Hydroxylamine HCl → HCID 136052354, compound

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), 1-(1-benzofuran-2-yl)-2-bromoethanone (1.0 mL) and N,N-dimethylformamide (20 mL) was added sodium hydride (0.19 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 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 (51.2 g), sodium hydrogencarbonate (1.4 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 tetrahydrofuran (20 mL), N,N′-carbonyldiimidazole (0.33 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.30 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 (5 mL) and ethanol (10 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 preparative HPLC to give the title compound as colorless crystals (0.17 g, 20%).

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. dissolutionThe residue was dissolved in tetrahydrofuran (20 mL)
11. additionN,N′-carbonyldiimidazole (0.33 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.30 mL) were added
12. stirringthe mixture was stirred at room temperature for 2 hr
13. additionThe reaction mixture was diluted with chloroform
14. washwashed successively with saturated aqueous potassium hydrogensulfate solution and saturated brine
15. dry with materialdried over anhydrous magnesium sulfate
16. customThe solvent was evaporated under reduced pressure
17. additionTo the obtained residue were added 20% sulfuric acid (5 mL) and ethanol (10 ml)
18. stirringthe mixture was stirred at 100° C. for 1 hr
19. extractionextracted with chloroform and water
20. washThe chloroform layer was washed with saturated brine
21. dry with materialdried over anhydrous magnesium sulfate
22. customThe solvent was evaporated under reduced pressure
23. customThe obtained residue was purified by preparative HPLC

ORD record

ord-89292066614a4a42a58a8379aa9ca05c

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08501750B2