1H-1,2,4-Triazole → 3-[1,2,4]Triazol-1-yl-pyridine-2-carbonitrile

HRID 1795268Notes

Reaction equation

[C:1]([C:3]1[C:8](F)=[CH:7][CH:6]=[CH:5][N:4]=1)#[N:2].C(=O)([O-])[O-].[Cs+].[Cs+].[NH:16]1[CH:20]=[N:19][CH:18]=[N:17]1>CN(C=O)C.O>[N:16]1([C:8]2[C:3]([C:1]#[N:2])=[N:4][CH:5]=[CH:6][CH:7]=2)[CH:20]=[N:19][CH:18]=[N:17]1

Participants

Conditions

Temperature: 65 °C

Procedure

To a solution of 2-cyano-3-fluoro-pyridine (2.99 g, 24.49 mmol, preparation described in Sakamoto et. al., Chem. Pharm. Bull. 1985, 33(2), 565–571) in DMF (30 ml) is added cesium carbonate (2.03 g, 29.39 mmol) and 1,2,4-triazole (2.03 g, 29.39 mmol) and the reaction mixture is stirred at 65° C. for 4 h. After cooling to room temperature, the mixture is diluted with water and extracted with EtOAc 3 times. The aqueous layer is saturated with LiCl and further extracted with EtOAc. The combined organic layer is dried on sodium sulfate, concentrated in vacuo. The crude product is purified by flash chromatography (silica gel, 2% MeOH containing 10% NH4OH in CH2Cl2 to 6%) to give 3-[1,2,4]triazol-1-yl-pyridine-2-carbonitrile. 1H NMR (CDCl3, 400 MHz) δ 8.95 (s, 1H); 8.8 (d, J=4 Hz, 1H); 8.24 (s, 1H); 8.22 (d, J=8.5 Hz, 1H); 7.75 (dd, J=4, 8.5 Hz, 1H).

Workup

temperatureAfter cooling to room temperature
extractionextracted with EtOAc 3 times
extractionfurther extracted with EtOAc
customThe combined organic layer is dried on sodium sulfate
concentrationconcentrated in vacuo
customThe crude product is purified by flash chromatography (silica gel, 2% MeOH containing 10% NH4OH in CH2Cl2 to 6%)

Sources & evidence

ORD record: ord-a5686d635e1f4e9f905ae2316ac9d293
Source dataset: uspto-grants-2006_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07026324B2

Reaction notes

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