Copper‐Assisted Synthesis of Novel Pyrazolo[3,4‐d]thiazoles

Abstract

Based on both the chemical and the biological importance of the pyrazole and the thiazole backbones, we report herein a convenient design of new pyrazolo[3,4-d]thiazoles for the development of molecules with a high therapeutic potential. The effective and appropriate strategy chosen consists of an intramolecular copper-catalysed N-arylation followed by the Liebeskind-Srogl cross-coupling reaction. The efficiency of copper and palladium catalysts for the first step of the synthesis was evaluated. These efforts allowed the synthesis of a variety of modulated heterobicycles.

Access and modulation of substituted 1-methyl-1,6-dihydropyrazolo[3,4-c]pyrazoles

“…The one-pot sequence for the synthesis of the bipyrazole 2a relies on previous studies on similar heterocycles. 23–26 The condensation step occurred quantitatively with a slight excess of phenylhydrazine. After a change of solvent and addition of the Ullmann-type catalysts, the expected fused heterocycle was obtained in an encouraging yield ( Table 1 , entry 1).…”

CYTOTOXIC EVALUATION OF ORIGINAL PYRAZOLO[3,4-d]THIAZOLES AND PYRAZOLO[3,4-c]PYRAZOLES

“…Condensation reactions with monosubstituted aromatic hydrazines followed by an intra-molecular copper-catalyzed, ligand-free N-cyclizations allowed the formation of original N1 modulated pyrazolo [3,4-d]thiazoles 2a-h. The fused system was submitted to a Liebeskind-Srogl cross-coupling reaction, by using various monosubstituted aromatic boronic acids, under microwave irradiation giving the trifunctionalized structures 3a-l (Figure 3) [16].…”