反应详情

3,5-Dimethyl-N-((R)-3-{4-[(4-methyl-pyridin-3-ylmethyl)-phenyl-amino]-piperidin-1-yl}-butyl)-terephthalamic acid (50.0 mg, 0.09 mmol), EDCI (19.9 mg, 0.10 mmol) and HOBT (14.1 mg, 0.10 mmol) were combined in DMF (4 mL) to give a pale yellow solution. To this solution was added isopropylamine (8.9 μL, 0.10 mmol) followed by DIPEA (19.7 μL, 0.11 mmol) and the resulting mixture was stirred at room temperature for 16 h. Standard workup according to General Procedure C gave the crude product as a tan oil. Purification by preparative TLC (91:8:1, CH2Cl2/MeOH/NH4OH) afforded N′-isopropyl-2,6-dimethyl-N-((R)-3-{4-[(4-methyl-pyridin-3-ylmethyl)-phenyl-amino]-piperidin-1-yl}-butyl)-terephthalamide as a white foam (10.1 mg, 19%). 1H NMR (CDCl3) δ 1.02 (br s, 3H), 1.22 (d, 6H, J=7 Hz), 1.83 (m, 3H), 2.22 (m, 1H), 2.29 (s, 3H), 2.34 (s, 6H), 2.55 (m, 1H), 2.80 (m, 4H), 3.38 (m, 1H), 3.62 (m, 1H), 3.76 (m, 1H), 4.10 (s, 2H), 4.23 (sext, 1H, J=6 Hz), 6.04 (d, 1H, J=7 Hz), 6.59 (d, 2H, J=8 Hz), 6.72 (t, 1H, J=7 Hz), 7.05 (d, 1H, J=5 Hz), 7.16 (t, 2H, J=8 Hz), 7.34 (br s, 1H), 7.39 (s, 2H), 8.27 (s, 1H), 8.33 (d, 1H, J=5 Hz). ES-MS m/z 570 (M+H), 593 (M+Na). Anal. Calcd. For C35H47N5O2: C, 73.78; H, 8.31; N, 12.29.

1. customto give a pale yellow solution
2. customgave the crude product as a tan oil
3. customPurification by preparative TLC (91:8:1, CH2Cl2/MeOH/NH4OH)