Hydrochloric Acid → HCID 178438508, Verbindung

A mixture of 4′-({4-[cis-4-(2-hydroxyethoxy)cyclohexyl]-2-methyl-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl}methyl)biphenyl-2-carbonitrile (0.44 g), 2,6-lutidine (0.15 mL), tert-butyl(dimethyl)silyl trifluoromethanesulfonate (0.29 mL) and tetrahydrofuran (5 mL) was stirred at room temperature for 1.5 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 obtained residue was added to a mixture of hydroxylammonium chloride (0.87 g), sodium hydrogen carbonate (1.4 g), and dimethyl sulfoxide (8 mL), which had been stirred at 40° C. for 30 min in advance, and the mixture was stirred at 90° C. for 24 hr. Ethyl acetate and water were added to the reaction mixture, 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 purification by silica gel column chromatography was dissolved in tetrahydrofuran (2 mL). N,N′-Carbonyldiimidazole (0.059 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.055 mL) were added, and the mixture was stirred at room temperature for 5 hr. Ethyl acetate and water were added to the reaction mixture, and the mixture was acidified with 1 M hydrochloric acid and 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 dissolved in tetrahydrofuran (10 mL). Tetrabutylammonium fluoride (0.77 mL, 1.0 M tetrahydrofuran solution) was added, and the mixture was stirred at 70° C. for 16 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 (0.051 g, 10%).

1. extractionthe mixture was extracted with ethyl acetate
2. washThe organic layer was washed with saturated brine
3. dry with materialdried over anhydrous magnesium sulfate
4. customThe solvent was evaporated under reduced pressure
5. additionthe obtained residue was added to a mixture of hydroxylammonium chloride (0.87 g), sodium hydrogen carbonate (1.4 g), and dimethyl sulfoxide (8 mL), which
6. stirringhad been stirred at 40° C. for 30 min in advance
7. stirringthe mixture was stirred at 90° C. for 24 hr
8. additionEthyl acetate and water were added to the reaction mixture
9. extractionthe mixture was extracted with ethyl acetate
10. washThe organic layer was washed with saturated brine
11. dry with materialdried over anhydrous magnesium sulfate
12. customThe solvent was evaporated under reduced pressure
13. customThe residue obtained by purification by silica gel column chromatography
14. stirringthe mixture was stirred at room temperature for 5 hr
15. extractionextracted with ethyl acetate
16. washThe organic layer was washed with saturated brine
17. dry with materialdried over anhydrous magnesium sulfate
18. customThe solvent was evaporated under reduced pressure
19. dissolutionthe residue was dissolved in tetrahydrofuran (10 mL)
20. additionTetrabutylammonium fluoride (0.77 mL, 1.0 M tetrahydrofuran solution) was added
21. stirringthe mixture was stirred at 70° C. for 16 hr
22. additionThe reaction mixture was added to 1 M hydrochloric acid
23. extractionthe mixture was extracted with ethyl acetate
24. washThe organic layer was washed with saturated brine
25. dry with materialdried over anhydrous magnesium sulfate
26. customThe solvent was evaporated under reduced pressure
27. customthe residue was purified by silica gel column chromatography

ORD-Eintrag

ord-6eff10ccd5804aafad9a08fb706b4ff7

Quelldatensatz

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08148383B2