Iodine → 6-Bromo-2-(4-iodo-2-methoxy-pyridin-3-yl)-4-methyl-1H-benzimidazole

HRID 1793705Notes

Reaction equation

HRID 1793705 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH3:10])[C:5]([NH2:9])=[C:6]([NH2:8])[CH:7]=1.[I:11][C:12]1[CH:17]=[CH:16][N:15]=[C:14]([O:18][CH3:19])[C:13]=1[CH:20]=O.II>CO>[Br:1][C:2]1[CH:3]=[C:4]([CH3:10])[C:5]2[N:9]=[C:20]([C:13]3[C:14]([O:18][CH3:19])=[N:15][CH:16]=[CH:17][C:12]=3[I:11])[NH:8][C:6]=2[CH:7]=1

Participants

5

Reactant 3

HCID 807IodineHCID 15163975-Bromo-3-methylbenzene-1,2-diamineHCID 100383814-Iodo-2-methoxynicotinaldehyde

Product 1

HCID 220213436-Bromo-2-(4-iodo-2-methoxy-pyridin-3-yl)-4-methyl-1H-benzimidazoleYield 46%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent3×

Procedure

To a solution of 5-bromo-3-methyl-1,2-phenylenediamine (4 g, 19.9 mmol) in methanol (80 mL) was added 4-iodo-2-methoxy-pyridine-3-carbaldehyde (5.23 g, 19.9 mmol) in methanol (20 mL) dropwise at 0° C. The resulting slurry was stirred for 30 min at room temperature. Then iodine (2.53 g, 9.95 mmol) in methanol (20 mL) was added via a dropping funnel. After 14 h, the reaction mixture was concentrated in vacuo, diluted with 5% Na2S2O3, and extracted with ethyl acetate. The combined organic layers were washed with water, brine, and dried over Na2SO4. After removal of solvent, the residue was purified by careful flash chromatography (20% EtOAc/hexane) to yield the title compound (4.05 g, 46%) as a yellow foam. 1H NMR (300 MHz, CDCl3) δ 7.86 (1H, d, J=5.31 Hz), 7.53 (1H, d, J=5.3 Hz), 7.26 (2H, broad s), 3.91 (3H, s), 2.63 (3H, s). LCMS (M+H)+ m/z 444 (t=1.39 min.).

Workup

  1. waitAfter 14 h
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. additiondiluted with 5% Na2S2O3
  4. extractionextracted with ethyl acetate
  5. washThe combined organic layers were washed with water, brine
  6. dry with materialdried over Na2SO4
  7. customAfter removal of solvent
  8. customthe residue was purified by careful flash chromatography (20% EtOAc/hexane)

Sources & evidence

ORD record
ord-4b00853eeb464eee89cdc6d5482df125
Source dataset
uspto-grants-2006_07
Patent number
US07081454B2

Reaction notes

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