Hydroxylamine HCl → 6-butyl-2-methyl-5-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-3-(2-phenylpropyl)pyrimidin-4(3H)-one

A mixture of 4′-[(4-butyl-2-methyl-6-oxo-1,6-dihydropyrimidin-5-yl)methyl]biphenyl-2-carbonitrile (1 g), sodium hydride (0.17 g) and N,N-dimethylformamide (10 mL) was stirred at room temperature for 10 min, (2-bromo-1-methylethyl)benzene (1.1 g) was added, and the mixture was stirred at 150° C. for 16 hr. The reaction mixture was diluted with ethyl acetate, washed with 5% 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 obtained by silica gel column chromatography was dissolved in dimethyl sulfoxide (5 mL), and added to a mixture of hydroxylammonium chloride (0.28 g), sodium hydrogen carbonate (0.40 g) and dimethyl sulfoxide (20 mL) previously stirred at 40° C. for 30 min. The reaction mixture was stirred at 90° C. for 16 hr, and diluted with ethyl acetate. The mixture was 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 (0.078 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.066 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 and the residue was purified by silica gel column chromatography to give the title compound as a colorless solid (0.12 g, 9%).

1. stirringthe mixture was stirred at 150° C. for 16 hr
2. washwashed with 5% aqueous potassium hydrogen sulfate solution
3. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
4. customThe solvent was evaporated under reduced pressure
5. customThe residue obtained by silica gel column chromatography
6. stirringpreviously stirred at 40° C. for 30 min
7. stirringThe reaction mixture was stirred at 90° C. for 16 hr
8. washThe mixture was washed with water
9. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
10. customThe solvent was evaporated under reduced pressure
11. dissolutionThe residue was dissolved in tetrahydrofuran (20 mL)
12. additionN,N′-carbonyldiimidazole (0.078 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.066 mL) were added
13. stirringthe mixture was stirred at room temperature for 2 hr
14. additionThe reaction mixture was diluted with ethyl acetate
15. washwashed with saturated aqueous potassium hydrogen sulfate solution
16. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
17. customThe solvent was evaporated under reduced pressure
18. customthe residue was purified by silica gel column chromatography

ORD record

ord-b824a0a409d743c6b6cd1378b6e0e575

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07998968B2