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

HRID 1524215Notes

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

Participants

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

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

Sources & evidence

ORD record: ord-f519780f3ec14a2fb76cd74c024e7875
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09079901B2

Reaction notes

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