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

HRID 2366774Notes

Reaction equation

HRID 2366774 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([NH:9][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:25]([C:28]1[CH:33]=[CH:32][C:31]([O:34][C:35]([F:38])([F:37])[F:36])=[CH:30][CH:29]=1)=[C:26]=[O:27]>N1C=CC=CC=1.C(OCC)(=O)C>[F:8][C:7]1[CH:6]=[CH:5][C:4]([NH:9][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:26](=[O:27])[NH:25][C:28]1[CH:33]=[CH:32][C:31]([O:34][C:35]([F:36])([F:38])[F:37])=[CH:30][CH:29]=1

Participants

5

Reactant 2

HCID 92298p-(Trifluoromethoxy)phenyl isocyanateHCID 86646062N-{5-[(3-amino-4-fluorophenyl)amino][1,3]thiazolo[5,4-b]pyridin-2-yl)cyclopropanecarboxamide

Product 1

HCID 58451264N-(5-{[4-fluoro-3-({[4-(trifluoromethoxy)phenyl]carbamoyl}amino)phenyl]amino}[1,3]thiazolo[5,4-b]pyridin-2-yl)cyclopropanecarboxamideYield 45.7%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

N-{5-[(3-Amino-4-fluorophenyl)amino][1,3]thiazolo[5,4-b]pyridin-2-yl}cyclopropanecarboxamide (200 mg, 0.58 mmol) was dissolved in pyridine (3.0 mL), 1-isocyanato-4-(trifluoromethoxy)benzene (132 μL, 0.88 mmol) was added, and the mixture was stirred at 70° C. for 8 hr. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (10 mL) and washed successively with water (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=5/95→50/50), and the obtained solution was concentrated under reduced pressure. The residue was recrystallized from ethyl acetate to give the title compound (145 mg, 45%) as a colorless powder.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washwashed successively with water (10 mL) and saturated brine (10 mL)
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe obtained residue was purified by basic silica gel column chromatography (ethyl acetate/hexane=5/95→50/50)
  6. concentrationthe obtained solution was concentrated under reduced pressure
  7. customThe residue was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-d0ed4985d5e24752a5b6aeb176fbb6e7
Source dataset
uspto-grants-2014_04
Patent number
US08697874B2

Reaction notes

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