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2-Fluoropyridine → 6-bromo-2-(pyridin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

HRID 2368023
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 2368023
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8](=[O:11])[NH:9][N:10]=2)[CH:7]=1.C([O-])([O-])=O.[K+].[K+].F[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=1>O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8](=[O:11])[N:9]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=3)[N:10]=2)[CH:7]=1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

5

Edukt 3

HCID 97462-FluoropyridineHCID 11430Potassium CarbonateHCID 120407986-bromo-2H,3H-[1,2,4]triazolo[4,3-a]pyridin-3-one

Produkt 1

HCID 580443756-bromo-2-(pyridin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-oneAusbeute 51 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
160 °C

Versuchsvorschrift

A mixture of 6-bromo-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (100 mg, 0.467 mmol), K2CO3 (129 mg, 0.94 mmol), and 2-fluoropyridine (1 mL) was placed in a sealed microwave vial and heated to 160° C. in a microwave reactor for 90 minutes. The reaction was cooled, diluted with water/EtOAC and the layers were separated. The organic layer was washed with NaHCO3 and brine. The organics were dried (MgSO4), filtered, concentrated and purified by flash chromatography (Rf=0.23, 1:2 hexanes:EtOAc) to afford 70 mg (51% y) 6-bromo-2-(pyridin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one, which was used directly in the next reaction (M+1=292.1). Compound 34 was synthesized according to the procedure disclosed in Example 1, however the reaction was done in 24 hours (28% y). C18H11F3N4O2, m/z (ESI)=373.2 [M+H]+. 1H NMR (δ, d6-DMSO, 400 MHz) 8.54-8.57 (m, 1H), 8.22 (t, J=1.2 Hz, 2H), 7.98-8.07 (m, 2H), 7.88 (dt, J=2.0, 8.4 Hz, 2H), 7.72 (dd, J=2.0, 9.6 Hz, 1H), 7.43-7.47 (m, 3H), 7.36-7.40 (m, 1H)

Aufarbeitung

  1. temperatureThe reaction was cooled
  2. customthe layers were separated
  3. washThe organic layer was washed with NaHCO3 and brine
  4. dry with materialThe organics were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by flash chromatography (Rf=0.23, 1:2 hexanes:EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-a53bde4d66d444c9a685e9227b819e70
Quelldatensatz
uspto-grants-2014_04
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08703759B2

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