反应详情

温度

25 °C

(R)-[1-(3-Amino-1-methyl-propyl)-piperidin-4-yl]-(4-methoxy-phenyl)-(4-methyl-pyridin-3-ylmethyl)-amine (0.070 g, 0.18 mmol), EDCI (0.039 g, 0.20 mmol) and HOBT (0.027 g, 0.20 mmol) were combined in DMF (5 mL) to give a pale yellow solution. To this solution was added 2-bromo-4-methyl-nicotinic acid (0.043 g, 0.20 mmol) followed by DIPEA (38 μL, 0.22 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, 89:10:1, v/v/v) afforded 2-bromo-N-((R)-3-{4-[(4-methoxy-phenyl)-(4-methyl-pyridin-3-ylmethyl)-amino]-piperidin-1-yl}-butyl)-4-methyl-nicotinamide (0.040 g, 38%) as a white foam. 1H NMR (CDCl3) δ 0.98 (d+m, 4H,), 1.07 (m, 1H), 1.57 (m, 2H), 1.84 (m, 3H), 2.13 (br t, 1H), 2.36 (s, 6H), 2.53 (br t, 1H), 2.75-2.88 (m, 3H), 3.24-3.33 (m, 2H), 3.71 (s, 3H), 3.82 (m, 1H), 3.88 (m, 2H), 6.61 (d, 2H, J=9.0 Hz), 6.69 (d, 2H, J=9.0 Hz), 6.97 (d, 1H, J=6.0 Hz), 7.03 (d, 1H, J=6.0 Hz), 7.94 (d, 1H, J=6.0 Hz), 8.25 (s, 1H), 8.30 (d, 1H, J=6.0 Hz), 8.52 (br s, 1H). 13C NMR (CDCl3) δ. ES-MS m/z 582 (M+H), 604 (M+Na). Anal. Calcd. for C30H38N5O2Br.0.25 CH2Cl2: C, 60.37; H, 6.45; N, 11.64. Found: C, 60.34; H, 6.47; N, 11.52.

1. customto give a pale yellow solution
2. customgave the crude product as a tan oil
3. customPurification by column chromatography on silica gel (Et2O:MeOH:NH4OH, 89:10:1, v/v/v)