Photocatalysis in a multi-capillary assembly microreactor: toward up-scaling the synthesis of 2H-indazoles as drug scaffolds

Abstract

Visible-light-promoted direct arylation of 2H-indazoles using phenyldiazonium salt enabled a single-step and fast synthesis (<1 min) of C3 arylated products in high yields (>65%) in a capillary microreactor, compared to the slow synthesis (18 h) in a flask. Moreover, scalable photocatalysis of a 2H-indazole based liver X-receptor modulator was performed by devising a compact multi-capillary assembly microreactor composed of vertically aligned 10 capillary tubes connected to 3D printed fluidic fixtures. Eventually, the assembly produced the drug on an ∼4 gram scale per hour by a one-flow automated process taken for 2.2 min from synthesis to product separation, which would be a breakthrough approach for pharmaceutical production.