(2,4-Dichloro-pyrimidin-5-yl-methyl)-(2-fluoro-4-methoxy-phenyl)amine → HCID 178491935, Verbindung

HRID 1243183Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1243183
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([CH2:9][NH:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][C:12]=2[F:19])=[CH:4][N:3]=1.C([Li])CCC.[C:25]([Si:29]([O:32][C@H:33]1[CH2:38][CH2:37][C@H:36]([N:39]=[C:40]=[O:41])[CH2:35][CH2:34]1)([CH3:31])[CH3:30])([CH3:28])([CH3:27])[CH3:26]>O1CCCC1.C(OCC)(=O)C>[C:25]([Si:29]([CH3:31])([CH3:30])[O:32][C@H:33]1[CH2:38][CH2:37][C@H:36]([N:39]2[C:6]3=[N:7][C:2]([Cl:1])=[N:3][CH:4]=[C:5]3[CH2:9][N:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][C:12]=3[F:19])[C:40]2=[O:41])[CH2:35][CH2:34]1)([CH3:28])([CH3:27])[CH3:26]

Komponenten

6

Edukt 3

HCID 21939275(2,4-Dichloro-pyrimidin-5-yl-methyl)-(2-fluoro-4-methoxy-phenyl)amineHCID 178418339ButyllithiumHCID 178455365HCID 178455365, Verbindung

Produkt 1

HCID 178491935HCID 178491935, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a solution of (2,4-dichloro-pyrimidin-5-yl-methyl)-(2-fluoro-4-methoxy-phenyl)amine (1.1 g, 3.64 mmol) (from Example 17a supra) in tetrahydrofuran (50 mL) at −78° C. was added n-butyllithium (2.5 M in hexanes, 1.75 mL, 4.37 mmol) (Aldrich). After stirring at −78° C. for 40 minutes, tert-butyl-(trans-4-isocyanato-cyclohexyloxy)-dimethyl-silane (1.12 g, 4.37 mmol) (from Example 17b supra) was added. The mixture was stirred at −70° C. for 1 hour and then at room temperature for 3 hours. It was diluted with ethyl acetate, washed with brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography eluting with ethyl acetate-hexanes (3:7 then 2:3) to give 1-[trans-4-(tert-butyl-dimethyl-silanyloxy)-cyclohexyl]-7-chloro-3-(2-fluoro-4-methoxy-phenyl)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one. (Yield 0.60 g, 33%).

Aufarbeitung

  1. stirringThe mixture was stirred at −70° C. for 1 hour
  2. waitat room temperature for 3 hours
  3. washwashed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash chromatography
  8. washeluting with ethyl acetate-hexanes (3:7

Quellen und Nachweise

ORD-Eintrag
ord-e438cd5c9fff4ae2b58442a950fdcb26
Quelldatensatz
uspto-grants-2006_10
Patentnummer
US07115740B2

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