Piperazine → HCID 22721176, compound

HRID 1582490Notes

Reaction equation

HRID 1582490 reaction equation
[C:1](Cl)(Cl)=[O:2].[Cl:5][C:6]1[CH:11]=[CH:10][C:9]([CH:12]2[CH:16]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=3)[NH:15][C:14]([C:24]3[C:29]([O:30][CH3:31])=[CH:28][CH:27]=[CH:26][C:25]=3[O:32][CH2:33][CH3:34])=[N:13]2)=[CH:8][CH:7]=1.C(N(CC)CC)C.[NH:42]1[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]1>C1COCC1.C(Cl)Cl.C(=O)(O)[O-].[Na+]>[Cl:5][C:6]1[CH:7]=[CH:8][C:9]([CH:12]2[CH:16]([C:17]3[CH:18]=[CH:19][C:20]([Cl:23])=[CH:21][CH:22]=3)[N:15]([C:1]([N:42]3[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]3)=[O:2])[C:14]([C:24]3[C:29]([O:30][CH3:31])=[CH:28][CH:27]=[CH:26][C:25]=3[O:32][CH2:33][CH3:34])=[N:13]2)=[CH:10][CH:11]=1

Participants

8

Reactant 4

HCID 4837PiperazineHCID 6371PhosgeneHCID 8471TriethylamineHCID 22720977HCID 22720977, compound

Product 1

HCID 22721176HCID 22721176, compoundYield 61%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Phosgene (0.147 mL, 0.283 mmol, 1.93 M in toluene) was added to a stirred solution of 4,5-bis-(4-chloro-phenyl)-2-(2-ethoxy-6-methoxy-phenyl)-4,5-dihydro-1H-imidazole (described in previous patent) (25 mg, 0.0566 mmol) and triethylamine (39 μL, 0.283 mmol) in THF (2 mL) at 0° C. over a period of 5 min. The mixture was stirred for 3 h and evaporated. The residue was dissolved in methylene chloride (2 mL) and added dropwise to a stirred solution of piperazine (24 mg, 0.283 mmol) in methylene chloride (2 mL) at room temperature for 3 h. The mixture was diluted with aqueous sodium bicarbonate and extracted with methylene chloride. The organic extracts were washed with brine and dried over sodium sulfate. Evaporation of the solvents and chromatography of the residue over silica gel using 0-10% methanol in methylene chloride gave [4,5-bis-(4-chloro-phenyl)-2-(2-ethoxy-6-methoxy-phenyl)-4,5-dihydro-imidazol-1-yl]-piperazin-1-yl-methanone (19 mg, 61%). HR-MS (ES, m/z) calculated for C29H31N4O3Cl2[(M+H)+]553.1768, observed 553.1770.

Workup

  1. customevaporated
  2. dissolutionThe residue was dissolved in methylene chloride (2 mL)
  3. extractionextracted with methylene chloride
  4. washThe organic extracts were washed with brine
  5. dry with materialdried over sodium sulfate
  6. customEvaporation of the solvents and chromatography of the residue over silica gel using 0-10% methanol in methylene chloride

Sources & evidence

ORD record
ord-737804230fd7486288043675edb8ab11
Source dataset
uspto-grants-2004_05
Patent number
US06734302B2

Reaction notes

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