(R)-[1-(3-Amino-1-methyl-propyl)-piperidin-4-yl]-[4-(2-methoxy-ethoxy)-phenyl]-(4-methyl-pyridin-3-ylmethyl)-amine (0.065 g, 0.15 mmol), EDCI (0.033 g, 0.17 mmol) and HOBT (0.023 g, 0.17 mmol) were combined in DMF (5 mL) to give a pale yellow solution. To this solution was added 2-chloro-4-methyl-nicotinic acid (0.029 g, 0.17 mmol) followed by DIPEA (54 μL, 0.31 mmol) and the resulting mixture was stirred at 25° C. for 16 h. Standard workup according to General Procedure C gave the crude product as a tan oil. Purification by column chromatography on silica gel (Et2O:MeOH:NH4OH, 88:10:2, v/v/v) afforded 2-chloro-N-((R)-3-{4-[[4-(2-methoxy-ethoxy)-phenyl]-(4-methyl-pyridin-3-ylmethyl)-amino]-piperidin-1-yl}-butyl)-4-methyl-nicotinamide (0.068 g, 76%) as a white foam. 1H NMR (CDCl3) δ 0.98 (d, 3H, J=6.0 Hz), 1.06 (m, 1H), 1.25 (m, 1H), 1.58 (m, 2H), 1.82 (m, 3H), 2.11 (br t, 1H), 2.35 (s, 6H), 2.50 (br t, 1H), 2.75-2.89 (m, 3H), 3.21-3.33 (m, 2H), 3.42 (s, 3H), 3.69 (t, 2H, J=4.5 Hz), 3.82 (m, 1H), 3.90 (m, 2H), 4.01 (t, 2H, J=4.5 Hz), 6.59 (d, 2H, J=9.0 Hz), 6.72 (d, 2H, J=9.0 Hz), 6.96 (d, 1H, J=6.0 Hz), 7.03 (d, 1H, J=6.0 Hz), 7.99 (d, 1H, J=6.0 Hz), 8.25 (s, 1H), 8.30 (d, 1H, J=3.0 Hz), 8.38 (br s, 1H). ES-MS m/z 580 (M+H). Anal. Calcd. for C32H42N5O3Cl.0.4 CH2Cl2: C, 63.37; H, 7.02; N, 11.40. Found: C, 63.28; H, 7.16; N, 11.60.
