药物艾乐替尼(Alectinib)合成检索总结报告.docx

该【药物艾乐替尼(Alectinib)合成检索总结报告】是由【鼠标】上传分享，beplayapp体育下载一共【5】页，该beplayapp体育下载可以免费在线阅读，需要了解更多关于【药物艾乐替尼(Alectinib)合成检索总结报告】的内容，可以使用beplayapp体育下载的站内搜索功能，选择自己适合的beplayapp体育下载，以下文字是截取该文章内的部分文字，如需要获得完整电子版，请下载此beplayapp体育下载到您的设备，方便您编辑和打印。药物艾乐替尼(Alectinib)合成检索总结报告一、艾乐替尼(Alectinib)简介艾乐替尼(Alectinib)于2015年12月11日在美国上市。艾乐替尼(Alectinib)用于经克唑替尼治疗后疾病进展或耐药的间变性淋巴瘤激酶(ALK)呈阳性、转移性的NSCLC患者。艾乐替尼(Alectinib)不良反应有:疲劳、便秘、水肿和肌痛。艾乐替尼(Alectinib)分子结构式如下:英文名称:Alectinib中文名称:艾乐替尼本文主要对艾乐替尼(Alectinib)的合成路线、关键中间体的合成方法及实验操作方法进行了文献检索并作出了总结。二、艾乐替尼(Alectinib)合成路线一 1?三、艾乐替尼(Alectinib)合成路线二 2?四、艾乐替尼(Alectinib)合成路线三五、艾乐替尼(Alectinib)合成路线四六、艾乐替尼(Alectinib)合成路线一检索总结报告(一)艾乐替尼(Alectinib)中间体3的合成(路线一)合成方法 实验步骤 参考文献2-(4-bromo-3-hydroxyphenyl)acetate?1?(,??mmol)?wasdissolved?in?pyridine?(,??mmol),?Trifluoromethane-??sulfonic?anhydride2?(?g,??mmol)?was?added?106995433;操作方法25°C?stirring?reaction?for?1?hour,?after?post-treatment?and(2017);?(A)一purification,?To?give?5-[(ethoxycarbonyl)?methyl]?-2-bromo-?Chinesephenyl?trifluoromethanesulfonate3?as?a?pale?yellow?solid(?g)?in?98%?yield.?(二)艾乐替尼(Alectinib)中间体5的合成(路线一) 3?合成方法实验步骤参考文献35?-?[(ethoxycarbonyl)?methyl]?-2-bromophenyl?triflate(,?)?was?dissolved?in?N,?N-?dimethylformamide?4CN106995433(250?mL)?,?4-?(4-piperidinyl)?morpholine?(,?;操作方法mmol),?sodium?methoxide?(,?),?the?reaction(2017);?(A)一mixture?was?stirred?100°C?for?12?hours,?the?reaction?solutionChinesewas?cooled?to?room?temperature?,?water?(150mL),?cooled?to?0°C?crystallization?4?hours,?filtered?to?give?4-bromo-2-?{3-[4-?(morpholin-4-yl)?piperidin-1-yl]?phenyl}?ethyl?acetate5,as?a?white?solid?(?g?of),?in?85%?yield.?(三)艾乐替尼(Alectinib)中间体6的合成(路线一)合成方法实验步骤参考文献4-Bromo-2-{3-[4-(morpholin-4-yl)?piperidin-1-yl]?phenyl}ethyl?acetate5?(,?)?was?dissolved?in?methanol?(250?mL?),?was?slowly?added?sodium?methoxide?(,?85.?2mmol),?cooled?to?about?C,0°?iodomethane?(,),?the?reaction?mixture?was?70°C?the?reactionCN106995433;2017操作方法stirred?for?4?hours,?the?reaction?solution?was?cooled?to?room();?(A)一temperature,?dilute?hydrochloric?acid?was?adjusted?to?neutral,Chineseand?concentrated?by?rotary?evaporation?to?dryness,?extracted?with?ethyl?acetate,?dried?over?magnesium?sulfate,?andconcentrated?by?rotary?evaporation?to?dryness,?recrystallizedfrom?methanol?to?give?4-bromo-2-?{3-?[4-?(morpholine?4-yl)piperidin?-?Buji]?phenyl}?-2-methyl-propionic?acid?ethylester?6,?off-white?solid?(?g?of),?in?89%?yield.?(四)艾乐替尼(Alectinib)中间体7的合成(路线一)合成方法 实验步骤 参考文献 ethyl?2-{4-bromo-3-[4-(morpholin-4-yl)piperidin-1-yl] 4phenyl}-2-methylpropionate?6?(?g,??mmol)?wasdissolved?in?1,4-dioxane(150?mL),?cooled?to?-C,78°?SlowlyCN107033125drop?the?diisobutylaluminum?hydride?(?g,??mmol)?in;操作方法n-hexane?solution.?The?reaction?was?stirred?atC??0°for?3(2017);?(A)一hours,?evaporated?to?dryness?under?reduced?pressure,Chineseneutralized?with?dilute?hydrochloric?acid,?extracted?withethyl?acetate,?washed?with?water?and?dried.?To?dry?andisopropanol?to?give?2-{4-bromo-3-[4-(morpholin-4-yl)piperidin-1-yl]phenyl}-2-methylpropanal?7,?pale?yellowsolid?(?g)?in?97%?yield(五)艾乐替尼(Alectinib)中间体9的合成(路线一)合成方法实验步骤参考文献2-{4-bromo-3-[4-(morpholin-4-yl)piperidin-1-yl]phenyl}-2-methylpropanal?7(?g,??mmol)?and?tert-butyl-2,82-dichloroacetate??(?g,??mmol)?were?dissolved?intetrahydrofuran?(200?mL),?cooled?in?an?ice?bath,?slowlyadded?sodium?tert-butoxide?(?g,??mmol),?warmed?toCN**********°C,?The?reaction?was?carried?out?for?6?hours,?then;2017操作方法tetrabutylammonium?chloride?(?g,??mmol)?was?added,();?(A)一stirred?at?room?temperature?for?an?additional?6?hours,Chinese.?adjusted?to?neutral?with?dilute?hydrochloric?acid,concentrated?to?dryness?by?steaming,?washed,?dried?anddried,?dried?over?magnesium?sulfate,?concentrated?to?drynessby?steam,?and?recrystallized?from?methanol?to?give?tert-butyl3-chloro-4-{4-bromo-3-[4-(morpholin-4-yl)piperidin-1-yl]phenyl}-4-methyl-2-oxopentanoate?9as?an?off-white?solid(?g)?in?88%?yield.?(六)艾乐替尼(Alectinib)中间体11的合成(路线一)合成方法 实验步骤 参考文献 tert-butyl?3-chloro-4-{4-bromo-3-[4-(morpholin-4-yl)- piperidin-1-yl]phenyl}-4-methyl-2-oxopentanoate?9(?g, 5