Uses
2-Chloro-3-iodo-4-pyridinamine can be used as a useful synthetic intermediate.
Synthesis
General procedure for the synthesis of 2-chloro-3-iodo-4-pyridinamine from 2-chloro-4-aminopyridine: To a 50 mL single-necked round-bottomed flask equipped with a magnetic stir bar, a reflux condenser tube, and a nitrogen inlet tube under nitrogen protection were added 2-chloro-4-aminopyridine (2.50 g, 19.4 mmol, 1.0 equiv.), sodium sulfate trihydrate (3.97 g, 29.2 mmol, 1.5 equiv.), iodine monochloride (3.47 g, 21.4 mmol, 1.1 equiv.) and glacial acetic acid (13.0 mL). 1.5 equiv), iodine monochloride (3.47 g, 21.4 mmol, 1.1 equiv) and glacial acetic acid (13.0 mL). The reaction mixture was heated at 70 °C and magnetically stirred for 16 hours. Complete consumption of the feedstock was confirmed by thin layer chromatography (TLC) and electron bombardment mass spectrometry (GC/MS-EI) analysis. Upon completion of the reaction, the mixture was cooled to room temperature and transferred to a dispensing funnel. Solid sodium bicarbonate (32.3 g) was carefully added in batches to quench the reaction, followed by water (75 mL) and ethyl acetate (75 mL). After complete release of the gas produced, the layers were left to stratify. The aqueous layer was separated and extracted with ethyl acetate (6 x 25 mL). All organic layers were combined, dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography with hexane/ethyl acetate as eluent (94:6 to 60:40 gradient elution) to afford 2-chloro-3-iodopyridin-4-amine as a light brown solid (2.21 g, 45% yield). The 1H NMR spectrum and low-resolution GC/MS (EI) mass spectrometry data of the product were consistent with those reported in the literature.
References
[1] European Journal of Medicinal Chemistry, 2017, vol. 128, p. 202 - 212
[2] Patent: EP2526945, 2012, A1. Location in patent: Page/Page column 63
[3] Patent: WO2013/10880, 2013, A1. Location in patent: Page/Page column 94
[4] Patent: EP2548876, 2013, A1. Location in patent: Paragraph 0368; 0369
[5] Patent: WO2014/207260, 2014, A1. Location in patent: Page/Page column 78
