反应详情

A solution of 35 mg (0.07 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, 0.013 mL (0.14 mmol) of aniline, 66 mg (0.14 mmol) of PyBrOP and 0.05 mL (0.23 mmol) of N,N-diisopropyl-N-ethylamine in 2 mL of DMF is stirred at RT for 2 d. The reaction mixture is diluted with 30 mL of 1N HCl and extracted with EtOAc (×3). The organic extract is washed with 1N HCl, brine, sat. NaHCO3 and brine, dried over MgSO4 and concentrated in vacuo to a yellow oil. Purification by reverse phase C-18 MPLC (70% methanol/TFA-H2O) gave 16 mg of the title compound as a white powder; m.p. 228°-9° C.; 1H NMR (d6 -DMSO 300 MHz, mixture of conformations) δ9.73 (s, 1H), 7.6-7.2 (m, 16H), 7.05 (m, 2H), 6.65 (d, 1H, J=8), 4.85 (m, 1H), 4.22 (m, 2H), 2.33 (m, 2H), 1.20 (s, 3H), 1.00 (m, 6H); low resolution MS (FAB) m/e 575 (MH+).

1. extractionextracted with EtOAc (×3)
2. extractionThe organic extract
3. washis washed with 1N HCl, brine, sat. NaHCO3 and brine
4. dry with materialdried over MgSO4
5. concentrationconcentrated in vacuo to a yellow oil
6. customPurification by reverse phase C-18 MPLC (70% methanol/TFA-H2O)