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P-Anisidine → 2-(2,6-Difluorophenyl)-5-(4-methoxyphenylamino)oxazole-4-carboxamide

HRID 389748
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 389748
Br[C:2]1[O:6][C:5]([C:7]2[C:12]([F:13])=[CH:11][CH:10]=[CH:9][C:8]=2[F:14])=[N:4][C:3]=1[C:15]([NH2:17])=[O:16].CC(C)([O-])C.[Na+].[CH3:24][O:25][C:26]1[CH:31]=[CH:30][C:29]([NH2:32])=[CH:28][CH:27]=1>FC(F)(F)C1C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:14][C:8]1[CH:9]=[CH:10][CH:11]=[C:12]([F:13])[C:7]=1[C:5]1[O:6][C:2]([NH:32][C:29]2[CH:30]=[CH:31][C:26]([O:25][CH3:24])=[CH:27][CH:28]=2)=[C:3]([C:15]([NH2:17])=[O:16])[N:4]=1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

6

Edukt 3

HCID 7732P-AnisidineHCID 23676156Sodium t-butoxideHCID 595875995-Bromo-2-(2,6-difluorophenyl)oxazole-4-carboxamide

Produkt 1

HCID 595874272-(2,6-Difluorophenyl)-5-(4-methoxyphenylamino)oxazole-4-carboxamideAusbeute 8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564
Bis(dibenzylideneacetone)palladium
Katalysator
HCID 7368(Trifluoromethyl)benzeneLösungsmittel

Reaktionsbedingungen

Temperatur
160 °C

Versuchsvorschrift

To a stirred, degassed solution of 5-bromo-2-(2,6-difluorophenyl)oxazole-4-carboxamide (0.125 g, 0.41 mmol) in trifluorotoluene (10.5 mL) was added tris(dibenzylideneacetone)dipalladium(0) (0.019 g, 0.02 mmol), (±)-2,2″-bis(diphenylphosphino)-1,1″-binaphthalene (0.026 g, 0.04 mmol), and sodium tert-butoxide (0.059 g, 0.62 mmol). This was followed by addition of p-anisidine (0.076 g, 0.62 mmol) after approximately 3 minutes stirring. The resulting reaction mixture was degassed, placed under an N2 atmosphere and heated in the microwave at 160° C. for 20 minutes. The solution was then washed with 2M aqueous HCl and brine, dried over MgSO4 and then passed through a MP-SH resin cartridge (500 mg). The solvent was removed in vacuo and the residue purified by preparative HPLC to afford 2-(2,6-difluorophenyl)-5-(4-methoxyphenylamino)oxazole-4-carboxamide (0.0037 g, 0.01 mmol, 8%) as a white solid. 1H NMR (DMSO) δ 3.74 (3H, s), 6.93 (2H, d), 7.29 (2H, br. s), 7.32 (2H, t), 7.37 (2H, d), 7.62 (1H, m), 9.17 (1H, br. s). LCMS (2) Rt: 2.80 min; m/z (ES+) 346.

Aufarbeitung

  1. customThe resulting reaction mixture
  2. customwas degassed
  3. washThe solution was then washed with 2M aqueous HCl and brine
  4. dry with materialdried over MgSO4
  5. customThe solvent was removed in vacuo
  6. customthe residue purified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-9cf0b62109f6464999b6db6b52f21b86
Quelldatensatz
uspto-grants-2013_02
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08378095B2

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