反应详情

温度

0 °C

To a solution of bisphosphonate 8 (400 mg, 0.98 mmol) in DMF (5 mL) at 0° C. was added DIEA (341 μL, 1.96 mmol) and HBTU (372 mg, 0.98 mmol). After stirring for 10 min at 0° C., the resulting activated ester solution was added to crude tripeptide 75 (0.98 mmol) and stirring was pursued for 2.5 h at 0° C. The reaction mixture was diluted with ethyl acetate, washed with H2O, 1N HCl solution, saturated NaHCO3 solution and saturated NaCl solution. The organic layer was dried over MgSO4, filtered and concentrated to dryness. The crude product was purified by silica gel chromatography on a Biotage™ flash chromatography system using a gradient of 0-10% methanol in ethyl acetate. Compound 76 was obtained as a colorless gum (652 mg, 92%). 1H NMR (400 MHz, CDCl3) δ 1.44 (s, 9H), 2.22-2.37 (m, 2H), 2.57 (t, J=6.4 Hz, 2H), 2.62 (tt, J=23.9, 7.0 Hz, 1H), 3.03-3.09 (m, 1H), 3.14-3.20 (m, 1H), 3.77-3.93 (m, 4H), 4.58-4.63 (m, 8H), 4.66-4.71 (m, 1H), 5.21-5.26 (m, 4H), 5.33-5.41 (m, 4H), 5.89-5.99 (m, 4H), 6.58-6.66 (m, 2H), 7.09 (d, J=8.2, 1H), 7.19-7.23 (m, 3H), 7.27-7.30 (m, 2H).

1. stirringstirring
2. waitwas pursued for 2.5 h at 0° C
3. washwashed with H2O, 1N HCl solution, saturated NaHCO3 solution and saturated NaCl solution
4. dry with materialThe organic layer was dried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated to dryness
7. customThe crude product was purified by silica gel chromatography on a Biotage™ flash chromatography system