Tetrahydrofuran → HCID 178438770, compound

Temperature

70 °C

A mixture of 2-(5-{[4-(4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}pyridin-2-yl)benzonitrile (0.42 g), tetrabutylammonium fluoride (1 M tetrahydrofuran solution, 1.1 mL) and tetrahydrofuran (20 mL) was stirred at 70° C. for 16 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 water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was dissolved in acetonitrile (20 mL), 1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one (0.31 g) was added, and the mixture was stirred at room temperature for 3 hr. Saturated aqueous sodium hydrogen carbonate solution and sodium thiosulfate were added to the reaction mixture, and the mixture was stirred at room temperature for 2 hr, 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. The obtained residue was dissolved in tetrahydrofuran (3 mL) and methanol (3 mL), sodium borohydride (0.016 g) was added, and the mixture was stirred at room temperature for 1 hr. After evaporation of the solvent under reduced pressure, the residue was extracted with water and ethyl acetate. The obtained ethyl acetate layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. To a solution (10 mL) of the obtained residue in toluene was added dropwise ethyl diazoacetate (0.14 mL) in the presence of rhodium(I) acetate (0.0012 g) at 80° C., and the mixture was stirred at the same temperature for 1 hr. The reaction mixture was concentrated, and the obtained residue was subjected to silica gel column chromatography to give the title compound as a colorless solid (0.06 g, 15%).

1. extractionthe mixture was extracted with ethyl acetate
2. washThe organic layer was washed with water
3. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
4. customThe solvent was evaporated under reduced pressure
5. dissolutionThe obtained residue was dissolved in acetonitrile (20 mL)
6. addition1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one (0.31 g) was added
7. stirringthe mixture was stirred at room temperature for 3 hr
8. additionSaturated aqueous sodium hydrogen carbonate solution and sodium thiosulfate were added to the reaction mixture
9. stirringthe mixture was stirred at room temperature for 2 hr
10. extractionextracted with ethyl acetate
11. washThe organic layer was washed with saturated brine
12. dry with materialdried over anhydrous magnesium sulfate
13. customThe solvent was evaporated under reduced pressure
14. dissolutionThe obtained residue was dissolved in tetrahydrofuran (3 mL)
15. additionmethanol (3 mL), sodium borohydride (0.016 g) was added
16. stirringthe mixture was stirred at room temperature for 1 hr
17. customAfter evaporation of the solvent under reduced pressure
18. extractionthe residue was extracted with water and ethyl acetate
19. washThe obtained ethyl acetate layer was washed with saturated brine
20. dry with materialdried over anhydrous magnesium sulfate
21. customThe solvent was evaporated under reduced pressure
22. additionTo a solution (10 mL) of the obtained residue in toluene was added dropwise ethyl diazoacetate (0.14 mL) in the presence of rhodium(I) acetate (0.0012 g) at 80° C.
23. stirringthe mixture was stirred at the same temperature for 1 hr
24. concentrationThe reaction mixture was concentrated

ORD record

ord-834ca4f5f38a4e2798850b7fb61a6d77

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09115136B2