Hydrochloric Acid → HCID 178472187, compound

HRID 1935725Notes

Reaction equation

HRID 1935725 reaction equation
[Cl-].[Mg+2].[Cl-].C(C(C([O-])=O)C([O-])=O)C.[K+].[K+].C1N=CN(C(N2C=NC=C2)=O)C=1.[CH3:27][O:28][C:29]1[CH:30]=[C:31](C(O)=O)[C:32]2[NH:36][C:35]([CH2:37][CH2:38][C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)=[N:34][C:33]=2[CH:45]=1.[Mg+2].[C:50]([O:56][CH2:57][CH3:58])(=[O:55])[CH2:51][C:52]([O-])=[O:53].C(OC(=O)CC([O-])=O)C.Cl.C(=O)(O)[O-].[Na+]>O.O1CCCC1.C(#N)C.C(N(CC)CC)C>[CH3:27][O:28][C:29]1[CH:30]=[C:31]([C:52](=[O:53])[CH2:51][C:50]([O:56][CH2:57][CH3:58])=[O:55])[C:32]2[NH:36][C:35]([CH2:37][CH2:38][C:39]3[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=3)=[N:34][C:33]=2[CH:45]=1

Participants

12

Reactant 7

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 516892Sodium BicarbonateHCID 5360315Magnesium ChlorideHCID 11066066CID 11066066HCID 86617294Potassium ethylmalonateHCID 178492732HCID 178492732, compound

Product 1

HCID 178472187HCID 178472187, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

Triethylamine (1.3 mL) and magnesium chloride (1.06 g) were added to anhydrous acetonitrile (15 mL) suspension of potassium ethylmalonate (1.58 g), and the mixture was vigorously stirred at room temperature for 18 hours under an atmosphere of argon. Next, a catalytically effective amount of N,N-dimethylaminopyridine and N,N-carbonyldiimidazole (663 mg) were added to anhydrous tetrahydrofuran (12 mL) suspension of 6-methoxy-2-(2-phenylethyl)benzimidazole-4-carboxylic acid (1.1 g) obtained in Reference Example 21, and the mixture was stirred for 2 hours under an atmosphere of argon. The reaction solution was added to the previously prepared suspension of ethyl malonate magnesium salt while cooling in an ice bath, and the mixture was stirred at room temperature for 2 hours. While cooling in an ice bath, this was diluted with water and adjusted to pH 1 with 4 N hydrochloric acid. At the same temperature, this was adjusted to pH 7 to 8 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 crystal (620 mg).

Workup

  1. customobtained in Reference Example 21
  2. stirringthe mixture was stirred for 2 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-2c9b7994f17e45e6a655c8e265269a04
Source dataset
uspto-grants-2002_05
Patent number
US06387938B1

Reaction notes

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