Triethylamine → 3-iodo-4-methyl-N-(4-(4-methyl-1H-imidazol-1-yl)-3(trifluoromethyl)phenyl)benzamide

HRID 535845Notes

Reaction equation

HRID 535845 reaction equation
[I:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH3:11])[C:5]([OH:7])=O.C(N(CC)CC)C.[CH3:19][C:20]1[N:21]=[CH:22][N:23]([C:25]2[CH:31]=[CH:30][C:28]([NH2:29])=[CH:27][C:26]=2[C:32]([F:35])([F:34])[F:33])[CH:24]=1>O=S(Cl)Cl.CN(C1C=CN=CC=1)C.C1COCC1>[I:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH3:11])[C:5]([NH:29][C:28]1[CH:30]=[CH:31][C:25]([N:23]2[CH:24]=[C:20]([CH3:19])[N:21]=[CH:22]2)=[C:26]([C:32]([F:35])([F:34])[F:33])[CH:27]=1)=[O:7]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 6216403-Iodo-4-methylbenzoic acidHCID 587242804-(4-Methyl-1H-imidazol-1-yl)-3-(trifluoromethyl)aniline

Product 1

HCID 867095623-iodo-4-methyl-N-(4-(4-methyl-1H-imidazol-1-yl)-3(trifluoromethyl)phenyl)benzamideYield 72.2%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolventHCID 24386Thionyl ChlorideSolvent

Procedure

A solution of 3-iodo-4-methylbenzoic acid (0.26 g, 1 mmol) in SOCl2 (5 mL) was refluxed for 3 hrs, then evaporated in vacuo to remove residual SOCl2. The residue was dissolved in 5 mL anhydrous THF and added to a solution of triethylamine (0.12 g, 1 mmol), 4-(4-methyl-1H-imidazol-1-yl)-3-(trifluoromethyl)aniline (0.24 g, 1 mmol) and DMAP (12 mg) in 5 mL anhydrous THF in dropwise. The result mixture was stirred at rt for 40 hrs, and evaporated in vacuo. To the residue water was added and extracted with EtOAc (20 mL×3), the organic layer was washed with brine, dried with Na2SO4, after filtration, the filtrate was purified by chromatography on silica gel (CH2Cl2/CH3OH 97:3) to give 0.4 g crude product. The crude product was triturated with PE/EtOAc to give the title compound 0.35 g as pale yellow solid (72.2%). 1H NMR (300 MHz, CDCl3) δ: 8.91 (1H, s), 8.37 (1H, s), 8.08-8.12 (2H, m), 7.86-7.83 (1H, d, J=8.4 Hz), 7.54 (1H, s), 7.34-7.36 (2H, m), 6.84 (1H, s), 2.50 (3H, s), 2.29 (3H, s). LCMS: m/z [M+H]+ 486.0493.

Workup

  1. customevaporated in vacuo
  2. customto remove residual SOCl2
  3. dissolutionThe residue was dissolved in 5 mL anhydrous THF
  4. customevaporated in vacuo
  5. additionTo the residue water was added
  6. extractionextracted with EtOAc (20 mL×3)
  7. washthe organic layer was washed with brine
  8. dry with materialdried with Na2SO4
  9. filtrationafter filtration
  10. customthe filtrate was purified by chromatography on silica gel (CH2Cl2/CH3OH 97:3)
  11. customto give 0.4 g crude product
  12. customThe crude product was triturated with PE/EtOAc

Sources & evidence

ORD record
ord-f588a35259d141b4a5429b12f07cb2b1
Source dataset
uspto-grants-2014_10
Patent number
US08859553B2

Reaction notes

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