Sodium Hydroxide → 3-({[4-({cyclohexyl[2-ethyl-5-(tetrahydro-2H-pyran-4-yl)thiophen-3-yl]methyl}amino)phenyl]carbonyl}amino)propanoic acid

HRID 1877213Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1877213
[CH:1]1([CH:7]([NH:21][C:22]2[CH:30]=[CH:29][C:25]([C:26]([OH:28])=O)=[CH:24][CH:23]=2)[C:8]2[CH:12]=[C:11]([CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[S:10][C:9]=2[CH2:19][CH3:20])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[NH2:32][CH2:33][CH2:34][C:35]([O:37]CC)=[O:36].O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.[Cl-].[NH4+].[OH-].[Na+]>CN(C)C=O.C(O)C.O1CCCC1.C(N(CC)CC)C>[CH:1]1([CH:7]([NH:21][C:22]2[CH:23]=[CH:24][C:25]([C:26]([NH:32][CH2:33][CH2:34][C:35]([OH:37])=[O:36])=[O:28])=[CH:29][CH:30]=2)[C:8]2[CH:12]=[C:11]([CH:13]3[CH2:14][CH2:15][O:16][CH2:17][CH2:18]3)[S:10][C:9]=2[CH2:19][CH3:20])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Komponenten

11

Edukt 6

HCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 458475beta-Alanine, ethyl ester, hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 685112004-({cyclohexyl[2-ethyl-5-(tetrahydro-2H-pyran-4-yl)thiophen-3-yl]methyl}amino)benzoic acid

Produkt 1

HCID 595294943-({[4-({cyclohexyl[2-ethyl-5-(tetrahydro-2H-pyran-4-yl)thiophen-3-yl]methyl}amino)phenyl]carbonyl}amino)propanoic acidAusbeute 54,2 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 702EthanolLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

To a mixture of 4-({cyclohexyl[2-ethyl-5-(tetrahydro-2H-pyran-4-yl)thiophen-3-yl]methyl}amino)benzoic acid (250 mg) synthesized above, ethyl β-alaninate hydrochloride (108 mg), 1-hydroxybenzotriazole monohydrate (108 mg) and triethylamine (98 μL) in N,N-dimethylformamide (10 mL) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (135 mg), and the mixture was stirred at room temperature for 2 hr. Saturated aqueous ammonium chloride solution was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by NH-silica gel column chromatography (ethyl acetate) to give a pale-yellow oil. To a mixture of the obtained oil, tetrahydrofuran (5 mL) and ethanol (5 mL) was added 1N aqueous sodium hydroxide solution (1 mL), and the mixture was stirred at room temperature for 3 hr, and concentrated under reduced pressure. The residue was dissolved in water (10 mL), and 1N hydrochloric acid (1 mL) was added at 0° C. The resulting precipitate was collected by filtration to give the title compound (158 mg, 54%) as a white solid.

Aufarbeitung

  1. customto quench
  2. customthe reaction
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed with saturated brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by NH-silica gel column chromatography (ethyl acetate)
  8. customto give a pale-yellow oil
  9. stirringthe mixture was stirred at room temperature for 3 hr
  10. concentrationconcentrated under reduced pressure
  11. dissolutionThe residue was dissolved in water (10 mL)
  12. addition1N hydrochloric acid (1 mL) was added at 0° C
  13. filtrationThe resulting precipitate was collected by filtration

Quellen und Nachweise

ORD-Eintrag
ord-3267e9e743b7434c8f454e8ae23f8ca4
Quelldatensatz
uspto-grants-2012_11
Patentnummer
US08309580B2

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