Description
2,4-Dichloro-3-nitropyridine is a halogenated pyridinium salt that has been shown to inhibit the influenza virus in vitro. This compound is also reactive with nucleophilic groups such as amines, alcohols, and thiols. 2,4-Dichloro-3-nitropyridine has been used for the synthesis of quinoline derivatives that have potential applications in autoimmune diseases or cancer. 2,4-Dichloro-3-nitropyridine has also been found to be an inhibitor of tumor necrosis factor alpha (TNFα) production by LPS stimulated human monocytes.
Uses
2,4-Dichloro-3-nitropyridine is a reactant in the discovery of Imigliptin, a novel selective dipeptidyl peptidase IV (DPP-4) inhibitor used in the treatment of type 2 diabetes.
Synthesis
The general procedure for the synthesis of 2,4-dichloro-3-nitropyridine from 4-hydroxy-3-nitropyridin-2(1H)-one is as follows:
Method A: Synthesis of 2,4-dichloro-3-nitropyridine: 15.0 g (96.2 mmol, 1.0 eq.) of 2,4-dihydroxy-3-nitropyridine was suspended in 200 mL of phosphorochloride and the reaction was heated at 90 °C for 20 hrs. Upon completion of the reaction, the mixture was cooled to room temperature and the volume was concentrated to about 50 mL by reduced pressure distillation.The concentrated residue was carefully poured into about 300 mL of ice water and subsequently extracted with ethyl acetate (3 x 150 mL). The organic phases were combined, dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent. The residue was redissolved in 30 mL of ethyl acetate and 30 mL of hexane was added. The product was separated by silica gel column chromatography with 50% ethyl acetate/hexane as eluent to give 17.4 g (90.2 mmol, 94% yield) of 2,4-dichloro-3-nitropyridine (V) as a colorless crystalline solid.
References
[1] Patent: US6307054, 2001, B1
[2] Patent: WO2010/8775, 2010, A1. Location in patent: Page/Page column 19-20
[3] Patent: EP1221444, 2002, A1
[4] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 15, p. 4986 - 4989
[5] Patent: US2014/94456, 2014, A1. Location in patent: Paragraph 0713-0714
