Development of an Efficient and Practical Route for the Multikilogram Manufacture of the SRC Kinase Inhibitor AZD0530

作者：Ford J Gair^*; O'Kearney McMullan Anne; Pointon Simon M; Powell Lyn; Siedlecki Paul S; Purdie Mark; Withnall Jane; O'Keefe Phil; Wood Frances

来源：Organic Process Research & Development, 2010, 14(5): 1088-1093.

DOI：10.1021/op100163m

In a previous publication (Org. Process Res. Dev. 2010, 14, DOI: 10.1021/op100161y) we described the process research and development of a manufacturing route for the potent SRC kinase inhibitor AZD0530. While the route was successfully used to manufacture 4.5 kg of AZD0530 difumarate, it was still relatively long, used two Mitsunobu couplings, and was, in our opinion, undesirable for manufacture on a larger scale. Herein we describe the research and development of a shorter, more practical synthesis of AZD0530 difumarate. The new route, which required fewer steps, scaled well to produce >80 kg of AZD0530 difumarate in an overall yield of 38%.

• 出版日期2010-10