Hydrochloric Acid → 2-[4-[((3S)-1-acetimidoyl-3-pyrrolidinyl)oxy]phenyl]-3-(5-amidino-2-benzofuranyl)propionic Acid Dihydrochloride

HRID 361940Notes

Reaction equation

HRID 361940 reaction equation
[ClH:1].Cl.[C:3]([C:6]1[CH:7]=[CH:8][C:9]2[O:13][C:12]([CH2:14][CH:15]([C:19]3[CH:24]=[CH:23][C:22]([O:25][C@H:26]4[CH2:30][CH2:29][NH:28][CH2:27]4)=[CH:21][CH:20]=3)[C:16]([OH:18])=[O:17])=[CH:11][C:10]=2[CH:31]=1)(=[NH:5])[NH2:4].Cl.[C:33](=[NH:38])(OCC)[CH3:34].[OH-].[Na+].Cl>O.O.C(#N)C>[ClH:1].[ClH:1].[C:33]([N:28]1[CH2:29][CH2:30][C@H:26]([O:25][C:22]2[CH:21]=[CH:20][C:19]([CH:15]([CH2:14][C:12]3[O:13][C:9]4[CH:8]=[CH:7][C:6]([C:3](=[NH:4])[NH2:5])=[CH:31][C:10]=4[CH:11]=3)[C:16]([OH:18])=[O:17])=[CH:24][CH:23]=2)[CH2:27]1)(=[NH:38])[CH3:34]

Participants

7

Reactant 4

HCID 313Hydrochloric Acid2×HCID 14798Sodium HydroxideHCID 2724290Ethanimidic acid, ethyl ester, hydrochloride (1:1)HCID 700725263-(5-Amidino-2-benzofuranyl)-2-[4-[((3S)-3-pyrrolidinyl)oxy]phenyl]propionic Acid Dihydrochloride

Product 1

HCID 700747532-[4-[((3S)-1-acetimidoyl-3-pyrrolidinyl)oxy]phenyl]-3-(5-amidino-2-benzofuranyl)propionic Acid DihydrochlorideYield 130.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

1.1 g of 3-(5-amidino-2-benzofuranyl)-2-[4-[((3S)-3-pyrrolidinyl)oxy]phenyl]propionic acid dihydrochloride was dissolved in 20 ml of water. During ice cooling and stirring, 1.4 g of ethyl acetimidate hydrochloride was added gradually to the thus prepared solution while adjusting the pH of the solution to 8.5 with 1N sodium hydroxide aqueous solution. The resulting mixture was stirred for 15 minutes with ice cooling, and then adjusted to pH 2.0 with dilute hydrochloric acid. After concentrating the resulting reaction solution to dryness, the thus obtained residue was subjected to reversed phase high performance liquid chromatography using a column packed with octadecyl-bonded silica gel and using a water/acetonitrile mixture as an elution solvent. Thereafter, the thus eluted fractions of interest were pooled, mixed with dilute hydrochloric acid, and then concentrated to dryness. In this way, 780 mg of the title compound was obtained in a solid form.

Workup

  1. stirringThe resulting mixture was stirred for 15 minutes with ice cooling
  2. concentrationAfter concentrating
  3. customthe resulting reaction solution to dryness
  4. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-7d45adabfb254377b9cefa05fe4703a4
Source dataset
uspto-grants-1999_02
Patent number
US05866577

Reaction notes

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