Hydrochloric Acid → 3-[{[4-({Cyclohexyl[2-ethyl-5-(2-methylpropanoyl)thiophen-3-yl]methyl}amino)phenyl]carbonyl}(methyl)amino]propanoic acid

HRID 1877262Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1877262
[CH:1]1([CH:7]([NH:20][C:21]2[CH:29]=[CH:28][C:24]([C:25]([OH:27])=O)=[CH:23][CH:22]=2)[C:8]2[CH:12]=[C:11]([C:13](=[O:17])[CH:14]([CH3:16])[CH3:15])[S:10][C:9]=2[CH2:18][CH3:19])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:30][NH:31][CH2:32][CH2:33][C:34]([O:36]CC)=[O:35].O.ON1C2C=CC=CC=2N=N1.Cl.[OH-].[Na+]>CN(C)C=O.C(O)C.O1CCCC1.C(N(CC)CC)C>[CH:1]1([CH:7]([NH:20][C:21]2[CH:29]=[CH:28][C:24]([C:25]([N:31]([CH3:30])[CH2:32][CH2:33][C:34]([OH:36])=[O:35])=[O:27])=[CH:23][CH:22]=2)[C:8]2[CH:12]=[C:11]([C:13](=[O:17])[CH:14]([CH3:15])[CH3:16])[S:10][C:9]=2[CH2:18][CH3:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Komponenten

10

Edukt 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 541480Ethyl 3-(methylamino)propanoateHCID 27960291-Hydroxybenzotriazole hydrateHCID 685154374-({Cyclohexyl[2-ethyl-5-(2-methylpropanoyl)thiophen-3-yl]methyl}amino)benzoic acid

Produkt 1

HCID 595295933-[{[4-({Cyclohexyl[2-ethyl-5-(2-methylpropanoyl)thiophen-3-yl]methyl}amino)phenyl]carbonyl}(methyl)amino]propanoic acidAusbeute 60,3 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 702EthanolLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

To a mixture of 4-({cyclohexyl[2-ethyl-5-(2-methylpropanoyl)thiophen-3-yl]methyl}amino)benzoic acid (139 mg) synthesized in Example 287 (8), ethyl 3-(methylamino)propanoate (53.0 mg), 1-hydroxybenzotriazole monohydrate (61.9 mg) and triethylamine (56 μL) in N,N-dimethylformamide (10 mL) 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (77.4 mg) was added, and the mixture was stirred at room temperature for 2.5 days. 1N Hydrochloric acid 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 silica gel column chromatography (40% ethyl acetate/hexane), and then purified by NH-silica gel column chromatography (ethyl acetate) to give a colorless 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 1 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 (101 mg, 60%) as a white solid.

Aufarbeitung

  1. additionwas added
  2. customto quench
  3. customthe reaction
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe extract was washed with saturated brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (40% ethyl acetate/hexane)
  9. custompurified by NH-silica gel column chromatography (ethyl acetate)
  10. customto give a colorless oil
  11. stirringthe mixture was stirred at room temperature for 1 hr
  12. concentrationconcentrated under reduced pressure
  13. dissolutionThe residue was dissolved in water (10 mL)
  14. addition1N hydrochloric acid (1 mL) was added at 0° C
  15. filtrationThe resulting precipitate was collected by filtration

Quellen und Nachweise

ORD-Eintrag
ord-eb3535fcc61c4e8e94f367de6db40e45
Quelldatensatz
uspto-grants-2012_11
Patentnummer
US08309580B2

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