Reaction Steps
To a solution of [1-((R)-3-amino-1-methyl-propyl)-piperidin-4-yl]-(4-methoxy-phenyl)-(4-methyl-pyridin-3-ylmethyl)-amine (41 mg, 0.11 mmol) in DMF (0.5 mL) was added 6-fluoro-2,4-dimethyl-nicotinic acid (27 mg, 0.16 mmol), HOBT (20 mg, 0.15 mmol), EDCI (29 mg, 0.15 mmol) and DIPEA (55 μL, 0.32 mmol). After the mixture was stirred at room temperature overnight brine (5 mL) was added, and the mixture was extracted with CH2Cl2 (2×5 mL). The organic extracts were combined and dried (Na2SO4). After filtration the solvent was removed under vacuum, and the residue was purified by flash chromatography on a silica gel column (50:1:0.1, CH2Cl2/MeOH/NH4OH) to afford the title compound as a white solid (40 mg, 67%). 1H NMR (CDCl3) δ 0.99 (d, 3H, J=6.6 Hz), 1.00 (m, 1H), 1.19 (m, 1H), 1.54 (m, 1H), 1.72 (m, 1H), 1.82 (br d, 2H, J=12.6 Hz), 2.12 (t, 1H, J=10.5 Hz), 2.32 (s, 3H), 2.34 (s, 3H), 2.47 (s, 3H), 2.48 (t, 1H, J=12.6 Hz), 2.65-2.85 (m, 3H), 3.15-3.45 (m, 2H), 3.72 (s, 3H), 3.82 (m, 1H), 3.96 (s, 2H), 6.51 (s, 1H), 6.60-6.76 (m, 4H), 7.03 (d, 1H, J=4.8 Hz), 8.08 (br. S, 1H), 8.25 (s, 1H), 8.29 (d, 1H, J=4.8 Hz). 13C NMR (CDCl3) δ 13.81, 19.08, 19.50, 22.26, 30.09, 30.90, 31.82, 39.89, 44.46, 47.79, 52.05, 55.92, 59.16, 59.94, 107.62 (d, 1C, J=146 Hz), 114.75 (2C), 120.21 (2C), 125.48, 132.05, 133.47, 142.68, 145.64, 148.27, 149.45, 150.58 (d, 1C, J=32 Hz), 153.08 (d, 1C, J=48 Hz), 162.64 (d, 1C, J=949 Hz), 162.88, 167.92. ES-MS m/z 533 (M+H). Anal. Calcd. For C31H40N5FO2.0.2CH2Cl2: C, 68.05; H, 7.39; N, 12.72. Found: C, 68.26; H, 7.78; N, 13.08.
