Sodium Hydroxide → 5-(5-Isopropyl-2,4-bis-methoxymethoxyphenyl)-4-[4-(4-methylpiperazin-1-ylmethyl)phenyl]-2,4-dihydro-[1,2,4]triazol-3-one

At room temperature, aqueous sodium hydroxide (1.0 M aqueous solution, 5 mL) was added to a dimethylsulfoxide (5 mL) solution of 3-(5-isopropyl-2,4-bis-methoxymethoxyphenyl)-4-[4-(4-methylpiperazin-1-ylmethyl)phenyl]-5-methanesulfonyl-[1,2,4]triazole (F652-08, 1.07 g, 1.86 mmol), and the mixture was heated for 3 hours under reflux. An additional aqueous sodium hydroxide (1.0 M aqueous solution, 5 mL) was added, and the mixture was heated under flux for further 1 hour. After returned to room temperature, the reaction mixture was extracted with ethyl acetate and chloroform. The combined extracts were washed twice with water and then with saturated sodium chloride solution, and dried over anhydrous sodium sulfate, and sodium sulfate was filtered off, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (NH silica, chloroform, methanol) to obtain 5-(5-isopropyl-2,4-bis-methoxymethoxyphenyl)-4-[4-(4-methylpiperazin-1-ylmethyl)phenyl]-2,4-dihydro-[1,2,4]triazol-3-one (F652-09, pale yellow foam, 900 mg, 95%)

1. temperaturethe mixture was heated for 3 hours
2. temperatureunder reflux
3. temperaturethe mixture was heated under flux for further 1 hour
4. customAfter returned to room temperature
5. extractionthe reaction mixture was extracted with ethyl acetate and chloroform
6. washThe combined extracts were washed twice with water
7. dry with materialwith saturated sodium chloride solution, and dried over anhydrous sodium sulfate, and sodium sulfate
8. filtrationwas filtered off
9. distillationthe solvent was distilled off under reduced pressure
10. customThe residue was purified by silica gel column chromatography (NH silica, chloroform, methanol)

ORD-Eintrag

ord-d3b54935804e435686584ddce7e9d109

Quelldatensatz

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08399464B2