反应详情

Dimethyl (cyanoimido)dithiocarbonate (0.07 g.) and 2-[2-(2,2-difluoroethyl)guanidino]-4-[(2-aminoethyl)thiomethyl]thiazole (0.15 g.) were dissolved in ethanol (3 ml.) and heated under reflux for 20 minutes. The solvent was evaporated and the residual gum was dissolved in ethanolic methylamine (33% w/v, 3 ml.) and allowed to stand at room temperature for 16 hours. The solvent was evaporated and the residual gum purified by preparative thin layer chromatography using ethyl acetate/methanol/ammonia 6:1:1 v/v/v as developing solvent. The appropriate zone of the chromatogram was isolated and extracted with methanol/ammonia 10:1 v/v. The solvent was evaporated and the residue was dissolved in ethyl acetate, filtered and added to a solution of maleic acid (0.1 g.) in ethyl acetate. The precipitate was filtered to give 2-[2-(2,2-difluoroethyl)guanidino]-4-[2-(2-cyano-3-methylguanidino)ethylthiomethyl]thiazole (0.11 g.), m.p. 108°-112° (decomp.) containing 1.25 molar equivalents of maleic acid.

1. temperatureheated
2. temperatureunder reflux for 20 minutes
3. customThe solvent was evaporated
4. dissolutionthe residual gum was dissolved in ethanolic methylamine (33% w/v, 3 ml.)
5. customThe solvent was evaporated
6. customthe residual gum purified by preparative thin layer chromatography
7. customThe appropriate zone of the chromatogram was isolated
8. extractionextracted with methanol/ammonia 10:1 v/v
9. customThe solvent was evaporated
10. dissolutionthe residue was dissolved in ethyl acetate
11. filtrationfiltered
12. additionadded to a solution of maleic acid (0.1 g.) in ethyl acetate
13. filtrationThe precipitate was filtered