1,3-Dichloroacetone → Mubritinib

HRID 352081

反応式

HRID 352081 の反応式
[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

参加物

11

反応物 4

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

生成物 1

HCID 6444692Mubritinib収率 86%

試薬・触媒・溶媒 6

HCID 1118Sulfuric Acid触媒HCID 74236Tetrabutylammonium Bromide触媒HCID 887Methanol溶媒HCID 962Water溶媒HCID 1140Toluene溶媒2 回HCID 8028Tetrahydrofuran溶媒

実験手順

(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%).

後処理

  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

出典と根拠

ORDレコード
ord-766109aca46e44f78c7d4237cb507b56
出典データセット
uspto-grants-2004_06
特許番号
US06743924B2

関連ノート

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