4-(Trifluoromethyl)phenyl isocyanate → N-(5-{[4-fluoro-3-({[4-(trifluoromethyl)phenyl]carbamoyl}amino)phenyl](methyl)amino}[1,3]thiazolo[5,4-b]pyridin-2-yl)cyclopropanecarboxamide

HRID 2366754ノート

反応式

HRID 2366754 の反応式
[NH2:1][C:2]1[CH:3]=[C:4]([N:9]([CH3:25])[C:10]2[N:15]=[C:14]3[S:16][C:17]([NH:19][C:20]([CH:22]4[CH2:24][CH2:23]4)=[O:21])=[N:18][C:13]3=[CH:12][CH:11]=2)[CH:5]=[CH:6][C:7]=1[F:8].[N:26]([C:29]1[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:31][CH:30]=1)=[C:27]=[O:28]>CN(C)C=O.C(OCC)(=O)C>[F:8][C:7]1[CH:6]=[CH:5][C:4]([N:9]([CH3:25])[C:10]2[N:15]=[C:14]3[S:16][C:17]([NH:19][C:20]([CH:22]4[CH2:23][CH2:24]4)=[O:21])=[N:18][C:13]3=[CH:12][CH:11]=2)=[CH:3][C:2]=1[NH:1][C:27](=[O:28])[NH:26][C:29]1[CH:34]=[CH:33][C:32]([C:35]([F:36])([F:38])[F:37])=[CH:31][CH:30]=1

参加物

5

反応物 2

HCID 737684-(Trifluoromethyl)phenyl isocyanateHCID 86646059N-{5-[(3-amino-4-fluorophenyl)(methyl)amino][1,3]thiazolo[5,4-b]pyridin-2-yl}cyclopropanecarboxamide

生成物 1

HCID 58451248N-(5-{[4-fluoro-3-({[4-(trifluoromethyl)phenyl]carbamoyl}amino)phenyl](methyl)amino}[1,3]thiazolo[5,4-b]pyridin-2-yl)cyclopropanecarboxamide収率 72.3%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

N-{5-[(3-Amino-4-fluorophenyl)(methyl)amino][1,3]thiazolo[5,4-b]pyridin-2-yl}cyclopropanecarboxamide (120 mg, 0.33 mmol) was dissolved in N,N-dimethylformamide (2.0 mL), 1-isocyanato-4-(trifluoromethyl)benzene (58 μL, 0.40 mmol) was added, and the mixture was stirred at room temperature for 12 hr. The reaction mixture was diluted with ethyl acetate (10 mL), and washed successively with saturated aqueous sodium hydrogen carbonate solution (10 ml) and saturated brine (10 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (ethyl acetate/hexane=30/70→100/0), and the obtained solution was concentrated under reduced pressure. The residue was recrystallized from ethyl acetate to give the title compound (130 mg, 71%) as a colorless powder.

後処理

  1. washwashed successively with saturated aqueous sodium hydrogen carbonate solution (10 ml) and saturated brine (10 mL)
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe obtained residue was purified by basic silica gel column chromatography (ethyl acetate/hexane=30/70→100/0)
  5. concentrationthe obtained solution was concentrated under reduced pressure
  6. customThe residue was recrystallized from ethyl acetate

出典と根拠

ORDレコード
ord-de2bf18d7f6c49b38c9a200d61f5b05b
出典データセット
uspto-grants-2014_04
特許番号
US08697874B2

反応ノート

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