1-Bromopropane → Itraconazole Impurity 8

HRID 1164233노트

반응식

HRID 1164233 반응식
[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

참가 물질

5

반응물 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

생성물 1

HCID 13368248Itraconazole Impurity 8수율 65%

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

반응 조건

온도
50 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-46c7565167ca451382304583251d063c
출처 데이터셋
uspto-grants-1983_01
특허 번호
US04368200

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