反应详情

To a stirred solution of 500 mg (1.98 mmol) 1-Phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-2,4-dione in 15 mL DMF is added 103 mg (2.58 mmol, 1.3 equiv) 60 wt % NaH at ambient temperature and stirred 0.5 h. To this solution is added 504 mg (1.98 mmol, 1.0 equiv) 2-Bromo-N-cyclopropyl-N-phenyl-acetamide, prepared as in Part A, in 1 mL DMF and stirred 18 h at ambient temperature. The solvent is removed in vacuo and the residue taken into 50 mL EtOAc, washed successively with H2O (30 mL), 1N HCl (30 mL), satd. NaHCO3 (30 mL), and brine (30 mL), dried (MgSO4), filtered and concentrated in vacuo to a brown oil. The crude product is purified by flash chromatography on 15 g silica gel eluted with EtOAc/Hexanes (1:1, 450 mL). Appropriate fractions were combined and concentrated in vacuo to give 572 mg (1.34 mmol) of N-Cyclopropyl-2-(2,4-dioxo-5-phenyl-2,3,4,5,tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-phenyl-acetamide as a white foam: 1H NMR (CDCl3, 300 MHz) δ7.50-7.07 (m, 13H), 6.92 (d, 1H, J=7.3), 3.60 (d, 1H, J=11.9), 3.51 (d, 1H, J=12.0), 3.30 (m, 1H), 0.86 (m, 2H), 0.60 (m, 2H); TLC Rf =0.35 (EtOAc/Hexanes, 2:1).

1. additionTo this solution is added
2. customThe solvent is removed in vacuo
3. washwashed successively with H2O (30 mL), 1N HCl (30 mL)
4. dry with materialNaHCO3 (30 mL), and brine (30 mL), dried (MgSO4)
5. filtrationfiltered
6. concentrationconcentrated in vacuo to a brown oil
7. customThe crude product is purified by flash chromatography on 15 g silica gel
8. washeluted with EtOAc/Hexanes (1:1, 450 mL)
9. concentrationconcentrated in vacuo