Development of a Scalable Synthesis of 4-Aminopyrimidin-5-ol, a Versatile Intermediate

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• 作者：Phuong T. Le ; Paul F. Richardson ; Neal W. Sach ; Shuibo Xin ; Shijian Ren ; Jiezhan Xiao ; Liangliang Xue
• 刊名：Organic Process Research & Development
• 出版年：2015
• 出版时间：June 19, 2015
• 年：2015
• 卷：19
• 期：6
• 页码：639-645
• 全文大小：316K
• ISSN：1520-586X

文摘

A robust process for the preparation of multigram quantities of 4-aminopyrimidin-5-ol (5) in good yield from an inexpensive and readily available pyrimidine starting material is described. An initial evaluation of the reported literature route for this material utilizing a de novo pyrimidine synthesis provided safety concerns over the scalability of several intermediates. In addition, a number of steps proceeded in mediocre yield, and involved chromatographic separations for the desired products. The newly developed route mitigates the safety concerns, reduces the number of steps from five to three, avoids column chromatography, leads to an 8-fold improvement in yield, and utilizes reagents, which are recognized to be more environmentally benign.