Pyridine → (S)-N-(3-(1-ethyl-1H-pyrazol-5-yloxy)-5-(pyridin-2-ylthio)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decan-2-yl)-1,2,4-thiadiazol-5-amine

HRID 1511060Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1511060
[N-:1]=[C:2]=[S:3].[Na+].N1C=CC=CC=1.CS(O[N:16]=[C:17](Cl)[C@H:18]1[CH2:22][O:21][C:20]2([CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)[O:19]1)(=O)=O.[CH2:29]([N:31]1[C:35]([O:36][C:37]2[C:38]([NH2:50])=[N:39][CH:40]=[C:41]([S:43][C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][N:45]=3)[CH:42]=2)=[CH:34][CH:33]=[N:32]1)[CH3:30]>CCOC(C)=O.[OH-].[Na+]>[CH2:29]([N:31]1[C:35]([O:36][C:37]2[C:38]([NH:50][C:2]3[S:3][N:16]=[C:17]([C@H:18]4[CH2:22][O:21][C:20]5([CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]5)[O:19]4)[N:1]=3)=[N:39][CH:40]=[C:41]([S:43][C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][N:45]=3)[CH:42]=2)=[CH:34][CH:33]=[N:32]1)[CH3:30]

Komponenten

7

Edukt 4

HCID 1049PyridineHCID 10953423IsothiocyanatosodiumHCID 674860483-(1-ethyl-1H-pyrazol-5-yloxy)-5-(pyridin-2-ylthio)pyridin-2-amineHCID 86644147(R)-N-(methylsulfonyloxy)-1,4-dioxaspiro[4.5]decane-2-carbimidoyl chloride

Produkt 1

HCID 68472914(S)-N-(3-(1-ethyl-1H-pyrazol-5-yloxy)-5-(pyridin-2-ylthio)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decan-2-yl)-1,2,4-thiadiazol-5-amineAusbeute 64,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8857Ethyl AcetateLösungsmittel2×HCID 14798Sodium HydroxideLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

To 75 mL of EtOAc was added sodium isothiocyanate (0.579 g, 7.15 mmol), pyridine (0.874 ml, 10.7 mmol) and (R)-N-(methylsulfonyloxy)-1,4-dioxaspiro[4.5]decane-2-carbimidoyl chloride (2.13 g, 7.15 mmol) and the reaction was heated to 50° C. for 30 minutes. The reaction mixture was added to 3-(1-ethyl-1H-pyrazol-5-yloxy)-5-(pyridin-2-ylthio)pyridin-2-amine (1.12 g, 3.57 mmol) and the reaction was stirred for 65 hours at 75° C. The reaction was cooled and diluted with 50 ml EtOAc and 75 ml 1N NaOH. The aqueous layer was extracted with EtOAc. The organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified over silica gel (75% EtOAc/Hexanes) to afford (S)-N-(3-(1-ethyl-1H-pyrazol-5-yloxy)-5-(pyridin-2-ylthio)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decan-2-yl)-1,2,4-thiadiazol-5-amine (1.24 g, 2.31 mmol, 64.5% yield) as a tan solid.

Aufarbeitung

  1. temperatureThe reaction was cooled
  2. extractionThe aqueous layer was extracted with EtOAc
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified over silica gel (75% EtOAc/Hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-18b7fd57d4544293a3e89870e8d0125b
Quelldatensatz
uspto-grants-2012_07
Patentnummer
US08212045B2

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