1-Ethyl-3-(3′-dimethylaminopropyl)carbodiimide (144 mg, 0.75 mmol) was added to a solution of [[2-((S)-3-butoxycarbonylaminopyrrolidin-1-yl)-2-oxo-ethyl]-(4-phenoxyphenyl)amino]acetic acid 20 (176 mg, 0.38 mmol), 1-hydroxy-7-azabenzotriazole (103 mg, 0.76 mmol), 3-fluoro-5-(trifluoromethyl)benzylamine (0.11 mL, 0.75 mmol) and N-methylmorpholine (0.11 mL, 1.02 mmol) in DMF (5 mL). The reaction mixture was stirred overnight at room temperature and then diluted with ethyl acetate and washed with 10% hydrochloric acid (×2), brine, saturated aqueous sodium bicarbonate (×2) and brine, dried (Na2SO4) and evaporated onto silica gel. Flash column chromatography, using ethyl acetate as the eluent, gave the title compound as a hard foam (82 mg, 34%). 1HNMR (300 MHz) (CDCl3) δ 1.45 (6H, s), 1.55 (3H, s), 1.75-2.40 (2H, m), 3.37-3.93 (5H, m), 3.95-4.40 (4H, m), 4.50-4.70 (2H, m), 6.46 (2H, m), 6.94 (4H, m), 7.03 (2H, m), 7.08 (1H, m), 7.30 (3H, m) and 10.06 (1H, m).
