Cesium carbonate → HCID 136063948, compound

Temperature

130 °C

A mixture of 4′-[(2-methyl-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)methyl]biphenyl-2-carbonitrile (0.8 g), 1-iodo-2,2-dimethylpropane (0.79 mL), cesium carbonate (1.3 g) and N,N-dimethylacetamide (10 mL) was stirred at 130° C. for 2 hr. The reaction mixture was diluted with ethyl acetate, and the mixture was washed with 5% aqueous potassium hydrogensulfate solution and then with 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 (0.38 g), sodium hydrogen carbonate (0.88 g) and dimethyl sulfoxide (10 mL), which had been stirred in advance at 40° C. for 30 min. The reaction mixture was stirred at 90° C. for 16 hr, and diluted with ethyl acetate, and the mixture was washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography, and dissolved in tetrahydrofuran (15 mL). N,N′-Carbonyldiimidazole (0.16 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.14 mL) were added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, and the mixture was washed with saturated aqueous potassium hydrogensulfate solution and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to give the title compound as a colorless solid (0.2 g, 20%).

1. washthe mixture was washed with 5% aqueous potassium hydrogensulfate solution
2. dry with materialwith saturated brine, and dried 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 in advance at 40° C. for 30 min
6. stirringThe reaction mixture was stirred at 90° C. for 16 hr
7. washthe mixture was washed with water
8. dry with materialwith saturated brine, and dried 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 tetrahydrofuran (15 mL)
12. additionN,N′-Carbonyldiimidazole (0.16 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.14 mL) were added
13. stirringthe mixture was stirred at room temperature for 2 hr
14. additionThe reaction mixture was diluted with ethyl acetate
15. washthe mixture was washed with saturated aqueous potassium hydrogensulfate solution
16. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
17. customThe solvent was evaporated under reduced pressure
18. customthe residue was purified by silica gel column chromatography

ORD record

ord-90f240a7709146099f185bff7c6b4429

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08592431B2