The general procedure for the synthesis of 6-(2-chloro-5-fluoropyrimidin-4-yl)-4-fluoro-1-isopropyl-2-methyl-6-boronic acid pinacol esteryl-1H-benzo[d]imidazole from 4-fluoro-1-isopropyl-2-methyl-6-boronic acid pinacol esteryl-1H-benzo[d]imidazole and 2,4-dichloro-5-fluoropyrimidine was carried out in the following manner: under nitrogen protection, the synthesized 6-(2-chloro-5-fluoropyrimidin-4-yl)-4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazole was prepared by applying the following method to the 4-fluoro-1-isopropyl-2-methyl-6-(4 ,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazole (318 mg, 1 mmol) and 2,4-dichloro-5-fluoropyrimidine (166 mg, 1 mmol) in suspension in 6 mL of acetonitrile was added to tetrakis(triphenylphosphine)palladium (115.6 mg, 0.1 mmol) and 2 mL of a saturated sodium carbonate aqueous solution. The reaction mixture was heated to 85 °C and stirred for 8 hours. After completion of the reaction, it was cooled to room temperature and extracted with a solvent mixture of chloroform and isopropanol (4:1, v/v). The organic layers were combined, washed with saturated saline, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography with the eluent being a mixture of dichloromethane and methanol (methanol v/v 0-10%) to afford 6-(2-chloro-5-fluoropyrimidin-4-yl)-4-fluoro-1-isopropyl-2-methyl-1H-benzoimidazole (277 mg, 86% yield) as a gray solid.LC-MS (m/z): 323.1 [M+H]+.
