反应详情

To a solution of 2-(6-(2,4-dimethoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetic acid (40 g, 124 mmol) in DMF (300 mL) was added tert-butyl (2-aminoethyl)carbamate (40 g, 250 mmol) and pyridine (30 mL), and the mixture was stirred at room temperature for 15 minutes. The solution was cooled to 0° C. and it was purged with nitrogen gas for 3 times. After 10 minutes, a 50% solution of T3P in DMF (109 mL) was added drop-wise at 0° C., and stirring was continued for 1 hour, whereupon the water/ice bath was removed and stirring was continued for 4 hours. The reaction solution was slowly poured into a stirring solution of aqueous HCl solution (2500 mL, 0.5 M), and the suspension was stirred at room temperature for 1 hour. The formed solid was filtered, and the filter cake was washed with 0.5M HCl solution (500 mL) followed by water (500 mL). The solid was dried in the vacuum oven at 50° C. for 20 hours to give 54.6 g of light beige powder. This solid was suspended in EtOAc (500 mL), heated to 70° C. under a stream of nitrogen gas with stirring for 1 hour, and then at room temperature for 18 h. The suspension was cooled down to 0° C., and the solid was filtered, the filter cake washed with cold (0° C.) EtOAc (100 mL) and dried in the vacuum oven at 50° C. for 9 hours to give 49.0 g of off-white solid. This solid was suspended in acetonitrile (300 mL), and stirred at 70° C. under a stream of nitrogen for 18 h. The mixture was cooled to 0° C., and the resultant solid was filtered, washed with cold acetonitrile (50 mL) and dried in the vacuum oven at 50° C. for 8 hours to give 46.5 g of off-white solid. This solid was suspended in EtOAc (350 mL), heated to 70° C. under a stream of nitrogen gas with stirring for 1 hour, and then at room temperature for 18 h. The suspension was cooled down to 0° C., and the solid was filtered, the filter cake washed with cold (0° C.) EtOAc (50 mL) and dried in the vacuum oven at 50° C. for 9 hours to give the title compound (45.4 g, 78.8%) as an off-white powder.

1. temperatureThe solution was cooled to 0° C.
2. customit was purged with nitrogen gas for 3 times
3. waitAfter 10 minutes
4. additiona 50% solution of T3P in DMF (109 mL) was added drop-wise at 0° C.
5. stirringstirring
6. waitwas continued for 1 hour, whereupon the water/ice bath
7. customwas removed
8. stirringstirring
9. waitwas continued for 4 hours
10. additionThe reaction solution was slowly poured into a stirring solution of aqueous HCl solution (2500 mL, 0.5 M)
11. stirringthe suspension was stirred at room temperature for 1 hour
12. filtrationThe formed solid was filtered
13. washthe filter cake was washed with 0.5M HCl solution (500 mL)
14. customThe solid was dried in the vacuum oven at 50° C. for 20 hours
15. customto give 54.6 g of light beige powder
16. temperatureheated to 70° C. under a stream of nitrogen gas
17. stirringwith stirring for 1 hour
18. waitat room temperature for 18 h
19. temperatureThe suspension was cooled down to 0° C.
20. filtrationthe solid was filtered
21. washthe filter cake washed with cold (0° C.) EtOAc (100 mL)
22. customdried in the vacuum oven at 50° C. for 9 hours