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

• Published in: Chemistry
• Main Authors: Thi Thanh Cham Bui, Hue Linh Luu, Thi Thanh Luong, Thi Ngoc Nguyen, Nguyet Suong Huyen Dao, Van Giang Nguyen, Dinh Luyen Nguyen, Nguyen Trieu Trinh, Van Hai Nguyen
• Format: Article
• Language: English
• Published: MDPI AG 2024-09-01
• Subjects: 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
• Online Access: https://www.mdpi.com/2624-8549/6/5/63

Due to its application as an anti-cancer drug, pazopanib (<b>1</b>) 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 <i>N</i>,2,3-trimethyl-2<i>H</i>-indazol-6-amine (<b>5</b>), which is a crucial building block in the synthesis of pazopanib from 3-methyl-6-nitro-1<i>H</i>-indazole (<b>6</b>). By alternating between the reduction and two methylation steps, compound <b>5</b> 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 <i>N</i>,<i>N</i>,2,3-tetramethyl-2<i>H</i>-indazol-6-amine (<b>5′</b>) 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.