Development of Scalable Syntheses of Selective PI3K inhibitors

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• 作者：Qinhua Huang ; Paul F. Richardson ; Neal W. Sach ; Jinjiang Zhu ; Kevin K.-C. Liu ; Graham L. Smith ; Daniel M. Bowles
• 刊名：Organic Process Research & Development
• 出版年：2011
• 出版时间：May 20, 2011
• 年：2011
• 卷：15
• 期：3
• 页码：556-564
• 全文大小：1054K
• 年卷期：v.15,no.3(May 20, 2011)
• ISSN：1520-586X

文摘

On the basis of a more practical and scalable route to an iodothiophene, an efficient and reliable synthesis has been developed for three selective PI3K inhibitors. From this advanced intermediate, the three title compounds were each prepared in five additional steps. Key learnings also include: high throughput experimentation (HTE) screening toward a more robust Suzuki coupling, a more efficient triazole synthesis, and an acid/base cleanup developed to purify the final compounds. The final enabled synthesis required no column chromatography.