2021

Accepted after revision: 29 November 2021

Article published online:
26 January 2022

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