1,3-Dichloroacetone → Mubritinib

HRID 352081

반응식

HRID 352081 반응식
[F:1][C:2]([F:15])([F:14])[C:3]1[CH:8]=[CH:7][C:6](/[CH:9]=[CH:10]/[C:11]([NH2:13])=[O:12])=[CH:5][CH:4]=1.Cl[CH2:17][C:18]([CH2:20]Cl)=O.[OH-].[K+].[N:24]1([CH2:29][CH2:30][CH2:31][CH2:32][C:33]2[CH:38]=[CH:37][C:36]([OH:39])=[CH:35][CH:34]=2)[CH:28]=[CH:27][N:26]=[N:25]1>C1(C)C=CC=CC=1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.S(=O)(=O)(O)O.CO.O.C1COCC1>[F:1][C:2]([F:14])([F:15])[C:3]1[CH:4]=[CH:5][C:6](/[CH:9]=[CH:10]/[C:11]2[O:12][CH:17]=[C:18]([CH2:20][O:39][C:36]3[CH:35]=[CH:34][C:33]([CH2:32][CH2:31][CH2:30][CH2:29][N:24]4[CH:28]=[CH:27][N:26]=[N:25]4)=[CH:38][CH:37]=3)[N:13]=2)=[CH:7][CH:8]=1

참가 물질

11

반응물 4

HCID 107931,3-DichloroacetoneHCID 14797Potassium HydroxideHCID 57090144-(Trifluoromethyl)cinnamamideHCID 121094944-(4-[1,2,3]Triazol-1-yl-butyl)phenol

생성물 1

HCID 6444692Mubritinib수율 86%

시약·촉매·용매 6

HCID 1118Sulfuric Acid촉매HCID 74236Tetrabutylammonium Bromide촉매HCID 887Methanol용매HCID 962Water용매HCID 1140Toluene용매2회HCID 8028Tetrahydrofuran용매

실험 절차

(E)-3-(4-(Trifluoromethyl)phenyl)-2-propenamide (4.00 g, 18.59 mmol) and 1,3-dichloroacetone (3.54 g, 27.89 mmol) were added to toluene (14 ml) and the mixture was subjected to refluxing azeotropic dehydration using a Dean-Stark tube for 3 hours. A solution of sulfuric acid (91 mg) in toluene (1 ml) was added at the same temperature and the mixture was further subjected to refluxing azeotropic dehydration for 3.5 hours. The reaction mixture was concentrated under reduced pressure, and THF (20 ml) and tetra(n-butyl) ammonium bromide (428 mg, 1.328 mmol) were added to the residue. 30% Aqueous potassium hydroxide solution (12.42 g, 66.4 mmol) was added dropwise at 20-30° C. and the mixture was stirred at the same temperature for 15 min. 4-[4-(1H-1,2,3-Triazol-1-yl)butyl]phenol (2.89 g, 13.28 mmol) was added and the mixture was refluxed under stirring for 2 hours. Water (13.4 ml) and methanol (20 ml) were added dropwise at the same temperature. After allowing to cool to room temperature and stirring, the mixture was stirred at the same temperature for 1 hour. The precipitated crystals were collected by filtration, washed with cold-methanol (40 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 (5.35 g, 11.42 mmol, yield 86%).

후처리

  1. temperatureto refluxing azeotropic dehydration
  2. customfor 3 hours
  3. temperatureto refluxing azeotropic dehydration for 3.5 hours
  4. additionwere added to the residue
  5. temperaturethe mixture was refluxed
  6. stirringunder stirring for 2 hours
  7. stirringstirring
  8. stirringthe mixture was stirred at the same temperature for 1 hour
  9. filtrationThe precipitated crystals were collected by filtration
  10. washwashed with cold-methanol (40 ml)
  11. customdried under reduced pressure

출처 및 근거

ORD 기록
ord-766109aca46e44f78c7d4237cb507b56
출처 데이터셋
uspto-grants-2004_06
특허 번호
US06743924B2

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