Diisopropylethylamine → Succinamide peptidomimetic, 20

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.

1. extractionextracted with 0.5 M HCl (2×10 mL), saturated NaHCO3, and brine
2. dry with materialThe organic layer is dried over MgSO4
3. filtrationfiltered
4. customevaporated
5. customAlternatively, the crude reaction
6. customcan be directly purified by mass-directed HPLC

ORD record

ord-353ce26bc88648e9893f635bcd29d0a1

Source dataset

uspto-grants-2008_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07314872B2