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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
Notes
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Reaction equation

HRID 2368023 reaction equation
[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
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
160 °C

Procedure

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)

Workup

  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)

Sources & evidence

ORD record
ord-a53bde4d66d444c9a685e9227b819e70
Source dataset
uspto-grants-2014_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08703759B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes