DFT‐calculations allow prediction of the reactivity of uncommon N‐heterocyclic scaffolds of pyrazolo[1,5‐a]pyrimidines and imidazo[1,2‐b]pyridazines and considerably facilitate their functionalization. The derivatization of these N‐heterocycles was realized using Grignard reagents for nucleophilic additions to 5‐chloropyrazolo[1,5‐a]pyrimidines and TMP2Zn ⋅ 2 MgCl2 ⋅ 2 LiCl allowed regioselective zincations. In the case of 6‐chloroimidazo[1,2‐b]pyridazine, bases such as TMP2Zn ⋅ MgCl2 ⋅ 2 LiCl, in the presence or absence of BF3 ⋅ OEt2, led to regioselective metalations at positions 3 or 8. Subsequent functionalizations were achieved with TMPMgCl ⋅ LiCl, producing various polysubstituted derivatives (up to penta‐substitution). X‐ray analysis confirmed the regioselectivity for key functional heterocycles.
Two fused N‐heterocyclic scaffolds were selectively functionalized giving access to novel pharmaceutical targets that offer a better life to the whole world. More information can be found in the Research Article by P. Knochel and co‐workers (DOI: 10.1002/chem.202200733).
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