Hydrochloric Acid → HCID 22240026, compound

4,5-Diamino-6-hydroxy-2-mercaptopyrimidine (15.0 g, 94.8 mmol) was dissolved in pyridine (200 mL), to the solution was added pivaloyl chloride (14.0 mL, 0.11 mol, 1.2 equivalents), and then the mixture was stirred at room temperature for 12 hours. After the reaction solution was concentrated, to the residue was added acetone, and the deposited solid (18.5 g, 81%) was collected by filtration. The resulting solid was dissolved in 0.5 mol/L aqueous sodium hydroxide (150 mL), to the solution was added methyl iodide (5.30 mL, 85.1 mmol, 1.1 equivalents), and the mixture was stirred overnight at room temperature. After the reaction mixture was cooled on an ice bath and adjusted to pH 6.5 with 4 mol/L hydrochloric acid, the deposited solid (19.6 g, 99%) was collected by filtration. To the resulting solid was added phosphorus oxychloride (60 mL, 0.643 mol, 8.4 equivalents) and the mixture was refluxed with heating for 5 hours. After the reaction solution was concentrated under reduced pressure and the solvent was azeotroped with toluene, ethyl acetate and saturated aqueous sodium hydrogen carbonate were carefully added to the residue, and then the mixture was stirred at room temperature for 30 minutes. The reaction mixture was extracted with ethyl acetate, the organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate, and then the solvent was evaporated. The residue was purified by silica gel column chromatography (chloroform:methanol=95:5) to obtain the title compound (16.7 g, 90%).

1. concentrationAfter the reaction solution was concentrated, to the residue
2. additionwas added acetone
3. filtrationthe deposited solid (18.5 g, 81%) was collected by filtration
4. dissolutionThe resulting solid was dissolved in 0.5 mol/L aqueous sodium hydroxide (150 mL), to the solution
5. stirringthe mixture was stirred overnight at room temperature
6. temperatureAfter the reaction mixture was cooled on an ice bath
7. filtrationthe deposited solid (19.6 g, 99%) was collected by filtration
8. temperaturethe mixture was refluxed
9. temperaturewith heating for 5 hours
10. concentrationAfter the reaction solution was concentrated under reduced pressure
11. customthe solvent was azeotroped with toluene, ethyl acetate and saturated aqueous sodium hydrogen carbonate
12. additionwere carefully added to the residue
13. stirringthe mixture was stirred at room temperature for 30 minutes
14. extractionThe reaction mixture was extracted with ethyl acetate
15. washthe organic layer was washed with saturated aqueous sodium chloride
16. dry with materialdried over anhydrous sodium sulfate
17. customthe solvent was evaporated
18. customThe residue was purified by silica gel column chromatography (chloroform:methanol=95:5)

ORD record

ord-fa701cd077c247db9bdaf793d5a964c3

Source dataset

uspto-grants-2006_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07005430B2