[F:1][C:2]([F:14])([F:13])[O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]=[C:11]=[O:12])=[CH:6][CH:5]=1.[NH2:15][CH:16]1[CH2:21][CH2:20][N:19]([C:22](=[O:28])[CH:23]([CH2:26][CH3:27])[CH2:24][CH3:25])[CH2:18][CH2:17]1.C(C(CC)C(O)=O)C.Cl>C1COCC1>[CH2:26]([CH:23]([CH2:24][CH3:25])[C:22]([N:19]1[CH2:18][CH2:17][CH:16]([NH:15][C:11]([NH:10][C:7]2[CH:6]=[CH:5][C:4]([O:3][C:2]([F:13])([F:14])[F:1])=[CH:9][CH:8]=2)=[O:12])[CH2:21][CH2:20]1)=[O:28])[CH3:27]To an ice cold solution of 4-(trifluoromethoxy)phenyl isocyanate (60.9 mg, 0.3 mmol) in THF (1.5 ml) was added 1-(4-aminopiperidin-1-yl)-2-ethylbutan-1-one (59.4 mg, 0.3 mmol), prepared via Example 14 and Example 15 using 2-ethylbutanoic acid. The reaction mixture was allowed to warm to rt and stirred overnight. 1 M HCl aqueous solution was added followed by extraction with EtOAc. Flash chromatography eluted with 50:1 DCM:MeOH followed by recrystallization from acetone afforded desired compound (65 mg, 54%) as a white solid. Mp 167.0-167.4° C. 1H NMR (600 MHz, DMSO-d6) δ 8.50 (s, 1H), 7.47 (d, J=9.0 Hz, 2H), 7.22 (d, J=8.4 Hz, 2H), 6.28 (d, J=7.8 Hz, 1H), 4.27 (brd, J=13.2 Hz, 1H), 3.95 (brd, J=15.6 Hz, 1H), 3.75-3.69 (m, 1H), 3.18 (t, J=11.1 Hz, 1H), 2.81 (t, J=10.8 Hz, 1H), 2.68-2.60 (m, 1H), 1.88 (d, J=10.8 Hz, 1H), 1.82 (d, J=10.8 Hz, 1H), 1.51-1.45 (m, 2H), 1.45-1.30 (m, 2H), 1.30-1.10 (m, 2H), 0.83-0.75 (m, 6H). F NMR (300 MHz, DMSO-d6) −57.545 (s).
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