Cesium carbonate → 3-[2,5-Difluoro-4-(methylsulfonyl)phenoxy]-5-[(1S)-2-hydroxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide

HRID 20553

Reaktionsgleichung

Reaktionsgleichung von HRID 20553
C(=O)([O-])[O-].[Cs+].[Cs+].[OH:7][C:8]1[CH:9]=[C:10]([CH:20]=[C:21]([O:23][C@@H:24]([CH3:27])[CH2:25][OH:26])[CH:22]=1)[C:11]([NH:13][C:14]1[CH:18]=[CH:17][N:16]([CH3:19])[N:15]=1)=[O:12].[F:28][C:29]1[CH:34]=[C:33]([S:35]([CH3:38])(=[O:37])=[O:36])[C:32]([F:39])=[CH:31][C:30]=1F>C(#N)C>[F:28][C:29]1[CH:34]=[C:33]([S:35]([CH3:38])(=[O:37])=[O:36])[C:32]([F:39])=[CH:31][C:30]=1[O:7][C:8]1[CH:9]=[C:10]([CH:20]=[C:21]([O:23][C@@H:24]([CH3:27])[CH2:25][OH:26])[CH:22]=1)[C:11]([NH:13][C:14]1[CH:18]=[CH:17][N:16]([CH3:19])[N:15]=1)=[O:12]

Komponenten

5

Edukt 3

HCID 10796Cesium carbonateHCID 467393961,2,4-Trifluoro-5-(methylsulfonyl)benzeneHCID 593468923-Hydroxy-5-{[(S)-2-hydroxy-1-methylethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide

Produkt 1

HCID 115402683-[2,5-Difluoro-4-(methylsulfonyl)phenoxy]-5-[(1S)-2-hydroxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamideAusbeute 1,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
160 °C

Versuchsvorschrift

Caesium carbonate (523 mg) was added to a solution of 3-hydroxy-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide (234 mg) and 1,2,4-trifluoro-5-(methylsulfonyl)benzene (169 mg) in acetonitrile (5 mL) was added. The mixture was heated in a sealed microwave vial to 160° C. for 7000 seconds and left to cool before being filtered and washed with acetonitrile (10 mL). The filtrate was evaporated in vacuo and chromatographed on silica, eluting with 0 to 10% methanol in ethyl acetate. This gave incomplete resolution so the mixture was purified by preparatory HPLC using a gradient of 5 to 95% acetonitrile in water to afford the desired compound (5.1 mg)

Aufarbeitung

  1. additionwas added
  2. waitleft
  3. temperatureto cool
  4. filtrationbefore being filtered
  5. washwashed with acetonitrile (10 mL)
  6. customThe filtrate was evaporated in vacuo
  7. customchromatographed on silica
  8. washeluting with 0 to 10% methanol in ethyl acetate
  9. customThis gave incomplete resolution so the mixture was purified by preparatory HPLC

Quellen und Nachweise

ORD-Eintrag
ord-f5db6578902c40369809c04aab9c4f72
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07745475B2

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