Organophosphorus-mediated N–N bond formation: facile access to 3-amino-2H-indazoles

Abstract

A convenient and efficient strategy has been devised to access 3-amino-2H-indazole derivatives in two steps from readily available starting materials. The conversion of 2-nitrobenzonitriles to substituted benzamidines followed by an organophosphorus-mediated reductive cyclization and a subsequent N-N bond formation afforded 3-amino-2H-indazoles in good to excellent yields.

A General One‐Pot Synthesis of 2H‐Indazoles Using an Organophosphorus–Silane System

“…To explore the flexibility and robustness of our one‐pot methodology and to expand the substrate scope further, we applied our method towards the synthesis of 3‐amino‐2 H ‐indazoles 64 (Table ) through the reductive cyclization of N ‐substituted 2‐nitrobenzamidines 63 . Whereas a high excess amount of 5 equivalents of tributylphosphine as the organophosphorus reagent was previously required for an effective reaction, we could again decrease this by applying our standard reaction conditions by using 0.8 equivalents of phospholene oxide.…”

“…General procedure for the synthesis of 3‐amino‐2 H ‐indazoles : Benzamidine derivatives 63 were synthesized according to a known procedure . Diphenylsilane (317.1 μL, 1.72 mmol) was added to a solution of benzamidine derivative 63 (0.33 mmol) and 3‐methyl‐1‐phenyl‐2‐phospholene 1‐oxide (101.8 mg, 0.53 mmol) in dry toluene (4 mL) in a sealed tube at RT.…”

Recent Advances in Indazole-Containing Derivatives: Synthesis and Biological Perspectives

“…Nazaré et al [ 29 ] demonstrated an organophosphorus-mediated reductive cyclization and a subsequent N-N bond formation of substituted benzamidines 40 to construct 3-amino-2 H -indazoles 41 ( Scheme 14 a). The substituted benzamidines 40 were synthesized from 2-nitrobenzonitriles 39 through a two-step sequence involving a trimethylaluminium-mediated conversion.…”

Probing 2H‐Indazoles as Templates for SGK1, Tie2, and SRC Kinase Inhibitors

“…While unsubstituted 1 H ‐indazoles and N1‐substituted‐1 H ‐indazoles are well represented in the chemical space and in particular populating the kinase ligand space, the 2 H ‐indazole framework is only rarely described. This is mainly attributed to the fact that until very recently, only a few direct methods allowed regioselective access to N2‐substituted 2 H ‐indazoles …”