Diisopropylethylamine → 3-Iodo-4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]benzamide

HRID 706837Notes

Reaction equation

HRID 706837 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.CCN(C(C)C)C(C)C.[CH3:21][C:22]1[N:23]=[CH:24][N:25]([C:27]2[CH:28]=[C:29]([CH:31]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:33]=2)[NH2:30])[CH:26]=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:30][C:29]1[CH:31]=[C:32]([C:34]([F:35])([F:36])[F:37])[CH:33]=[C:27]([N:25]2[CH:26]=[C:22]([CH3:21])[N:23]=[CH:24]2)[CH:28]=1)=[O:7]

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 6216403-Iodo-4-methylbenzoic acidHCID 120028253-(4-Methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)aniline

Product 1

HCID 177521583-Iodo-4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]benzamideYield 84.3%

Reagents, catalysts & solvents 3

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

Procedure

A solution of 3-iodo-4-methylbenzoic acid (1.31 g, 5 mmol) in SOCl2 (10 mL) was refluxed for 2 hrs, then evaporated in vacuo to remove residual SOCl2. The residue was dissolved in 5 mL anhydrous THF and added to a solution of DIPEA (0.77 g, 6 mmol), 3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)aniline (1.21 g, 5 mmol) and DMAP (24 mg) in 10 mL anhydrous THF in dropwise. The result mixture was stirred at rt for 20 hrs, and evaporated in vacuo. To the residue water was added and extracted with EtOAc (50 mL×3) then CH2Cl2. The combined organic layers were evaporated in vacuo to give crude product. The crude product was triturated with CH2Cl2/EtOAc to give the title compound 2.04 g as a colorless solid (84.3%). 1H NMR (300 MHz, DMSO-d6) δ: 10.67 (1 H, s), 8.46 (1 H, d, J=1.5 Hz), 8.27 (1 H, s), 8.21 (1 H, s), 8.14 (1 H, s), 7.93-7.96 (1 H, dd, J=1.5 and 7.5 Hz), 7.74 (1 H, s), 7.50-7.55 (2 H, m), 2.46 (3 H, s), 2.19 (3 H, s). LCMS: m/z [M+H]+ 486.0211.

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 (50 mL×3)
  7. customThe combined organic layers were evaporated in vacuo
  8. customto give crude product
  9. customThe crude product was triturated with CH2Cl2/EtOAc

Sources & evidence

ORD record
ord-ad95506c75e249d2b955733cb18524e6
Source dataset
uspto-grants-2015_11
Patent number
US09174996B2

Reaction notes

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