Synlett 2020; 31(05): 459-462
DOI: 10.1055/s-0039-1690825
letter
© Georg Thieme Verlag Stuttgart · New York

1,2-Dihydropyridazines as Versatile Synthetic Intermediates

Thomas K. Britten
a  Department of Chemistry, Lancaster University, Bailrigg, LA1 4YB, UK   Email: [email protected]
,
Paul D. Kemmitt
b  Medicinal Chemistry, Research and Early Development, Oncology R & D, AstraZeneca, Cambridge, CB10 1XL, UK
,
Nathan R. Halcovitch
a  Department of Chemistry, Lancaster University, Bailrigg, LA1 4YB, UK   Email: [email protected]
,
a  Department of Chemistry, Lancaster University, Bailrigg, LA1 4YB, UK   Email: [email protected]
› Author Affiliations
Funding from AstraZeneca [CASE Top-Up Award to T.K.B. (2015–2019)] is gratefully acknowledged.
Further Information

Publication History

Received: 29 December 2019

Accepted after revision: 28 January 2020

Publication Date:
13 February 2020 (online)


Published as part of the Special Section 11th EuCheMS Organic Division Young Investigator Workshop

Abstract

The reactivity of 1,2-dihydropyridazines under various conditions is described, leading to the formation of a variety of products, including 2-aminopyrroles, phenylenediamines, and several novel heterocyclic motifs.

Supporting Information

 
  • References and Notes

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  • 6 Methyl 2-[(Methoxycarbonyl)amino]-1H-pyrrole-1-carboxylate (2a); Typical ProcedureA solution of 1,2-dihydropyridazine 1a (520 mg, 2.62 mmol, 1.0 equiv) in o-xylene (5 mL) was refluxed for 5 h under argon. Purification by flash column chromatography [silica gel, hexane–EtOAc (100% hexane to 9:1)] gave a white solid; yield: 320 mg (1.61 mmol, 62%); mp 46–47 °C; Rf = 0.35 (hexane–EtOAc, 2:1). FTIR (ATR): 3349 (NH), 2950, 1724 (C=O) cm–1. 1H NMR (400 MHz, CDCl3): δ = 9.05 (br s, 1 H, NH), 6.85 (dd, J = 3.6, 1.8 Hz, 1 H, Ar–H), 6.42–6.32 (br m, 1 H, Ar–H), 6.13 (t, J = 3.6 Hz, 1 H, Ar–H), 3.95 (s, 3 H, OMe), 3.77 (s, 3 H, OMe). 13C NMR (100 MHz, CDCl3): δ = 153.1 (C=O), 152.4 (C=O), 130.5 (Ar–C), 114.0 (Ar–CH), 111.6 (Ar–CH), 98.4 (Ar–CH), 54.2 (OMe), 52.6 (OMe). HRMS (APCI): m/z [M + H]+calcd for C8H11N2O4: 199.0713; found: 199.0712. Note: To prevent degradation, the 2-aminopyrroles must be stored in the freezer under an inert atmosphere.
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