反应详情

温度

100 °C

A mixture of 64 g (0.4 mol) of (4-cyanophenyl)guanidine, 98.4 g (1.2 mol) sodium acetate and 76.6 g (0.44 mol) diethyl(ethoxymethylene)malonate in 600 ml N-methyl-pyrrolidinone (NMP) was heated to 100° C. and stirred for 1 hour at that temperature. 81 ml of demineralized water was added and the reaction mixture was further heated to reflux temperature. About 120 ml of the solvent was evaporated until the temperature of the reaction mixture reached the range of 155° C. to 160° C. Subsequently the reaction mixture was refluxed during 72 hours. The whole is allowed to cool to 20-25° C. and 25 g filtration aid was added. After stirring the mixture for 1 hour at 20-25° C., the precipitate was filtered off and washed with 50 ml of NMP. The solvent was distilled off under vacuum and the residue was heated to 130° C. 375 ml acetic acid was added dropwise (during 15 minutes) to the heated residue while keeping the temperature at 130° C. After addition of the acetic acid, the mixture was heated to 150° C. and stirred at that temperature for 15 minutes. Subsequently, the mixture was allowed to cool to 20-25° C. The formed precipitate was filtered off and washed with ethanol (1×250 ml and 1×100 ml). 500 ml ethanol was added to the washed precipitate and this mixture was heated and refluxed for 1 hour. After cooling to 20-25° C., the precipitate was filtered off, washed with 100 ml ethanol and dried at 50° C. under vacuum during 16 hours. Yield: 80.5 g of 4-[(1,4-dihydro-4-oxo-2-pyrimidinyl)amino]benzonitrile (75.9% yield).

1. temperaturethe reaction mixture was further heated
2. temperatureto reflux temperature
3. customAbout 120 ml of the solvent was evaporated until the temperature of the reaction mixture
4. customthe range of 155° C. to 160° C
5. temperatureSubsequently the reaction mixture was refluxed during 72 hours
6. temperatureto cool to 20-25° C.
7. filtration25 g filtration aid
8. additionwas added
9. stirringAfter stirring the mixture for 1 hour at 20-25° C.
10. filtrationthe precipitate was filtered off
11. washwashed with 50 ml of NMP
12. distillationThe solvent was distilled off under vacuum
13. temperaturethe residue was heated to 130° C
14. addition375 ml acetic acid was added dropwise (during 15 minutes) to the heated residue
15. customat 130° C
16. additionAfter addition of the acetic acid
17. temperaturethe mixture was heated to 150° C.
18. stirringstirred at that temperature for 15 minutes
19. temperatureto cool to 20-25° C
20. filtrationThe formed precipitate was filtered off
21. washwashed with ethanol (1×250 ml and 1×100 ml)
22. addition500 ml ethanol was added to the washed precipitate
23. temperaturethis mixture was heated
24. temperaturerefluxed for 1 hour
25. temperatureAfter cooling to 20-25° C.
26. filtrationthe precipitate was filtered off
27. washwashed with 100 ml ethanol
28. customdried at 50° C. under vacuum during 16 hours