反应详情

To a mixture of 4′-[(6-ethyl-2,4-dioxo-3,4-dihydrothieno[2,3-d]pyrimidin-1(2H)-yl)methyl]biphenyl-2-carbonitrile (1.5 g), 2-bromo-1-(4-ethoxyphenyl)ethanone (1.14 g) and N,N-dimethylformamide (30 mL) was added sodium hydride (0.19 g), and the mixture was stirred at room temperature for 1 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 residue obtained by silica gel column chromatography was dissolved in dimethyl sulfoxide (5 mL), and the mixture was added to a mixture of hydroxylammonium chloride (1 g), sodium hydrogencarbonate (1.15 g) and dimethyl sulfoxide (10 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 purified by silica gel column chromatography and dissolved in methylene chloride (20 mL). N,N′-Carbonyldiimidazole (0.3 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.25 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. The obtained residue was purified by preparative HPLC to give the title compound as colorless crystals (0.38 g, 16%).

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. customThe residue obtained by silica gel column chromatography
5. stirringhad been stirred at 40° C. for 30 min in advance
6. stirringThe reaction mixture was stirred at 90° C. for 16 hr
7. washwashed successively with water and saturated brine
8. dry with materialdried over anhydrous magnesium sulfate
9. customThe solvent was evaporated under reduced pressure
10. customThe residue was purified by silica gel column chromatography
11. dissolutiondissolved in methylene chloride (20 mL)
12. additionN,N′-Carbonyldiimidazole (0.3 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.25 mL) were added
13. stirringthe mixture was stirred at room temperature for 2 hr
14. additionThe reaction mixture was diluted with chloroform
15. washwashed successively with saturated aqueous potassium hydrogensulfate solution and saturated brine
16. dry with materialdried over anhydrous magnesium sulfate
17. customThe solvent was evaporated under reduced pressure
18. customThe obtained residue was purified by preparative HPLC