Potassium Hydroxide → [[(2,6-Difluorophenyl)carbonyl](1-{[2-fluoro-6-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-3-yl)amino]methyl bis(1,1-dimethylethyl) phosphate

HRID 1946352

Reaktionsgleichung

Reaktionsgleichung von HRID 1946352
[F:1][C:2]1[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[C:3]=1[C:4]([NH:6][C:7]1[CH:11]=[CH:10][N:9]([CH2:12][C:13]2[C:18]([C:19]([F:22])([F:21])[F:20])=[CH:17][CH:16]=[CH:15][C:14]=2[F:23])[N:8]=1)=[O:5].[P:29]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])([O:31][CH2:32]Cl)=[O:30].[OH-].[K+]>CN(C)C=O>[P:29]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])([O:39][C:40]([CH3:41])([CH3:43])[CH3:42])([O:31][CH2:32][N:6]([C:4]([C:3]1[C:2]([F:1])=[CH:27][CH:26]=[CH:25][C:24]=1[F:28])=[O:5])[C:7]1[CH:11]=[CH:10][N:9]([CH2:12][C:13]2[C:18]([C:19]([F:21])([F:22])[F:20])=[CH:17][CH:16]=[CH:15][C:14]=2[F:23])[N:8]=1)=[O:30]

Komponenten

5

Edukt 3

HCID 14797Potassium HydroxideHCID 11701630Di-tert-butyl (chloromethyl) phosphateHCID 46945384Gsk-5498A

Produkt 1

HCID 59547970[[(2,6-Difluorophenyl)carbonyl](1-{[2-fluoro-6-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-3-yl)amino]methyl bis(1,1-dimethylethyl) phosphate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A solution of 2,6-difluoro-N-(1-{[2-fluoro-6-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-3-yl)benzamide (for a preparation see Example 29)(61.25 g, 153 mmol), chloromethyl bis(1,1-dimethylethyl) phosphate (for a preparation see Intermediate 60)(47.6 g, 184 mmol) and potassium hydroxide (14.18 g, 215 mmol) in N,N-dimethylformamide (500 ml) was stirred at ambient temperature for 7 days. The reaction mixture was partitioned between ethyl acetate (350 ml) and water/brine (250 ml, 1:1 volume/volume). The organic phase was washed with brine (250 ml) and dried over magnesium sulphate. The solvent was removed in vacuo. The sample was loaded in dichloromethane and purified on a silica Redisep cartridge 1500 g using a gradient of 0-75% ethyl acetate-cyclohexane over 8 column volumes. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a colourless gum (which started to crystallise to a white solid (72.44 g); LCMS: (System 8) MH+=622, tRET=3.40 min.

Aufarbeitung

  1. customThe reaction mixture was partitioned between ethyl acetate (350 ml) and water/brine (250 ml, 1:1 volume/volume)
  2. washThe organic phase was washed with brine (250 ml)
  3. dry with materialdried over magnesium sulphate
  4. customThe solvent was removed in vacuo
  5. custompurified on a silica Redisep cartridge 1500 g
  6. customevaporated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-40daeab8295542e8b7ad97be4a230473
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08399436B2

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