反应详情

A mixture of (3R)-3-amino-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-1,4-benzodiazepine (Shi et al. Tetrahedron 1999, 55, 909) (507 mg, 1.52 mmol), (±)-6′-carboxy-3′,4′-dihydro-1′H-spiro[imidazolidine-4,2′-naphthalene]-2,5-dione (described in Intermediate 1) (396 mg, 1.52 mmol), EDC (438 mg, 2.28 mmol), HOBT (308 mg, 2.01 mmol), and N,N-diisopropylethylamine (0.795 mL, 4.56 mmol) was stirred in DMF (5 mL) at ambient temperature for 18 h. The crude mixture was partitioned between saturated aqueous NaHCO3 (25 mL) and CH2Cl2 (25 mL), and the aqueous phase was extracted further with CH2Cl2 (2×25 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated to dryness. The crude product was purified by silica gel chromatography, eluting with a gradient of CH2Cl2:MeOH—100:0 to 95:5 to provide the title compound as an off-white solid. MS: m/z=576 (M+1). HRMS: m/z=576.1840; calculated m/z=576.1853 for C30H24F3N5 O4.

1. customThe crude mixture was partitioned between saturated aqueous NaHCO3 (25 mL) and CH2Cl2 (25 mL)
2. extractionthe aqueous phase was extracted further with CH2Cl2 (2×25 mL)
3. dry with materialThe combined organic extracts were dried over Na2SO4
4. filtrationfiltered
5. concentrationconcentrated to dryness
6. customThe crude product was purified by silica gel chromatography
7. washeluting with a gradient of CH2Cl2