1-Bromopropane → Itraconazole Impurity 8

HRID 1154743

Reaktionsgleichung

Reaktionsgleichung von HRID 1154743
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][N:12]([C:15]3[CH:20]=[CH:19][C:18]([N:21]4[CH:25]=[N:24][NH:23][C:22]4=[O:26])=[CH:17][CH:16]=3)[CH2:11][CH2:10]2)=[CH:5][CH:4]=1.[H-].[Na+].Br[CH2:30][CH2:31][CH3:32]>CS(C)=O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:10][CH2:11][N:12]([C:15]3[CH:20]=[CH:19][C:18]([N:21]4[CH:25]=[N:24][N:23]([CH2:30][CH2:31][CH3:32])[C:22]4=[O:26])=[CH:17][CH:16]=3)[CH2:13][CH2:14]2)=[CH:5][CH:4]=1

Komponenten

5

Edukt 3

HCID 78401-BromopropaneHCID 24758Sodium hydrideHCID 42465972,4-Dihydro-4-(4-(4-(4-methoxyphenyl)piperazin-1-yl)phenyl)-3H-1,2,4-triazol-3-one

Produkt 1

HCID 13368248Itraconazole Impurity 8Ausbeute 65 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 679Dimethyl SulfoxideLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

10 Parts of 2,4-dihydro-4-{4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl}-3H-1,2,4-triazol-3-one are dissolved in 300 parts of dimethyl sulfoxide at 100° C. Then there are added 1.6 parts of sodium hydride dispersion 50% and stirring is continued while the mixture is allowed to cool to about 50° C. 3.9 Parts of 1-bromopropane are added and the whole is stirred overnight at room temperature. The reaction mixture is poured onto water and the product is extracted with trichloromethane. The extract is washed with water, dried, filtered and evaporated. The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (98:2 by volume) as eluent. The pure fractions are collected and the eluent is evaporated. The residue is triturated in 2-propanol. The product is filtered off and dried; yielding 7.5 parts (65%) of 2,4-dihydro-4-{4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl}-2-propyl-3H-1,2,4 -triazol-3-one.

Aufarbeitung

  1. stirringthe whole is stirred overnight at room temperature
  2. additionThe reaction mixture is poured onto water
  3. extractionthe product is extracted with trichloromethane
  4. washThe extract is washed with water
  5. customdried
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue is purified by column-chromatography over silica gel using
  9. additiona mixture of trichloromethane and methanol (98:2 by volume) as eluent
  10. customThe pure fractions are collected
  11. customthe eluent is evaporated
  12. customThe residue is triturated in 2-propanol
  13. filtrationThe product is filtered off
  14. customdried

Quellen und Nachweise

ORD-Eintrag
ord-3892382c06fd4adea71bfc5a35e96fe7
Quelldatensatz
uspto-grants-1984_12
Patentnummer
US04490530

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