Dimethyl Sulfoxide → HCID 136052292, compound

To a mixture of 4′-{[6-ethyl-3-{2-[2-(hydroxymethyl)-1H-imidazol-1-yl]ethyl}-2,4-dioxo-3,4-dihydrothieno[2,3-d]pyrimidin-1(2H)-yl]methyl}biphenyl-2-carbonitrile (0.5 g), methyl iodide (0.08 mL) and N,N-dimethylformamide (10 mL) was added 60% sodium hydride (0.047 g), and the mixture was stirred at room temperature for 2 hr. Water was added to the reaction mixture, and the mixture was extracted with methylene chloride. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated. 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 (0.57 g), sodium hydrogencarbonate (0.82 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 ethyl acetate, 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 (15 mL), washed with N,N′-carbonyldiimidazole (0.18 g). Then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.16 mL) was 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 residue was purified by silica gel column chromatography to give the title compound as colorless crystals (0.14 gm, 26%).

1. extractionthe mixture was extracted with methylene chloride
2. washThe organic layer was washed with saturated brine
3. dry with materialdried over anhydrous magnesium sulfate
4. customthe solvent was evaporated
5. customThe residue obtained by silica gel column chromatography
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. washwashed successively with water and saturated brine
9. dry with materialdried over anhydrous magnesium sulfate
10. customThe solvent was evaporated under reduced pressure
11. dissolutionThe residue was dissolved in methylene chloride (15 mL)
12. washwashed with N,N′-carbonyldiimidazole (0.18 g)
13. additionThen 1,8-diazabicyclo[5.4.0]undec-7-ene (0.16 mL) was 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. customThe residue was purified by silica gel column chromatography

ORD record

ord-eb00a686836e4436ba27981bccb5700c

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08501750B2