N-Hydroxyacetamidine → 5-(4-Iodo-2-methoxyphenyl)-3-methyl-1,2,4-oxadiazole

HRID 272700Notes

Reaction equation

HRID 272700 reaction equation
[I:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[C:4]([O:11][CH3:12])[CH:3]=1.CN(C(O[N:21]1N=N[C:23]2C=CC=[N:27][C:22]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.C(=NO)(N)C>CN(C=O)C>[I:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]2[O:8][N:27]=[C:22]([CH3:23])[N:21]=2)=[C:4]([O:11][CH3:12])[CH:3]=1

Participants

7

Reactant 5

HCID 30926N-HydroxyacetamidineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 134507564-Iodo-2-methoxybenzoic acid

Product 1

HCID 692184875-(4-Iodo-2-methoxyphenyl)-3-methyl-1,2,4-oxadiazoleYield 39%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-iodo-2-methoxy benzoic acid (83 mg, 0.3 mmol), HATU (114 mg, 0.3 mmol), DIEA (26 μL, 0.15 mmol), and HOBt (8 mg, 0.06 mmol) in DMF was stirred at room temperature for 5 minutes. Acetamide oxime (22 mg, 0.3 mmol) was added, and reaction was stirred for 30 minutes at room temperature. The reaction was then heated to 110° C. for 16 hours. Cooled to room temperature. Partitioned between ethyl acetate and water. The organic layer was washed with brine, dried (MgSO4), filtered, and concentrated under vacuum. The residue was purified by HPLC to provide 37 mg (39%) of desired product. MS (ESI) m/e 317 (M+H)+, 1H NMR (300 MHz, DMSO-d6): □ 7.70 (d, J=8.14 Hz, 1H), 7.64 (d, J=1.36 Hz, 1H), 7.53 (dd, J=8.31-1.53 Hz, 1H), 3.94 (s, 3H), 2.40 (s, 3H).

Workup

  1. customreaction
  2. stirringwas stirred for 30 minutes at room temperature
  3. temperatureThe reaction was then heated to 110° C. for 16 hours
  4. temperatureCooled to room temperature
  5. customPartitioned between ethyl acetate and water
  6. washThe organic layer was washed with brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated under vacuum
  10. customThe residue was purified by HPLC

Sources & evidence

ORD record
ord-4ce947c228d14b578fb09dc10cdefc76
Source dataset
uspto-grants-2008_11
Patent number
US07456169B2

Reaction notes

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