Synthesis of Indeno[1,2-b]indole-9,10-diones: Toward a One-Pot, Two-Step Reaction

Abstract Indeno[1,2-b]indole was shown to be a key scaffold for the design of new bioactive molecules in oncology (e.g., inhibitors of protein kinase CK2 and inhibitors of the breast cancer resistance protein ABCG2). Depending on the synthetic route chosen, a large variety of specific functionalizations can be achieved. In order to develop new indeno[1,2-b]indole-9,10-diones as CK2 inhibitors, four functionalized indeno[1,2-b]indoles were synthesized using a two-step reaction described in the literature. Given that the reactions reported led to unexpected results, such as incomplete reaction progress, very low yields, and significant formation of by-products, we first optimized the quantities of reagents (AcOH and N,N,N′,N′-tetraethyl sulfurous diamide) and the types of solvents used in the synthetic steps. Then, based on these optimal reaction conditions, a one-pot, two-step reaction was developed to maximize yields and standardize the process, thereby making it more convenient and straightforward.