Development of a Synthetic Route to Vonoprazan via Atom Transfer Radical Cyclization

Abstract

In this Note, a new synthetic route to vonoprazan via atom transfer radical cyclization (ATRC) is described. The pivotal 1,3,5-trisubstituted pyrrole ring of vonoprazan has been accomplished by ATRC, the subsequent aromatization which simultaneously occurred with the introduction of N-methylamine moiety into the cyclic imine, and the sulfonylation at the 1-position of pyrrole. Furthermore, our approach enabled the synthesis of vonoprazan on a 0.7 kg scale without the isolation of intermediates throughout the process.