1-Phenyl-1,2-propanedione → 3-(5-methyl-4-phenyl-1H-imidazol-2-yl)-3,4-dihydro-1H-isoquinoline

HRID 1823931Notes

Reaction equation

HRID 1823931 reaction equation
C(OC([N:8]1[CH:17]([CH:18]=O)[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9]1)=O)(C)(C)C.[C:20]1([C:26](=O)[C:27](=O)[CH3:28])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C([O-])(=O)C.[NH4+:35].[NH4+:36].[OH-]>CC(O)=O>[CH3:28][C:27]1[NH:36][C:18]([CH:17]2[CH2:16][C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH2:9][NH:8]2)=[N:35][C:26]=1[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

6

Reactant 4

HCID 113631-Phenyl-1,2-propanedioneHCID 14923Ammonium HydroxideHCID 517165Ammonium AcetateHCID 12190329tert-Butyl 3-formyl-3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 219141423-(5-methyl-4-phenyl-1H-imidazol-2-yl)-3,4-dihydro-1H-isoquinoline

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

3-Formyl-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (1.83 g, 7 mmol) was combined with AcOH (25 mL) to which was immediately added 1-phenyl-propane-1,2-dione (3.11 g, 21 mmol) and NH4OAc (13.49 g, 175 mmol). The reaction mixture was then placed on a steam bath and heated under an argon atmosphere for 20 minutes. The reaction mixture was cooled in an ice bath and then added to an ice slurry (44 g). The resulting mixture was basified by addition of concentrated NH4OH (50 mL) and then extracted twice with diethyl ether (150 mL each). The combined organic phases were dried over MgSO4, filtered and concentrated to yield crude product. This material was purified by preparative HPLC to yield the title compound as a white solid.

Workup

  1. customThe reaction mixture was then placed on a steam bath
  2. temperatureheated under an argon atmosphere for 20 minutes
  3. temperatureThe reaction mixture was cooled in an ice bath
  4. extractionextracted twice with diethyl ether (150 mL each)
  5. dry with materialThe combined organic phases were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto yield crude product
  9. customThis material was purified by preparative HPLC

Sources & evidence

ORD record
ord-7647c46102f94ab582024f138e0c065e
Source dataset
uspto-grants-2006_05
Patent number
US07041681B2

Reaction notes

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