3-Bromomethyl-pyridine-2-carbonitrile

Synthesis

Example 75: Synthesis of 3-(bromomethyl)pyridine-2-carbonitrile (1) SYNTHESIS STEPS: To a 100 mL round bottom flask was added 2-cyano-3-methylpyridine (2.36 g, 20.0 mmol), N-bromosuccinimide (NBS, 7.82 g, 43.9 mmol), and carbon tetrachloride (CCl4, 50 mL). The reaction mixture was stirred under reflux conditions for 16 hours. After completion of the reaction, the mixture was cooled to room temperature. The solid product was collected by filtration and washed with 50% ethyl acetate/hexane mixture. Subsequently, the solvent was removed by distillation under reduced pressure and the residue was purified by silica gel column chromatography using 30% ethyl acetate/hexane as eluent to give 3-(bromomethyl)pyridine-2-carbonitrile (2.56 g, 65.0% yield). Mass spectrometry analysis (ESI positive ion mode) m/z: calculated values for C7H5BrN2: 196.0, 198.0; measured values: 197.0, 199.0. 1H NMR (300 MHz, CDCl3) δ ppm: 4.64 (s, 2H), 7.54 (dd, J = 8.04, 4.68 Hz, 1H), 7.92 (dd, J = 8.04, 1.61 Hz, 1H), 8.66 (dd, J = 4.75, 1.53 Hz, 1H).

References

[1] Journal of Medicinal Chemistry, 2011, vol. 54, # 13, p. 4735 - 4751
[2] Patent: WO2009/155121, 2009, A2. Location in patent: Page/Page column 126-127
[3] Patent: WO2015/103317, 2015, A1. Location in patent: Page/Page column 184; 185
[4] Patent: US2006/281750, 2006, A1. Location in patent: Page/Page column 26
[5] ACS Medicinal Chemistry Letters, 2011, vol. 2, # 8, p. 559 - 564