4-(Trifluoromethyl)phenyl isocyanate → N-{6-[2-chloro-4-fluoro-5-({[4-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-7-cyano-1,3-benzothiazol-2-yl}cyclopropanecarboxamide

HRID 455202Notes

Reaction equation

HRID 455202 reaction equation
[NH2:1][C:2]1[C:3]([F:27])=[CH:4][C:5]([Cl:26])=[C:6]([CH:25]=1)[O:7][C:8]1[CH:22]=[CH:21][C:11]2[N:12]=[C:13]([NH:15][C:16]([CH:18]3[CH2:20][CH2:19]3)=[O:17])[S:14][C:10]=2[C:9]=1[C:23]#[N:24].[N:28]([C:31]1[CH:36]=[CH:35][C:34]([C:37]([F:40])([F:39])[F:38])=[CH:33][CH:32]=1)=[C:29]=[O:30]>CN(C)C=O.C(OCC)(=O)C>[Cl:26][C:5]1[CH:4]=[C:3]([F:27])[C:2]([NH:1][C:29](=[O:30])[NH:28][C:31]2[CH:36]=[CH:35][C:34]([C:37]([F:38])([F:40])[F:39])=[CH:33][CH:32]=2)=[CH:25][C:6]=1[O:7][C:8]1[CH:22]=[CH:21][C:11]2[N:12]=[C:13]([NH:15][C:16]([CH:18]3[CH2:20][CH2:19]3)=[O:17])[S:14][C:10]=2[C:9]=1[C:23]#[N:24]

Participants

5

Reactant 2

HCID 737684-(Trifluoromethyl)phenyl isocyanateHCID 86644692N-[6-(5-amino-2-chloro-4-fluorophenoxy)-7-cyano-1,3-benzothiazol-2-yl]cyclopropanecarboxamide

Product 1

HCID 59454471N-{6-[2-chloro-4-fluoro-5-({[4-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-7-cyano-1,3-benzothiazol-2-yl}cyclopropanecarboxamideYield 52.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

N-[6-(5-Amino-2-chloro-4-fluorophenoxy)-7-cyano-1,3-benzothiazol-2-yl]cyclopropanecarboxamide (150 mg, 0.372 mmol) produced in Example 23(vi) was dissolved in N,N-dimethylformamide (1.5 mL), 1-isocyanato-4-(trifluoromethyl)benzene (69 μL, 0.484 mmol) was added, and the mixture was stirred at room temperature for 12 hr. The reaction mixture was diluted with ethyl acetate (10 mL), washed successively with 5% aqueous sodium hydrogen carbonate solution (5 mL) and saturated brine (5 mL), and dried over anhydrous sodium sulfate. Insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (methanol/ethyl acetate=0/100→5/95), and the obtained solution was concentrated under reduced pressure. The residue was recrystallized from acetone/n-hexane to give the title compound (115 mg, 52%) as a white powder.

Workup

  1. washwashed successively with 5% aqueous sodium hydrogen carbonate solution (5 mL) and saturated brine (5 mL)
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationInsoluble material was filtered off
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe obtained residue was purified by basic silica gel column chromatography (methanol/ethyl acetate=0/100→5/95)
  6. concentrationthe obtained solution was concentrated under reduced pressure
  7. customThe residue was recrystallized from acetone/n-hexane

Sources & evidence

ORD record
ord-a5c0b2429b0b49aab52a15fe751c90e4
Source dataset
uspto-grants-2013_07
Patent number
US08497274B2

Reaction notes

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