Thiophene-3-carboxylic acid → N-(3-Iodo-4-methylphenyl)thiophene-3-carboxamide

HRID 1246018Notes

Reaction equation

HRID 1246018 reaction equation
[S:1]1[CH:5]=[CH:4][C:3]([C:6]([OH:8])=O)=[CH:2]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.[I:43][C:44]1[CH:45]=[C:46]([CH:48]=[CH:49][C:50]=1[CH3:51])[NH2:47].CCN(C(C)C)C(C)C>CN(C=O)C>[I:43][C:44]1[CH:45]=[C:46]([NH:47][C:6]([C:3]2[CH:4]=[CH:5][S:1][CH:2]=2)=[O:8])[CH:48]=[CH:49][C:50]=1[CH3:51]

Participants

7

Reactant 5

HCID 6918Thiophene-3-carboxylic acidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 1188893-Iodo-p-toluidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 21914512N-(3-Iodo-4-methylphenyl)thiophene-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Thiophene-3-carboxylic acid (2.75 g, 21.45 mmol) and HATU (8.15 g, 21.45 mmol) in DMF (25 ml) were stirred at room temperature for 15 mins. HOBT (2.9 g, 21.45 mmol), 3-iodo-4-methylaniline (5.0 g, 21.45 mmol) and DIPEA (11.2 ml, 64.35 mmol) were added and the reaction stirred at room temperature for 16 hrs. The solvent was evaporated under vacuum and the residue partitioned between ethyl acetate (100 ml) and aqueous sodium carbonate (10%, 100 ml). The aqueous layer was extracted with ethyl acetate (50 ml) and the combined organic phases washed with hydrochloric acid (2N, 75 ml), water (75 ml) and brine (75 ml). The organic phase was dried (magnesium sulphate) and absorbed onto silica. The silica was applied to a flash silica column and eluted with cyclohexane/ethyl acetate (4:1). The solvent was evaporated from the product fractions under vacuum to give N-(3-iodo-4-methylphenyl)thiophene-3-amide. LCMS: retention time 3.69 min, MH+ 344. NMR: δH [2H6]-DMSO 10.06,(1H, b), 8.34,(1H, m), 8.29,(1H, d), 7.70,(1H, dd) 7.66,(1H, dd), 7.62,(1H, dd), 7.30,(1H, d), 2.34,(3H, s).

Workup

  1. customThe solvent was evaporated under vacuum
  2. customthe residue partitioned between ethyl acetate (100 ml) and aqueous sodium carbonate (10%, 100 ml)
  3. extractionThe aqueous layer was extracted with ethyl acetate (50 ml)
  4. washthe combined organic phases washed with hydrochloric acid (2N, 75 ml), water (75 ml) and brine (75 ml)
  5. dry with materialThe organic phase was dried (magnesium sulphate)
  6. customabsorbed onto silica
  7. washeluted with cyclohexane/ethyl acetate (4:1)
  8. customThe solvent was evaporated from the product fractions under vacuum

Sources & evidence

ORD record
ord-eeb938be8452489bbf859fc63142a80a
Source dataset
uspto-grants-2006_10
Patent number
US07125898B2

Reaction notes

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