反应详情

温度

0 °C

To a solution of 6 (5.05 g, 22.0 mmol) in CH2Cl2 (50 mL) at 0° C. was added 1,3-dimethylbarbituric acid (DMBA) (3.78 g, 24.2 mmol)and Pd(PPh3)4 (0.15 g, 0.13 mmol) After 10 minutes, a solution of 5 (8.40 g, 22.0 mmol) in DMF (25 mL) was added followed by diisopropylethylamine (DIPEA) (7.66 mL, 44.1 mmol), (2.98 g, 22.0 mmol) and EDC (5.06 g, 26.4 mmol). The solution was stirred at 0° C. for 10 minutes then at room temperature for 18 hours. The reaction was diluted with EtOAc (200 mL), washed with 0.5N NaHSO4 (2×200 mL), 10% NaHCO3 (2×200 mL), saturated NaCl (1×150 mL), dried over anhydrous MgSO4, and evaporated to dryness. Flash column chromatography on silica gel using CH2Cl2/MeOH, (99/1 to 98/2%) afforded the title compound as a white solid (11.20 g, 77% yield): 1H-NMR (500 MHz, CDCl3) δ1.08 (s, 9H), 1.27 (t, 3H), 1.85–1.99 (m, 1H), 2.00–2.06 (m. 1H), 2.07–2.18 (m, 1H), 2.32–2.48 (m, 2H), 2.78–2.89 (m, 1H), 3.62–3.76 (m, 2H), 3.82–3.96 (m, 2H), 4.39 (s, 1H), 4.54–4.60 (m, 1H), 4.62–4.76 (m, 1H), 4.85 (d, 1H), 6.57 (d, 1H), 6.73 (d, 1H), 7.38 (d, 1H), 7.49 (d, 1H), 7.72 (s, 1H). Analytical HPLC (cyano column): 13.10 min. LC-MS (ES+) m/e=509.4 (M+H), m.p.=96–99 ° C.

1. waitat room temperature for 18 hours
2. washwashed with 0.5N NaHSO4 (2×200 mL), 10% NaHCO3 (2×200 mL), saturated NaCl (1×150 mL)
3. dry with materialdried over anhydrous MgSO4
4. customevaporated to dryness