Water → tert-Butyl-(1S,3R)-3-(6-tosyl-6H-pyrrolo[2,3-e][1, 2, 4]triazolo[4,3-a]pyrazin-1-yl)cyclopentylcarbamate

HRID 2204588Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2204588
[S:1]([N:11]1[C:15]2=[N:16][CH:17]=[C:18]([NH:20][NH:21][C:22]([C@@H:24]3[CH2:28][CH2:27][C@H:26]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:25]3)=O)[N:19]=[C:14]2[CH:13]=[CH:12]1)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2].O=S(Cl)Cl.CCOC(C)=O.O>O1CCOCC1>[C:32]([O:31][C:30](=[O:36])[NH:29][C@H:26]1[CH2:27][CH2:28][C@@H:24]([C:22]2[N:19]3[C:14]4[CH:13]=[CH:12][N:11]([S:1]([C:4]5[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=5)(=[O:2])=[O:3])[C:15]=4[N:16]=[CH:17][C:18]3=[N:20][N:21]=2)[CH2:25]1)([CH3:34])([CH3:35])[CH3:33]

Komponenten

6

Edukt 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 24386Thionyl ChlorideHCID 58009789tert-butyl (1S,3R)-3-(2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinecarbonyl)cyclopentylcarbamate

Produkt 1

HCID 58009863tert-Butyl-(1S,3R)-3-(6-tosyl-6H-pyrrolo[2,3-e][1, 2, 4]triazolo[4,3-a]pyrazin-1-yl)cyclopentylcarbamateAusbeute 85,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a solution of tert-butyl (1S,3R)-3-(2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinecarbonyl)cyclopentylcarbamate (9.30 g, 18.1 mmol) in 1,4-dioxane (100 mL) was added TEA (10.0 mL, 72.3 mmol) and SOCl2 (2.11 mL, 28.9 mmol). The mixture was heated at about 80° C. for about 1.5 h. The reaction mixture was cooled to ambient temperature, EtOAc and water were added, and the layers were separated. The aqueous solution was extracted with EtOAc (2×100 mL) and the combined organic layers were washed with saturated aqueous NaHCO3 and brine (100 mL each). The organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by silica gel chromatography eluting with a gradient of 25-100% EtOAc in DCM to give tert-butyl-(1S,3R)-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentylcarbamate (7.65 g, 85%): LC/MS (Table 2, Method a) Rt=2.37 min; MS m/z: 497 (M+H)+.

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. customthe layers were separated
  3. extractionThe aqueous solution was extracted with EtOAc (2×100 mL)
  4. washthe combined organic layers were washed with saturated aqueous NaHCO3 and brine (100 mL each)
  5. dry with materialThe organic extracts were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material was purified by silica gel chromatography
  9. washeluting with a gradient of 25-100% EtOAc in DCM

Quellen und Nachweise

ORD-Eintrag
ord-042e01a9ce444bedbc2008c8894dd3fc
Quelldatensatz
uspto-grants-2016_06
Patentnummer
US09365579B2

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