1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → [(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl]2-[5-[[tert-butyl(dimethyl)silyl]oxymethyl]-2-thienyl]acetate

HRID 2279948Notes

Reaction equation

HRID 2279948 reaction equation
[Si:1]([O:8][CH2:9][C:10]1[S:14][C:13]([CH2:15][C:16]([OH:18])=[O:17])=[CH:12][CH:11]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Cl:19][C:20]1[CH:21]=[N+:22]([O-:40])[CH:23]=[C:24]([Cl:39])[C:25]=1[CH2:26][C@@H:27]([C:29]1[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[C:31]([O:37][CH3:38])[CH:30]=1)O.Cl.CN(C)CCCN=C=NCC>ClCCl.CN(C)C1C=CN=CC=1>[Cl:39][C:24]1[CH:23]=[N+:22]([O-:40])[CH:21]=[C:20]([Cl:19])[C:25]=1[CH2:26][C@H:27]([O:17][C:16](=[O:18])[CH2:15][C:13]1[S:14][C:10]([CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])=[CH:11][CH:12]=1)[C:29]1[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[C:31]([O:37][CH3:38])[CH:30]=1

Participants

6

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 595637742-(5-((Tert-butyldimethylsilyloxy)methyl)thiophen-2-yl)acetic acidHCID 71092494(S)-3,5-dichloro-4-(2-(3,4-dimethoxyphenyl)-2-hydroxyethyl)pyridine 1-oxide

Product 1

HCID 131733496[(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl]2-[5-[[tert-butyl(dimethyl)silyl]oxymethyl]-2-thienyl]acetateYield 46%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-[5-[[tert-butyl(dimethyl)silyl]oxymethyl]-2-thienyl]acetic acid (995 mg, 3.48 mmol) in dichloromethane (40 mL) was added (S)-3,5-dichloro-4-(2-(3,4-dimethoxyphenyl)-2-hydroxyethyl)pyridine 1-oxide (1.43 g, 4.17 mmol), followed by 4-(dimethylamino)-pyridine (212 mg, 1.74 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (1.33 g, 6.96 mmol). The resultant solution was stirred at room temperature for 72 h. The reaction solution was washed with saturated aqueous sodium bicarbonate (2×30 mL), the organic phase passed through a hydrophobic frit and concentrated in vacuo. The residue was purified by silica gel chromatography, eluting with 0-100% ethyl acetate in iso-hexane to give the title compound as a pale yellow oil (980 mg, 46%).

Workup

  1. washThe reaction solution was washed with saturated aqueous sodium bicarbonate (2×30 mL)
  2. concentrationconcentrated in vacuo
  3. customThe residue was purified by silica gel chromatography
  4. washeluting with 0-100% ethyl acetate in iso-hexane

Sources & evidence

ORD record
ord-919488c27dec451187e8c22a10e5443b
Source dataset
uspto-grants-2015_09
Patent number
US09133185B2

Reaction notes

Loading…