反应详情

To a solution of (R)-ethyl 4-(3′-chlorobiphenyl-4-yl)-3-(2-hydrazinyl-2-oxoacetamido)butanoate, intermediate 12, (289 mg, 0.72 mmol) in THF (8.5 mL) is added CDI (139 mg, 0.86 mmol) at room temperature. After stirring for 18 hour at room temperature, the reaction is quenched with H2O and 1M HCl, and the crude is diluted with EtOAc. The organic layer is washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The obtained residue is purified by RP-HPLC (SunFire C18, H2O (0.1% TFA)/CH3CN) and then lyophilized to give (R)-ethyl 4-(3′-chlorobiphenyl-4-yl)-3-(5-oxo-4,5-dihydro-1,3,4-oxadiazole-2-carboxamido)butanoate (100 mg). HPLC retention time=1.67 minutes (condition A); MS (m+1)=430.2; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.14 (t, J=7.1 Hz, 3H) 2.52-2.70 (m, 2H) 2.84 (dd, J=13.7, 8.4 Hz, 1H) 2.90 (dd, J=13.7, 8.4 Hz, 1H) 4.02 (q, J=7.1 Hz, 2H) 4.42-4.58 (m, 1H) 7.30 (d, J=8.1 Hz, 2H) 7.37-7.43 (m, 1H) 7.47 (t, J=7.8 Hz, 1H) 7.57-7.66 (m, 3H) 7.70 (t, J=1.9 Hz, 1H) 8.98 (d, J=8.8 Hz, 1H) 12.94 (s, 1H).

1. customthe reaction is quenched with H2O and 1M HCl
2. additionthe crude is diluted with EtOAc
3. washThe organic layer is washed with brine
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customThe obtained residue is purified by RP-HPLC (SunFire C18, H2O (0.1% TFA)/CH3CN)