Hydroxylamine HCl → 3-[2-(5-chloro-2-thienyl)-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

Temperature

40 °C

A mixture of hydroxylammonium chloride (1.21 g), sodium hydrogencarbonate (1.83 g) and dimethyl sulfoxide (20 mL) was stirred at 40° C. for 30 min, 4′-{[3-[2-(5-chloro-2-thienyl)-2-oxoethyl]-6-ethyl-2,4-dioxo-3,4-dihydrothieno[2,3-d]pyrimidin-1(2H)-yl]methyl}biphenyl-2-carbonitrile (0.79 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 obtained by silica gel column chromatography was dissolved in methylene chloride (20 mL), N,N′-carbonyldiimidazole (0.28 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.24 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 (50 ml). 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 preparative HPLC to give the title compound as colorless crystals (0.32 g, 36%).

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 obtained by silica gel column chromatography
6. stirringthe mixture was stirred at room temperature for 2 hr
7. washwashed successively with saturated aqueous potassium hydrogensulfate solution and saturated brine
8. dry with materialdried over anhydrous magnesium sulfate
9. customThe solvent was evaporated under reduced pressure
10. additionTo the obtained residue were added 20% sulfuric acid (10 mL) and ethanol (50 ml)
11. stirringThe mixture was stirred at 100° C. for 1 hr
12. extractionextracted with chloroform and water
13. washThe chloroform layer was washed with saturated brine
14. dry with materialdried over anhydrous magnesium sulfate
15. customThe solvent was evaporated under reduced pressure
16. customThe obtained residue was purified by preparative HPLC

ORD record

ord-7e9a369418dc4776b6a0a5d6f4a1dfaa

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08501750B2