An Alternative Method for Synthesizing <i>N</i>,2,3-Trimethyl-2<i>H</i>-indazol-6-amine as a Key Component in the Preparation of Pazopanib

Abstract

Due to its application as an anti-cancer drug, pazopanib (1) has attracted the interest of many researchers, and several studies on pazopanib synthesis have been reported over the years. This paper provides a novel route for synthesizing N,2,3-trimethyl-2H-indazol-6-amine (5), which is a crucial building block in the synthesis of pazopanib from 3-methyl-6-nitro-1H-indazole (6). By alternating between the reduction and two methylation steps, compound 5 was obtained in a yield comparable (55%) to what has been reported (54%). It is noteworthy that the last step of N2-methylation also yielded N,N,2,3-tetramethyl-2H-indazol-6-amine (5′) as a novel compound. Furthermore, the data presented in this paper can serve as a valuable resource for future research aimed at further refining the process of synthesizing pazopanib and its derivatives.

Keywords

• 3-methyl-6-nitro-1<i>H</i>-indazole
• pazopanib
• <i>N</i>,<i>N</i>,2,3-tetramethyl-2<i>H</i>-indazol-6-amine
• <i>N</i>,2,3-trimethyl-2<i>H</i>-indazol-6-amine