反应详情

温度

50 °C

A solution of 0.19 g (0.38 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, 0.15 g (0.76 mmol) of t-butyl 3-aminobenzoate, 0.35 g (0.76 mmol) of PyBrOP and 0.27 mL (1.5 mmol) of N,N-diisopropyl-N-ethylamine in 2 mL of DMF is stirred at 50° C. for 17 h. The reaction mixture is diluted with 30 mL of H2O and extracted with EtOAc (×3). The organic extract is washed with H2O, 1N HCl, and brine, dried over MgSO4 and concentrated in vacuo to a brown foam. The crude product is dissolved in 2 mL of CH2Cl2 and 0.3 mL (3.8 mmol) of TFA added. After stirring at RT for 1 d, the reaction mixture is concentrated in vacuo to a brown oil. Purification by reverse phase C-18 MPLC (60-80% methanol/TFA-H2O) gave 99 mg of the title compound as a white powder: 1H NMR (CDCl3 300 MHz, mixture of conformations) δ8.8-6.8 (m, 20H), 5.07 (m, 1H), 4.78 (d, 1H, J=12), 3.79 (d, 1H, J=12), 2.70 (q, 2H, J=10), 1.70 (s, 3H), 1.09 (m, 6H); low resolution MS (FAB) m/e 619 (MH+); Anal. (C36H34N4O6.0.75 TFA.H2O) Calc. C, 62.4; H, 5.1; N, 7.8; Found: C, 62.4; H, 5.2; N, 7.7.

1. extractionextracted with EtOAc (×3)
2. extractionThe organic extract
3. washis washed with H2O, 1N HCl, and brine
4. dry with materialdried over MgSO4
5. concentrationconcentrated in vacuo to a brown foam
6. dissolutionThe crude product is dissolved in 2 mL of CH2Cl2
7. stirringAfter stirring at RT for 1 d
8. concentrationthe reaction mixture is concentrated in vacuo to a brown oil
9. customPurification by reverse phase C-18 MPLC (60-80% methanol/TFA-H2O)