Pyridine → 6-Amidino-1-carbamoylmethyl-2-naphthyl 4-dimethylaminobenzoate.dihydrochloride

HRID 1419228Notes

Reaction equation

HRID 1419228 reaction equation
N1C=CC=CC=1.[CH3:7][N:8]([CH3:18])[C:9]1[CH:17]=[CH:16][C:12]([C:13]([OH:15])=[O:14])=[CH:11][CH:10]=1.[ClH:19].[C:20]([C:23]1[CH:24]=[C:25]2[C:30](=[CH:31][CH:32]=1)[C:29]([CH2:33][C:34](=[O:36])[NH2:35])=[C:28](O)[CH:27]=[CH:26]2)(=[NH:22])[NH2:21].C1CCC(N=C=NC2CCCCC2)CC1>CN(C1C=CN=CC=1)C.C(C(C)=O)C.O.C(O)(=O)C>[ClH:19].[ClH:19].[CH3:7][N:8]([CH3:18])[C:9]1[CH:17]=[CH:16][C:12]([C:13]([O:15][C:28]2[CH:27]=[CH:26][C:25]3[C:30](=[CH:31][CH:32]=[C:23]([C:20](=[NH:21])[NH2:22])[CH:24]=3)[C:29]=2[CH2:33][C:34](=[O:36])[NH2:35])=[O:14])=[CH:11][CH:10]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 10868DicyclohexylcarbodiimideHCID 120924-(Dimethylamino)benzoic acidHCID 1364542706-Amidino-1-carbamoylmethyl-2-naphthol.hydrochloride

Product 1

HCID 701308236-Amidino-1-carbamoylmethyl-2-naphthyl 4-dimethylaminobenzoate.dihydrochlorideYield 133.7%

Reagents, catalysts & solvents 2

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

Procedure

40 Milliliters of 20% hydrous pyridine was added to 3.0 g of 4-dimethylaminobenzoic acid, 1.77 g of 6-amidino-1-carbamoylmethyl-2-naphthol.hydrochloride, 2.65 g of DCC and 130.9 mg of DMAP, followed by stirring for 2 hours under cooling with ice and then 24 hours at room temperature. Then, the precipitate was collected by filtration and washed with a small amount of pyridine. To this collected precipitate were added 60 ml of DMF and 20 ml of water to dissolve the precipitate with heating, followed by stirring for 2 hours under cooling with ice. Then, insoluble matter was filtered off and the filtrate was concentrated under reduced pressure. To the residue were added 15 ml of DMF and 10 ml of water to dissolve the residue. The solution was added dropwise to 400 ml of acetone, followed by stirring for 24 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 methyl ethyl ketone-water-acetic acid (80:15:5) as an eluent, and the desired fractions were collected and the solvent was distilled off under reduced pressure. The residue was suspended in 15 ml of methanol, 5 ml of DMF and 0.9 ml of concentrated hydrochloric acid, and the suspension was added dropwise to a mixed liquid of 200 ml of acetone and 100 ml of ether, followed by stirring for 24 hours under cooling with ice. Then, the precipitate was collected by filtration to obtain 1.96 g of the desired product.

Workup

  1. temperatureunder cooling with ice
  2. custom24 hours
  3. customat room temperature
  4. filtrationThen, the precipitate was collected by filtration
  5. washwashed with a small amount of pyridine
  6. additionTo this collected precipitate were added 60 ml of DMF and 20 ml of water
  7. dissolutionto dissolve the precipitate
  8. temperaturewith heating
  9. stirringby stirring for 2 hours
  10. temperatureunder cooling with ice
  11. filtrationThen, insoluble matter was filtered off
  12. concentrationthe filtrate was concentrated under reduced pressure
  13. additionTo the residue were added 15 ml of DMF and 10 ml of water
  14. dissolutionto dissolve the residue
  15. additionThe solution was added dropwise to 400 ml of acetone
  16. stirringby stirring for 24 hour
  17. temperatureunder cooling with ice
  18. filtrationThe precipitate was collected by filtration
  19. customto obtain a crude product
  20. customthe desired fractions were collected
  21. distillationthe solvent was distilled off under reduced pressure
  22. addition5 ml of DMF and 0.9 ml of concentrated hydrochloric acid, and the suspension was added dropwise to a mixed liquid of 200 ml of acetone and 100 ml of ether
  23. stirringby stirring for 24 hours
  24. temperatureunder cooling with ice
  25. filtrationThen, the precipitate was collected by filtration

Sources & evidence

ORD record
ord-d0d162e905cc44d1990fd3daa3b6f533
Source dataset
uspto-grants-1999_03
Patent number
US05885990

Reaction notes

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