2-氨基-4-氟吡啶合成工艺研究

2-氨基-4-氟吡啶是制备酪氨酸激酶抑制剂、PI3K抑制剂和醛固酮合酶抑制剂等酶抑制剂的重要中间体。已报道的制备方法均存在一些缺陷,难以满足工业化生产。本文以4-氯吡啶-2-甲酰胺为原料,经酰胺脱水、卤素交换、氰基水解、霍夫曼降解等反应得到目标化合物。产物结构经1H NMR和GC-MS确证。本文采用的合成方法简单、反应条件温和、产物收率及纯度高,总收率达48.5%,GC纯度达到99.5%以上,适合工业化生产。

Synthesis research of 2-amino-4-fluoropyridine

2-Amino-4-fluoropyridine is an important intermediate in synthesis of tyrosine kinase inhibitor,PI3K inhibitor and aldosterone synthase inhibitor etc.All the reported preparation methods have some defects and are not suitable for industrial production.In this paper,the target compound was obtained by the reaction of dehydration,halogen exchange,hydrolysis and Hoffmann degradation,using 4-chloropyridine-2-carboxamide as starting material.The structure of product was confirmed by 1H NMR and GC-MS.The synthesis route adopted in this paper had the advantages of simple synthesis method,mild reaction conditions,high product yield and purity.The total yield was up to 48.5%,GC purity was over 99.5%.This process was suitable for large-scale industrial production.