Reaction Steps
1-(1-(5-Bromopyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)-3-cyclopentylurea (64 mg, 0. 12 mmol), morpholine (1.3 eq), Pd2(dba)3 (0.2 eq), Xantphos (0.6 eq) and Na—O-t-Bu (3.2 eq) were stirred in toluene (0.5 mL) at room temperature. The reaction mixture was purged with N2 several times and then was heated at 100° C. for 3.5 h. The reaction mixture was cooled to room temperature, and Et2O was added. The resulting solution was washed with H2O, brine, dried (MgSO4), filtered, and concentrated to dryness. The residue was purified by chromatography (silica gel, hexanes/EtOAc) to give 1-cyclopentyl-3-(1-(3-fluoro-5-(trifluoromethyl)phenyl)-1-(5-morpholinopyridin-2-yl)-2-phenylethyl)urea (39 mg, yield: 60.9%). LC-MS ESI 557.28 (M+H) (10-90% MeOH in H2O with 0.1% TFA in a 4-min run, retention time=3.63 min); 1H NMR (400 MHz, CDCl3) δ ppm 7.94 (d, J=2.9 Hz, 1 H), 7.57 (s, 1 H), 7.40 (d, J=10.0 Hz, 1 H), 7.28 (s, 1 H), 7.24-7.17 (m, 2 H), 7.14 (d, J=7.3 Hz, 1 H), 7.09 (t, J=7.5 Hz, 2 H), 7.02 (d, J=8.8 Hz, 1 H), 6.66 (d, J=7.6 Hz, 2 H), 4.48 (d, J=12.5 Hz, 1 H), 4.34 (d, J=7.1 Hz, 1 H), 4.00-3.91 (m, 1 H), 3.90-3.87 (m, 4 H), 3.56 (d, J=12.5 Hz, 1 H), 3.18 (m, 4 H), 2.09-2.01 (m, 1 H), 1.92-1.83 (m, 1 H), 1.68-1.57(m, 4 H), 1.49-1.40 (m, 1H), 1.32-1.24 (m, 1 H).
