An Improved Synthesis of 2,3-Diamino-5,6-dichloropyrazine: A Useful Heterocyclic Scaffold

Jake M. Rigby; Andrew Chantry; Andrew M. Hemmings; Christopher J. Richards; G. Richard Stephenson; Thomas E. Storr

doi:10.1055/s-0043-1775410

Synthesis, Table of Contents

Synthesis 2024; 56(23): 3587-3592
DOI: 10.1055/s-0043-1775410

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An Improved Synthesis of 2,3-Diamino-5,6-dichloropyrazine: A Useful Heterocyclic Scaffold

Jake M. Rigby ∗

^aSchool of Chemistry, Pharmacy and Pharmacology, University of East Anglia, Norwich NR4 7TJ, UK

,

Andrew Chantry

^bSchool of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK

,

Andrew M. Hemmings

^bSchool of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK

,

Christopher J. Richards

^aSchool of Chemistry, Pharmacy and Pharmacology, University of East Anglia, Norwich NR4 7TJ, UK

,

G. Richard Stephenson

^aSchool of Chemistry, Pharmacy and Pharmacology, University of East Anglia, Norwich NR4 7TJ, UK

,

Thomas E. Storr

^aSchool of Chemistry, Pharmacy and Pharmacology, University of East Anglia, Norwich NR4 7TJ, UK

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Abstract

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Abstract

2,3-Diamino-5,6-dichloropyrazine represents a valuable but underexplored heterocyclic building block. Due to the use of harsh conditions and lack of selectivity surrounding the known literature synthesis, we developed a more accessible and selective three-step route from 2-aminopyrazine. Challenging conditions are avoided by using a high-yielding dichlorination with N-chlorosuccinimide (NCS), which is followed by a regioselective amination. The installation of the last chlorine atom using 1-chloro-1,2-benziodoxol-3(1H)-one is rapid, enabling access to 2,3-diamino-5,6-dichloropyrazine in an improved overall yield (41%).

Key words

pyrazine - heterocyclic building block - synthesis - chlorination - 2,3-diamino-5,6-dichloropyrazine

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References

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