Synthesis
The general procedure for the synthesis of 4-iodo-5-methylpyridin-2-amine from 2-fluoro-4-iodo-5-methylpyridine was as follows: 2-fluoro-4-iodo-5-methylpyridine (3.00 g, 12.7 mmol) was mixed with concentrated aqueous ammonium hydroxide (3.5 mL, 90 mmol) in DMSO (17 mL) to form a white suspension. The reaction mixture was placed in a microwave reactor and reacted at 140 °C for 4 hours. After the reaction was completed, it was cooled to room temperature. The reaction mixture was diluted with EtOAc and water to separate the organic and aqueous layers. The aqueous layer was extracted with EtOAc (3 x 50 mL), all organic layers were combined and concentrated under reduced pressure. The concentrated residue was adsorbed onto silica gel and purified by fast silica gel chromatography with an elution gradient of 0 to 10% MeOH in DCM solution, resulting in 4-iodo-5-methylpyridin-2-amine (800 mg, 27% yield) as a white solid. The product was confirmed by 1H NMR (300 MHz, DMSO-d6, 27 °C): δ 2.13 (s, 3H), 5.81 (s, 2H), 6.99 (s, 1H), 7.75 (s, 1H). Mass spectral analysis showed m/z: ES+ [M+H]+ 235.
References
[1] Patent: US2016/376287, 2016, A1. Location in patent: Paragraph 0957
[2] Patent: WO2011/26904, 2011, A1. Location in patent: Page/Page column 131
[3] Patent: WO2012/87519, 2012, A1. Location in patent: Page/Page column 122
