3-(Trifluoromethyl)benzeneacetic acid → HCID 46219899, compound

HRID 2366794Notes

Reaction equation

HRID 2366794 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][C:23]=1[F:24])[O:5][C:6]1[N:11]=[C:10]2[S:12][C:13]([NH:15][C:16]([CH:18]3[CH2:20][CH2:19]3)=[O:17])=[N:14][C:9]2=[CH:8][CH:7]=1.[F:25][C:26]([F:38])([F:37])[C:27]1[CH:28]=[C:29]([CH2:33][C:34](O)=[O:35])[CH:30]=[CH:31][CH:32]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C(=O)C.N1C=CC=CC=1.C(OCC)(=O)C>[F:24][C:23]1[CH:22]=[CH:21][C:4]([O:5][C:6]2[N:11]=[C:10]3[S:12][C:13]([NH:15][C:16]([CH:18]4[CH2:20][CH2:19]4)=[O:17])=[N:14][C:9]3=[CH:8][CH:7]=2)=[CH:3][C:2]=1[NH:1][C:34](=[O:35])[CH2:33][C:29]1[CH:30]=[CH:31][CH:32]=[C:27]([C:26]([F:37])([F:25])[F:38])[CH:28]=1

Participants

7

Reactant 3

HCID 676953-(Trifluoromethyl)benzeneacetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86646022N-[5-(3-amino-4-fluorophenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]cyclopropanecarboxamide

Product 1

HCID 46219899HCID 46219899, compoundYield 34%

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
90 °C

Procedure

N-[5-(3-Amino-4-fluorophenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]cyclopropanecarboxamide (150 mg, 0.44 mmol) produced in Example 16(vi) was dissolved in N,N-dimethylacetamide (3.0 mL)/pyridine (9.0 mL), [3-(trifluoromethyl)phenyl]acetic acid (110 mg, 0.52 mmol) and 0-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (330 mg, 0.65 mmol) were added, and the mixture was stirred at 90° C. for 2 hr. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (27 mL), and washed successively with water (27 mL) and saturated brine (27 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/heptane to give the title compound (78 mg, 34%) as a colorless powder.

Workup

  1. additionwere added
  2. temperatureThe reaction mixture was cooled to room temperature
  3. washwashed successively with water (27 mL) and saturated brine (27 mL)
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained residue was purified by basic silica gel column chromatography (ethyl acetate/hexane=50/50→100/0)
  7. concentrationthe obtained solution was concentrated under reduced pressure
  8. customThe residue was recrystallized from ethyl acetate/heptane

Sources & evidence

ORD record
ord-606a5a6a339340838ce43aeecaa041f3
Source dataset
uspto-grants-2014_04
Patent number
US08697874B2

Reaction notes

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