Triethylamine → ethyl 2-[4-[((2R)-1-acetimidoyl-2-pyrrolidinyl)methoxy]phenyl]-2-ethoxycarbonyl-3-(5-amidinobenzo[b]thien-2-yl)propionate dihydrochloride

HRID 1901374Notes

Reaction equation

HRID 1901374 reaction equation
[ClH:1].Cl.[C:3]([C:6]1[CH:39]=[CH:38][C:9]2[S:10][C:11]([CH2:13][C:14]([C:33]([O:35][CH2:36][CH3:37])=[O:34])([C:20]3[CH:25]=[CH:24][C:23]([O:26][CH2:27][C@H:28]4[CH2:32][CH2:31][CH2:30][NH:29]4)=[CH:22][CH:21]=3)[C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:12][C:8]=2[CH:7]=1)(=[NH:5])[NH2:4].Cl.[C:41](=[NH:46])(OCC)[CH3:42].C(N(CC)CC)C>C(O)C>[ClH:1].[ClH:1].[C:41]([N:29]1[CH2:30][CH2:31][CH2:32][C@@H:28]1[CH2:27][O:26][C:23]1[CH:22]=[CH:21][C:20]([C:14]([C:33]([O:35][CH2:36][CH3:37])=[O:34])([CH2:13][C:11]2[S:10][C:9]3[CH:38]=[CH:39][C:6]([C:3](=[NH:4])[NH2:5])=[CH:7][C:8]=3[CH:12]=2)[C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:25][CH:24]=1)(=[NH:46])[CH3:42]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 2724290Ethanimidic acid, ethyl ester, hydrochloride (1:1)HCID 70072932ethyl 3-(5-amidinobenzo[b]thien-2-yl)-2-ethoxycarbonyI-2-[4-[((2R)-2-pyrrolidinyl)methoxy]phenyl]propionate dihydrochloride

Product 1

HCID 70075082ethyl 2-[4-[((2R)-1-acetimidoyl-2-pyrrolidinyl)methoxy]phenyl]-2-ethoxycarbonyl-3-(5-amidinobenzo[b]thien-2-yl)propionate dihydrochloride

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

1.0 g of ethyl 3-(5-amidinobenzo[b]thien-2-yl)-2-ethoxycarbonyI-2-[4-[((2R)-2-pyrrolidinyl)methoxy]phenyl]propionate dihydrochloride was dissolved in 20 ml of ethanol, followed by the addition of 0.42 g of ethyl acetimidate hydrochloride. 0.51 g of triethylamine was added to the thus prepared solution during stirring under ice cooling, and the resulting mixture was warmed up to room temperature and stirred for 18 hours. Thereafter, the solvent was distilled off to obtain ethyl 2-[4-[((2R)-1-acetimidoyl-2-pyrrolidinyl)methoxy]phenyl]-2-ethoxycarbonyl-3-(5-amidinobenzo[b]thien-2-yl)propionate dihydrochloride. The thus obtained ester compound was dissolved in 50 ml of 5N hydrochloric acid and refluxed under heating for 60 minutes. After distilling off the solvent, the resulting residue was subjected to column chromatography using a column packed with a highly porous polymer type synthetic adsorbent (styrene-divinylbenzene polymer: Diaion HP-20) and using a water/acetonitrile mixture as an elution solvent. Fractions of interest were pooled and concentrated, and the resulting 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, 360 mg of the title compound was obtained in the form of a light yellow solid.

Workup

  1. stirringstirred for 18 hours
  2. distillationThereafter, the solvent was distilled off

Sources & evidence

ORD record
ord-d4583b140c6a40c9baf8fa8bb7fc9aae
Source dataset
uspto-grants-1996_11
Patent number
US05576343

Reaction notes

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