Abstract
Erlotinib is an orally administered,highly effective,specific epidermal growth factor receptor tyrosine kinase inhibitor,used to treat non-small cell lung cancer and pancreatic cancer.The traditional synthetic methods for Erlotinib exhibit long reaction time and safety concern.Herein,we describe a novel five-step route for the synthesis of Erlotinib in flow.These five steps comprise etherification,nitration,reduction,addition and cyclization reactions.All steps were optimized and converted to continuous flow process,which drastically reduces the reaction time and considerably improves the process safety as well as the total yield.Enabled by five continuous flow units,Erlotinib is efficiently afforded with an E-factor of 38,an overall yield of 83％,and a total residence time of 25.1 min.Majority steps in this process have been optimized for quantitative conversion,which offers the possibility of telescoping the entire process.
基金项目
国家自然科学基金(21878088)
国家自然科学基金(21476077)
Key Projects of Shanghai Science and Technology Commission(18DZ1112703)
NETL
NSTL
万方数据