1H-1,2,4-Triazole → 5-Bromo-3-methyl-2-(1H-1,2,4-triazol-1-yl)benzonitrile

HRID 1502759Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]([CH3:11])[C:5](F)=[C:6]([CH:9]=1)[C:7]#[N:8].C(=O)([O-])[O-].[K+].[K+].[NH:18]1[CH:22]=[N:21][CH:20]=[N:19]1>CN(C=O)C.O>[Br:1][C:2]1[CH:3]=[C:4]([CH3:11])[C:5]([N:18]2[CH:22]=[N:21][CH:20]=[N:19]2)=[C:6]([CH:9]=1)[C:7]#[N:8]

Participants

Conditions

Temperature: 140 °C

Procedure

To a stirred solution of 5-bromo-2-fluoro-3-methylbenzonitrile (1.0 g, 47.716 mmol), in DMF (10.0 mL) was added potassium carbonate (1.95 g, 14.14 mmol) followed by 1H-1,2,4-triazole (0.811 g, 9.433 mmol) at ambient temperature. The reaction mixture was heated to 140° C. for 18 h. The reaction mixture was cooled to ambient temperature, diluted with water and extracted with ethyl acetate (2×100 mL). The combined ethyl acetate layer was washed with brine and dried over Na2SO4 and concentrated under reduced pressure to afford the crude compound purified by flash column chromatography (SiO2, 100-200 mesh; eluting with 30% ethyl acetate/pet ether) to afford the title compound as a pink solid (0.6 g, 49%): 1H NMR (400 MHz, CDCl3) δ 8.39 (s, 1H), 8.23 (s, 1H), 7.91 (d, J=2.4 Hz, 2H), 2.21 (s, 3H), ESIMS m/z 262.57 ([M+H]+); IR (thin film) 2231, 554 cm−1.

Workup

temperatureThe reaction mixture was cooled to ambient temperature
extractionextracted with ethyl acetate (2×100 mL)
washThe combined ethyl acetate layer was washed with brine
dry with materialdried over Na2SO4
concentrationconcentrated under reduced pressure
customto afford the crude compound
custompurified by flash column chromatography (SiO2, 100-200 mesh; eluting with 30% ethyl acetate/pet ether)

Sources & evidence

ORD record: ord-712a966ef8564a759d6ae5bb2bbe924c
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09210927B2

Reaction notes

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