5446-92-4 , The common heterocyclic compound, 5446-92-4, name is 2-Methoxy-5-nitropyridine, molecular formula is C6H6N2O3, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.
Preparation of 5-Methoxy-1H-pyrrolo[3,2-b]pyridine-3-carbaldehyde (Formula 10); 2-Methoxy-5-nitro-pyridine (Formula 6, 4 g, 25.6 mmole) and 4-chlorophenoxyacetonitrile (Formula 7, 4.8 g, 28.5 mmole) were dissolved in THF (58 mL). The resulting solution was slowly added to a solution of t-BuOK (6.3 g, 56.3 mmole) in THF dry (60 mL) at -10 C. The reaction mixture was stirred for 3 h at -10 C., and then water was added. The aqueous layer was extracted with EtOAc. The combined organic layers were dried on Na2SO4 and evaporated to give a crude that was purified by silica gel column chromatography (eluent: petroleum ether/EtOAc 8:2) to give (6-methoxy-3-nitro-pyridin-2-yl)-acetonitrile (Formula 8, Yield: 50%. MS (m/z): 194.1 (MH+)).To a solution of (6-methoxy-3-nitro-pyridin-2-yl)-acetonitrile (Formula 8, 1 g, 5.18 mmole) in EtOH (30 mL), 10% Pd/C was added. The mixture was hydrogenated at 45 psi at room temperature overnight. The catalyst was filtered off and the solvent was evaporated. The crude product was purified by silica gel column chromatography (eluent: petroleum ether/EtOAc 8:2) to give 5-methoxy-1H-pyrrolo[3,2-b]pyridine (Formula 9, Yield: 64%. MS (m/z): 149 (MH+).To a solution of 5-methoxy-1H-pyrrolo[3,2-b]pyridine (Formula 9, 498 mg, 3.36 mmole) in 33% acetic acid (5.2 mL), hexamethylenetetramine (714 mg, 5.05 mmole) was added. The reaction mixture was refluxed for 4 hours. After cooling, the reaction was extracted with EtOAc. The combined organic layers were dried on Na2SO4 and evaporated to give a crude that was purified twice by silica gel column chromatography (eluent: methylene chloride/MeOH 95:5) to give 5-methoxy-1H-pyrrolo[3,2-b]pyridine-3-carbaldehyde (Formula 10, Yield: 27%. MS (m/z): 177.17 (MH+)).
According to the analysis of related databases, 5446-92-4, the application of this compound in the production field has become more and more popular.
Reference:
Patent; Wyeth; US2009/298820; (2009); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem