Dimethyl Sulfoxide → HCID 136052343, compound

Temperature

50 °C

A mixture of hydroxylammonium chloride (0.83 g), sodium hydrogencarbonate (1.26 g) and dimethyl sulfoxide (8 mL) was stirred at 50° C. for 30 min, 4′-{[3-(3,3-dimethyl-2-oxo-4-{[(1,1,2,2-tetramethylpropyl)silyl]oxy}butyl)-6-ethyl-2,4-dioxo-3,4-dihydrothieno[2,3-d]pyrimidin-1(2H)-yl]methyl}biphenyl-2-carbonitrile (0.92 g) was added, and the mixture was stirred at 90° C. for 20 hr. After allowing to cool to room temperature, ethyl acetate and water were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography and dissolved in tetrahydrofuran (8 ml). N,N′-Carbonyldiimidazole (0.29 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.27 mL) were added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, washed successively with 1N hydrochloric acid and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was dissolved in tetrahydrofuran (7 mL), tetrabutylammonium fluoride (0.51 g) was added, and the mixture was stirred at room temperature for 3 hr. To the reaction mixture were added ethyl acetate and water, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the title compound as a colorless amorphous solid (0.21 g, 25%).

1. stirringthe mixture was stirred at 90° C. for 20 hr
2. temperatureto cool to room temperature
3. extractionthe mixture was extracted with ethyl acetate
4. washThe organic layer was washed successively with water and saturated brine
5. dry with materialdried over anhydrous magnesium sulfate
6. customThe solvent was evaporated under reduced pressure
7. customThe residue was purified by silica gel column chromatography
8. dissolutiondissolved in tetrahydrofuran (8 ml)
9. additionN,N′-Carbonyldiimidazole (0.29 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.27 mL) were added
10. stirringthe mixture was stirred at room temperature for 2 hr
11. additionThe reaction mixture was diluted with ethyl acetate
12. washwashed successively with 1N hydrochloric acid and saturated brine
13. dry with materialdried over anhydrous magnesium sulfate
14. customThe solvent was evaporated under reduced pressure
15. dissolutionThe residue was dissolved in tetrahydrofuran (7 mL)
16. additiontetrabutylammonium fluoride (0.51 g) was added
17. stirringthe mixture was stirred at room temperature for 3 hr
18. additionTo the reaction mixture were added ethyl acetate and water
19. extractionthe mixture was extracted with ethyl acetate
20. washThe organic layer was washed successively with water and saturated brine
21. dry with materialdried over anhydrous magnesium sulfate
22. customThe solvent was evaporated under reduced pressure
23. customThe obtained residue was purified by silica gel column chromatography

ORD record

ord-f2691e5c09af4a3fa0272ba808ef82d2

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08501750B2