Synthesis
The general procedure for the synthesis of 6-amino-5-bromonicotinonitrile from 2-amino-5-cyanopyridine is as follows:
Step 1: To a solution of 6-aminonicotinonitrile (102 mg, 0.86 mmol) in acetic acid (2 mL) was added a solution of bromine in acetic acid (0.86 mmol). The mixture was stirred at room temperature for 2 hours. After completion of the reaction, the solvent was removed by distillation under reduced pressure. The crude product was purified by rapid chromatography on silica gel (eluent: hexane/ethyl acetate, 3:1, v/v) to afford the title compound 6-amino-5-bromonicotinonitrile (110 mg, 65% yield).
The product characterization data are as follows:
1H-NMR (DMSO, 300 MHz): δ 8.26 (d, 1H, J = 2.0 Hz), 8.10 (d, 1H, J = 2.0 Hz), 7.24 (bs, 2H).
MS (APCI Neg): m/z 196, 198.
References
[1] Patent: WO2005/90337, 2005, A1. Location in patent: Page/Page column 42-43
[2] Patent: WO2008/60907, 2008, A2. Location in patent: Page/Page column 38
[3] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 9, p. 2073 - 2078
[4] Patent: US2015/266872, 2015, A1. Location in patent: Paragraph 0783; 0784
[5] Patent: EP3372601, 2018, A1. Location in patent: Paragraph 0743; 0744
