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Indole and pyrazole are two important scaffolds in the field of medicinal chemistry. Compounds bearing indole and/or pyrazole moiety have been extensively investigated for a wide range of biological applications. Of them, compounds containing both indole and pyrazole moieties (also termed as indole‐pyrazole hybrids) are of particular interest since synergistic pharmacological activities may be gained comparing to those with each individual pharmacophore. Indole‐pyrazole hybrids can be classified into two general classes of direct‐linked hybrids and spacer‐linked hybrids. For each class, it can be sub‐divided into indole‐C2 pyrazole hybrids, indole‐C3 pyrazole hybrids and indole‐C4/5/6/7 pyrazole hybrids based on the substitution position of pyrazole on the indole moiety. Many types of indole‐pyrazole hybrids have been reported with good antimicrobial, anticancer, antitumor, anti‐inflammatory, anti‐oxidant activities etc. However, no papers have been noted to comprehensively summarize the chemical synthesis of these important indole‐pyrazole hybrids as bioactive compounds except for a few reviews focusing on the synthesis of each individual indole‐ and pyrazole‐containing derivatives. Thus, we here present a comprehensive and updated review focusing on the progress of chemical synthesis of all types of indole‐pyrazole hybrids in order to provide a better understanding of the indole‐pyrazole hybrids to researchers in the fields of synthetic chemistry and to facilitating drug development.

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2-Amino-4H-benzo[h]chromene-3-carbonitrile and 2-amino-5-oxo-4H,5H-pyrano[3,2-c]chromene-3-carbonitrile are two important pharmacophores with extensive applications in medicinal chemistry. The multicomponent Knoevenagel-Michael reaction is one of the most efficient strategies to construct these two scaffolds. Previous efforts have been made in converting the traditional organic solvents to eco-friendly solvents including H2O generally in the presence of complex catalysts. Here we present our work of using sodium fluoride (NaF) as the catalyst to synthesize a wide scope of the two types of substrates starting from α- or β-naphthol or 4-hydroxycoumarin. Using 12 mol% NaF under the microwave irradiation condition, the reactions were completed within 15–25 min with all the yields exceeding 85%. The reaction products were purified simply by washing with H2O and can be further purified by crystallization with MeOH. The analysis of green chemistry-related parameters suggested that the current method was highly environmentally benign, highlighting the potential of this method in the use of drug discovery and development.

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