反应详情

To a stirring solution of 110 mg (0.17 mmol) of 2-[3-(1-Benzyl-1H-indazol-3-ylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-(4-methoxy-phenyl) acetamide in 15 mL of a 10% solution of formic acid in absolute ethanol is added 100 mg of 10% palladium on carbon. The resulting black suspension is heated at reflux for 24 h, then cooled to RT. The reaction mixture is filtered through Celite to remove the catalyst and the solvent removed in vacuo. Purification of the residue by gradient silica gel flash column chromatography using hexane/EtOAc 3/2 up to 2/3 as eluent followed by further purification via reverse phase MPLC using a C-18 column and 60% acetonitrile/40% H2O as eluent and lyophilization afforded 62 mg of the title compound as a white amorphous solid: 1H NMR (CDCl3, 300 MHz) δ7.81 (d, 1H, J=8.0), 7.41-6.90 (m, 17H), 5.00 (m, 1H), 4.23 (m, 3H), 3.84 (s, 3H), 3.79 (d, 1H, J=7.9), 3.61 (dd, 1H, J=5.8, 16.1), 1.06 (m, 6H); low resolution MS (FAB)m/e 588 (MH+), 423, 223; Anal. (C35H33N5O4.H2O) Calcd. C, 70.45; H, 5.91; N, 11.74 Found C, 70.62; H, 5.76; N, 11.78.

1. temperatureThe resulting black suspension is heated
2. temperatureat reflux for 24 h
3. filtrationThe reaction mixture is filtered through Celite
4. customto remove the catalyst
5. customthe solvent removed in vacuo
6. customPurification of the residue by gradient silica gel flash column chromatography
7. customfollowed by further purification via reverse phase MPLC