Dimethylformamide → HCID 136146790, compound

Temperature

70 °C

To a solution of 4′-{[1-(4-hydroxyphenyl)-2-methyl-6-oxo-4-propyl-1,6-dihydropyrimidin-5-yl]methyl}biphenyl-2-carbonitrile (1.0 g) and 1-iodo-2,2-dimethylpropane (0.92 mL) in N,N-dimethylformamide (10 mL) was added cesium carbonate (1.5 g), and the mixture was stirred at 70° C. for 12 hr. The reaction mixture was allowed to cool to room temperature, ethyl acetate and water were added, 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 and the residue was added to a mixture of hydroxylammonium chloride (1.3 g), sodium hydrogen carbonate (1.9 g) and dimethyl sulfoxide (10 mL), which had been stirred at 40° C. for 30 min, and the mixture was stirred at 90° C. for 18 hr. The mixture was allowed to cool to room temperature, ethyl acetate and water were added to the reaction mixture, and the aqueous layer was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was dissolved in tetrahydrofuran (10 mL). N,N′-carbonyldiimidazole (0.37 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.35 mL) were added, and the mixture was stirred at room temperature for 3 hr. The reaction mixture was diluted with ethyl acetate, washed with 1 M hydrochloric acid and then 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 (0.78 g, 60%).

1. temperatureto cool to room temperature
2. extractionthe mixture was extracted with ethyl acetate
3. washThe organic layer was washed with saturated brine
4. dry with materialdried over anhydrous magnesium sulfate
5. customThe solvent was evaporated
6. additionthe residue was added to a mixture of hydroxylammonium chloride (1.3 g), sodium hydrogen carbonate (1.9 g) and dimethyl sulfoxide (10 mL), which
7. stirringhad been stirred at 40° C. for 30 min
8. stirringthe mixture was stirred at 90° C. for 18 hr
9. temperatureto cool to room temperature
10. additionethyl acetate and water were added to the reaction mixture
11. extractionthe aqueous layer was extracted with ethyl acetate
12. washThe organic layer was washed with saturated brine
13. dry with materialdried over anhydrous magnesium sulfate
14. customThe solvent was evaporated
15. dissolutionthe residue was dissolved in tetrahydrofuran (10 mL)
16. additionN,N′-carbonyldiimidazole (0.37 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.35 mL) were added
17. stirringthe mixture was stirred at room temperature for 3 hr
18. additionThe reaction mixture was diluted with ethyl acetate
19. washwashed with 1 M hydrochloric acid
20. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
21. customThe solvent was evaporated under reduced pressure
22. customthe residue was purified by silica gel column chromatography

ORD record

ord-80079df4bbef40459dfb1c4f09fb0b51

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07998968B2