Reliable Functionalization of 5,6‐Fused Bicyclic N‐Heterocycles Pyrazolopyrimidines and Imidazopyridazines via Zinc and Magnesium Organometallics
Saroj Kumar Rout, Agonist Kastrati, Harish Jangra, Kuno Schwärzer, А. Ш. Сунагатуллина, Maximilien Garny, Fabio Lima, Cara E. Brocklehurst, Konstantin Karaghiosoff, Hendrik Zipse, Paul Knochel
Abstract
Abstract 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 TMP 2 Zn ⋅ 2 MgCl 2 ⋅ 2 LiCl allowed regioselective zincations. In the case of 6‐chloroimidazo[1,2‐ b ]pyridazine, bases such as TMP 2 Zn ⋅ MgCl 2 ⋅ 2 LiCl, in the presence or absence of BF 3 ⋅ OEt 2 , 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.