Dicyclohexylcarbodiimide → Desethyl-N-acetylprocainamide

HRID 904941Notes

Reaction equation

HRID 904941 reaction equation
[C:1]([NH:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=O)=[CH:7][CH:6]=1)(=[O:3])[CH3:2].O[N:15]1[C:19](=O)[CH2:18][CH2:17][C:16]1=O.C1([N:28]=C=NC2CCCCC2)CCCCC1>N1C=CC=CC=1>[CH3:17][CH2:16][NH:15][CH2:19][CH2:18][NH:28][C:9]([C:8]1[CH:7]=[CH:6][C:5]([NH:4][C:1]([CH3:2])=[O:3])=[CH:13][CH:12]=1)=[O:11]

Participants

5

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 19266p-Acetamidobenzoic acidHCID 80170N-Hydroxysuccinimide

Product 1

HCID 155689Desethyl-N-acetylprocainamide

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To 1.79 g of para-acetamidobenzoic acid and 1.15 g of N-hydroxysuccinimide dissolved in 15 ml of pyridine was added 2.3 g of N,N'-dicyclohexylcarbodiimide. The reaction mixture was cooled at 4 C.° for two hours and then filtered to remove crystals which had formed. The crystals were washed with approximately 2 ml of acetone and the pyridine filtrate and acetone washings were then combined. To the combined mixture was added 0.88 g of N-ethylethylenediamine. The resulting mixture was stirred for two hours and then cooled at 4 C.° for about twenty-four hours to yield a second crop of crystals. The crystals were removed from the mixture by filtration and then rinsed with acetone. The two crops of crystals (approximately 2.0 g) were combined and then dissolved in 50 ml of distilled water. The pH of the resulting mixture was adjusted to pH 10 using a 6 N sodium hydroxide solution. A white precipitate, desethyl-N-acetylprocainamide formed and was removed by filtration and dried in a dessicator. To 10 mg of the desethyl-N-acetyl-procainamide was added 10 mg of 4-[(4,6-dichlorotriazin-2-yl)-amino]fluorescein dissolved in 1 ml of methanol. The mixture was allowed to react for ten minutes, and the crude product which had formed was purified using silica gel thin-layer chromatographic techniques employing a developing solvent comprising a 1:1 mixture of chloroform:acetone to yield a desethyl-N-acetyl-procainamide-DTAF conjugate of the formula: ##STR8##

Workup

  1. temperatureThe reaction mixture was cooled at 4 C.° for two hours
  2. filtrationfiltered
  3. customto remove crystals which
  4. customhad formed
  5. washThe crystals were washed with approximately 2 ml of acetone
  6. additionTo the combined mixture was added 0.88 g of N-ethylethylenediamine
  7. temperaturecooled at 4 C.° for about twenty-four hours
  8. customto yield a second crop of crystals
  9. customThe crystals were removed from the mixture by filtration
  10. washrinsed with acetone
  11. dissolutiondissolved in 50 ml of distilled water

Sources & evidence

ORD record
ord-9e0b7d6a82f845bab83b61882fd778a5
Source dataset
uspto-grants-1983_12
Patent number
US04420568

Reaction notes

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