Methanol → 2-(4-methanesulfonyl-phenyl)-3-[3-(tetrahydropyran-2-yloxy)-cyclopentyl]-N-thiazol-2-yl-propionamide

HRID 854798Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 854798
[NH2:1][C:2]1[S:3][CH:4]=[CH:5][N:6]=1.C[O:8][C:9](=O)[CH:10]([C:24]1[CH:29]=[CH:28][C:27]([S:30]([CH3:33])(=[O:32])=[O:31])=[CH:26][CH:25]=1)[CH2:11][CH:12]1[CH2:16][CH2:15][CH:14]([O:17][CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][O:19]2)[CH2:13]1.C[O-].[Mg+2].C[O-].CO>>[CH3:33][S:30]([C:27]1[CH:26]=[CH:25][C:24]([CH:10]([CH2:11][CH:12]2[CH2:16][CH2:15][CH:14]([O:17][CH:18]3[CH2:23][CH2:22][CH2:21][CH2:20][O:19]3)[CH2:13]2)[C:9]([NH:1][C:2]2[S:3][CH:4]=[CH:5][N:6]=2)=[O:8])=[CH:29][CH:28]=1)(=[O:32])=[O:31]

Komponenten

5

Edukt 4

HCID 887MethanolHCID 21552-AminothiazoleHCID 164537Methanol, magnesium salt (2:1)HCID 674821052-(4-Methanesulfonyl-phenyl)-3-[3-(tetrahydropyran-2-yloxy)-cyclopentyl]-propionic acid methyl ester

Produkt 1

HCID 219589652-(4-methanesulfonyl-phenyl)-3-[3-(tetrahydropyran-2-yloxy)-cyclopentyl]-N-thiazol-2-yl-propionamideAusbeute 40 %

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

2-Aminothiazole (259 mg, 2.58 mmol) and 2-(4-methanesulfonyl-phenyl)-3-[3-(tetrahydropyran-2-yloxy)-cyclopentyl]-propionic acid methyl ester (1.06 g, 2.58 mmol) were treated with a solution of magnesium methoxide in methanol (7.4 wt. % , 14.76 mL, 10.32 mmol). The reaction mixture was then concentrated in vacuo to approximately one-half the volume of methanol. The resulting reaction mixture was heated under reflux for 24 h. The reaction mixture was allowed to cool to 25° C. and then filtered through a pad of celite. The pad of celite was washed well with ethyl acetate until the washings indicated the absence of product by thin layer chromatography. The filtrate was then washed with a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 1/2 hexanes/ethyl acetate) afforded 2-(4-methanesulfonyl-phenyl)-3-[3-(tetrahydropyran-2-yloxy)-cyclopentyl]-N-thiazol-2-yl-propionamide (494 mg, 40%) as a yellow foam: mp 68-70° C. (foam to gel); FAB-HRMS m/e calcd for C23H30N2O5S2 (M+H)+ 479.1674. found 479.1666.

Aufarbeitung

  1. concentrationThe reaction mixture was then concentrated in vacuo to approximately one-half the volume of methanol
  2. customThe resulting reaction mixture
  3. temperaturewas heated
  4. temperatureunder reflux for 24 h
  5. filtrationfiltered through a pad of celite
  6. washThe pad of celite was washed well with ethyl acetate until the washings
  7. washThe filtrate was then washed with a saturated aqueous sodium chloride solution
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-e14dfb15f6bc4be8bd20f1288ff49a23
Quelldatensatz
uspto-grants-2007_08
Patentnummer
US07259166B2

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