反应详情

Intermediate (52) was stirred in ethanol (150 ml). The mixture was acidified with HCl/2-propanol (±60 ml)+water (2 ml). The mixture was stirred for 15 minutes. The solvent was evaporated at 60° C. Ethanol was added to the residue. The solvent was evaporated. A mixture of methanol in water (70:30; 200 ml) was added to the residue and the mixture was stirred, then warmed slightly until complete dissolution. The acidic solution was added dropwise (over 30 minutes, under argon) to a solution of KOCN (0.100 mol) in a mixture of methanol in water (70:30; 100 ml), stirred at room temperature pH went from ±8 to ±6). The reaction mixture was stirred for 19 hours at room temperature. More KOCN (0.32 g) was added and the reaction mixture was stirred for 90 minutes at room temperature. More KOCN (0.9 g) was added and the reaction mixture was stirred for 75 minutes at room temperature, then for 6 days at 95° C. The reaction mixture was cooled. Concentrated HCl (20 ml) was added dropwise. The reaction mixture was stirred for 2 hours at 95° C., then stood overnight at room temperature. The precipitate was filtered off, and the filtrate was stirred and cooled for 3 hours on an ice-bath. The resulting precipitate was filtered off and dried, yielding 19.6 g of 1-[3-[bis(phenylmethyl)amino]propyl]dihydro-2,4(1H,3H)-pyrimidinedione (intermediate 53).

1. customThe solvent was evaporated at 60° C
2. additionEthanol was added to the residue
3. customThe solvent was evaporated
4. additionA mixture of methanol in water (70:30; 200 ml)
5. additionwas added to the residue
6. stirringthe mixture was stirred
7. temperaturewarmed slightly until complete dissolution
8. stirringstirred at room temperature
9. stirringThe reaction mixture was stirred for 19 hours at room temperature
10. stirringthe reaction mixture was stirred for 90 minutes at room temperature
11. stirringthe reaction mixture was stirred for 75 minutes at room temperature
12. waitfor 6 days at 95° C
13. temperatureThe reaction mixture was cooled
14. stirringThe reaction mixture was stirred for 2 hours at 95° C.
15. waitstood overnight at room temperature
16. filtrationThe precipitate was filtered off
17. stirringthe filtrate was stirred
18. temperaturecooled for 3 hours on an ice-bath
19. filtrationThe resulting precipitate was filtered off
20. customdried