Preparation of methyl 3-chloro-4-(5-(4,7-dimethylbenzofuran-2-yl)-1,2,4-thiadiazole-3-yl)benzoate: 0.323 mmol of 3-bromo-5-(4,7-dimethylbenzofuran-2-yl)-1,2,4-thiadiazole, ethyl 4-boron-3-chlorobenzoate, 0.388 mmol of K3PO4·H2O, 0.647 mmol of Pd(Ph3P)4, 0.03 mmol of DMF (2 mL), and 0.5 mL of H2O were added to a sealed tube. The mixture was heated in a microwave reactor at 130 °C for 15 min. The mixture was cooled to RT and partitioned between DCM (10 mL) and H2O (3 mL). The organic solution was washed with water (3 mL), passed through a phase separation column, and concentrated under vacuum. The residue was purified by silica gel chromatography in isohexane (0-10% EtOAc) to give methyl 3-chloro-4-(5-(4,7-dimethylbenzofuran-2-yl)-1,2,4-thiadiazol-3-yl)benzoate.
Ethyl 4-boron-3-chlorobenzoate can be used as a pharmaceutical synthesis intermediate in the Suzuki coupling reaction. CN107207488 reports that ethyl 4-boron-3-chlorobenzoate can be used to prepare 3-chloro-4-(5-(4,7-dimethylbenzofuran-2-yl)-1,2,4-thiadiazol-3-yl)benzoic acid, which selectively activates retinoic acid receptor β (RARβ) (e.g., RARβ2) in vitro or in vivo.
