Trifluoroacetic acid → (2r,5s)-n-(2-Acetyl-4-pyridyl)-4-(4-cyano-3-trifluoromethylphenyl)-2,5-dimethylpiperazine-1-carboxamide

HRID 1838266노트

반응식

HRID 1838266 반응식
FC(F)(F)C(O)=O.C(O[C:13](=[O:24])[NH:14][C:15]1[CH:20]=[CH:19][N:18]=[C:17]([C:21](=[O:23])[CH3:22])[CH:16]=1)(C)(C)C.ClC(OC1C=CC=CC=1)=O.[CH3:35][C@H:36]1[CH2:41][NH:40][C@H:39]([CH3:42])[CH2:38][N:37]1[C:43]1[CH:50]=[CH:49][C:46]([C:47]#[N:48])=[C:45]([C:51]([F:54])([F:53])[F:52])[CH:44]=1>N1C=CC=CC=1.O.C(Cl)(Cl)Cl>[C:21]([C:17]1[CH:16]=[C:15]([NH:14][C:13]([N:40]2[CH2:41][C@H:36]([CH3:35])[N:37]([C:43]3[CH:50]=[CH:49][C:46]([C:47]#[N:48])=[C:45]([C:51]([F:53])([F:52])[F:54])[CH:44]=3)[CH2:38][C@H:39]2[CH3:42])=[O:24])[CH:20]=[CH:19][N:18]=1)(=[O:23])[CH3:22]

참가 물질

8

반응물 4

HCID 6422Trifluoroacetic acidHCID 15891Phenyl chloroformateHCID 11391932trans-4-(2,5-Dimethylpiperazin-1-yl)-2-trifluoromethylbenzonitrileHCID 69108642tert-Butyl (2-acetylpyridin-4-yl)carbamate

생성물 1

HCID 69108626(2r,5s)-n-(2-Acetyl-4-pyridyl)-4-(4-cyano-3-trifluoromethylphenyl)-2,5-dimethylpiperazine-1-carboxamide수율 46.8%

시약·촉매·용매 3

HCID 962Water용매HCID 1049Pyridine용매2회HCID 6212Chloroform용매

실험 절차

While stirring with ice-cooling, 12.5 ml of trifluoroacetic acid was added to 12.5 ml of chloroform solution containing 1.41 g of 2-acetyl-4-pyridinylcarbamic acid t-butyl ester. The mixture was immediately warmed up to room temperature and stirred for 2 hours and 40 minutes. The solvent was evaporated under reduced pressure to obtain a crude amine. This compound was dissolved in 25 ml of pyridine, and the solution was mixed with 0.83 ml of phenyl chloroformate while stirring with ice-cooling and then immediately warmed up to room temperature. After 8 hours and 30 minutes, this was mixed with 10 ml of pyridine solution containing 1.4 g of (2S,5R)-4-(2,5-dimethylpiperazin-1-yl)-2-trifluoromethylbenzonitrile and heated under reflux for 1 hour. The reaction mixture cooled to room temperature was mixed with water and extracted with chloroform. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate, and then the solvent was evaporated under reduced pressure. The residue was purified by a silica gel column chromatography to obtain 1.03 g of the title compound from methanol-chloroform (1:99, v/v) eluate.

후처리

  1. temperaturecooling
  2. stirringstirred for 2 hours and 40 minutes
  3. customThe solvent was evaporated under reduced pressure
  4. customto obtain a crude amine
  5. stirringwhile stirring with ice-
  6. temperaturecooling
  7. temperatureimmediately warmed up to room temperature
  8. temperatureheated
  9. temperatureunder reflux for 1 hour
  10. temperatureThe reaction mixture cooled to room temperature
  11. extractionextracted with chloroform
  12. washThe organic layer was washed with saturated brine
  13. dry with materialdried over anhydrous sodium sulfate
  14. customthe solvent was evaporated under reduced pressure
  15. customThe residue was purified by a silica gel column chromatography

출처 및 근거

ORD 기록
ord-10c8687f646a4311aa64dab58e98542f
출처 데이터셋
uspto-grants-2004_01
특허 번호
US06673799B1

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