Reaktion #51614

Reaktionsgleichung

N″-cyano-N-[1-[(3,4-dihydro-2H-1-benzopyran-2-yl)methyl]-4-piperidinyl]-N′-(2,2-dimethoxyethyl)guanidine

HCl

Na2CO3

→

[1-[1-[(3,4-dihydro-2H-1-benzopyran-2-yl)methyl]-4-piperidinyl]-1H-imidazol-2-yl]cyanamide

(±)-[1-[1-[(3,4-dihydro-2H-1-benzopyran-2-yl)methyl]-4-piperidinyl]-1H-imidazol-2-yl]urea

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturrefluxed for 100 minutes
2. 2
   Sonstigeto obtain
3. 3
   Sonstigea clear separation
4. 4
   SonstigeThe organic layer was separated
5. 5
   workup.ADDITIONDCM was added
6. 6
   Waschenthe whole was washed with water
7. 7
   Sonstigedried
8. 8
   Filtrationfiltered
9. 9
   Sonstigethe solvent was evaporated
10. 10
    SonstigeThe residue was separated
11. 11
    Sonstigepurified by column chromatography over silica gel (separation first compound: eluent: CH2Cl2/CH3OH 95/5; separation second compound: CH2Cl2/(CH3OH/NH3) 90/10)
12. 12
    SonstigeThe two pure fraction groups were collected
13. 13
    Sonstigetheir solvent was evaporated
14. 14
    SonstigeEach residue was crystallized from ACN
15. 15
    FiltrationEach precipitate was filtered off
16. 16
    Sonstigedried

Vorschrift

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).

Quelle