Dicyclohexylamine → N-[2-(4-benzhydrylpiperazino)ethyl]-3-hydroxy-5-(3-pyridylmethoxy)-2-naphthamide

HRID 1110013

Reaction equation

HRID 1110013 reaction equation
C1(NC2CCCCC2)CCCCC1.[OH:14][C:15]1[C:16]([C:33](O)=[O:34])=[CH:17][C:18]2[C:23]([CH:24]=1)=[C:22]([O:25][CH2:26][C:27]1[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=1)[CH:21]=[CH:20][CH:19]=2.C(Cl)(=O)C(C)(C)C.[CH:43]([N:56]1[CH2:61][CH2:60][N:59]([CH2:62][CH2:63][NH2:64])[CH2:58][CH2:57]1)([C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>C(N(CC)CC)C.C(Cl)Cl>[CH:43]([N:56]1[CH2:57][CH2:58][N:59]([CH2:62][CH2:63][NH:64][C:33]([C:16]2[C:15]([OH:14])=[CH:24][C:23]3[C:18](=[CH:19][CH:20]=[CH:21][C:22]=3[O:25][CH2:26][C:27]3[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=3)[CH:17]=2)=[O:34])[CH2:60][CH2:61]1)([C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1

Participants

7

Reactant 4

HCID 7582DicyclohexylamineHCID 62493Pivaloyl chlorideHCID 47424562-(4-Benzhydrylpiperazino)ethaneamineHCID 158880873-Hydroxy 5-(3-pyridylmethoxy)-2-naphtoic acid

Product 1

HCID 19018752N-[2-(4-benzhydrylpiperazino)ethyl]-3-hydroxy-5-(3-pyridylmethoxy)-2-naphthamideYield 78%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 8471TriethylamineSolvent

Procedure

19.1 g (40.0 mM) of dicyclohexylamine salt of 3-hydroxy 5-(3-pyridylmethoxy)-2-naphtoic acid was dissolved in 11.2 ml (80.0 mM) of triethylamine and 500 ml of anhydrous methylene chloride. Thereto was dropwise added, at -20° C., a solution of 9.6 ml (80.0 mM) of pivaloyl chloride in 10 ml of anhydrous methylene chloride. The resulting mixture was stirred for 2 hours. Thereto was dropwise added a solution of 17.4 g (56.0 mM) of 2-(4-benzhydrylpiperazino)ethaneamine in 20 ml of anhydrous methylene chloride. The mixture was stirred for 2 hours. The reaction mixture was washed with water and then with a saturated aqueous sodium chloride solution, and dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was dissolved in 600 ml of methanol. Thereto was added 160 ml of an aqueous solution containing 16.56 g (120.0 mM) of potassium carbonate. Stirring was conducted at room temperature for 1 hour. The solvent was removed by distillation under reduced pressure. The residue was dissolved in 1000 ml of ethyl acetate. The solution was washed with water, a saturated aqueous ammonium chloride solution and a saturated aqueous sodium chloride solution in this order, and dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by silica gel chromatography to obtain 18.3 g of the title compound at a yield of 78%. The properties of the compound are shown in Table 7.

Workup

  1. additionThereto was dropwise added, at -20° C.
  2. stirringThe mixture was stirred for 2 hours
  3. washThe reaction mixture was washed with water
  4. dry with materialwith a saturated aqueous sodium chloride solution, and dried over anhydrous sodium sulfate
  5. customThe solvent was removed by distillation under reduced pressure
  6. dissolutionThe residue was dissolved in 600 ml of methanol
  7. additionThereto was added 160 ml of an aqueous solution
  8. additioncontaining 16.56 g (120.0 mM) of potassium carbonate
  9. stirringStirring
  10. waitwas conducted at room temperature for 1 hour
  11. customThe solvent was removed by distillation under reduced pressure
  12. dissolutionThe residue was dissolved in 1000 ml of ethyl acetate
  13. washThe solution was washed with water
  14. dry with materiala saturated aqueous ammonium chloride solution and a saturated aqueous sodium chloride solution in this order, and dried over anhydrous sodium sulfate
  15. customThe solvent was removed by distillation under reduced pressure
  16. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-e85dcfd67a3943349eea3d9cb6a5e93a
Source dataset
uspto-grants-1994_06
Patent number
US05324728

Linked notes

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