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
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
Affiliations
Thi Thanh Cham Bui
Faculty of Pharmaceutical Chemistry and Technology, Hanoi University of Pharmacy, 13-15 Le Thanh Tong Street, Hoan Kiem District, Hanoi 110402, Vietnam
Hue Linh Luu
Faculty of Pharmaceutical Chemistry and Technology, Hanoi University of Pharmacy, 13-15 Le Thanh Tong Street, Hoan Kiem District, Hanoi 110402, Vietnam
Thi Thanh Luong
Faculty of Chemical Technology, Hanoi University of Industry, 298 Cau Dien Street, Tu Liem North District, Hanoi 143510, Vietnam
Thi Ngoc Nguyen
Faculty of Pharmaceutical, Thai Nguyen University of Medicine and Pharmacy, 284 Luong Ngoc Quyen Street, Thai Nguyen City, Thai Nguyen 251540, Vietnam
Nguyet Suong Huyen Dao
Faculty of Pharmaceutical Chemistry and Technology, Hanoi University of Pharmacy, 13-15 Le Thanh Tong Street, Hoan Kiem District, Hanoi 110402, Vietnam
Van Giang Nguyen
Faculty of Pharmaceutical Chemistry and Technology, Hanoi University of Pharmacy, 13-15 Le Thanh Tong Street, Hoan Kiem District, Hanoi 110402, Vietnam
Dinh Luyen Nguyen
Faculty of Pharmaceutical Chemistry and Technology, Hanoi University of Pharmacy, 13-15 Le Thanh Tong Street, Hoan Kiem District, Hanoi 110402, Vietnam
Nguyen Trieu Trinh
College of Engineering, Science and Environment, Center for Organic Electronics, University of Newcastle, Newcastle, NSW 2308, Australia
Van Hai Nguyen
Faculty of Pharmaceutical Chemistry and Technology, Hanoi University of Pharmacy, 13-15 Le Thanh Tong Street, Hoan Kiem District, Hanoi 110402, Vietnam
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.
