Ethyl Acetate → (S)-2-{3-[4-(4-Fluoro-phenoxy)-phenyl]-ureido}-3-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-propionamide

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To a solution of (S)-2-amino-3-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-propionamide (Example 9, step C) (0.079 g, 0.3 mmol) in THF (3 mL) was added 4-(4-fluoro-phenoxy)-phenylamine (0.124 g, 0.61 mmol). After addition of 1,1′-carbonyldiimidazole (0.063 g, 0.39 mmol), the reaction mixture was heated to 65° C. for 6 h. EtOAc (10 mL) and H2O (10 mL) were then added. The aqueous layer was extracted with EtOAc (3×20 mL) and CH2Cl2 (2×20 mL). The combined organic layers were washed with brine and dried (Na2SO4), and the solvent was removed. Column chromatography using 2–20% MeOH/CH2Cl2 gave 0.04 g (27%) of the desired product. MS (electrospray): mass calculated for C28H31FN4O3, 490.24; m/z found, 491.2 [M+H]+. 1H NMR (400 MHz, CDCl3): 7.8 (s, 1H), 7.23–7.15 (m, 5H), 6.92–6.88 (m, 3H), 6.83–6.79 (m, 2H), 6.77–6.75 (m, 2H), 6.64 (d, J=8.2 Hz, 1H), 4.58 (dd, J=14.6, 8.0 Hz, 1H), 3.29–3.13 (m, 2H), 3.09 (dd, J=13.5, 6.5 Hz, 1H), 2.96 (dd, J=13.4, 8.0 Hz, 1H), 2.54–2.48 (m, 3H), 2.42–2.37 (m, 6H), 1.70–1.67 (m, 4H).

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