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 2366754노트

반응식

HRID 2366754 반응식
[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

참가 물질

5

반응물 2

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

생성물 1

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

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-de2bf18d7f6c49b38c9a200d61f5b05b
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08697874B2

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