反应详情

温度

0 °C

To a solution of (3S,7S)-3-amino-1-methyl-7-phenylazepan-2-one (2e) (57 mg) in DCM (3 mL) at 0° C. under N2 was added N-[(3,5-difluorophenyl)acetyl]-L-alanine (95 mg), HOBt-hydrate (88 mg), EDAC.HCl (75 mg) and N-methyl morpholine (42 mg). The reaction mixture was stirred 1 h at 0° C. and 3H at room temperature, then diluted with 30% Hexanes/EtOAc (100 mL). The organic phase was consecutively washed with H2O, 0.2 N HCl, saturated NaHCO3, and brine, dried (Na2SO4), filtered and evaporated. The crude product was purified by flash chromatography (2% MeOH/DCM) to afford the title compound as an off-white solid (80 mg, 70%). 1H NMR (300 MHz, CDCl3) δ 1.40 (d, 3H), 1.51 (m, 1H), 1.90-2.01 (m, 3H), 2.12-2.15 (m, 2H), 2.52 (s, 3H), 3.55 (s, 2H), 4.47-4.56 (m, 1H), 4.92-5.00 (m, 2H), 6.29 (bd, 1H), 6.69-6.76 (m, 1H), 6.84 (bd, 2H), 7.27-7.41 (m, 6H). MS APCI, m/z=444 (M+1)/466 (M+Na). LC/MS 2.54 min., Method A.

1. washThe organic phase was consecutively washed with H2O, 0.2 N HCl, saturated NaHCO3, and brine
2. dry with materialdried (Na2SO4)
3. filtrationfiltered
4. customevaporated
5. customThe crude product was purified by flash chromatography (2% MeOH/DCM)