반응 #43557

반응 방정식

2-(R)-(2-Cyclohexyl-ethyl)-4-morpholin-4-yl-4-oxo-butyric acid

HATU

(S)—N1-(4-Trifluoromethoxy-phenyl)-propane-1,2-diamine

DIPEA

→

title compound

2-(R)-(2-Cyclohexyl-ethyl)-N-[1-(S)-methyl-2-(4-trifluoromethoxy-phenylamino)-ethyl]-4-morpholin-4-yl-4-oxo-butyramide

용매

ethyl acetate

CH2Cl2

DMF

반응 조건

후처리

1. 1
   추출extracted with 0.5 M HCl (2×10 mL), saturated NaHCO3, and brine
2. 2
   건조The organic layer is dried over MgSO4
3. 3
   여과filtered
4. 4
   기타evaporated
5. 5
   기타Alternatively, the crude reaction
6. 6
   기타can be directly purified by mass-directed HPLC

실험 절차

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.

출처