Dimethyl Sulfoxide → 3-[2-(3-bromo-4-methoxyphenyl)-2-oxoethyl]-6-ethyl-1-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione

温度

40 °C

A mixture of hydroxylammonium chloride (1.8 g), sodium hydrogencarbonate (2.75 g) and dimethyl sulfoxide (20 mL) was stirred at 40° C. for 30 min, 4′-{[3-[2-(3-bromo-4-methoxyphenyl)-2-oxoethyl]-6-ethyl-2,4-dioxo-3,4-dihydrothieno[2,3-d]pyrimidin-1(2H)-yl]methyl}biphenyl-2-carbonitrile (1 g) was added, and the mixture was stirred at 90° C. for 16 hr. The reaction mixture was 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 (40 mL). N,N′-Carbonyldiimidazole (0.26 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.22 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 dissolved in methylene chloride (50 mL), iodine acid (0.51 g) was added, and the mixture was stirred at room temperature for 16 hr. The reaction mixture was washed successively with water 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 a colorless amorphous solid (0.17 g, 16%).

1. stirringthe mixture was stirred at 90° C. for 16 hr
2. washwashed successively with water and saturated brine
3. dry with materialdried over anhydrous magnesium sulfate
4. customThe solvent was evaporated under reduced pressure
5. customThe residue was purified by silica gel column chromatography
6. dissolutiondissolved in methylene chloride (40 mL)
7. additionN,N′-Carbonyldiimidazole (0.26 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.22 mL) were added
8. stirringthe mixture was stirred at room temperature for 2 hr
9. additionThe reaction mixture was diluted with chloroform
10. washwashed successively with saturated aqueous potassium hydrogensulfate solution and saturated brine
11. dry with materialdried over anhydrous magnesium sulfate
12. customThe solvent was evaporated under reduced pressure
13. dissolutionThe obtained residue was dissolved in methylene chloride (50 mL)
14. additioniodine acid (0.51 g) was added
15. stirringthe mixture was stirred at room temperature for 16 hr
16. washThe reaction mixture was washed successively with water and saturated brine
17. dry with materialdried over anhydrous magnesium sulfate
18. customThe solvent was evaporated under reduced pressure
19. customThe obtained residue was purified by preparative HPLC

ORDレコード

ord-319e1b67b480482da9eeb735a78db342

出典データセット

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08501750B2