Bromomethyl 4-methoxyphenyl ketone → HCID 136052310, compound

To a mixture of 4′-[(2,4-dioxo-6-propyl-3,4-dihydrothieno[2,3-d]pyrimidin-1(2H)-yl)methyl]-3′-fluorobiphenyl-2-carbonitrile (1 g), 2-bromo-1-(4-methoxyphenyl)ethanone (0.67 g) and N,N-dimethylformamide (15 mL) was added sodium hydride (0.14 g), and the mixture was stirred at room temperature for 4 hr. The reaction mixture was diluted with ethyl acetate, washed successively with 5% aqueous potassium hydrogensulfate solution and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was dissolved in dimethyl sulfoxide (5 mL), and added to a mixture of hydroxylammonium chloride (1.41 g), sodium hydrogencarbonate (2.13 g) and dimethyl sulfoxide (20 mL), which had been stirred at 40° C. for 30 min in advance. The reaction mixture was stirred at 90° C. for 16 hr, diluted with chloroform, washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was dissolved in methylene chloride (40 mL), N,N′-carbonyldiimidazole (0.33 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.28 mL) were added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with chloroform, washed successively with saturated aqueous potassium hydrogensulfate solution and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. To the obtained residue were added 20% sulfuric acid (10 mL) and ethanol (20 ml), and the mixture was stirred at 100° C. for 1 hr, and extracted with chloroform and water. The chloroform layer was washed with 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 colorless crystals (0.57 g, 53%).

1. washwashed successively with 5% aqueous potassium hydrogensulfate solution and saturated brine
2. dry with materialdried over anhydrous magnesium sulfate
3. customThe solvent was evaporated under reduced pressure
4. dissolutionThe obtained residue was dissolved in dimethyl sulfoxide (5 mL)
5. additionadded to a mixture of hydroxylammonium chloride (1.41 g), sodium hydrogencarbonate (2.13 g) and dimethyl sulfoxide (20 mL), which
6. stirringhad been stirred at 40° C. for 30 min in advance
7. stirringThe reaction mixture was stirred at 90° C. for 16 hr
8. additiondiluted with chloroform
9. washwashed successively with water and saturated brine
10. dry with materialdried over anhydrous magnesium sulfate
11. customThe solvent was evaporated under reduced pressure
12. dissolutionThe residue was dissolved in methylene chloride (40 mL)
13. additionN,N′-carbonyldiimidazole (0.33 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.28 mL) were added
14. stirringthe mixture was stirred at room temperature for 2 hr
15. additionThe reaction mixture was diluted with chloroform
16. washwashed successively with saturated aqueous potassium hydrogensulfate solution and saturated brine
17. dry with materialdried over anhydrous magnesium sulfate
18. customThe solvent was evaporated under reduced pressure
19. additionTo the obtained residue were added 20% sulfuric acid (10 mL) and ethanol (20 ml)
20. stirringthe mixture was stirred at 100° C. for 1 hr
21. extractionextracted with chloroform and water
22. washThe chloroform layer was washed with saturated brine
23. dry with materialdried over anhydrous magnesium sulfate
24. customThe solvent was evaporated under reduced pressure
25. customThe obtained residue was purified by silica gel column chromatography

ORD record

ord-c3b0d4e000d74831949aca79e410ba3a

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08501750B2