反应详情

To a stirring solution of 233 mg (0.47 mmol) of [1-(Isopropyl-phenyl-carbamoylmethyl)-3-methyl-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl]-acetic acid, prepared as in Intermediate 7, in 2 mL DMF is added 98 mg (0.51 mmol, 1.1 equiv) of EDC and 76 mg (0.56 mmol, 1.2 equiv) of HOBT. The resulting solution is stirred 5 min, then 75 mL (0.61 mmol, 1.3 equiv) of a 30% solution of ammonium hydroxide is added. The solution is stirred 2 h at RT, then poured into 30 mL of EtOAc and extracted H2O (1×30 mL) and NaHCO3 (1×30 mL). The organic layer is separated, dried (MgSO4), and the solvent removed in vacuo. Purification of the resulting grey solid via reverse phase MPLC using a C-18 column and 60% acetonitrile/40% H2O with 0.1% TFA as eluent followed by lyophilization afforded 35 mg of the title compound as a white amorphous solid: 1H NMR (CDCl3, 300 MHz, mixture of conformers) δ7.47-6.80 (m, 14H), 6.70 (s, br, 0.5H), 5.84 (s, br, 0.5H), 5.03 (m, 1H), 4.63 (d, 0.5H, J=16.6), 4.35 (d, 0.5H, J=16.3), 4.08 (d, 0.5H, J=16.6), 3.74 (d, 0.5H, J=16.3), 3.10 (m, 1H), 2.46 (d, 0.5H, J=14.7), 2.23 (d, 0.5H, J=14.7), 1.65 (s, 1.5H), 1.16 (m, 7.5H); low resolution MS (FAB)m/e 499 (MH+).

1. stirringThe solution is stirred 2 h at RT
2. extractionextracted H2O (1×30 mL) and NaHCO3 (1×30 mL)
3. customThe organic layer is separated
4. dry with materialdried (MgSO4)
5. customthe solvent removed in vacuo
6. customPurification of the resulting grey solid via reverse phase MPLC