With the rapid development of chemical substances, we look forward to future research findings about 23056-33-9.
A common compound: 23056-33-9, name is 2-Chloro-4-methyl-5-nitropyridine,molecular formula is C6H5ClN2O2, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below., 23056-33-9
A solution of 2-chloro-4-methyl-5-nitropyridine (5.13 g, 29.73 mmol) in concentrated sulfuric acid (42 mL) was cooled to 0 C., and chromium trioxide (9.81 g, 98.1 mmol) was added. The mixture was stirred at 0 C. for 1 hour and then warmed to room temperature, with an oil bubbler attached, for overnight stirring. The reaction mixture was poured onto ice (300 ml) and diluted with water (150 ml). The mixture was warmed to room temperature, and the solid was filtered and then dried under vacuum to yield 2-chloro-5-nitroisonicotinic acid. To a stirred solution of the above material (5.3 g, 26.17 mmol) in methanol (50 ml) was added chloroform (200 ml). TMS-diazomethane as a solution in hexane (2M) was added dropwise until the color of the reaction mixture remained yellow (20 mL). The residual TMS-diazomethane was quenched by addition of acetic acid, and the solvent was removed under reduced pressure. The oily residue was subjected to silica gel chromatography eluted with 50-70% ethyl acetate in hexane to provide methyl 2-chloro-5-nitroisonicotinate. A solution of the above material (5.66 g, 26.13 mmol), methyl 4′-(aminomethyl)-3,3′-difluorobiphenyl-2-carboxylate (7.971 g, 28.75 mmol, prepared according to procedures described in WO 03/066577), and triethylamine (3.97 g, 39.20 mmol) in methanol (100 ml) was stirred at room temperature overnight. The solution was then heated at 60 C. for 4 hours and cooled to ambient temperature for continued stirring over the weekend. Solvent was removed, and the residue was subjected to silica gel chromatography eluted with 25-50% ethyl acetate in hexane to provide methyl 2-({[3,3′-difluoro-2′-(methoxycarbonyl)biphenyl-4-yl]methyl}amino)-5-nitroisonicotinate as a yellow solid. A solution of the above material (9.3 g, 20.33 mmol) in methanol (330 ml) was purged with nitrogen, and 10% Pd/C catalyst (1 g) was added. The reaction vessel was again purged with nitrogen and then with hydrogen from a balloon. After 23 hours of stirring under hydrogen, nitrogen was bubbled through the solution for 10 minutes prior to filtration through a celite pad. The filtrate was concentrated under reduced pressure to provide methyl 5-amino-2-({[3,3′-difluoro-2′-(methoxycarbonyl)biphenyl-4-yl]methyl}amino)isonicotinate. Into a solution of the above material (8.45 g, 19.77 mmol) in THF (440 ml) at 0 C. were added hypophosphorous acid (50% solution in water, 110 ml) and sodium nitrite (2.73 g, 39.54 mmol). After 10 minutes of stirring, a catalytic amount of copper (I) oxide was added every 30 minutes for 7.5 hours. The reaction mixture was partitioned between ethyl acetate and water, and the aqueous layer was extracted with additional ethyl acetate. The combined organic layers were washed with saturated sodium bicarbonate and brine, then dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was subjected to silica gel chromatography eluted with 20-40% ethyl acetate in hexane to provide methyl 2-({[3,3′-difluoro-2′-(methoxycarbonyl)biphenyl-4-yl]methyl}amino)isonicotinate. To a stirred solution of the above material (3.96 g, 9.60 mmol) in methanol (85 ml) was added 1N NaOH (11.5 ml), and the solution was heated at 40 C. for 3.5 hours. Solvent was removed under reduced pressure prior to dilution with water. The aqueous solution was washed with diethyl ether twice, and the residual diethyl ether in the aqueous solution was removed under reduced pressure. The aqueous solution was neutralized by addition of 1N HCl (11.5 ml), and the resulting thick suspension was heated (70 C.) and then slowly cooled to ambient temperature before being cooled to 0 C. for 30 minutes. The solid was filtered and dried under vacuum, providing the title compound as a white solid. LRMS (ES, M+H+): 399. 1H NMR (CD3OD, 400 MHz) delta 8.04 (d, J=5.6 Hz, 1H), 7.55 (m, 1H), 7.44 (t, J=8 Hz, 1H), 7.23 (m, 3H), 7.10 (m, 3H), 4.65 (s, 2H), 3.66 (s, 3H).
With the rapid development of chemical substances, we look forward to future research findings about 23056-33-9.
Reference:
Patent; Wood, Michael R.; Bock, Mark G.; Books, Kathy M.; Freidinger, Roger M.; Kim, June J.; US2006/122236; (2006); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem