Chemical Properties
4-Chloropyridine-2-carboxamide has active reactivity and special solvation ability, and can undergo dehydration, de-CO, introduction of amino groups, introduction of acyl groups, and cyclization in addition to the reaction involving three hydrogens].
Uses
4-Chloropyridine-2-carboxamide, is a versatile building block used in synthesis of various chemical compounds.
Synthesis
General procedure for the synthesis of 4-chloropyridine-2-carboxamide from 4-chloropyridine-2-carboxylic acid: a non-homogeneous mixture formed by 4-chloropyridine-2-carboxylic acid (TCI America, 5.4 g, 34.2 mmol, 1.0 equiv.) and thionyl chloride (30 mL) was heated and refluxed for 2 hr at 80 °C. Upon completion of the reaction, the mixture was cooled to room temperature and concentrated under reduced pressure to remove excess thionyl chloride. The resulting residue was placed in an ice bath and a methanol solution of ammonia (7 N, 45 mL) was slowly added and stirred under ice bath conditions for 15 minutes. The ice bath was then removed and the reaction mixture was allowed to gradually warm up to room temperature and stirring was continued for 3 hours. At the end of the reaction, the solvent was removed by concentration under reduced pressure and the residue was purified by recrystallization from ethyl acetate to afford the target product 4-chloropyridine-2-carboxamide (5.14 g, 96% yield) as a white solid. The product was characterized by 1H NMR (DMSO-d6): δ 8.61-8.63 (m, 1H), 8.21 (m, 1H), 8.03-8.04 (m, 1H), 7.76-7.83 (m, 2H); the mass spectrum (ESI+) showed m/z 157 ([M+H]+).
References
[1] Patent: US2005/245530, 2005, A1. Location in patent: Page/Page column 39
[2] Patent: US2007/78140, 2007, A1. Location in patent: Page/Page column 25
[3] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 14, p. 4323 - 4329
[4] Patent: WO2014/22116, 2014, A2. Location in patent: Paragraph 0212
[5] Patent: US2015/37280, 2015, A1. Location in patent: Paragraph 0414
