1-Chloro-2-isocyanato-4-(trifluoromethyl)benzene → HCID 58451286, compound

HRID 2366757Notes

Reaction equation

HRID 2366757 reaction equation
[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].[Cl:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:29][C:28]=1[N:37]=[C:38]=[O:39]>CN(C)C=O.C(OCC)(=O)C>[Cl:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:29][C:28]=1[NH:37][C:38]([NH: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[CH2:23][CH2:24]4)=[O:21])=[N:18][C:13]3=[CH:12][CH:11]=2)[CH:5]=[CH:6][C:7]=1[F:8])=[O:39]

Participants

5

Reactant 2

HCID 27332631-Chloro-2-isocyanato-4-(trifluoromethyl)benzeneHCID 86646059N-{5-[(3-amino-4-fluorophenyl)(methyl)amino][1,3]thiazolo[5,4-b]pyridin-2-yl}cyclopropanecarboxamide

Product 1

HCID 58451286HCID 58451286, compoundYield 78%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

N-{5-[(3-Amino-4-fluorophenyl)(methyl)amino][1,3]thiazolo[5,4-b]pyridin-2-yl}cyclopropanecarboxamide (120 mg, 0.34 mmol) produced in Example 1(x) was dissolved in N,N-dimethylformamide (1.5 mL), 1-chloro-2-isocyanato-4-(trifluoromethyl)benzene (60 μL, 0.40 mmol) was added, and the mixture was stirred at room temperature for 6 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=50/50→100/0), and the obtained solution was concentrated under reduced pressure. The residue was recrystallized from ethyl acetate to give the title compound (152 mg, 78%) as a colorless powder.

Workup

  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=50/50→100/0)
  5. concentrationthe obtained solution was concentrated under reduced pressure
  6. customThe residue was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-7391bccf58fb4397bfb89a0a267a7b38
Source dataset
uspto-grants-2014_04
Patent number
US08697874B2

Reaction notes

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