用苯甲酰化氯法拉濱中間體和甲醇合成氯法拉濱

論文編號:HG305   論文字?jǐn)?shù):12699,頁數(shù):29

摘  要

 在過去10年中兒童無反應(yīng)或復(fù)發(fā)性ALL的治療一直處于一個平臺期，大部分復(fù)發(fā)的兒童預(yù)后仍不佳，因而我們?nèi)孕枰�繼續(xù)開發(fā)新而有效的治療藥物。氯法拉濱為這些患兒帶來了希望，同時(shí)氯法拉濱在復(fù)發(fā)或抵抗性急性髓細(xì)胞性白血病患兒中也顯示希望。
 本實(shí)驗(yàn)用苯甲酰化氯法拉濱中間體和甲醇合成氯法拉濱，對反應(yīng)條件進(jìn)行優(yōu)化，探索不同溫度及催化劑投入量大小對產(chǎn)品收率、純度以及反應(yīng)時(shí)間的影響。經(jīng)過多組實(shí)驗(yàn)論證，總結(jié)出最適的反應(yīng)條件及優(yōu)化的實(shí)驗(yàn)步驟，通過結(jié)構(gòu)分析，確認(rèn)產(chǎn)物為氯法拉濱。
 
 

關(guān)鍵詞    氯法拉濱   甲醇   絕對無水甲醇   檢測
 

Abstract

 In the past 10 year’s children in non-response or relapse of ALL treatment has been in a period of a platform, most of the children recurrence prognosis is still poor, so we still need to continue to develop new and effective treatments. Clofarabine for these children has brought hope and clofarabine in the resistance or recurrence of acute myeloid leukemia patients in the hope that the show also.
 Benzoyl use of clofarabine intermediates and methanol synthesis clofarabine satisfied that the conditions to optimize and explore different temperature catalyst volume and size of the yield, purity and the reaction time of impact. After experimental demonstration group, summed up the optimum conditions for the release should be optimized and the experimental steps. Compared with the past, product quality, yield and reaction time have a significant improvement .

 Key words   clofarabine   methanol sodium     anhydrous methanol detection

 目   錄
 
 文獻(xiàn)綜述
1.1氯法拉濱的研發(fā)背景……………………………………………………1
1.2氯法拉濱的國內(nèi)外生產(chǎn)狀況……………………………………………1
1.3氯法拉濱的理化性質(zhì)……………………………………………………1
1.4氯法拉濱的作用機(jī)制……………………………………………………2
1.5氯法拉濱的藥效學(xué)………………………………………………………3
1.6氯法拉濱的藥動學(xué)………………………………………………………4
1.7氯法拉濱的臨床研究……………………………………………………4
 1.7.1單用……………………………………………………………………5
 1.7.2聯(lián)合治療………………………………………………………………6
1.8氯法拉濱與其他藥物的相互作用  ……………………………………6
1.9氯法拉濱的不良反應(yīng)  …………………………………………………6
1.10氯法拉濱的開發(fā)前景 …………………………………………………7

 實(shí)驗(yàn)部分
2.1確定目標(biāo)化物……………………………………………………………8
 2.2設(shè)計(jì)合成路線……………………………………………………………9
2.3氯法拉濱的制備工藝研究………………………………………………12
 2.3.1化學(xué)反應(yīng)式及反映條件………………………………………………12
 2.3.2實(shí)驗(yàn)儀器、試劑………………………………………………………12
 2.3.3合成工藝的研究………………………………………………………13
2.4溫度對制備工藝的影響…………………………………………………14
2.5催化劑投入量對制備工藝的影響………………………………………15
2.6氯法拉濱的純化…………………………………………………………17

 產(chǎn)品分析                                                                           
3.1紅外吸收光譜……………………………………………………………18
3.2紫外吸收光譜……………………………………………………………20
3.3質(zhì)譜………………………………………………………………………21
3.4綜合分析…………………………………………………………………22

結(jié)論
4.1合成路線…………………………………………………………………23
4.2合成步驟…………………………………………………………………23
致謝 ……………………………………………………………………………………24
參考文獻(xiàn)………………………………………………………………………………25