Background and overview of preparation and application examples of 5-bromo-2-methoxy-4-methyl-3-nitropyridine
5-Bromo-2-methoxy-4-methyl-3-nitropyridine is an organic intermediate that can be prepared from 2-chloro-4-methyl-3-nitropyridine as raw material 2 -Methoxy-4-methyl-3-nitropyridine, and then bromination gives 5-bromo-2-methoxy-4-methyl-3-nitropyridine.
Preparation and application examples of 5-bromo-2-methoxy-4-methyl-3-nitropyridine
Preparation and application examples of 5-bromo-2-methoxy-4-methyl-3-nitropyridine Preparation of 2-methoxy-4-methyl-3-nitropyridine
A solution of 2-chloro-4-methyl-3-nitropyridine (250g, 1.45mol) in methanol (1.0L) was added dropwise to (2h) stirred and cooled (0°C) sodium methoxide (250g). 4.63 mol) in methanol (850 mL). After addition, the mixture was heated to reflux for 23 h, at which time TLC indicated that the reaction was complete. The mixture was concentrated under reduced pressure to a volume of approximately 900 mL and quenched by addition of water (1.5 L). The resulting solid was collected by filtration, washed with water and dried under reduced pressure to give the title compound (250 g, 100% yield) as a brown solid. 1H NMR (MHz, DMSO-d6): δ 8.22 (d, J=5.2Hz, 1H), 7.10 (d, J=5.6Hz, 1H), 3.92 (s, 3H), 2.26 (s, 3H).
Examples of preparation and application of 5-bromo-2-methoxy-4-methyl-3-nitropyridine 5-bromo-2-methoxy-4-methyl-3-nitro Preparation of pyridine
Sodium acetate (365g, 5.37mol) was added to a stirred solution of 2-methoxy-4-methyl-3-nitropyridine (250g, 1.49mol) in acetic acid (1.5L) at ambient temperature. , then add dropwise (30min) Br2 (639g, 4.00mol). After addition, the mixture was heated at 80 °C for 12 h, at which time TLC indicated that the reaction was complete. The mixture was cooled (0°C) and quenched by adding 10% Na2SO3 aqueous solution (1.5L) and saturated Na2SO3 aqueous solution (1.5L) successively. The resulting solid was collected by filtration, washed with water, and dried under reduced pressure to obtain the title compound (302 g, 82.2% yield) as a light yellow solid. 1H NMR (MHz, DMSO-d6): δ 8.25 (s, 1H), 3.94 (s, 3H), 2.29 (s, 3H).
Preparation and application examples of 5-bromo-2-methoxy-4-methyl-3-nitropyridine
5-Bromo-2-methoxy-4-methyl-3-nitropyridine can be used to prepare an adamantane-containing compound having the following structure.
This type of compound can be used to treat castration-resistant prostate cancer.
References
[1] [Chinese invention of ammonium pentaborate, Chinese invention authorization] CN201580072351.6 Bromo domain inhibitors and their uses
[2] From Pethoxycarbonylbenzeneboronic acid CT Int. Appl., 2019184919, 03 Oct 2019
