Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• compounds 6, 18, and 21 via natural bond orbital (NBO) analyses which further support the suggested reaction pathways. Keywords: DFT; indazole; indazole substitution; mechanism; N1-substituted indazole; N2-substituted indazole; regioselectivity; Introduction Indazoles constitute an important class of

• the treatment of paroxysmal nocturnal hemoglobinuria, and CPI-637 (2), an inhibitor of both cyclic-AMP response element binding protein (CBP) and adenoviral E1A binding protein [14][15][16]. The N2-substituted indazole analogs pazopanib (3), an FDA-approved tyrosine kinase inhibitor used for the

• simple and mild method to selectively generate N1- or N2-substituted indazole analogs when the substituents appear to favor one over the other. Ideally, it would be greatly beneficial if the desired high regioselectivity on N1 or N2 could be achieved when commercially available chemicals, such as