Pyridine → HCID 136026878, compound

A mixture of 4′-{[4-(cyclopropylmethyl)-2-methyl-6-oxo-1,6-dihydropyrimidin-5-yl]methyl}biphenyl-2-carbonitrile (1.0 g), (2,3-dihydro-1-benzofuran-5-yl)boronic acid (1.0 g), copper(II) acetate (1.0 g), pyridine (1.0 mL), triethylamine (1.0 mL), molecular sieves 4 A (2.0 g) and dichloromethane (15 mL) was stirred for 6 days. The reaction mixture was diluted with ethyl acetate, and the insoluble material was filtered off. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography. The obtained residue was dissolved in dimethyl sulfoxide (2.5 mL), and added to a mixture of hydroxylammonium chloride (1.8 g), sodium hydrogen carbonate (2.5 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, 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 (50 mL), N,N′-carbonyldiimidazole (0.44 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.41 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 (0.61 g, 46%).

1. filtrationthe insoluble material was filtered off
2. concentrationThe filtrate was concentrated under reduced pressure
3. customthe residue was purified by silica gel column chromatography
4. dissolutionThe obtained residue was dissolved in dimethyl sulfoxide (2.5 mL)
5. additionadded to a mixture of hydroxylammonium chloride (1.8 g), sodium hydrogen carbonate (2.5 g) and dimethyl sulfoxide (10 mL)
6. stirringpreviously stirred at 40° C. for 30 min
7. stirringThe reaction mixture was stirred at 90° C. for 16 hr
8. additiondiluted with ethyl acetate
9. washThe mixture was washed with water
10. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
11. customThe solvent was evaporated under reduced pressure
12. dissolutionThe residue was dissolved in tetrahydrofuran (50 mL)
13. additionN,N′-carbonyldiimidazole (0.44 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.41 mL) were added
14. stirringthe mixture was stirred at room temperature for 2 hr
15. additionThe reaction mixture was diluted with ethyl acetate
16. washwashed with saturated aqueous potassium hydrogen sulfate solution
17. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
18. customThe solvent was evaporated under reduced pressure
19. customthe residue was purified by silica gel column chromatography

ORD record

ord-71dbd83a2d6b4d0985a18294e1e5f79d

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07998968B2