Lithium Hydroxide → 2-[(3-bromobenzyl)thio]-1-{3-[methyl(2-pyridin-2-ylethyl)amino]propyl}-1H-benzimidazole-5-carboxylic acid

HRID 1727420Notes

Reaction equation

HRID 1727420 reaction equation
[OH-].[Li+].[Br:3][C:4]1[CH:5]=[C:6]([CH:35]=[CH:36][CH:37]=1)[CH2:7][S:8][C:9]1[N:13]([CH2:14][CH2:15][CH2:16][N:17]([CH3:26])[CH2:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=2)[C:12]2[CH:27]=[CH:28][C:29]([C:31]([O:33]C)=[O:32])=[CH:30][C:11]=2[N:10]=1>O1CCCC1.O>[Br:3][C:4]1[CH:5]=[C:6]([CH:35]=[CH:36][CH:37]=1)[CH2:7][S:8][C:9]1[N:13]([CH2:14][CH2:15][CH2:16][N:17]([CH3:26])[CH2:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=2)[C:12]2[CH:27]=[CH:28][C:29]([C:31]([OH:33])=[O:32])=[CH:30][C:11]=2[N:10]=1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 69026672methyl 2-[(3-bromobenzyl)thio]-1-{3-[methyl(2-pyridin-2-ylethyl)amino]propyl}-1H-benzimidazole-5-carboxylate

Product 1

HCID 690294842-[(3-bromobenzyl)thio]-1-{3-[methyl(2-pyridin-2-ylethyl)amino]propyl}-1H-benzimidazole-5-carboxylic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Lithium hydroxide (0.315 g, 3 eq) is added to a solution of methyl 2-[(3-bromobenzyl)thio]-1-{3-[methyl(2-pyridin-2-ylethyl)amino]propyl}-1H-benzimidazole-5-carboxylate (1.03 g, 1 eq) in a mixture of tetrahydrofuran (10 ml) and water (5 ml). The mixture is heated under reflux for 18 hours then cooled down to ambient temperature and concentrated under reduced pressure at 40° C. Ethyl acetate and water are added to the residue. The mixture is acidified by adding acetic acid to pH 5. After decanting and extracting, the combined organic phases are dried over sodium sulphate and concentrated under reduced pressure. Purification by flash chromatography on silica gel (eluent: dichloromethane/methanol 95/5 to 80/20) produces the expected compound in the form of a foam (0.85 g, 85% yield).

Workup

  1. temperatureThe mixture is heated
  2. temperatureunder reflux for 18 hours
  3. concentrationconcentrated under reduced pressure at 40° C
  4. additionEthyl acetate and water are added to the residue
  5. additionby adding acetic acid to pH 5
  6. customAfter decanting
  7. extractionextracting
  8. dry with materialthe combined organic phases are dried over sodium sulphate
  9. concentrationconcentrated under reduced pressure
  10. customPurification by flash chromatography on silica gel (eluent: dichloromethane/methanol 95/5 to 80/20)

Sources & evidence

ORD record
ord-89e0d6f371504068b9018d12f569d7ca
Source dataset
uspto-grants-2009_02
Patent number
US07495110B2

Reaction notes

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