Dicyclohexylcarbodiimide → 6-amidino-1-methoxycarbonylmethyl-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino]benzoate

HRID 1419247Notes

Reaction equation

HRID 1419247 reaction equation
[NH:1]1[CH2:5][CH2:4][N:3]=[C:2]1[NH:6][C:7]1[CH:15]=[CH:14][C:10]([C:11]([OH:13])=[O:12])=[CH:9][CH:8]=1.CS([O-])(=O)=O.[C:21]([C:24]1[CH:25]=[C:26]2[C:31](=[CH:32][CH:33]=1)[C:30]([CH2:34][C:35]([O:37][CH3:38])=[O:36])=[C:29](O)[CH:28]=[CH:27]2)(=[NH:23])[NH2:22].C1CCC(N=C=NC2CCCCC2)CC1>CN(C1C=CN=CC=1)C.C(C(C)=O)C.O.C(O)(=O)C.N1C=CC=CC=1>[NH:3]1[CH2:4][CH2:5][N:1]=[C:2]1[NH:6][C:7]1[CH:8]=[CH:9][C:10]([C:11]([O:13][C:29]2[CH:28]=[CH:27][C:26]3[C:31](=[CH:32][CH:33]=[C:24]([C:21](=[NH:22])[NH2:23])[CH:25]=3)[C:30]=2[CH2:34][C:35]([O:37][CH3:38])=[O:36])=[O:12])=[CH:14][CH:15]=1

Participants

8

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 85257Methanesulfonate2×HCID 129159(4-(4,5-Dihydro-1H-imidazol-2-yl)amino)benzoic acidHCID 1363653376-Amidino-1-methoxycarbonylmethyl-2-naphthol

Product 1

HCID 867539746-amidino-1-methoxycarbonylmethyl-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino]benzoateYield 27.1%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolventHCID 131721204Methyl ethyl ketone acetic acid waterSolvent

Procedure

60 Milliliters of 20% hydrous pyridine was added to 2.8 g of 4-[(4,5-dihydro-1H-imidazol-2-yl)amino]benzoic acid.methanesulfonate, 3.0 g of 6-amidino-1-methoxycarbonylmethyl-2-naphthol.methanesulfonate, 4.19 g of DCC and 103.4 mg of DMAP, followed by stirring for 2 hours under cooling with ice and 48 hours at room temperature. The precipitate was filtered and the filtrate was concentrated under reduced pressure. To the residue was added 15 ml of DMF. The solution was added dropwise to a mixed liquid of 500 ml of acetone and 300 ml of ether, followed by stirring for 24 hours under cooling with ice. Then, 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. To the residue were added 40 ml of methanol and 0.83 ml of methanesulfonic acid. The resulting solution was added dropwise to 400 ml of acetone, followed by stirring for 30 minutes under cooling with ice. Then, the precipitate was collected by filtration to obtain 1.4 g of the desired product.

Workup

  1. filtrationThe precipitate was filtered
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. additionTo the residue was added 15 ml of DMF
  4. additionThe solution was added dropwise to a mixed liquid of 500 ml of acetone and 300 ml of ether
  5. stirringby stirring for 24 hours
  6. temperatureunder cooling with ice
  7. filtrationThen, the precipitate was collected by filtration
  8. customto obtain a crude product
  9. customthe desired fractions were collected
  10. distillationthe solvent was distilled off under reduced pressure
  11. additionTo the residue were added 40 ml of methanol and 0.83 ml of methanesulfonic acid
  12. additionThe resulting solution was added dropwise to 400 ml of acetone
  13. stirringby stirring for 30 minutes
  14. temperatureunder cooling with ice
  15. filtrationThen, the precipitate was collected by filtration

Sources & evidence

ORD record
ord-3e64cd423ad34128bf0897b66accea49
Source dataset
uspto-grants-1999_03
Patent number
US05885990

Reaction notes

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