Sodium Hydroxide → Mubritinib

HRID 352077

反応式

HRID 352077 の反応式
[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.[OH-].[Na+].[N:36]1([CH2:41][CH2:42][CH2:43][CH2:44][C:45]2[CH:50]=[CH:49][C:48](O)=[CH:47][CH:46]=2)[CH:40]=[CH:39][N:38]=[N:37]1>C1COCC1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CO.O>[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:48]3[CH:47]=[CH:46][C:45]([CH2:44][CH2:43][CH2:42][CH2:41][N:36]4[CH:40]=[CH:39][N:38]=[N:37]4)=[CH:50][CH:49]=3)[N:4]=2)=[CH:11][CH:12]=1

参加物

10

反応物 5

HCID 14798Sodium HydroxideHCID 31297Methanesulfonyl chloride2 回HCID 81531Diisopropylethylamine2 回HCID 121094944-(4-[1,2,3]Triazol-1-yl-butyl)phenolHCID 129928474-(hydroxymethyl)-2-[(E)-2-[4-(trifluoromethyl)phenyl]ethenyl]-1,3-oxazole

生成物 1

HCID 6444692Mubritinib収率 89.1%

試薬・触媒・溶媒 4

HCID 74236Tetrabutylammonium Bromide触媒HCID 887Methanol溶媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒3 回

実験手順

The obtained 4-(hydroxymethyl)-2-[(E)-2-[4-(trifluoromethyl)phenyl]ethenyl]-1,3-oxazole (567 g, 2.11 mol) and diisopropylethylamine (340 g, 2.63 mol) were added to THF (3.4 L). A solution of methanesulfonyl chloride (302 g, 2.63 mol) in THF (567 ml) was added dropwise under ice-cooling. The mixture was stirred at the same temperature for 1 hour and diisopropylethylamine (27.3 g, 0.21 mol), methanesulfonyl chloride (24.2 g, 0.21 mol) and THF (57 ml) solution were added. The mixture was stirred under reflux for 1.5 hours. After allowing to cool to room temperature, 15% aqueous sodium hydroxide (1.96 kg, 7.35 mol) was added dropwise. 4-[4-(1H-1,2,3-Triazol-1-yl)butyl]phenol (503 g, 2.32 mol) and tetra(n-butyl) ammonium bromide (68.0 g, 0.21 mol) were added at the same temperature, and the mixture was refluxed for 4 hours under stirring. Water (3.1 L) and methanol (7.4 L) were added dropwise at the same temperature. After allowing to cool to room temperature, the mixture was stirred at the same temperature for 1 hour. The precipitated crystals were collected by filtration, washed with THF/methanol/water (1:1:2) (2.8 L), water (2.8 L) and cold-methanol (2.8 L) 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 (883 g, 1.88 mol, yield 85%).

後処理

  1. temperaturecooling
  2. stirringThe mixture was stirred
  3. temperatureunder reflux for 1.5 hours
  4. temperaturethe mixture was refluxed for 4 hours
  5. stirringunder stirring
  6. temperatureto cool to room temperature
  7. stirringthe mixture was stirred at the same temperature for 1 hour
  8. filtrationThe precipitated crystals were collected by filtration
  9. washwashed with THF/methanol/water (1:1:2) (2.8 L), water (2.8 L)
  10. dry with materialcold-methanol (2.8 L) and dried under reduced pressure

出典と根拠

ORDレコード
ord-252ae74d593c40f89f11f01947237fbe
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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