Hydrochloric Acid → HCID 178484554, compound

HRID 1935722Notes

Reaction equation

HRID 1935722 reaction equation
[Cl-].[Mg+2].[Cl-].[C:4](N1C=CN=C1)([N:6]1[CH:10]=[CH:9]N=[CH:7]1)=O.[C:16]1([CH2:22][CH2:23][C:24]2[NH:25][C:26]3[C:32]([C:33]([OH:35])=O)=[CH:31][CH:30]=[CH:29][C:27]=3[N:28]=2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.Cl.C(=O)(O)[O-:38].[Na+]>CN(C)C(=O)C.O1CCCC1.ClCCl.N1C=CC=CC=1>[CH3:4][N:6]([CH3:7])[C:10](=[O:38])[CH2:9][C:33]([C:32]1[C:26]2[NH:25][C:24]([CH2:23][CH2:22][C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)=[N:28][C:27]=2[CH:29]=[CH:30][CH:31]=1)=[O:35]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 516892Sodium BicarbonateHCID 5360315Magnesium ChlorideHCID 178524248HCID 178524248, compound

Product 1

HCID 178484554HCID 178484554, compound

Reagents, catalysts & solvents 4

HCID 1049PyridineSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent2×

Procedure

Pyridine (0.365 mL) and magnesium chloride (215 mg) were added to dry dichloromethane (2.2 mL) solution of N,N-dimethylacetamide, and the mixture was vigorously stirred at room temperature for 1.5 hours under an atmosphere of argon. Next, a catalytically effective amount of N,N-dimethylaminopyridine and 1,1′-carbonyldiimidazole (134 mg) were added to anhydrous tetrahydrofuran (2 mL) suspension of 2-(2-phenylethyl)benzimidazole-4-carboxylic acid (0.2 g) obtained in Reference Example 3, and the mixture was stirred for 1.5 hours under an atmosphere of argon. The reaction solution was added to the previously prepared N,N-dimethylacetamide suspension of magnesium salt while cooling in an ice bath, and the mixture was stirred at room temperature for 2 hours. This was diluted with ice water and adjusted to pH 1 with 1 N hydrochloric acid while cooling in an ice bath. At the same temperature, this was neutralized with saturated sodium bicarbonate aqueous solution and extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate, and then the solvent was evaporated under a reduced pressure. The resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate) and the desired fraction was concentrated to obtain the title compound as colorless crystal (43 mg).

Workup

  1. customobtained in Reference Example 3
  2. stirringthe mixture was stirred for 1.5 hours under an atmosphere of argon
  3. temperaturewhile cooling in an ice bath
  4. stirringthe mixture was stirred at room temperature for 2 hours
  5. temperaturewhile cooling in an ice bath
  6. extractionextracted with ethyl acetate
  7. washThe organic layer was washed with brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. customthe solvent was evaporated under a reduced pressure
  10. customThe resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate)
  11. concentrationthe desired fraction was concentrated

Sources & evidence

ORD record
ord-8f253081dc8445fd87589970631a26b3
Source dataset
uspto-grants-2002_05
Patent number
US06387938B1

Reaction notes

Loading…