Pyridine → 6-amidino-1-(2-carbamoylethyl)-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino]-benzoate.dihydrochloride

HRID 1419219Notes

Reaction equation

HRID 1419219 reaction equation
N1C=CC=CC=1.[ClH:7].[NH:8]1[CH2:12][CH2:11][N:10]=[C:9]1[NH:13][C:14]1[CH:22]=[CH:21][C:17]([C:18]([OH:20])=[O:19])=[CH:16][CH:15]=1.Cl.[C:24]([C:27]1[CH:28]=[C:29]2[C:34](=[CH:35][CH:36]=1)[C:33]([CH2:37][CH2:38][C:39](=[O:41])[NH2:40])=[C:32](O)[CH:31]=[CH:30]2)(=[NH:26])[NH2:25].C1CCC(N=C=NC2CCCCC2)CC1>CN(C1C=CN=CC=1)C.C(C(C)=O)C.O.C(O)(=O)C.O>[ClH:7].[ClH:7].[NH:10]1[CH2:11][CH2:12][N:8]=[C:9]1[NH:13][C:14]1[CH:15]=[CH:16][C:17]([C:18]([O:20][C:32]2[CH:31]=[CH:30][C:29]3[C:34](=[CH:35][CH:36]=[C:27]([C:24](=[NH:25])[NH2:26])[CH:28]=3)[C:33]=2[CH2:37][CH2:38][C:39](=[O:41])[NH2:40])=[O:19])=[CH:21][CH:22]=1

Participants

8

Reactant 4

HCID 1049PyridineHCID 10868DicyclohexylcarbodiimideHCID 688307174-[(4,5-dihydro-1H-imidazol-2-yl)amino]-benzoic acid.hydrochlorideHCID 1364542756-Amidino-1-(2-carbamoylethyl)-2-naphthol.hydrochloride

Product 1

HCID 701388966-amidino-1-(2-carbamoylethyl)-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino]-benzoate.dihydrochlorideYield 17.1%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 131721204Methyl ethyl ketone acetic acid waterSolvent

Procedure

45 Milliliters of 20% hydrous pyridine was added to 2.71 g of 4-[(4,5-dihydro-1H-imidazol-2-yl)amino]benzoic acid.hydrochloride, 3.0 g of 6-amidino-1-(2-carbamoylethyl)-2-naphthol.hydrochloride, 2.52 g of DCC and 124.6 mg of DMAP, followed by stirring for 2 hours under cooling with ice and 6 days under cooling with water. The precipitate was filtered and the filtrate was concentrated under reduced pressure. To the residue was added 15 ml of DMF, and a small amount of insoluble matter was filtered off. The filtrate was added dropwise to 400 ml of acetone, followed by stirring for 1 hour under cooling with ice and 24 hours under cooling with water. The supernatant was decanted, and to the residue was added 15 ml of methanol, followed by stirring for 1 hour under cooling with ice. The precipitate was collected by filtration to obtain a crude product. Then, the product was subjected to silica gel column chromatography using a mixed liquid of methyl ethyl ketone-water-acetic acid (80:15:5) as an eluent solvent, and the desired fractions were collected and the solvent was distilled off under reduced pressure. The residue was dissolved in 5 ml of DMF and 200 μl of concentrated hydrochloric acid, and the solution was added dropwise to 200 ml of acetone. After stirring for 1 hour under cooling with ice and then 24 hours under cooling with water, the precipitate was collected by filtration to obtain 495.4 mg of the desired product.

Workup

  1. temperatureunder cooling with ice and 6 days
  2. filtrationThe precipitate was filtered
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. additionTo the residue was added 15 ml of DMF
  5. filtrationa small amount of insoluble matter was filtered off
  6. additionThe filtrate was added dropwise to 400 ml of acetone
  7. stirringby stirring for 1 hour
  8. temperatureunder cooling with ice and 24 hours
  9. temperatureunder cooling with water
  10. customThe supernatant was decanted
  11. additionto the residue was added 15 ml of methanol
  12. stirringby stirring for 1 hour
  13. temperatureunder cooling with ice
  14. filtrationThe precipitate was collected by filtration
  15. customto obtain a crude product
  16. customthe desired fractions were collected
  17. distillationthe solvent was distilled off under reduced pressure
  18. dissolutionThe residue was dissolved in 5 ml of DMF
  19. addition200 μl of concentrated hydrochloric acid, and the solution was added dropwise to 200 ml of acetone
  20. stirringAfter stirring for 1 hour
  21. temperatureunder cooling with ice
  22. temperature24 hours under cooling with water
  23. filtrationthe precipitate was collected by filtration

Sources & evidence

ORD record
ord-53b9912db7d44656b563ff7bd7b7a154
Source dataset
uspto-grants-1999_03
Patent number
US05885990

Reaction notes

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