4,6-Dimethylpyrimidin-2-ol → 2-[5-chloro-4-(4,6-dimethyl-pyrimidin-2-yloxy)-6-oxo-6H-pyridazin-1-yl]-3-cyclopentyl-propionic acid methyl ester

HRID 2381388Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2381388
[CH3:1][O:2][C:3](=[O:20])[CH:4]([N:11]1[C:16](=[O:17])[C:15]([Cl:18])=[C:14](Cl)[CH:13]=[N:12]1)[CH2:5][CH:6]1[CH2:10][CH2:9][CH2:8][CH2:7]1.[CH3:21][C:22]1[CH:27]=[C:26]([CH3:28])[N:25]=[C:24]([OH:29])[N:23]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH3:1][O:2][C:3](=[O:20])[CH:4]([N:11]1[C:16](=[O:17])[C:15]([Cl:18])=[C:14]([O:29][C:24]2[N:25]=[C:26]([CH3:28])[CH:27]=[C:22]([CH3:21])[N:23]=2)[CH:13]=[N:12]1)[CH2:5][CH:6]1[CH2:10][CH2:9][CH2:8][CH2:7]1

Komponenten

5

Edukt 3

HCID 95084,6-Dimethylpyrimidin-2-olHCID 11430Potassium CarbonateHCID 668757843-cyclopentyl-2-(4,5-dichloro-6-oxo-6H-pyridazin-1-yl)-propionic acid methyl ester2×

Produkt 1

HCID 668753332-[5-chloro-4-(4,6-dimethyl-pyrimidin-2-yloxy)-6-oxo-6H-pyridazin-1-yl]-3-cyclopentyl-propionic acid methyl esterAusbeute 38,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

A solution of 3-cyclopentyl-2-(4,5-dichloro-6-oxo-6H-pyridazin-1-yl)-propionic acid methyl ester (Intermediate 79 step 1, 15.4 g, 48 mmol) in N,N-dimethylformamide (150 mL) was treated with 4,6-dimethyl-pyrimidin-2-ol (5.98 g, 48 mmol) and potassium carbonate (8 g, 58 mmol). The reaction was heated at reflux for 12 h. At this time, the reaction was cooled to 25° C. and concentrated in vacuo. The residue was partitioned between water and methylene chloride. The aqueous layer was back extracted with methylene chloride. The combined organics were washed with a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated in vacuo. Chromatography (5/1 petroleum ether/ethyl acetat) afforded 2-[5-chloro-4-(4,6-dimethyl-pyrimidin-2-yloxy)-6-oxo-6H-pyridazin-1-yl]-3-cyclopentyl-propionic acid methyl ester (7.47 g, 38%).

Aufarbeitung

  1. temperatureThe reaction was heated
  2. temperatureat reflux for 12 h
  3. concentrationconcentrated in vacuo
  4. customThe residue was partitioned between water and methylene chloride
  5. extractionThe aqueous layer was back extracted with methylene chloride
  6. washThe combined organics were washed with a saturated aqueous sodium chloride solution
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-982de2f1b4384acf817c795df252e140
Quelldatensatz
uspto-grants-2012_09
Patentnummer
US08258134B2

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