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There is significant interest in the development of process routes for active pharmaceutical ingredients using C–H arylation methodology. An efficient and practical synthetic route for febuxostat (1), which is the first non-purine-type xanthine oxidase inhibitor, was established via palladium- and copper-catalyzed C–H arylation of thiazole with aryl bromide. The catalyst loading was reduced to 0.1 mol % for the intermolecular C–H arylation, and a three-step synthesis produced febuxostat in 89% overall yield with excellent selectivity

Process Development of Febuxostat Using Palladium- and Copper-Catalyzed C–H Arylation

Masato Komiyama* , Hideyoshi Tsuchiya, Mitsuru Teramoto, Naoki Yajima, Masayuki Kurokawa, Kunio Minamizono, Naoki Tsuchiya, Yoshiaki Kato, Yoshinori Sato, and Masahiko Dohi

Active Pharmaceutical Ingredient Technology Section, Pharmaceutical Preparation Department, Teijin Pharma Limited, 2-1 Hinode-cho, Iwakuni-shi, Yamaguchi 740-8511, Japan

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.8b00164

*E-mail: m.komiyama@teijin.co.jp.

https://pubs.acs.org/doi/10.1021/acs.oprd.8b00164

1 (22.5 g, 98%) as a whitish solid. ¹H NMR (400 MHz, CDCl₃): δ 8.20 (d, J = 2.4 Hz, 1H), 8.11 (dd, J = 9.0 Hz, 2.4 Hz, 1H), 7.03 (d, J = 9.0 Hz, 1H), 3.91 (d, J = 6.6 Hz, 2H), 2.80 (s, 3H), 2.23–2.20 (m, 1H), 1.20 (d, J = 6.8 Hz, 6H).

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“ALL FOR DRUGS” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This is a compilation for educational purposes only. P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent

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