Preparation and application background and overview of methyl 2-chloromethylpyridine-3-carboxylate
2-Chloromethylpyridine-3-carboxylic acid methyl ester is a pharmaceutical intermediate, which can be obtained by chlorination of 2-methylnicotinic acid methyl ester as raw material. There are reports in the literature that it can be used to prepare a TLRs agonist.
Preparation and application of methyl 2-chloromethylpyridine-3-carboxylate
Add 2-methylnicotinate methyl ester (10.0g, 66.2mmol), m-chloroperoxybenzoic acid (16.3g, 94.5mmol) and dichloromethane (140mL) into a 250mL single-neck reaction bottle. Stir at room temperature overnight, add saturated sodium bicarbonate solution to adjust the pH to 7-8, extract with dichloromethane (50 mL×2), combine the organic layers, wash with saturated brine, and dry over anhydrous sodium sulfate. Filter, and distill the dimethyl sulfoxide solvent under reduced pressure. Add phosphorus oxychloride (60 mL) to the residue, and heat to reflux and stir for 4 hours. Phosphorus oxychloride was removed by distillation under reduced pressure. The resulting residue was poured into ice water and neutralized with sodium carbonate solid to weak alkalinity. Extracted with ethyl acetate (60mL×3), combined the organic layers, and washed with saturated brine. Dry over anhydrous sodium sulfate. The calcium carbonate was filtered, and the solvent was evaporated under reduced pressure. The obtained residue was separated by flash column chromatography (ethyl acetate/petroleum ether = 0% to 30%) to obtain the compound 2-chloromethylpyridine-3-carboxylic acid methyl ester ( 1.94g, yield: 16%) as orange oil.
Preparation and application of methyl 2-chloromethylpyridine-3-carboxylate
Methyl 2-chloromethylpyridine-3-carboxylate can be used to prepare benzazepine derivatives with the following structure. This type of compound has a good regulatory effect on TLRs and can effectively treat, alleviate and/or Prevent various related diseases caused by immune suppression, such as cancer, autoimmune diseases, infection, inflammation, transplant rejection, graft-versus-host disease, etc.
References
[1] [Invented in China, authorized by China] CN201710308602.7 Benzazepine derivatives, their preparation methods, pharmaceutical compositions and applications
