A mixture of 4-(2-chloro-pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester (100 mg, 0.33 mmol), 3-chlorobenzylamine (0.65 mL, 5.3 mmol) and potassium carbonate (71 mg, 0.67 mmol) in ethanol (5 mL) was heated at reflux for 7 days. The reaction mixture was cooled to room temperature, poured into H2O (15 mL) and extracted with EtOAc (2×20 mL). The combined organic extracts were washed with H2O (3×15 mL), brine, dried (Na2SO4) and concentrated in vacuo. The residue was purified by preparative TLC (10% MeOH in CH2Cl2) to give a yellow solid. The yellow solid was triturated with MeOH (1 mL) and the solid was collected by filtration to give intermediate (I-3a) as a white solid (48.5 mg).
