Piperazine → HCID 22720998, compound

HRID 1582482Notes

Reaction equation

HRID 1582482 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][CH3:38])=[CH:33][C:32]=3[O:39][CH:40]3[CH2:44][CH2:43][CH2:42][CH2:41]3)=[N:20]2)=[CH:15][CH:14]=1.[NH:45]1[CH2:50][CH2:49][NH:48][CH2:47][CH2:46]1.C(=O)(O)[O-].[Na+]>C1COCC1.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:45]3[CH2:50][CH2:49][NH:48][CH2:47][CH2:46]3)=[O:2])[C:21]([C:31]3[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][C:32]=3[O:39][CH:40]3[CH2:41][CH2:42][CH2:43][CH2:44]3)=[N:20]2)=[CH:17][CH:18]=1

Participants

8

Reactant 5

HCID 4837PiperazineHCID 6371PhosgeneHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 10152061HCID 10152061, compound

Product 1

HCID 22720998HCID 22720998, compoundYield 81%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Phosgene (0.48 mL, 0.925 mmol, 1.93 M in toluene) was added dropwise to a mixture of triethylamine (0.14 mL, 1.0 mmol) and 4,5-bis-(4-chloro-phenyl)-2-(2-cyclopentyloxy-4-methoxy-phenyl)-4,5-dihydro-1H-imidazole (89 mg in THF (2 mL) at 0° C. The reaction mixture was stirred for 1 h at 0° C. and evaporated. The residue was kept under high vacuum for 30 min. Methylene chloride (2 mL) was added to the residue and the solution was added dropwise to a solution of piperazine (0.24 g, 2.78 mmol) in methylene chloride (2 mL) at 0° C. 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 layer was extracted with 0.5 N HCl (2×50 mL). The combined aqueous layers were cooled to 0° C. and basified using 2 N NaOH. The mixture was extracted with methylene chloride (3×50 mL). The organic extracts were dried over sodium sulfate and evaporated. Flash chromatography of the residue over silica gel using 3-6% methanol in methylene chloride gave [4,5-Bis-(4-chloro-phenyl)-2-(2-cyclopentyloxy-4-methoxy-phenyl)-4,5-dihydro-imidazol-1-yl]-piperazin-1-yl-methanone (89 mg, 81%). HR-MS (ES, m/z) calculated for C32H35N4O3Cl2[(M+H)+]593.2081, observed 593.2084.

Workup

  1. customevaporated
  2. waitThe residue was kept under high vacuum for 30 min
  3. additionMethylene chloride (2 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. extractionThe organic layer was extracted with 0.5 N HCl (2×50 mL)
  8. temperatureThe combined aqueous layers were cooled to 0° C.
  9. extractionThe mixture was extracted with methylene chloride (3×50 mL)
  10. dry with materialThe organic extracts were dried over sodium sulfate
  11. customevaporated

Sources & evidence

ORD record
ord-a56e84afc129450ab7b0e0637e0cd8f2
Source dataset
uspto-grants-2004_05
Patent number
US06734302B2

Reaction notes

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