Sodium hydride → 4-[({4-[4-cyclopropyl-2-(2-trifluoromethoxy-phenyl)-2H-pyrazol-3-ylmethoxy]-2-methyl-phenyl}-methyl-amino)-methyl]-2-methoxy-benzoic acid methyl ester

HRID 2261869Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2261869
[H-].[Na+].[CH:3]1([C:6]2[CH:10]=[N:9][N:8]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][C:18]([F:21])([F:20])[F:19])[C:7]=2[CH2:22][O:23][C:24]2[CH:29]=[CH:28][C:27]([NH:30][CH3:31])=[C:26]([CH3:32])[CH:25]=2)[CH2:5][CH2:4]1.[CH3:33][O:34][C:35](=[O:46])[C:36]1[CH:41]=[CH:40][C:39]([CH2:42]Br)=[CH:38][C:37]=1[O:44][CH3:45]>CN(C=O)C.O>[CH3:33][O:34][C:35](=[O:46])[C:36]1[CH:41]=[CH:40][C:39]([CH2:42][N:30]([C:27]2[CH:28]=[CH:29][C:24]([O:23][CH2:22][C:7]3[N:8]([C:11]4[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=4[O:17][C:18]([F:20])([F:21])[F:19])[N:9]=[CH:10][C:6]=3[CH:3]3[CH2:4][CH2:5]3)=[CH:25][C:26]=2[CH3:32])[CH3:31])=[CH:38][C:37]=1[O:44][CH3:45]

Komponenten

6

Edukt 3

HCID 24758Sodium hydrideHCID 11288398Methyl 4-(bromomethyl)-2-methoxybenzoateHCID 57443372{4-[4-Cyclopropyl-2-(2-trifluoromethoxy-phenyl)-2H-pyrazol-3-ylmethoxy]-2-methyl-phenyl}-methyl-amine

Produkt 1

HCID 675285424-[({4-[4-cyclopropyl-2-(2-trifluoromethoxy-phenyl)-2H-pyrazol-3-ylmethoxy]-2-methyl-phenyl}-methyl-amino)-methyl]-2-methoxy-benzoic acid methyl esterAusbeute 68 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

Sodium hydride (60% in mineral oil, 30 mg, 0.75 mmol) is added to a solution of {4-[4-cyclopropyl-2-(2-trifluoromethoxy-phenyl)-2H-pyrazol-3-ylmethoxy]-2-methyl-phenyl}-methyl-amine (0.31 g, 0.75 mmol) and 4-bromomethyl-2-methoxy-benzoic acid methyl ester (0.320 g, 1.23 mmol) in DMF (3 mL) at room temperature. The reaction is heated to 40° C. for 2 h. The mixture is diluted with water and is extracted with ethyl acetate. The combined organic layers are washed with brine and dried over MgSO4. The crude residue is purified via radial chromatography (2 mm plate, 20 to 40 THF-heptane) to afford 4-[({4-[4-cyclopropyl-2-(2-trifluoromethoxy-phenyl)-2H-pyrazol-3-ylmethoxy]-2-methyl-phenyl}-methyl-amino)-methyl]-2-methoxy-benzoic acid methyl ester (303 mg, 68%). ES/MS m/e 596.0 (M+1).

Aufarbeitung

  1. extractionis extracted with ethyl acetate
  2. washThe combined organic layers are washed with brine
  3. dry with materialdried over MgSO4
  4. customThe crude residue is purified via radial chromatography (2 mm plate, 20 to 40 THF-heptane)

Quellen und Nachweise

ORD-Eintrag
ord-4f5488de012c4c929a05300be613ddee
Quelldatensatz
uspto-grants-2010_12
Patentnummer
US07846960B2

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