Synthesis of Indolo[1,2-b]indazole Derivatives via Copper(I)-Catalyzed Intramolecular Amination Reaction

Abstract

A versatile method for preparation of indolo[1,2-b]indazole derivatives was developed by using an intramolecular amination reaction of 1-aminoindoline derivatives in reaction with CuI/PHAN/K₂CO₃ (250 mol%) in 1,4-dioxane at 105 °C. The method provides indoles fused with indazole rings in good yields.

Keywords:

• Anticancer activity
• Cu(I)-catalysis
• indolo[1,2-b]indazole
• intramolecular amination

ACKNOWLEDGMENTS

This work was partially supported by the National Natural Science Foundation of China (Grants 20472062 and 20672079) and the Natural Science Foundation of Jiangsu Province (No. BK2006048).

Notes

^a Reaction conditions: A mixture of 5a (1 mmol), CuI (0.05 mmol), ligand (0.1 mmol), base (2.5 mmol), and solvent (3 mL) in a pressure tube was heated at 110 °C for 20 h.

^b Isolated yields after silica gel chromatography.

Notes. PHAN, 1,10-phenanthroline; TCHDA, trans-1,2-cyclohexanediamine; EDA, ethylenediamine; and DMEDA, N,N′-dimethylenediamine.

^a Reaction conditions: A mixture of 5 (1 mmol), CuI (0.05 mmol), PHAN (0.1 mmol), K₂CO₃ (2.5 mmol), and 1,4-dioxane (3 mL) was reacted in a pressure tube at 110 °C for 20 h.

^b Yields are isolated yields after chromatography.

^c Time was prolonged to 40 h.