7-iodo-3-isobutyl-3H-benzoimidazole-5-carboxylic acid methyl ester → 3-Isobutyl-7-(5-methyl-pyridin-2-yl)-3H-benzoimidazole-5-carboxylic acid methyl ester

HRID 446236Notes

Reaction equation

HRID 446236 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:17]=[C:16](I)[C:8]2[N:9]=[CH:10][N:11]([CH2:12][CH:13]([CH3:15])[CH3:14])[C:7]=2[CH:6]=1)=[O:4].[Br-].[CH3:20][C:21]1[CH:22]=[CH:23][C:24]([Zn+])=[N:25][CH:26]=1>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3]([C:5]1[CH:17]=[C:16]([C:24]2[CH:23]=[CH:22][C:21]([CH3:20])=[CH:26][N:25]=2)[C:8]2[N:9]=[CH:10][N:11]([CH2:12][CH:13]([CH3:15])[CH3:14])[C:7]=2[CH:6]=1)=[O:4]

Participants

5

Reactant 2

HCID 596277737-iodo-3-isobutyl-3H-benzoimidazole-5-carboxylic acid methyl esterHCID 178427808HCID 178427808, compound

Product 1

HCID 596277643-Isobutyl-7-(5-methyl-pyridin-2-yl)-3H-benzoimidazole-5-carboxylic acid methyl esterYield 57.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 7-iodo-3-isobutyl-3H-benzoimidazole-5-carboxylic acid methyl ester (400 mg, 1.12 mmol) in THF (4 mL) was added Pd(PPh3)4 (65 mg, 0.056 mmol), followed by 5-methyl-pyridinyl zinc bromide (2.68 mL of 0.5M solution in THF, 1.34 mmol). The reaction mixture was stirred overnight at room temperature, then quenched by addition of saturated aqueous NH4Cl solution. The mixture was partitioned between water and ethyl acetate, and the organic layer was separated, dried over MgSO4, filtered and concentrated under reduced pressure. Purification by column chromatography gave 207 mg (57%) of 3-Isobutyl-7-(5-methyl-pyridin-2-yl)-3H-benzoimidazole-5-carboxylic acid methyl ester.

Workup

  1. customquenched by addition of saturated aqueous NH4Cl solution
  2. customThe mixture was partitioned between water and ethyl acetate
  3. customthe organic layer was separated
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customPurification by column chromatography

Sources & evidence

ORD record
ord-3904f1a2f84f4933b5edd15f24e473d3
Source dataset
uspto-grants-2013_07
Patent number
US08476457B2

Reaction notes

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