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) δ 1.08 (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