These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
Optimized Synthesis of 7-Aza-Indazoles by Diels–Alder Cascade and Associated Process Safety
preprintsubmitted 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.