N-(1-{[4-chloro-2-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-3-yl)-2,6-difluorobenzamide → 2,6-Difluoro-N-(1-{[4-(1-methylethyl)-2-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-3-yl)benzamide

HRID 1946404Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1946404
Cl[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[CH:13]=[CH:12][C:11]([NH:14][C:15](=[O:24])[C:16]3[C:21]([F:22])=[CH:20][CH:19]=[CH:18][C:17]=3[F:23])=[N:10]2)=[C:4]([C:25]([F:28])([F:27])[F:26])[CH:3]=1.[CH:29]([Mg]Br)([CH3:31])[CH3:30]>C1COCC1.CN1CCCC1=O.C/C(/[O-])=C/C(C)=O.C/C(/[O-])=C/C(C)=O.C/C(/[O-])=C/C(C)=O.[Fe+3]>[F:23][C:17]1[CH:18]=[CH:19][CH:20]=[C:21]([F:22])[C:16]=1[C:15]([NH:14][C:11]1[CH:12]=[CH:13][N:9]([CH2:8][C:5]2[CH:6]=[CH:7][C:2]([CH:29]([CH3:31])[CH3:30])=[CH:3][C:4]=2[C:25]([F:28])([F:27])[F:26])[N:10]=1)=[O:24]

Komponenten

6

Edukt 2

HCID 46945199N-(1-{[4-chloro-2-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-3-yl)-2,6-difluorobenzamideHCID 178418365HCID 178418365, Verbindung

Produkt 1

HCID 595479432,6-Difluoro-N-(1-{[4-(1-methylethyl)-2-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-3-yl)benzamide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 5483663Ferric acetylacetonateKatalysatorHCID 8028TetrahydrofuranLösungsmittel2×HCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Versuchsvorschrift

To a solution of N-(1-{[4-chloro-2-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-3-yl)-2,6-difluorobenzamide (for a preparation see Example 80)(100 mg, 0.241 mmol) in a mixture of THF (0.9 ml) and N-methyl-2-pyrrolidone (0.1 ml) was added iron(III) acetylacetonate (17 mg, 0.048 mmol, Aldrich). The resulting red solution was stirred for 10 min and then treated with a solution of 15% isopropylmagnesium bromide in THF (1.2 ml, 0.60 mmol, Fluorochem) at ambient temperature. The solution was stirred at room temperature under nitrogen overnight. The reaction mixture was quenched with methanol (1 ml) and the solvent removed in vacuo. The residue was dissolved in 1:1 MeOH:DMSO (2 ml) and purified by MDAP (Method B) on Sunfire C18 column using Acetonitrile-Water with a Formic acid modifier. The solvent was evaporated in vacuo to give the title compound as a yellow solid (26 mg); LCMS: (System 4) MH+=424, tRET=3.41 min.

Aufarbeitung

  1. stirringThe solution was stirred at room temperature under nitrogen overnight
  2. customThe reaction mixture was quenched with methanol (1 ml)
  3. customthe solvent removed in vacuo
  4. dissolutionThe residue was dissolved in 1:1 MeOH
  5. customDMSO (2 ml) and purified by MDAP (Method B) on Sunfire C18 column
  6. customThe solvent was evaporated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-392c1b4c0c9d4d62919d3fecf1b575b0
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08399436B2

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