Method for preparing apatinib

• Main Authors: HAN JIAN, CHEN CHUNJI, SHI YUBO, WANG AIRU, LIU SHULIANG
• Format: Patent
• Language: Chinese; English
• Published: 05.06.2020
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY

The invention provides a method for preparing apatinib, which comprises the following steps: in the presence of a catalyst, directly mixing 1-(4-aminophenyl) cyclopentylcarbonitrile with 2-[(pyridine-4-methyl)amino]nicotinic acid intermediate alcohol ester to carry out amidation reaction, thereby obtaining the apatinib. According to the invention, the prejudice of the prior art is overcome; by insisting on exploring the amidation reaction of ester and amine, the method for preparing apatinib is screened out, the materials can be directly mixed for reaction without a dropwise addition operation, so that synthesis and purification are very simple and convenient, the cost is low, the product purity is very high, and the yield is very high regardless of ester or amine raw materials, which canbe increased by a couple dozens of percentage points compared with the prior art. 本发明提供了制备阿帕替尼的方法，包括在催化剂存在下，使1-(4-氨基苯基)环戊基甲腈与2-[(吡啶-4-甲基)氨基]烟酸中级醇酯直接混合以进行酰胺化反应，得到阿帕替尼。本发明克服了现有技术的偏见，坚持探索酯与胺酰胺化反应，筛到了一种制备阿帕替尼的方法，其物料可直接混合反应，无需滴加，合