3-Thiophenacetic acid → HCID 86657974, compound

HRID 2366792Notes

Reaction equation

HRID 2366792 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.[S:25]1[CH:29]=[CH:28][C:27]([CH2:30][C:31](O)=[O:32])=[CH:26]1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>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:31](=[O:32])[CH2:30][C:27]1[CH:28]=[CH:29][S:25][CH:26]=1

Participants

6

Reactant 3

HCID 234043-Thiophenacetic 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 86657974HCID 86657974, compoundYield 68%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

N-[5-(3-Amino-4-fluorophenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]cyclopropanecarboxamide (55 mg, 0.16 mmol) produced in Example 16(vi) was dissolved in pyridine (2.0 mL), thiophen-3-ylacetic acid (45 mg, 0.32 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (120 mg, 0.32 mmol) were added, and the mixture was stirred at 80° C. for 12 hr. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (5 mL), and washed successively with 5% aqueous ammonium chloride solution (5 mL), saturated aqueous sodium hydrogen carbonate solution (5 mL) and saturated brine (5 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=40/60→100/0), and the obtained solution was concentrated under reduced pressure. The obtained residue was washed with ethyl acetate/heptane to give the title compound (51 mg, 68%) as a colorless powder.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washwashed successively with 5% aqueous ammonium chloride solution (5 mL), saturated aqueous sodium hydrogen carbonate solution (5 mL) and saturated brine (5 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=40/60→100/0)
  6. concentrationthe obtained solution was concentrated under reduced pressure
  7. washThe obtained residue was washed with ethyl acetate/heptane

Sources & evidence

ORD record
ord-8ac0c155bd7b4f2180020c0973df3a92
Source dataset
uspto-grants-2014_04
Patent number
US08697874B2

Reaction notes

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