Scalable Synthesis of TRPV1 Antagonist Bipyridinyl Benzimidazole Derivative via the Suzuki-Miyaura Reaction and Selective SeO 2 Oxidation

In this study, a kilogram-scale synthesis of a potent TRPV1 antagonist, is described. To synthesize bipyridinyl benzimidazole derivative , we have developed a scalable Suzuki-Miyaura reaction capable of providing a key intermediate, 6'-methyl-3-(trifluoromethyl)-2,3'-bipyridine , on a kilogram scale. Then, unlike the existing oxidation reaction pathway, two synthetic routes that can be applied to mass production of bipyridinyl carboxylic acid intermediate or aldehyde intermediate were developed by appropriately controlling the oxidation reaction using a selenium dioxide oxidizing agent. Using our developed synthetic procedure, which includes Suzuki-Miyaura coupling, selective selenium dioxide oxidation, and benzimidazole formation, multi-kilogram-scale bi-pyridinyl benzimidazole derivative can be synthesized.