N-(4-(azetidin-3-yloxy)phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide (1 g, 1.805 mmol), (S)-2-methylbutanoic acid (0.221 g, 2.166 mmol), and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.519 g, 2.71 mmol) were combined in in dimethylformamide (9.03 mL) at room temperature. 1-Hydroxybenzotriazole hydrate (0.415 g, 2.71 mmol) and diisopropylethylamine (0.946 ml, 5.42 mmol) were added and the reaction mixture was stirred overnight at room temperature. Water and dichloromethane were added and the organics were removed by pipet. Concentration and reverse phase chromatography gave (S)—N-(4-(1-(2-methylbutanoyl)azetidin-3-yloxy)phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide. 1H NMR (300 MHz, DMSO-d6) δ 8.56 (d, J=2.4 Hz, 1H), 8.48 (dd, J=4.7, 1.6 Hz, 1H), 8.41 (s, 1H), 7.86 (dt, J=7.9, 2.0 Hz, 1H), 7.46-7.37 (m, 3H), 6.76 (d, J=8.9 Hz, 2H), 4.96 (dd, J=6.3, 3.4 Hz, 1H), 4.62-4.53 (m, 1H), 4.36 (d, J=15.9 Hz, 2H), 4.32-4.22 (m, 1H), 4.11-4.02 (m, 1H), 3.98-3.81 (m, 3H), 3.75 (dd, J=10.6, 3.9 Hz, 1H), 2.36-2.20 (m, 1H), 1.59-1.39 (m, 1H), 1.38-1.20 (m, 1H), 0.96 (dd, J=6.8, 3.9 Hz, 3H), 0.82 (q, J=7.2 Hz, 3H); MS (ESI(+)) m/e 409 (M+H)11.
