Uses
2-Chloro-4-amino-5-nitropyridine is an intermediate of benzimidazole derivatives used to treat diseases such as bone development disorders; it is also an intermediate of a PLK1 recombinant protein inhibitor used to treat cell proliferation disorders, especially cancer.
Synthesis
2-Chloro-4-nitroaminopyridine (CAS: 14432-13-4, 10.0 g) was used as a raw material, which was carefully dissolved in 100 mL of concentrated sulfuric acid at room temperature, followed by heating the reaction at 100 °C for 1 h. The reaction was carried out at room temperature. Upon completion of the reaction, the reaction solution was cooled to room temperature and slowly poured into 250 g of crushed ice. The pH of the mixture was adjusted to 3 with concentrated ammonium hydroxide under ice bath conditions, ensuring that the temperature was maintained below 20 °C. Subsequently, the resulting yellow solid was separated and the aqueous layer was extracted with ethyl acetate (200 mL × 3). The organic layers were combined, concentrated, and the residue was purified by silica gel column chromatography (eluent ratio: hexane:EtOAc = 4:1 to pure EtOAc, v/v) to give 6.0 g of 4-amino-2-chloro-3-nitropyridine in 70% yield and 2.0 g of 4-amino-2-chloro-5-nitropyridine in 25% yield.
The properties of 4-amino-2-chloro-3-nitropyridine were as follows: melting point 179-181 °C; UV(H2O) λmax 238.0 nm (ε 13586, pH 11); 1H-NMR (DMSO, 500 MHz) δ 7.91 (d, J = 6.0 Hz, 1H), 7.37 (s, 2H), 6.83 (d, J = 6.0 Hz, 1H); 13C-NMR (DMSO, 500 MHz) δ 7.91 (d, J = 6.0 Hz, 1H), 7.37 (s, 2H), 6.83 (d, J = 6.0 Hz, 1H); 1.0 g 4-amino-2-chloro-5-nitropyridine, yield 25%. 1H); 13C-NMR (DMSO, 125 MHz) δ 149.54, 149.24, 142.69, 142.33, 122.45.
The 1H-NMR (DMSO, 500 MHz) data of 4-amino-2-chloro-5-nitropyridine were as follows: δ 8.85 (s, 1H), 7.37 (s, 2H), 6.96 (s, 1H).
References
[1] Patent: WO2007/47793, 2007, A2. Location in patent: Page/Page column 87
[2] Roczniki Chemii, 1956, vol. 30, p. 1139,1144
[3] Chem.Abstr., 1957, p. 12089
[4] Nucleosides, nucleotides and nucleic acids, 2004, vol. 23, # 1-2, p. 67 - 76
[5] Organic and Biomolecular Chemistry, 2013, vol. 11, # 38, p. 6526 - 6545
