Hydrochloric Acid → 4-{[(4-tert-Butylcyclohexyl)(1-methyl-1H-benzimidazol-2-yl)amino]methyl}-benzoic acid

HRID 229988Notes

Reaction equation

HRID 229988 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[N:10]([CH2:21][C:22]1[CH:31]=[CH:30][C:25]([C:26]([O:28]C)=[O:27])=[CH:24][CH:23]=1)[CH:11]1[CH2:16][CH2:15][CH:14]([C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:13][CH2:12]1.CI.[H-].[Na+].N1C2C=CC=CC=2N[CH:37]=1.[Li+].[OH-].Cl>C1COCC1.O.CCOC(C)=O.O>[C:17]([CH:14]1[CH2:13][CH2:12][CH:11]([N:10]([CH2:21][C:22]2[CH:23]=[CH:24][C:25]([C:26]([OH:28])=[O:27])=[CH:30][CH:31]=2)[C:2]2[N:1]([CH3:37])[C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[N:3]=2)[CH2:16][CH2:15]1)([CH3:18])([CH3:20])[CH3:19]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 5798BenzimidazoleHCID 6328Methyl iodide2×HCID 24758Sodium hydride2×HCID 68837482Methyl 4-{[1H-benzimidazol-2-yl(4-tert-butylcyclohexyl)amino]methyl}-benzoate

Product 1

HCID 688367154-{[(4-tert-Butylcyclohexyl)(1-methyl-1H-benzimidazol-2-yl)amino]methyl}-benzoic acid

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 22728543Water ethylacetateSolvent

Procedure

To the title compound from Example 1 Step C (0.72 mmol, 300 mg) in 5 mL of THF was added MeI (1 mmol, 67 μL), followed by NaH (1 mmol, 40 mg of 60% dispersion in mineral oil) (exothermic, H2 evolution). After 1 h starting benzimidazole was still present, so the reaction was treated with additional MeI (1 mmol) and NaH (1 mmol). After 1 h the reaction was complete (HPLC A: 2.38). The mixture was concentrated under reduced pressure and the residue was taken up in 6 mL of dioxane. A solution of LiOH (7 mmol, 172 mg) in 2 mL of H2O was added and the resulting mixture was stirred at ambient temperature overnight. The mixture was poured into EtOAc/H2O, and acidified with 2 N HCl until two clear layers formed after agitation. The organic layer was collected and the aqueous layer was washed with EtOAc. The combined organic phase was dried with MgSO4 and concentrated under reduced pressure affording product as a yellow solid. MS (ESI): m/z 420 (M+H). HPLC A: 2.09 min.

Workup

  1. waitAfter 1 h the reaction was complete
  2. concentrationThe mixture was concentrated under reduced pressure
  3. customformed after agitation
  4. customThe organic layer was collected
  5. washthe aqueous layer was washed with EtOAc
  6. dry with materialThe combined organic phase was dried with MgSO4
  7. concentrationconcentrated under reduced pressure
  8. customaffording product as a yellow solid
  9. custom2.09 min.

Sources & evidence

ORD record
ord-604a2c314b76461187b33ca9300a5c97
Source dataset
uspto-grants-2009_07
Patent number
US07563815B2

Reaction notes

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