Pyridine → HCID 136146888, compound

To a suspension of 4′-[(4-butyl-2-methyl-6-oxo-1,6-dihydropyrimidin-5-yl)methyl]biphenyl-2-carbonitrile (3.0 g), (1-oxo-2,3-dihydro-1H-inden-5-yl)boronic acid (2.87 g), triethylamine (6.0 mL), pyridine (3.0 mL) and molecular sieves 4 A (6.0 g) in tetrahydrofuran (50 mL) was added copper(II) acetate (3.0 g), and the mixture was stirred for 2 days. The reaction mixture was diluted with ethyl acetate and the insoluble material was filtered off through celite. The filtrate was concentrated and the residue was crudely purified by silica gel column chromatography. To a solution of the crudely purified product in ethanol (8 mL) was added sodium tetrahydroboron (0.083 g), and the mixture was stirred for 3 hr. Ethyl acetate and water were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was evaporated. The residue was added to a mixture of hydroxylammonium chloride (0.83 g), sodium hydrogen carbonate (1.2 g) and dimethyl sulfoxide (6 mL) previously stirred at 40° C. for 30 min, and the mixture was stirred at 90° C. for 18 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, and the solvent was evaporated. The residue was dissolved in tetrahydrofuran (10 mL), N,N′-carbonyldiimidazole (0.21 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.20 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 (0.12 g, 18%).

1. filtrationthe insoluble material was filtered off through celite
2. concentrationThe filtrate was concentrated
3. customthe residue was crudely purified by silica gel column chromatography
4. additionTo a solution of the crudely purified product in ethanol (8 mL) was added sodium tetrahydroboron (0.083 g)
5. stirringthe mixture was stirred for 3 hr
6. additionEthyl acetate and water were added to the reaction mixture
7. extractionthe mixture was extracted with ethyl acetate
8. washThe organic layer was washed with saturated brine
9. dry with materialdried over anhydrous magnesium sulfate
10. customthe solvent was evaporated
11. additionThe residue was added to a mixture of hydroxylammonium chloride (0.83 g), sodium hydrogen carbonate (1.2 g) and dimethyl sulfoxide (6 mL)
12. stirringpreviously stirred at 40° C. for 30 min
13. stirringthe mixture was stirred at 90° C. for 18 hr
14. additionethyl acetate and water were added
15. extractionthe mixture was extracted with ethyl acetate
16. washThe organic layer was washed with saturated brine
17. dry with materialdried over anhydrous magnesium sulfate
18. customthe solvent was evaporated
19. dissolutionThe residue was dissolved in tetrahydrofuran (10 mL)
20. additionN,N′-carbonyldiimidazole (0.21 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.20 mL) were added
21. stirringthe mixture was stirred at room temperature for 3 hr
22. additionThe reaction mixture was diluted with ethyl acetate
23. washwashed with 1 M hydrochloric acid
24. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
25. customThe solvent was evaporated under reduced pressure
26. customthe residue was purified by silica gel column chromatography

ORD record

ord-1c5ad3ef11384480a9440cc8c42dff26

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07998968B2