反应详情

A mixture of N″-cyano-N-[1-[(3,4-dihydro-2H-1-benzopyran-2-yl)methyl]-4-piperidinyl]-N′-(2,2-dimethoxyethyl)guanidine (0.0153 mol) and HCl (0.5 N, 46 ml) in THF (160 ml) was stirred and refluxed for 100 minutes. Ice-water was added. Na2CO3 was added portionwise to obtain a clear separation. The organic layer was separated, DCM was added, the whole was washed with water, dried, filtered and the solvent was evaporated. The residue was separated and purified by column chromatography over silica gel (separation first compound: eluent: CH2Cl2/CH3OH 95/5; separation second compound: CH2Cl2/(CH3OH/NH3) 90/10). The two pure fraction groups were collected and their solvent was evaporated. Each residue was crystallized from ACN. Each precipitate was filtered off and dried, yielding 1.75 g [1-[1-[(3,4-dihydro-2H-1-benzopyran-2-yl)methyl]-4-piperidinyl]-1H-imidazol-2-yl]cyanamide (compound 59) and 0.48 g (±)-[1-[1-[(3,4-dihydro-2H-1-benzopyran-2-yl)methyl]-4-piperidinyl]-1H-imidazol-2-yl]urea (compound 66).

1. temperaturerefluxed for 100 minutes
2. customto obtain
3. customa clear separation
4. customThe organic layer was separated
5. additionDCM was added
6. washthe whole was washed with water
7. customdried
8. filtrationfiltered
9. customthe solvent was evaporated
10. customThe residue was separated
11. custompurified by column chromatography over silica gel (separation first compound: eluent: CH2Cl2/CH3OH 95/5; separation second compound: CH2Cl2/(CH3OH/NH3) 90/10)
12. customThe two pure fraction groups were collected
13. customtheir solvent was evaporated
14. customEach residue was crystallized from ACN
15. filtrationEach precipitate was filtered off
16. customdried