2,6-Lutidine → HCID 136026775, compound

Temperature

0 °C

A mixture of 4′-{[4-butyl-1-(2-hydroxy-3,3-dimethylbutyl)-2-methyl-6-oxo-1,6-dihydropyrimidin-5-yl]methyl}biphenyl-2-carbonitrile (0.21 g), tert-butyl(dimethyl)silyl trifluoromethanesulfonate (0.36 mL), 2,6-lutidine (0.16 mL) and tetrahydrofuran (10 mL) was stirred at 0° C. for 3 hr. The reaction mixture was diluted with ethyl acetate, washed with water and then 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 dimethyl sulfoxide (5 mL), and added to a mixture of hydroxylammonium chloride (0.97 g), sodium hydrogen carbonate (1.47 g) and dimethyl sulfoxide (10 mL) previously stirred at 40° C. for 30 min. The reaction mixture was stirred at 90° C. for 16 hr. The mixture was diluted with ethyl acetate, washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was dissolved in tetrahydrofuran (20 mL), N,N′-carbonyldiimidazole (0.14 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.12 mL) were added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, washed with saturated aqueous potassium hydrogen sulfate solution and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was dissolved in tetrahydrofuran (20 mL), tetrabutylammonium fluoride (1.0 M tetrahydrofuran solution, 3.5 mL) was added, and the mixture was stirred at room temperature for 3 hr. The reaction mixture was extracted with 1 M hydrochloric acid and ethyl acetate, and the ethyl acetate 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 colorless amorphous crystals (0.2 g, 55%).

1. washwashed with water
2. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
3. customThe solvent was evaporated under reduced pressure
4. customThe residue obtained by silica gel column chromatography
5. stirringpreviously stirred at 40° C. for 30 min
6. stirringThe reaction mixture was stirred at 90° C. for 16 hr
7. washwashed with water
8. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
9. customThe solvent was evaporated under reduced pressure
10. dissolutionThe residue was dissolved in tetrahydrofuran (20 mL)
11. additionN,N′-carbonyldiimidazole (0.14 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.12 mL) were added
12. stirringthe mixture was stirred at room temperature for 2 hr
13. additionThe reaction mixture was diluted with ethyl acetate
14. washwashed with saturated aqueous potassium hydrogen sulfate solution
15. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
16. customThe solvent was evaporated under reduced pressure
17. dissolutionThe residue was dissolved in tetrahydrofuran (20 mL)
18. additiontetrabutylammonium fluoride (1.0 M tetrahydrofuran solution, 3.5 mL) was added
19. stirringthe mixture was stirred at room temperature for 3 hr
20. extractionThe reaction mixture was extracted with 1 M hydrochloric acid and ethyl acetate
21. washthe ethyl acetate layer was washed with saturated brine
22. dry with materialdried over anhydrous magnesium sulfate
23. customThe solvent was evaporated under reduced pressure
24. customthe residue was purified by silica gel column chromatography

ORD record

ord-ebe621ffb3284b0da94a8b481be57bd1

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07998968B2