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 met...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.展开更多
Compression tests were performed at room temperature to investigate the effects of hydrogenation temperature on compressive properties of Ti6 Al4 V alloy treated by continuous multistep hydrogenation treatment(CMHT).P...Compression tests were performed at room temperature to investigate the effects of hydrogenation temperature on compressive properties of Ti6 Al4 V alloy treated by continuous multistep hydrogenation treatment(CMHT).Pressure-composition isotherms and micro structures were also studied.Results showed that the equilibrium hydrogen pressure increased,and the hydrogen absorption rate decreased with the increase of hydrogenation temperature.The amounts ofβphase andα"martensite increased first and then decreased when Ti6 Al4 V alloy was treated by four times CMHT with the increase of hydrogenation temperature.Hydrogenation temperature played a different role on the compressive properties of CMHT-treated Ti6 Al4 V alloy.The ultimate compression of Ti6 Al4 V alloy treated by 11 times CMHT at850℃increased by 83.3%as compared to the as-received Ti6 Al4 V alloy.The compressive properties of Ti6 Al4 V alloy were dependent on the amounts of different phases and microstructures when Ti6 Al4 V alloy was treated by CMHT at different temperatures.展开更多
基金the National Natural Science Foundation of China(Nos.21878088, 21476077)Key Projects of Shanghai Science and Technology Commission (No.18DZ1112703) for financial support。
文摘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financially supported by the National Natural Science Foundation of China(No.51875157)the University Natural Science Research Project of Anhui Province(No.KJ2019A0894)the Fundamental Research Funds for the Central Universities(No.JD2019JGPY0016)。
文摘Compression tests were performed at room temperature to investigate the effects of hydrogenation temperature on compressive properties of Ti6 Al4 V alloy treated by continuous multistep hydrogenation treatment(CMHT).Pressure-composition isotherms and micro structures were also studied.Results showed that the equilibrium hydrogen pressure increased,and the hydrogen absorption rate decreased with the increase of hydrogenation temperature.The amounts ofβphase andα"martensite increased first and then decreased when Ti6 Al4 V alloy was treated by four times CMHT with the increase of hydrogenation temperature.Hydrogenation temperature played a different role on the compressive properties of CMHT-treated Ti6 Al4 V alloy.The ultimate compression of Ti6 Al4 V alloy treated by 11 times CMHT at850℃increased by 83.3%as compared to the as-received Ti6 Al4 V alloy.The compressive properties of Ti6 Al4 V alloy were dependent on the amounts of different phases and microstructures when Ti6 Al4 V alloy was treated by CMHT at different temperatures.
