To a solution of 2′-fluoro-4′-methyl-5-[(5S)-5-(2-pyridinyl)-4,5-dihydro-3-isoxazolyl]-3-biphenylcarboxylic acid (125 mg, 0.227 mmol) in N,N-dimethylformamide (1 mL) were added (1S)-1-(4H-1,2,4-triazol-3-yl)ethanamine hydrochloride salt (52 mg, 0.283 mmol), EDC (65 mg, 0.340 mmol), HOAT (9 mg, 0.068 mmol) and triethylamine (95 μL, 0.680 mmol). The reaction mixture was stirred at ambient temperature for 18 h. Water was added. Purification by reverse phase HPLC(C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.05% ammonium hydroxide), and concentration gave the free base. Concentrate was taken up in dichloromethane into which hydrogen chloride gas was bubbled. Concentration gave the title compound as the hydrochloride salt (94.0 mg). HRMS 471.1977 (M+1). 1H NMR (500 MHz, CD 30D): δ 8.94 (s, 1H); 8.78 (d, J=5.6 Hz, 1H); 8.53 (t, J=7.7 Hz, 1H); 8.25 (t, J=1.7 Hz, 1H); 8.16 (t, J=1.6 Hz, 1H); 8.11-8.07 (m, 2H); 7.94 (t, J=6.6 Hz, 1H); 7.46 (t, J=7.9 Hz, 1H); 7.15-7.07 (m, 2H); 6.18 (dd, J=11.4, 6.6 Hz, 1H); 5.50-5.45 (m, 1H); 4.21 (dd, J=17.3, 11.5 Hz, 1H); 3.86 (dd, J=20.8, 7.9 Hz, 1H); 2.41 (s, 3H); 1.74 (d, J=7.1 Hz, 3H).
