(2S,3S,5R)-2-Benzyl-3-[(5-bromo-pyrimidin-2-yl)-(3-chloro-5-trifluoromethyl-benzyl)-amino]-5-ethyl-pyrrolidine-1-carboxylic acid isopropyl ester (0.042 mmol; 27 mg), tetrakis(triphenylphosphine) palladium (0.0042 mmol; 4.9 mg), 1-methylpyrazol-4-boronic acid pinacol ester (0.063 mmol; 13 mg) and sodium carbonate (0.084 mmol; 8.9 mg) are dissolved in 1,2-dimethoxyethane (0.8 mL) and water (0.08 mL) at room temperature. The mixture is stirred at 90° C. for 17 hours, and then cooled to ambient temperature. To the mixture is added brine and the solution is extracted three times with EtOAc. The combined organic layer is washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The obtained residue is purified by silica gel column chromatography (eluent: n-hexane/EtOAc) to give (2S,3S,5R)-2-Benzyl-3-{(3-chloro-5-trifluoromethyl-benzyl)-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-5-ethyl-pyrrolidine-1-carboxylic acid isopropyl ester (13.6 mg, 51%); ESI-MS m/z: 641 [M+1]+, Retention time 2.62 min (condition A).
