Water → Ethyl 4-(2-{(3,5-bis-trifluoromethyl-benzyl)-[2-(6-chloro-pyrimidin-4-yloxy)-5-trifluoromethyl-benzyl]-amino}-pyrimidin-5-yloxy)-butyrate

HRID 604133Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 604133
[F:1][C:2]([F:43])([F:42])[C:3]1[CH:4]=[C:5]([CH:35]=[C:36]([C:38]([F:41])([F:40])[F:39])[CH:37]=1)[CH2:6][N:7]([CH2:23][C:24]1[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][C:25]=1[OH:34])[C:8]1[N:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:10][N:9]=1.[H-].[Na+].[Cl:46][C:47]1[CH:52]=[C:51](Cl)[N:50]=[CH:49][N:48]=1.O>CN(C)C=O.C(OCC)(=O)C>[F:43][C:2]([F:1])([F:42])[C:3]1[CH:4]=[C:5]([CH:35]=[C:36]([C:38]([F:39])([F:40])[F:41])[CH:37]=1)[CH2:6][N:7]([CH2:23][C:24]1[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][C:25]=1[O:34][C:51]1[CH:52]=[C:47]([Cl:46])[N:48]=[CH:49][N:50]=1)[C:8]1[N:9]=[CH:10][C:11]([O:14][CH2:15][CH2:16][CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:12][N:13]=1

Komponenten

7

Edukt 4

HCID 962WaterHCID 24758Sodium hydrideHCID 709434,6-Dichloropyrimidine2×HCID 86626825Ethyl 4-{2-[(3,5-bis-trifluoromethyl-benzyl)-(2-hydroxy-5-trifluoromethyl-benzyl)-amino]-pyrimidin-5-yloxy}-butyrate

Produkt 1

HCID 86626879Ethyl 4-(2-{(3,5-bis-trifluoromethyl-benzyl)-[2-(6-chloro-pyrimidin-4-yloxy)-5-trifluoromethyl-benzyl]-amino}-pyrimidin-5-yloxy)-butyrateAusbeute 68,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

Ethyl 4-{2-[(3,5-bis-trifluoromethyl-benzyl)-(2-hydroxy-5-trifluoromethyl-benzyl)-amino]-pyrimidin-5-yloxy}-butyrate (300 mg) is dissolved in N,N-dimethylformamide (5 ml) and thereto are added sodium hydride (60%) (29 mg) and 4,6-dichloro-pyrimidine (107 mg) under ice-cooling, and the mixture is stirred for 30 minutes, and the reaction solution is cooled to room temperature, and thereto is added 4,6-dichloro-pyrimidine (107 mg), and the mixture is stirred for 30 minutes. To the reaction solution are added water and ethyl acetate, and the mixture is separated, and the organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=49:1→17:1) to give ethyl 4-(2-{(3,5-bis-trifluoromethyl-benzyl)-[2-(6-chloro-pyrimidin-4-yloxy)-5-trifluoromethyl-benzyl]-amino}-pyrimidin-5-yloxy)-butyrate (244 mg). MS (m/z): 738/740 [M+H]+

Aufarbeitung

  1. temperaturecooling
  2. stirringthe mixture is stirred for 30 minutes
  3. customthe mixture is separated
  4. washthe organic layer is washed with a saturated brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=49:1→17:1)

Quellen und Nachweise

ORD-Eintrag
ord-c736762d4e974696ac5828d6c6588203
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07906517B2

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