A new synthesis of tafamidis via zinc-MsOH mediated reductive cyclisation strategy

Advances in the synthetic strategies of benzoxazoles using 2-aminophenol as a precursor: an up-to-date review

“…Karumanchi and colleagues 75 reported the synthesis of tafamidis ( 14 ), a benzoxazole derivative via a two-step synthesis. In the first step, o -benzoylation of 3-hydroxy-4-nitrobenzoic acid ( 12 ) was undertaken using 3,5-dichlorobenzoyl chloride ( 13 ) and K 2 CO 3 in aq.…”

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“…The use of a simple zinc-MsOH as a catalyst renders the protocol suitable for large-scale synthesis, providing a valuable synthetic tool for industrial application reductive cyclization reaction. The stoichiometry of the reaction was also very important: the main product benzoxazole-based 117 was obtained when using Zn (5 moles) and MsOH (15 times) at 100-110 • C. Interestingly, when using acetic acid (60 • C) instead of MsOH, the N-acylated corresponding intermediate 120 was obtained (Figure 3) [71].…”

“…Recently, the FDA approved tafamidis for the treatment of heart disease (cardiomyopathy) that is caused by transthyretin-mediated amyloidosis (ATTR-CM) in adults. ATTR is caused by an abnormal deposit of specific proteins known as amyloids in the body’s organs and tissues [ 71 ].…”

“…The stoichiometry of the reaction was also very important: the main product benzoxazole-based 117 was obtained when using Zn (5 moles) and MsOH (15 times) at 100–110 °C. Interestingly, when using acetic acid (60 °C) instead of MsOH, the N -acylated corresponding intermediate 120 was obtained ( Figure 3 ) [ 71 ].…”