Piperazine → HCID 22721020, compound

HRID 1582488Notes

Reaction equation

HRID 1582488 reaction equation
[C:1](Cl)(Cl)=[O:2].C(N(CC)CC)C.[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([CH:19]2[CH:23]([C:24]3[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=3)[NH:22][C:21]([C:31]3[CH:36]=[CH:35][C:34]([O:37][CH2:38][CH3:39])=[CH:33][C:32]=3[O:40][CH:41]([CH3:43])[CH3:42])=[N:20]2)=[CH:15][CH:14]=1.[NH:44]1[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]1.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[Cl:12][C:13]1[CH:14]=[CH:15][C:16]([CH:19]2[CH:23]([C:24]3[CH:25]=[CH:26][C:27]([Cl:30])=[CH:28][CH:29]=3)[N:22]([C:1]([N:44]3[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]3)=[O:2])[C:21]([C:31]3[CH:36]=[CH:35][C:34]([O:37][CH2:38][CH3:39])=[CH:33][C:32]=3[O:40][CH:41]([CH3:42])[CH3:43])=[N:20]2)=[CH:17][CH:18]=1

Participants

7

Reactant 5

HCID 4837PiperazineHCID 6371PhosgeneHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 10217285HCID 10217285, compound

Product 1

HCID 22721020HCID 22721020, compoundYield 8.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Phosgene (0.325 mL, 0.64 mmol, 1.93 M in toluene) was added dropwise to a mixture of triethylamine (0.126 mL, 0.896 mmol) and 4,5-bis-(4-chloro-phenyl)-2-(4-ethoxy-2-isopropoxy-phenyl)-4,5-dihydro-1H-imidazole (60 mg, 0.128 mmol) in methylene chloride (5 mL) at 0° C. The reaction mixture was stirred for 30 min at 0° C. and evaporated. The residue was kept under high vacuum for 30 min. Methylene chloride (5 mL) was added to the residue and the solution was added dropwise to a solution of piperazine (0.22 mg, 2.56 mmol) in methylene chloride (5 mL) at 0° C. over 15 min. After 1 h, the reaction was worked up with aqueous sodium bicarbonate. The mixture was extracted with methylene chloride and washed with water and brine. The organic extracts were dried over sodium sulfate and evaporated. Purification using reverse phase HPLC gave [4,5-bis-(4-chloro-phenyl)-2-(4-ethoxy-2-isopropoxy-phenyl)-4,5-dihydro-imidazol-1-yl]-piperazin-1-yl-methanone (6.5 mg, 8%). HR-MS (ES, m/z) calculated for C31H35N4O3Cl2[(M+H)+]581.2081, observed 581.2086.

Workup

  1. customevaporated
  2. waitThe residue was kept under high vacuum for 30 min
  3. additionMethylene chloride (5 mL) was added to the residue
  4. waitAfter 1 h
  5. extractionThe mixture was extracted with methylene chloride
  6. washwashed with water and brine
  7. dry with materialThe organic extracts were dried over sodium sulfate
  8. customevaporated
  9. customPurification

Sources & evidence

ORD record
ord-3eafdcd4d1f541a38b0417aecd717c72
Source dataset
uspto-grants-2004_05
Patent number
US06734302B2

Reaction notes

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