Sodium Iodide → 2-Butyl-4-chloro-1-[[1-(2-cyanophenyl)-1H-indol-4-yl]methyl]-1H-imidazole-5-carboxylic acid, 2-methyl-1-(2,2-dimethyl-1-oxopropoxy)propyl ester

HRID 1492488Notes

Reaction equation

HRID 1492488 reaction equation
[CH2:1]([C:5]1[N:6]([CH2:14][C:15]2[CH:23]=[CH:22][CH:21]=[C:20]3[C:16]=2[CH:17]=[CH:18][N:19]3[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[C:30]#[N:31])[C:7]([C:11]([OH:13])=[O:12])=[C:8]([Cl:10])[N:9]=1)[CH2:2][CH2:3][CH3:4].[I-].[Na+].[C:34](=[O:37])([O-])[O-:35].[Cs+].[Cs+]>CN(C)C=O.C(OCC)(=O)C>[CH2:1]([C:5]1[N:6]([CH2:14][C:15]2[CH:23]=[CH:22][CH:21]=[C:20]3[C:16]=2[CH:17]=[CH:18][N:19]3[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[C:30]#[N:31])[C:7]([C:11]([O:13][CH:14]([O:35][C:34](=[O:37])[C:25]([CH3:30])([CH3:26])[CH3:24])[CH:15]([CH3:23])[CH3:16])=[O:12])=[C:8]([Cl:10])[N:9]=1)[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 3

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 189503772-butyl-4-chloro-1-[[1-(2-cyanophenyl)-1H-indol-4-yl]methyl]-1H-imidazole-5-carboxylic acid

Product 1

HCID 571238372-Butyl-4-chloro-1-[[1-(2-cyanophenyl)-1H-indol-4-yl]methyl]-1H-imidazole-5-carboxylic acid, 2-methyl-1-(2,2-dimethyl-1-oxopropoxy)propyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture containing 2-butyl-4-chloro-1-[[1-(2-cyanophenyl)-1H-indol-4-yl]methyl]-1H-imidazole-5-carboxylic acid (550 mg, 1.27 mmol, prepared as described in part C of Example 9), the title A compound (979 mg, 5.08 mmol), sodium iodide (381 mg, 2.54 mmol) and cesium carbonate (1.86 g, 5.72 mmol) in 2.5 mL of dimethylformamide was heated at 60° C. for 7 hours in a stoppered flask. Upon cooling the reaction mixture was diluted with 110 mL of ethyl acetate and filtered. The organic extract was rinsed with three 15 mL portions of pH 4 buffer, 20 mL of 1:1, water:brine and 30 mL of brine, then dried over anhydrous magnesium sulfate and concentrated in vacuo to afford 1.3 g of crude product. Chromatography on 75 g of silica gel eluted with 4:1, hexanes:ethyl acetate yielded 567 mg of the title B compound.

Workup

  1. temperatureUpon cooling the reaction mixture
  2. filtrationfiltered
  3. extractionThe organic extract
  4. washwas rinsed with three 15 mL portions of pH 4 buffer
  5. dry with material20 mL of 1:1, water:brine and 30 mL of brine, then dried over anhydrous magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customto afford 1.3 g of crude product
  8. washChromatography on 75 g of silica gel eluted with 4:1, hexanes
  9. customethyl acetate yielded 567 mg of the title B compound

Sources & evidence

ORD record
ord-62c8f80142ac4dfaa26a5d452acc05b9
Source dataset
uspto-grants-1994_12
Patent number
US05374615

Reaction notes

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