有机化学 ›› 2019, Vol. 39 ›› Issue (9): 2676-2680.DOI: 10.6023/cjoc201902020 上一篇    下一篇

研究简报

磷脂酰基醇3-激酶抑制剂甲磺酸普喹替尼的合成

沈大冬a, 朱金林b, 吴国锋b, 盛力b, 高浩凌b, 王普a   

  1. a 浙江工业大学药学院 杭州 310032;
    b 浙江医药股份有限公司研究院 绍兴 312500
  • 收稿日期:2019-02-20 修回日期:2019-03-25 出版日期:2019-09-25 发布日期:2019-04-19
  • 通讯作者: 沈大冬, 王普 E-mail:shendadong@126.com;wangpu@zjut.edu.cn
  • 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

Shen Dadonga, Zhu Jinlinb, Wu Guofengb, Sheng Lib, Gao Haolingb, Wang Pua   

  1. a College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310032;
    b Research & Development Center, Zhejiang Medicine Co., Ltd., Shaoxing 312500
  • Received:2019-02-20 Revised:2019-03-25 Online:2019-09-25 Published:2019-04-19
  • Contact: 10.6023/cjoc201902020 E-mail:shendadong@126.com;wangpu@zjut.edu.cn
  • Supported by:

    Project supported by the Significant New Drugs Development (No. 2008ZX09101-048).

甲磺酸普喹替尼是一种新颖的磷脂酰基醇3-激酶(PI3K)抑制剂,临床实验结果显示对肿瘤治疗有较好的效果.报道了公斤级合成该抑制剂的方法,以2,6-二氯嘌呤为起始原料,通过氨基上保护、区域选择性SN2亲核取代反应、Buchwald-Hartwig偶联反应,氨基脱保护成盐合成了甲磺酸普喹替尼,该法操作简单,总收率达到48%,为其放大生产提供了有效途径.

关键词: PI3K抑制剂, 普喹替尼, 合成

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