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Triethylamine → N-(3,4,5-Trimethoxyphenyl)-3-(5-methyl-3-(2-iodo-6-fluoro-phenyl)isoxazol-4-oyl)aminophenyl Acetamide

HRID 434056
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 434056
[C:1]([C:4]1[C:5]([C:10]2[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]=2[I:17])=[N:6][O:7][C:8]=1[CH3:9])([OH:3])=O.C(Cl)(=O)C(Cl)=O.[NH2:24][C:25]1[CH:26]=[C:27]([CH2:31][C:32]([NH:34][C:35]2[CH:40]=[C:39]([O:41][CH3:42])[C:38]([O:43][CH3:44])=[C:37]([O:45][CH3:46])[CH:36]=2)=[O:33])[CH:28]=[CH:29][CH:30]=1.C(N(CC)CC)C>ClCCl.C1COCC1.CN(C=O)C>[CH3:42][O:41][C:39]1[CH:40]=[C:35]([NH:34][C:32](=[O:33])[CH2:31][C:27]2[CH:28]=[CH:29][CH:30]=[C:25]([NH:24][C:1]([C:4]3[C:5]([C:10]4[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]=4[I:17])=[N:6][O:7][C:8]=3[CH3:9])=[O:3])[CH:26]=2)[CH:36]=[C:37]([O:45][CH3:46])[C:38]=1[O:43][CH3:44]
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

8

Edukt 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 179306454-Carboxy-5-methyl-3-(2-iodo-6-fluoro-phenyl)isoxazoleHCID 187562602-(3-aminophenyl)-N-(3,4,5-trimethoxyphenyl)acetamide

Produkt 1

HCID 70026384N-(3,4,5-Trimethoxyphenyl)-3-(5-methyl-3-(2-iodo-6-fluoro-phenyl)isoxazol-4-oyl)aminophenyl AcetamideAusbeute 51,7 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideKatalysatorHCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of 4-carboxy-5-methyl-3-(2-iodo-6-fluoro-phenyl)isoxazole (1.75 g, 5 mmol) in dichloromethane (30 ml) and THF (1 ml) was added oxalyl chloride (0.88 ml, 10 mmol, 2 eq.) under N2, then DMF (3 drops) to initiate the reaction. The reaction was stirred for 2 h, concentrated, and re-dissolved in dichloromethane (50 ml) under N2. A solution of 2-(3-aminophenyl)-N-(3,4,5-trimethoxyphenyl)acetamide (1.59, 5 mmol) in THF (14 ml) was added, cooled to 0° C., and then added triethylamine (0.7 ml, 5 mmol), and stirred for 17 h. Crude reaction was partitioned between ethyl acetate and 1N HCl. The organic layer was washed with H2O and brine, dried (MgSO4), filtered and concentrated. The crude material was titrated with diethyl ether (3×) and purified by flash chromatography (silica gel) using 1-10% acetone in dichloromethane to give the title compound (1.67 g, 51%).

Aufarbeitung

  1. customthe reaction
  2. concentrationconcentrated
  3. dissolutionre-dissolved in dichloromethane (50 ml) under N2
  4. customCrude reaction
  5. customwas partitioned between ethyl acetate and 1N HCl
  6. washThe organic layer was washed with H2O and brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. custompurified by flash chromatography (silica gel)

Quellen und Nachweise

ORD-Eintrag
ord-820dd343512d42b9afcdd38fd9b57cd6
Quelldatensatz
uspto-grants-2003_12
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US06670373B1

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