Diisopropylethylamine → Succinamide peptidomimetic, 20

Participants

Reaction Steps

2-(R)-(2-Cyclohexyl-ethyl)-4-morpholin-4-yl-4-oxo-butyric acid (98 mg, 0.33 mmol, 1.0 eq.) dissolved in DMF (2 mL) and treated with HATU (137 mg, 0.36 mmol, 1.1 eq.), (S)—N1-(4-Trifluoromethoxy-phenyl)-propane-1,2-diamine (85 mg, 0.36 mmol, 1.1 eq.) and DIPEA (63 μL, 0.36 mmol, 1.1 eq.). Alternatively CH2Cl2 can be used as the reaction solvent based on starting material solubility. The reaction is monitored by LC/MS. The reaction mixture is diluted with ethyl acetate (20 mL) and extracted with 0.5 M HCl (2×10 mL), saturated NaHCO3, and brine. The organic layer is dried over MgSO4, filtered and evaporated. Alternatively, the crude reaction can be directly purified by mass-directed HPLC. Mass-directed HPLC provides the title compound as a white solid after evaporation and lyophilization: 1H NMR (CD3OD, 400 MHz) δ 0.74-0.82 (m, 2H), 1.08-1.65 (m, 13H), 1.21 (d, J=6.8 Hz, 3H), 2.38 (dd, J=4.8, 15.6 Hz, 1H), 2.65 (m, 1H), 2.74 (dd, J=9.6, 15.6 Hz, 1H), 3.10 (m, 2H), 3.54-3.66 (m, 8H), 4.11 (m, 1H), 6.45 (m, 2H), 6.97 (m, 2H). HPLC-MS calcd. for C26H38F3N3O4 (M+H+) 514.3, found 514.2.

Provenance & Evidence