Reaktion #606920

Reaktionsgleichung

methylmagnesium bromide

ethyl trans-3-{6-[(2′-cyano-3-fluorobiphenyl-4-yl)methyl]-5-oxo-7-propyl[1,2,4]triazolo[1,5-a]pyrimidin-4(5H)-yl}cyclobutanecarboxylate

sodium hydroxide

hydrochloric acid

hydrochloric acid

→

title compound

Ausbeute 60.0%

4′-{[4-(trans-3-acetylcyclobutyl)-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}-3′-fluorobiphenyl-2-carbonitrile

Ausbeute 60.0%

Lösungsmittel

tetrahydrofuran

tetrahydrofuran

ethanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeAfter evaporation of the solvent under reduced pressure
2. 2
   Extraktionthe residue was extracted with ethyl acetate
3. 3
   WaschenThe organic layer was washed with saturated brine
4. 4
   Trocknendried over anhydrous magnesium sulfate
5. 5
   SonstigeThe solvent was evaporated under reduced pressure
6. 6
   workup.ADDITIONthe residue was mixed with N,O-dimethylhydroxyamine hydrochloride (0.24 g), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.48 g), 1-hydroxybenzotriazole (0.33 g), triethylamine (0.69 mL) and N,N-dimethylformaldehyde (10 mL)
7. 7
   workup.STIRRINGthe mixture was stirred at room temperature for 14 hr
8. 8
   workup.ADDITIONThe reaction mixture was added to 1 M hydrochloric acid
9. 9
   Extraktionthe mixture was extracted with ethyl acetate
10. 10
    WaschenThe organic layer was washed with saturated brine
11. 11
    Trocknendried over anhydrous magnesium sulfate
12. 12
    SonstigeThe solvent was evaporated under reduced pressure
13. 13
    SonstigeThe residue obtained by silica gel column chromatography
14. 14
    workup.STIRRINGthe mixture was stirred at 0° C. for 1 hr
15. 15
    Extraktionthe mixture was extracted with ethyl acetate
16. 16
    WaschenThe organic layer was washed with saturated brine
17. 17
    Trocknendried over anhydrous magnesium sulfate
18. 18
    SonstigeThe solvent was evaporated under reduced pressure
19. 19
    Sonstigethe residue was purified by silica gel column chromatography

Vorschrift

A mixture of ethyl trans-3-{6-[(2′-cyano-3-fluorobiphenyl-4-yl)methyl]-5-oxo-7-propyl[1,2,4]triazolo[1,5-a]pyrimidin-4(5H)-yl}cyclobutanecarboxylate (0.86 g), tetrahydrofuran (10 mL), ethanol (10 mL) and 1 M aqueous sodium hydroxide solution (10 mL) was stirred at room temperature for 2 hr. The reaction mixture was neutralized with 1 M hydrochloric acid. After evaporation of the solvent under reduced pressure, the residue was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, the residue was mixed with N,O-dimethylhydroxyamine hydrochloride (0.24 g), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.48 g), 1-hydroxybenzotriazole (0.33 g), triethylamine (0.69 mL) and N,N-dimethylformaldehyde (10 mL), and the mixture was stirred at room temperature for 14 hr. The reaction mixture was added to 1 M hydrochloric acid, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue obtained by silica gel column chromatography was dissolved in tetrahydrofuran (10 mL), methylmagnesium bromide (6.6 mL, 1.0 M tetrahydrofuran solution) was added dropwise at 0° C., and the mixture was stirred at 0° C. for 1 hr. The reaction mixture was added to 1 M hydrochloric acid, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to give the title compound as a colorless solid (0.49 g, 60%).

Quelle