Synthesis of 8-Bromo-7-chloro[1,2,4]triazolo[4,3-c]pyrimidines, Their Ring Rearrangement to [1,5-c] Analogues, and Further Diversification

Caifei Tang; Chao Wang; Zhiming Li; Quanrui Wang

doi:10.1055/s-0034-1378453

Synthesis, Table of Contents

Synthesis 2014; 46(20): 2734-2746
DOI: 10.1055/s-0034-1378453

paper

Synthesis of 8-Bromo-7-chloro[1,2,4]triazolo[4,3-c]pyrimidines, Their Ring Rearrangement to [1,5-c] Analogues, and Further Diversification

Caifei Tang

Department of Chemistry, Fudan University, Shanghai 200433, P. R. of China Fax: +86(21)65641740 Email: qrwang@fudan.edu.cn

,

Chao Wang

Department of Chemistry, Fudan University, Shanghai 200433, P. R. of China Fax: +86(21)65641740 Email: qrwang@fudan.edu.cn

,

Zhiming Li

Department of Chemistry, Fudan University, Shanghai 200433, P. R. of China Fax: +86(21)65641740 Email: qrwang@fudan.edu.cn

,

Quanrui Wang*

Department of Chemistry, Fudan University, Shanghai 200433, P. R. of China Fax: +86(21)65641740 Email: qrwang@fudan.edu.cn

› Author Affiliations

Abstract

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Abstract

8-Bromo-7-chloro[1,2,4]triazolo[4,3-c]pyrimidines were prepared by bromine-mediated oxidative cyclization of the aldehyde-derived hydrazones. The structure of one such product was unambiguously confirmed by single-crystal X-ray analysis. While the C-5 unsubstituted 1,2,4-triazolo[4,3-c]pyrimidine chemotype is extremely susceptible to ring isomerization at ambient conditions, the C-5-substituted analogues were found to be quite stable, permitting isolation in pure form. Nevertheless, they can still be converted into the 1,2,4-triazolo[1,5-c]pyrimidines by base- or acid-promoted Dimroth rearrangement. The presence of halogen functionalities on the pyrimidine nucleus renders the products useful as versatile synthetic intermediates for the easy diversification, as evidenced by palladium-catalyzed Kumada cross-couplings and Buchwald–Hartwig amination, as well as direct aromatic substitution.

Key words

hydrazones - oxidation - nitrogen heterocycles - triazolopyrimidines - rearrangement

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References

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