Study On Synthesis Of 2-Amino-5-Fluoropyridine

2-Amino-5-fluoropyridine is an important intermediate of LBM415 which is the peptide deformylase inhibitor, the inhibitor of caspases-3 and antibiotic DW-116 et al. And it was synthesized from 2-aminopyridine as the raw material via nitrification, amino acetylation, reduction of nitro, diazolization, Schiemann reaction and hydrolysis of acetyl. The method simplified the experimental operation, avoided the preparation of 2-chloro-5-aminopyridine which was reported in another method, and solved some problems such as the separation of the intermediate products, low yield and purity of the products.The optimal reaction conditions (temperature, time, molar yield) were asfollows. Nitrification: 45℃, 2h, 41%; amino acetylation: reflux, 1h, 96.3%; reduction of nitro: reflux, 1h, 90%; diazolization: -5-0℃, 2h, 81.4%;Schiemann reaction: 130℃, 0.5h, hydrolysis of acetyl: reflux, 2.5h, the totalyield of this two steps was 51.6%. The melting point of the product was the same as those reported in literatures, and the structure of the target product was affirmed by ~1H-NMR and IR.