2,6-Lutidine → HCID 136146713, compound

To a solution of 4′-{[2-ethyl-1-(4-{[4-(hydroxymethyl)cyclohexyl]oxy}phenyl)-6-oxo-4-propyl-1,6-dihydropyrimidin-5-yl]methyl}biphenyl-2-carbonitrile (0.4 g) and 2,6-lutidine (0.25 mL) in dichloromethane (6 mL) was added tert-butyl(dimethyl)silyl trifluoromethanesulfonate (0.33 mL) under ice-cooling, and the mixture was stirred for 1 hr. The reaction mixture was diluted with ethyl acetate, washed with 1 M hydrochloric acid and then with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was dissolved in dimethyl sulfoxide (6 mL), hydroxylammonium chloride (0.85 g) and sodium hydrogen carbonate (1.2 g) were added, and the mixture was stirred at 90° C. for 24 hr. The mixture was allowed to cool to room temperature, water was added to the reaction mixture, and the precipitated solid was collected by filtration. The obtained solid was dissolved in ethyl acetate. The solution was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated and the residue was dissolved in tetrahydrofuran (8 mL). N,N′-carbonyldiimidazole (0.17 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.16 mL) were added, and the mixture was stirred at room temperature for 30 min. The reaction mixture was diluted with ethyl acetate, washed with 1 M hydrochloric acid and then with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was dissolved in tetrahydrofuran (5 mL), tetrabutylammonium fluoride (1.6 mL, 1.0 M tetrahydrofuran solution) was added, and the mixture was stirred for 2 hr. The reaction mixture was diluted with ethyl acetate, washed with 1 M hydrochloric acid and saturated brine, and dried over anhydrous sodium 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 (0.26 g, 77%).

1. temperaturecooling
2. washwashed with 1 M hydrochloric acid
3. dry with materialwith saturated brine, and dried over anhydrous sodium sulfate
4. customThe solvent was evaporated under reduced pressure
5. dissolutionThe residue was dissolved in dimethyl sulfoxide (6 mL)
6. additionhydroxylammonium chloride (0.85 g) and sodium hydrogen carbonate (1.2 g) were added
7. stirringthe mixture was stirred at 90° C. for 24 hr
8. additionwater was added to the reaction mixture
9. filtrationthe precipitated solid was collected by filtration
10. dissolutionThe obtained solid was dissolved in ethyl acetate
11. washThe solution was washed with saturated brine
12. dry with materialdried over anhydrous sodium sulfate
13. customThe solvent was evaporated
14. dissolutionthe residue was dissolved in tetrahydrofuran (8 mL)
15. additionN,N′-carbonyldiimidazole (0.17 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.16 mL) were added
16. stirringthe mixture was stirred at room temperature for 30 min
17. additionThe reaction mixture was diluted with ethyl acetate
18. washwashed with 1 M hydrochloric acid
19. dry with materialwith saturated brine, and dried over anhydrous sodium sulfate
20. customThe solvent was evaporated under reduced pressure
21. dissolutionThe residue was dissolved in tetrahydrofuran (5 mL)
22. additiontetrabutylammonium fluoride (1.6 mL, 1.0 M tetrahydrofuran solution) was added
23. stirringthe mixture was stirred for 2 hr
24. additionThe reaction mixture was diluted with ethyl acetate
25. washwashed with 1 M hydrochloric acid and saturated brine
26. dry with materialdried over anhydrous sodium sulfate
27. customThe solvent was evaporated under reduced pressure
28. customthe residue was purified by silica gel column chromatography

ORD record

ord-466e548fa3f0458a9ffad30336106552

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07998968B2