Reaction Steps
N-((R)-3-{4-[(4-Methoxy-phenyl)-(4-methyl-pyridin-3-ylmethyl)-amino]-piperidin-1-yl}-butyl)-3,5-dimethyl-terephthalamic acid (0.070 g, 0.12 mmol), EDCI (0.026 g, 0.13 mmol) and HOBT (0.019 g, 0.13 mmol) were combined in DMF (5 mL) to give a pale yellow solution. To this solution was added dimethylamine (2M in THF) (94 μL, 0.18 mmol) followed by DIPEA (33 μL, 0.18 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 (CH2Cl2:MeOH:NH4OH, 93:5:2, v/v/v) afforded N-((R)-3-{4-[(4-methoxy-phenyl)-(4-methyl-pyridin-3-ylmethyl)-amino]-piperidin-1-yl}-butyl)-2,6, N′,N′-tetramethyl-terephthalamide (0.028 g, 38%) as a white foam. 1H NMR (CDCl3) δ 0.99 (d, 3H, J=6.0 Hz), 1.26 (m, 1H), 1.37 (m, 1H), 1.62 (m, 2H), 1.78-1.85 (m, 3H), 2.14 (br t, 1H), 2.33 (s+m, 8H), 2.47 (br t, 1H), 2.74 (m, 3H), 2.94 (s, 3H), 3.06 (s, 3H), 3.32-3.46 (m, 2H), 3.66 (m, 1H), 3.72 (s, 3H), 4.10 (s, 2H), 6.66 (d, 2H, J=9.0 Hz), 6.73 (d, 2H, J=9.0 Hz), 6.93 (br t, 1H), 7.02 (d, 1H, J=3.0 Hz), 7.05 (s, 2H), 8.29 (s, 1H), 8.31 (d, 1H, J=6.0 Hz). 13C NMR (CDCl3) δ 13.8, 19.2, 19.6, 29.9, 30.7, 32.8, 39.0, 39.9, 44.8, 47.6, 51.8, 56.0, 58.8, 58.9, 114.8, 119.4, 125.3, 126.4, 133.8, 134.8, 143.0, 145.4, 148.3, 149.6. ES-MS m/z 586 (M+H), 608 (M+Na). Anal. Calcd. for C35H47N5O3.0.2 CH2Cl2: C, 70.14; H, 7.93; N, 11.62. Found: C, 70.06; H, 8.03; N, 11.54.
