反应详情

温度

0 °C

To a solution of (3S,7S)-3-amino-1-(cyclopylmethyl)-7-(4-methoxyphenyl)-1,3,4,7-tetrahydro-2H-azepin-2-one (11e) (35 mg) in DCM (3 mL) at 0° C. under N2 was added N-[(2S)-2-hydroxy-4-methylpentanoyl]-L-leucine (7b) (30 mg), HOBt-hydrate (41 mg), EDAC.HCl (35 mg) and N-methyl morpholine (25 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 (60 mg, 95%). 1H NMR (300 MHz, CDCl3) δ 0.40 (m, 2H), 0.58 (m, 2H), 0.74 (m, 1H), 0.87 (d, 6H), 1.26 (m, 1H), 1.53, (m, 2H), 1.59 (m, 1H), 1.67 (m, 2H), 2.00 (m, 2H), 3.20 (m, 2H), 3.66 (s, 1H), 3.89 (m, 1H), 4.28 (m, 1H), 4.96 (m, 1H), 5.32 (m, 1H), 6.13 (bd, 1H), 6.48 (m, 1H), 6.85-6.94 (m, 4H). MS APCI, m/z=514 (M+1). LC/MS 2.47 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)