反应详情

To a solution of (R)-3-[N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-(5-oxo-1-phenyl-4,5-dihydro-1H-[1,2,4]triazole-3-carbonyl)hydrazino]-2-hydroxypropionic acid (200 mg, 335 μmol) in dry DMF (6 mL) was added bromomethyl acetate (76 mg, 503 μmol), NaI (101 mg, 670 μmol), and 2,6-dimethylpyridine (143 mg, 1.3 mmol) in portions at room temperature. The resulting mixture was stirred at room temperature for 8 hours. Water (12 mL) was added and the mixture was extracted with EtOAc (3×10 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography (PE:EtOAc=3:1) to yield the title compound as a white solid (15 mg). LC-MS: 597.7 [M+H]+. 1H NMR (CDCl3, 400 MHz,) δ 2.02 (s, 3H), 3.37 (br, 2H), 4.22 (br, 2H), 4.38 (br, 1H), 5.78-6.02 (m, 2H), 7.15-7.20 (m, 1H), 7.40-7.45 (m, 2H), 7.50-7.91 (m, 7H), 8.15-8.17 (m, 2H).

1. extractionthe mixture was extracted with EtOAc (3×10 mL)
2. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
3. concentrationconcentrated in vacuo
4. customThe residue was purified by column chromatography (PE:EtOAc=3:1)