Sodium hydride → 4-(tert-butyl)-N-[3-{2-[(5-fluoro-2-pyrimidinyl)oxy]ethoxy}-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]benzenesulfonamide

HRID 1368588Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1368588
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15]2[N:19]([CH3:20])[N:18]=[C:17]([O:21][CH2:22][CH2:23][OH:24])[C:16]=2[C:25]2[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Cl[C:35]1[N:40]=[CH:39][C:38]([F:41])=[CH:37][N:36]=1.[Cl-].[NH4+]>O1CCCC1.CC(N(C)C)=O.C(OCC)(=O)C>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([S:11]([NH:14][C:15]2[N:19]([CH3:20])[N:18]=[C:17]([O:21][CH2:22][CH2:23][O:24][C:35]3[N:40]=[CH:39][C:38]([F:41])=[CH:37][N:36]=3)[C:16]=2[C:25]2[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=2)(=[O:12])=[O:13])=[CH:9][CH:10]=1)([CH3:4])([CH3:3])[CH3:2]

Komponenten

8

Edukt 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 5834662-Chloro-5-fluoropyrimidineHCID 222820434-(tert-butyl)-N-[3-(2-hydroxyethoxy)-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]benzenesulfonamide

Produkt 1

HCID 222819924-(tert-butyl)-N-[3-{2-[(5-fluoro-2-pyrimidinyl)oxy]ethoxy}-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]benzenesulfonamideAusbeute 12,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 31374DimethylacetamideLösungsmittel

Versuchsvorschrift

To 4-(tert-butyl)-N-[3-(2-hydroxyethoxy)-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]benzenesulfonamide (Example 2, 126 mg) in tetrahydrofuran (5 ml) at room temperature under an atmosphere of nitrogen was added sodium hydride (60% dispersion in oil, 34 mg) and the reaction mixture was stirred for 5 minutes. To the reaction mixture was added a solution of 2-chloro-5-fluoropyrimidine (50 mg) in dimethyl acetamide (1 ml) and the reaction was stirred for a further 16 hours. The reaction was poured cautiously into a stirred mixture of saturated aqueous ammonium chloride solution (10 ml) and ethyl acetate (10 ml). The organic fraction was separated, dried over magnesium sulphate, filtered and concentrated under reduced pressure. The residue was purified by preparative HPLC on a 5μ ODS Phenomenex Magellen™ column with gradient elution of acetonitrile (5% to 95%) and 0.1M NH4OAc (95% to 5%) to yield the title compound as a white solid (19 mg).

Aufarbeitung

  1. stirringthe reaction was stirred for a further 16 hours
  2. customThe organic fraction was separated
  3. dry with materialdried over magnesium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by preparative HPLC on a 5μ ODS Phenomenex Magellen™ column with gradient elution of acetonitrile (5% to 95%) and 0.1M NH4OAc (95% to 5%)

Quellen und Nachweise

ORD-Eintrag
ord-dacec9378b374855bfed9fbc6fe518fa
Quelldatensatz
uspto-grants-2003_06
Patentnummer
US06573270B1

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