BF₃·OEt₂ mediated metal-free one-pot sequential multiple annulation cascade (SMAC) synthesis of complex and diverse tetrahydroisoquinoline fused hybrid molecules

Abstract

A highly efficient and distinct BF3·OEt2 mediated metal-free SMAC protocol for the synthesis of complex and diverse hybrid molecules viz. indazole fused tetrahydroisoquinolinoquinoxalines, and tetrahydroisoquinolinodiazepine has been developed. The transformation is based on sequential cascade processes involving 2H-indazole formation and deprotection Pictet-Spengler cyclization steps in one-pot fashion. The protocol demonstrates the utility of sequential multiple annulations in a cascade fashion. The present one-pot protocol uses the Solid State Melt Reaction (SSMR) strategy for the synthesis of the intermediate 2H-indazole. The method is operationally simple and represents a new approach for C-C, three C-N and N-N bond formation with a wide substrate scope.

Recent Advances in Indazole-Containing Derivatives: Synthesis and Biological Perspectives

“…Indazole derivatives scarcely occur in nature, but this particular nucleus in a variety of synthetic compounds possesses a wide range of pharmacological activities, such as anti-inflammatory, antiarrhythmic, antitumor, antifungal, antibacterial, and anti-HIV activities [ 3 , 4 , 5 , 6 , 7 , 8 ].…”

Oxidative cross-dehydrogenative coupling (CDC) via C(sp2)–H bond functionalization: tert-butyl peroxybenzoate (TBPB)-promoted regioselective direct C-3 acylation/benzoylation of 2H-indazoles with aldehydes/benzyl alcohols/styrenes

“…Progressively, the (2-bromophenyl)(2-(4-methoxyphenyl)-2H-indazol-3-yl)methanone 12 was synthesized by the reaction of 1a with o-bromobenzaldehyde using our optimized reaction conditions which on further subjection to Pd-catalyzed biaryl coupling leads to the formation of a novel class of heterocycles, i.e., 3-methoxy-9H-dibenzo [4,5:6,7]azepino[1,2-b]indazol-9-one 13 in 75% yield, which can be utilized for medicinal chemistry applications. 13 In addition, the synthesized benzoylated product 3a on subjection to NaBH 4 reduction in methanol furnished the reduced hydroxylated product, i.e., (2-(4-methoxyphenyl)-2H-indazol-3-yl)(p-tolyl)methanol 14, in 90% yield, which can be utilized further for derivatization/functionalization and other organic transformations.…”

“…Melting points were taken in open capillaries on Sisco melting point apparatus and are presented uncorrected. 1 H NMR and 13 C NMR spectra were recorded on a JEOL ECS-400 spectrometer (2-channel console with a exible broadband RF performance), which was operating at 400 MHz for 1 H and 100 MHz for 13 C NMR and utilized CDCl 3 and DMSO-d6 as solvents for sample preparation. Tetramethylsilane (d 0.00 ppm) and CDCl 3 both served as internal standards in 1 H NMR (d 7.246 ppm) and 13 C (d 77.0 ppm) NMR.…”

Synthesis, spectral, crystal structure, drug‐likeness, in silico, and in vitro biological screening of halogen [Cl, Br] substituted N‐phenylbenzo[g]indazole derivatives as antimicrobial agents

“…Researchers from all over the world are very much motivated to develop heterocyclic compounds consisting indazole moiety that possess a wide range of biological and pharmaceutical applications [3]. Indazole compounds with pyrazole nucleus exhibit antibacterial [4,5], antifungal [4,6], antitubercular [7], antimicrobial [8], antiproliferative [9], antiarrhythmic [10], antitumor [11], and anti‐HIV [12] activities. Several benzo[ g ]indazole derivatives possess a high binding affinity for estrogen receptor [13], inhibition of protein kinase C‐β [14], and HIV protease inhibition [15].…”