磷脂酰基醇3-激酶抑制剂甲磺酸普喹替尼的合成
收稿日期: 2019-02-20
修回日期: 2019-03-25
网络出版日期: 2019-04-19
基金资助
重大新药创制（No.2008ZX09101-048）资助项目.
Development of Synthesis of Phosphatidylinositol 3-Kinases Inhibitor Puquitinib Mesylate
Received date: 2019-02-20
Revised date: 2019-03-25
Online published: 2019-04-19
Supported by
Project supported by the Significant New Drugs Development (No. 2008ZX09101-048).
沈大冬 , 朱金林 , 吴国锋 , 盛力 , 高浩凌 , 王普 . 磷脂酰基醇3-激酶抑制剂甲磺酸普喹替尼的合成[J]. 有机化学, 2019 , 39(9) : 2676 -2680 . DOI: 10.6023/cjoc201902020
Puquitinib mesylate is a novel phosphatidylinositol 3-kinases (PI3K) inhibitor, which has been shown to be effective in the treatment of cancer. A convenient protocol for the synthesis of the compound at kilogram scale is described, using 2,6-dichloropurine as starting material through amino-protection, SN2 reaction with high regioselectivity, Buchwald-Hartwig coupling reaction, amino-deprotection and salt-forming reaction. The process is easy to operate and provides an effective way at kilogram scale produce with 48% yield in total.
Key words： PI3K inhibitor; puquitinib; synthesis
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