Background and overview of the preparation method of 5-nitro-2-methoxypyridine
5-Nitro-2-methoxypyridine, also called 2-methoxy-5-aminopyridine, is the intermediate of malaridine. Malaridine is a new antimalarial drug synthesized by the Institute of Parasitic Diseases of the Chinese Academy of Medical Sciences in the early 1970s. Its chemical name is 2-methoxy-7-10-[(3′,5′-bistetrahydropyrrole). Methyl)-4′-hydroxyamphetyl]benzo[b]1,5-naphthyridine.
Preparation method of 5-nitro-2-methoxypyridine
A green and environmentally friendly preparation method, with high product purity and yield, simple production process, less three wastes and by-products in the production process, and has economic and environmental significance.
Preparation method of 5-nitro-2-methoxypyridine (1) Synthesis of 2-amino-5-nitropyridine
Add 18.82g (0.2mol) of 2-aminopyridine and 75.3g of dichloroethane into the reactor, stir to dissolve methoxypyridine, and slowly add fuming solution with a mass ratio of 1:1.3 below 10°C. 43.29g of mixed acid composed of nitric acid/concentrated sulfuric acid was added dropwise and reacted at 58°C for 10 hours. The reaction liquid changed from light yellow to wine red. After the reaction is completed, the temperature is cooled to room temperature, washed with water to pH 5.5, the organic layer is decompressed to recover dichloroethane, the residue is slowly poured into ice water, a dark yellow precipitate is precipitated, filtered, washed with water, and dried to obtain 2-amino-5- Nitropyridine 25.64g, HPLC purity is 98.57%, yield is 90.85%.
Preparation method of 5-nitro-2-methoxypyridine (2) Synthesis of 2-hydroxy-5-nitropyridine
Dissolve 13.9g (0.1mol) of 2-amino-5-nitropyridine in 55.6g of dilute hydrochloric acid with a mass concentration of 15%, and add 20% NaNO2 dropwise below 0°C. 48.3g of aqueous solution. After the dropwise addition, the reaction was incubated at 5°C for 30 minutes. The reaction solution was concentrated under reduced pressure, cooled to precipitate a light yellow solid, washed with ice water, and dried to obtain 12.48g of 2-hydroxy-5-nitropyridine. The HPLC purity was 98.35%, the yield is 87.61%.
References
[1] [Chinese invention] CN201510955049.7 A method for preparing fluorophenylboronic acid from pyronaridine intermediate 2-methoxy-5-aminopyridine
