反应详情

To a solution of 2-methoxyoxazole-5-carboxylic acid, intermediate 22, (68 mg, 0.47 mmol) in DMF (2 mL) and DCM (2 mL) is added (2R,4S)-ethyl 4-amino-5-(biphenyl-4-yl)-2-methylpentanoate hydrochloride (150 mg, 0.43 mmol), HATU (246 mg, 0.65 mmol), and triethylamine (180 μL, 1.29 mmol). After stirring the reaction for 2 hours at room temperature, the reaction is quenched with H2O, and the crude is diluted in 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 (2R,4S)-ethyl 5-(biphenyl-4-yl)-4-(2-methoxyoxazole-5-carboxamido)-2-methylpentanoate (175 mg). HPLC retention time=1.71 minutes (condition A); MS 437.5 (M+1); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.20 (d, J=7.1 Hz, 3H) 1.25 (t, J=7.1 Hz, 3H) 1.65 (ddd, J=14.3, 10.0, 4.3 Hz, 1H) 1.96-2.10 (m, 1H) 2.63 (ddd, J=9.4, 7.1, 4.2 Hz, 1H) 2.92 (dd, J=13.9, 6.3 Hz, 1H) 2.99 (dd, J=13.9, 6.3 Hz, 1H) 4.11 (s, 3H) 4.12-4.18 (m, 2H) 4.34-4.54 (m, 1H) 6.15 (d, J=8.8 Hz, 1H) 7.28 (d, J=8.3 Hz, 2H) 7.31-7.37 (m, 1H) 7.40-7.47 (m, 3H) 7.54 (d, J=8.3 Hz, 2H) 7.59 (dd, J=8.3, 1.26 Hz, 2H)

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