Reliable Functionalization of 5,6-Fused Bicyclic N-Heterocycles Pyrazolopyrimidines and Imidazopyridazines via Zinc and Magnesium Organometallics.

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 TMP₂ Zn ⋅ 2 MgCl₂  ⋅ 2 LiCl allowed regioselective zincations. In the case of 6-chloroimidazo[1,2-b]pyridazine, bases such as TMP₂ Zn ⋅ 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-substit

SUBMITTER: Kumar Rout S 

PROVIDER: S-EPMC9321601 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature