1-Methylimidazole → N-Methyl-5-(1-methyl-1H-imidazol-2-yl)-N-propyl-isophthalamic acid methyl ester

HRID 732548Notes

Reaction equation

HRID 732548 reaction equation
C([Li])CCC.[CH3:6][N:7]1[CH:11]=[CH:10][N:9]=[CH:8]1.[CH3:12][O:13][C:14](=[O:29])[C:15]1[CH:27]=[C:26](I)[CH:25]=[C:17]([C:18]([N:20]([CH3:24])[CH2:21][CH2:22][CH3:23])=[O:19])[CH:16]=1>C1COCC1.[Cl-].[Zn+2].[Cl-].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:12][O:13][C:14](=[O:29])[C:15]1[CH:27]=[C:26]([C:8]2[N:7]([CH3:6])[CH:11]=[CH:10][N:9]=2)[CH:25]=[C:17]([C:18]([N:20]([CH3:24])[CH2:21][CH2:22][CH3:23])=[O:19])[CH:16]=1

Participants

7

Reactant 3

HCID 13901-MethylimidazoleHCID 21086185Methyl 3-iodo-5-{[methyl(propyl)amino]carbonyl}benzoateHCID 178418339Butyllithium

Product 1

HCID 68814383N-Methyl-5-(1-methyl-1H-imidazol-2-yl)-N-propyl-isophthalamic acid methyl ester

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Add n-butyl lithium (2.0 M in pentane, 0.78 mL, 1.55 mmol) dropwise over 30 min to a previously nitrogen-flushed, flame-dried vessel containing 1-methyl-1H-imidazole (0.12 mL, 1.5 mmol) in THF (10 mL) at −78° C., and stir for 30 min at the same temperature. Warm the solution to 0° C. and add dropwise zinc (II) chloride (1.0 M in diethyl ether, 4.5 mL, 4.5 mmol) over 10 min. Stir the mixture at the same temperature for 1 h and at room temperature for 30 min. Add 5-iodo-N-methyl-N-propyl-isophthalamic acid methyl ester (361 mg, 1.0 mmol) and tetrakis(triphenylphosphine)palladium (0) (12 mg) under nitrogen before heating the reaction to reflux for 20 min. Cool to room temperature, concentrate and purify (silica gel chromatography, eluting with 0:100 to 8:92 methanol:dichloromethane) to give the title compound.

Workup

  1. customflushed
  2. customflame-dried vessel
  3. stirringStir the mixture at the same temperature for 1 h
  4. waitat room temperature for 30 min
  5. customthe reaction
  6. temperatureto reflux for 20 min
  7. temperatureCool to room temperature
  8. concentrationconcentrate
  9. custompurify
  10. wash(silica gel chromatography, eluting with 0:100 to 8:92 methanol:dichloromethane)

Sources & evidence

ORD record
ord-9b8d4945412646038107095b0ca1e4ca
Source dataset
uspto-grants-2009_09
Patent number
US07585885B2

Reaction notes

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