反应详情

[(R)-1-(3′-Chloro-biphenyl-4-ylmethyl)-3-methanesulfonylamino-3-oxo-propyl]-carbamic acid tert-butyl ester (150 mg, 0.321 mmol) is treated with 4M HCl in dioxane. After being stirred at room temperature for 1 h, the reaction mixture is concentrated in vacuo. To this residue in DCM (2 mL) are added succinic anhydride (48.2 mg, 0.482 mmol) and triethylamine (0.112 mL, 0.803 mmol). After being stirred at room temperature for 2 h, the reaction mixture is diluted with EtOAc and washed with 1M HCl and brine. The organic layer is dried over Na2SO4 and concentrated. The residue is purified by reverse phase HPLC (SunFire C18, 0.1% TFA in H2O/CH3CN) to give N—[(R)-1-(3′-chloro-biphenyl-4-ylmethyl)-3-methanesulfonylamino-3-oxo-propyl]-succinamic acid (63 mg). HPLC retentions time=1.32 minutes (condition A); MS (m+1)=467; 1H NMR (400 Mz, DMSO-d6) δ ppm 2.22-2.29 (m, 2H), 2.32-2.54 (m, 4H), 2.77 (d, 2H, J=6.82 Hz), 3.17 (s, 3H), 4.31 (dt, 1H, J=7.33, 13.9 Hz), 7.28 (d, 2H, J=8.08 Hz), 7.38-7.43 (m, 1H), 7.48 (t, 1H, J=7.83 Hz), 7.62 (d, 3H, J=8.34 Hz), 7.70 (t, 1H, J=2.02 Hz), 7.89 (d, 1H, J=8.34 Hz), 11.70 (s, 1H), 12.04 (s, 1H).

1. concentrationthe reaction mixture is concentrated in vacuo
2. stirringAfter being stirred at room temperature for 2 h
3. washwashed with 1M HCl and brine
4. dry with materialThe organic layer is dried over Na2SO4
5. concentrationconcentrated
6. customThe residue is purified by reverse phase HPLC (SunFire C18, 0.1% TFA in H2O/CH3CN)