Diisopropylethylamine → N-(2-(5-chloro-1H-indol-3-yl)ethyl)-5-(hydroxy(phenyl)methyl)isoxazole-3-carboxamide

HRID 1918748

Reaktionsgleichung

Reaktionsgleichung von HRID 1918748
[OH:1][CH:2]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:3]1[O:7][N:6]=[C:5]([C:8]([O:10]CC)=O)[CH:4]=1.Cl.[Cl:20][C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[NH:26][CH:25]=[C:24]2[CH2:30][CH2:31][NH2:32].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>O1CCCC1.[OH-].[Na+].O.CN(C=O)C.C(OCC)(=O)C>[Cl:20][C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[NH:26][CH:25]=[C:24]2[CH2:30][CH2:31][NH:32][C:8]([C:5]1[CH:4]=[C:3]([CH:2]([OH:1])[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[O:7][N:6]=1)=[O:10]

Komponenten

10

Edukt 4

HCID 81531DiisopropylethylamineHCID 28274945-Chloro-1H-indole-3-ethylamine monohydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66831982Ethyl 5-(hydroxy(phenyl)methyl)isoxazole-3-carboxylate

Produkt 1

HCID 66832076N-(2-(5-chloro-1H-indol-3-yl)ethyl)-5-(hydroxy(phenyl)methyl)isoxazole-3-carboxamideAusbeute 95,6 %

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 962WaterLösungsmittel2×HCID 6228DimethylformamideLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 14798Sodium HydroxideLösungsmittel

Versuchsvorschrift

A mixture of ethyl 5-(hydroxy(phenyl)methyl)isoxazole-3-carboxylate (0.534 g; 2.16 mmol) in tetrahydrofurane (6 mL) and sodium hydroxide in water (2M, 5.4 mL) was stirred at room temperature for 1 hour and diluted in water, extracted with dichloromethane and the waters acidified with HCl 6N in water to pH 2 extracted with ethyl acetate, the organic layer was dried and concentrated under reduced pressure. The residue was added to a mixture of 2-(5-chloro-1H-indol-3-yl)ethanamine hydrochloride (0.5 g; 2.16 mmol), HATU (0.822 g; 2.16 mmol), N,N diisopropylethylamine (0.932 mL; 5.41 mmol), in DMF (12 mL) and was stirred at room temperature overnight. The reaction mixture was diluted in ethyl acetate, washed with sodium disulphate, sodium carbonate and brine, dried and concentrated under reduced pressure. The crude mixture was purified by flash chromatography on silica (eluent 20 to 100% ethyl acetate in heptane) to yield 0.817 g (95%) of N-(2-(5-chloro-1H-indol-3-yl)ethyl)-5-(hydroxy(phenyl)methyl)isoxazole-3-carboxamide as a white solid.

Aufarbeitung

  1. extractionextracted with dichloromethane
  2. extractionextracted with ethyl acetate
  3. customthe organic layer was dried
  4. concentrationconcentrated under reduced pressure
  5. stirringwas stirred at room temperature overnight
  6. washwashed with sodium disulphate, sodium carbonate and brine
  7. customdried
  8. concentrationconcentrated under reduced pressure
  9. customThe crude mixture was purified by flash chromatography on silica (eluent 20 to 100% ethyl acetate in heptane)

Quellen und Nachweise

ORD-Eintrag
ord-24c5c254e6e341df9944f04dbbd309c9
Quelldatensatz
uspto-grants-2013_12
Patentnummer
US08618138B2

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