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Optimized Synthesis of 7-Aza-Indazoles by Diels–Alder Cascade and Associated Process Safety

preprint
submitted on 14.04.2020, 11:38 and posted on 16.04.2020, 07:54 by Nicolas Brach, Vincent Le Fouler, Vincent Bizet, Marian Lanz, Pascale Hoehn, Fabrice Gallou, Corinne Bailly, Michael Parmentier, Nicolas Blanchard
Although pyrimidines are not among the most reac-tive partners in intramolecular inverse-electron de-mand [4πs+2πs] reactions with alkynes, they could be activated under mild and practical conditions, leading to fused nitrogen-containing heterocycles. We report an optimized synthesis of a 5-iodo-7-aza-indazole by a one-pot Diels–Alder cascade that starts from a pyrimidine substituted in the 2-position by an (alkynyl)hydrazone. The safety of the process was carefully studied by DSC studies. Eventually, a selection of cross-coupling reactions of 17 was studied and allowed the introduction of carbon- and nitrogen-based nucleophiles at the C5-position in good to excellent yields.

Funding

Université de Haute-Alsace

Université de Strasbourg

CNRS

History

Email Address of Submitting Author

n.blanchard@unistra.fr

Institution

Université de Haute-Alsace, Université de Strasbourg, CNRS

Country

France

ORCID For Submitting Author

0000-0002-3097-0548

Declaration of Conflict of Interest

no conflict of interest

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