Sodium Hydroxide → Mubritinib

HRID 352075노트

반응식

HRID 352075 반응식
[OH:1][CH2:2][C:3]1[N:4]=[C:5](/[CH:8]=[CH:9]/[C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=2)[O:6][CH:7]=1.C(N(C(C)C)CC)(C)C.CS(Cl)(=O)=O.[N:34]1([CH2:39][CH2:40][CH2:41][CH2:42][C:43]2[CH:48]=[CH:47][C:46](O)=[CH:45][CH:44]=2)[CH:38]=[CH:37][N:36]=[N:35]1.[OH-].[Na+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCCC1>[F:17][C:16]([F:19])([F:18])[C:13]1[CH:14]=[CH:15][C:10](/[CH:9]=[CH:8]/[C:5]2[O:6][CH:7]=[C:3]([CH2:2][O:1][C:46]3[CH:45]=[CH:44][C:43]([CH2:42][CH2:41][CH2:40][CH2:39][N:34]4[CH:38]=[CH:37][N:36]=[N:35]4)=[CH:48][CH:47]=3)[N:4]=2)=[CH:11][CH:12]=1

참가 물질

8

반응물 5

HCID 14798Sodium HydroxideHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 121094944-(4-[1,2,3]Triazol-1-yl-butyl)phenolHCID 129928474-(hydroxymethyl)-2-[(E)-2-[4-(trifluoromethyl)phenyl]ethenyl]-1,3-oxazole

생성물 1

HCID 6444692Mubritinib수율 92.7%

시약·촉매·용매 2

HCID 74236Tetrabutylammonium Bromide촉매HCID 8028Tetrahydrofuran용매

실험 절차

The obtained 4-(hydroxymethyl)-2-[(E)-2-[4-(trifluoromethyl)phenyl]ethenyl]-1,3-oxazole (1.00 g, 3.71 mmol) and diisopropylethylamine (0.95 mL, 5.44 mmol) were added to THF (tetrahydrofuran) (15 ml). Methanesulfonyl chloride (0.45 mL, 5.81 mmol) was added dropwise under ice-cooling. The mixture was stirred at the same temperature for 1 hour. 4-[4-(1H-1,2,3-Triazol-1-yl)butyl]phenol (900 mg, 4.14 mmol) and tetra(n-butyl)ammonium bromide (60 mg, 0.19 mmol) were added at the same temperature. A 2N aquous sodium hydroxide solution (7.5 mL, 15.0 mmol) was added dropwise at not more than 15° C. and the mixture was stirred with reflux for 1 hour. After allowing to cool to room temperature and stirring, the organic layer was concentrated under reduced pressure. Ethanol (20 ml) was added to the residue, and the mixture was stirred with reflux. Water (20 ml) was added dropwise at the same temperature. After allowing to cool to room temperature and stirring, the mixture was ice-cooled. The precipitated crystals were collected by filtration, washed with water (20 ml) and dried under reduced pressure to give 1-[4-[4-[[2-[(E)-2-[4-(trifluoromethyl)phenyl]ethenyl]-1,3-oxazol-4-yl]methoxy]phenyl]butyl]-1H-1,2,3-triazole (1.61 g, 3.44 mmol, yield 88%).

후처리

  1. temperaturecooling
  2. stirringthe mixture was stirred
  3. temperaturewith reflux for 1 hour
  4. stirringstirring
  5. concentrationthe organic layer was concentrated under reduced pressure
  6. additionEthanol (20 ml) was added to the residue
  7. stirringthe mixture was stirred
  8. temperaturewith reflux
  9. additionWater (20 ml) was added dropwise at the same temperature
  10. temperatureto cool to room temperature
  11. stirringstirring
  12. temperaturecooled
  13. filtrationThe precipitated crystals were collected by filtration
  14. washwashed with water (20 ml)
  15. customdried under reduced pressure

출처 및 근거

ORD 기록
ord-01bca1d1a4d447b7b15e7fd8e294b316
출처 데이터셋
uspto-grants-2004_06
특허 번호
US06743924B2

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