Facile synthesis of 1H-imidazo[1,2-b]pyrazoles via a sequential one-pot synthetic approach

Abstract

Summary5-Aminopyrazole-4-carbonitrile and ethyl 5-aminopyrazole-4-carboxylate, as potential trifunctional building blocks are introduced in a facile, chemo- and regioselective multicomponent assembly of imidazo[1,2-b]pyrazoles via the Groebke–Blackburn–Bienaymé reaction (GBB reaction). Besides the synthetic elaboration of a green-compatible isocyanide-based access in three-component mode, we describe an operationally simple, one-pot two-step GBB protocol for the rapid construction of a 46 membered imidazo[1,2-b]pyrazole library with yields up to 83%.

The Groebke‐Blackburn‐Bienaymé Reaction

“…Overview of GBB catalysts that performed best in reported catalyst screenings (single hits were omitted for clarification). TiO 2 NPs (nanopowders) [170] TMSCl 7 [37,38,53,152,155,169,176] ZnO NPs [116] Montmorillonite K-10 clay 6 [19,64,65,70,121,192] Methanesulfonic acid [52] Magnesium chloride (MgCl 2 ) 5 [134,136,193,194] Zeolite HY [195] Ytterbium triflate (Yb(OTf) 3 ) 4 HCl dioxane 4 [72,73,84,117] Bromodimethylsulfonium bromide (BDMS) [69] Indium triflate (In(OTf) 3 ) 3 [108,109,122] γ-Fe 2 O 3 @SiO 2 -OSO 3 H [71] Trifluoroacetic acid (TFA) 2 [82,165] Cationic polyurethane dispersions (CPUDs) [76] Bismuth chloride (BiCl 3 ) 2 [81,91] pTsCl [77] Silica sulfuric acid 2 [126,148] Iodine [135] Lanthanum chloride (LaCl 3 •7H 2 O) 2 [92,104] (TBBDA) [83] Piperidine 2 [162,163] (PBBS)…”

Synthesis, cytotoxic characterization, and SAR study of imidazo[1,2‐b]pyrazole‐7‐carboxamides

“…The most facile approach for the assembly of the imidazo[1,2‐ b ]‐pyrazole framework is the Groebke–Blackburn–Bienaymé three‐component (GBB‐3CR) reaction . By employing this one‐step operation, highly functionalized imidazo[1,2‐ b ]pyrazoles can be accessed from 3‐aminopyrazoles, aldehydes, and isocyanides as starting materials in the presence of Brønsted or Lewis acid catalysts.…”

Unusual rearrangement of imidazo[1,5-a]imidazoles and imidazo[1,2-b]pyrazoles into imidazo[1,5-a]pyrimidines and pyrazolo[1,5-a]pyrimidines

“…To prepare the desired compound 4k, the optimization of the reaction conditions was needed. Indeed, we examined the following different conditions reported in the literature 18,19 (Table 4).…”