有机化学人才网 | 最新人才 | 最新职位 | 技术交易 | 药物合成 |
   
全站搜索: |
  您当前位置:网站首页 >> 药物合成路线图解
 

药物详细合成路线

Name Fulvestrant;ZD-9238;ZM-182780;ZD-182780;ICI-182780;Faslodex
Chemical Name 7alpha-[9-(4,4,5,5,5-Pentafluoropentylsulfinyl)nonyl]estra-1,3,5(10)-triene-3,17beta-diol
CAS 129453-61-8
Related CAS
Formula C32H47F5O3S
Structure
Formula Weight 606.78559
Stage 上市-2002
Company AstraZeneca (Originator)
Activity/Mechanism Breast Cancer Therapy, Oncolytic Drugs, Antiestrogens
Syn. Route 2
Route 1
protection of 9-bromononan-1-ol (i) with tert-butyldimethylsilyl chloride and imidazole in thf gives the silyl ether (ii), which reacts with mg in the same solvent to yield the grignard reagent (iii). reaction of compound (iii) with cui affords the corresponding organocuprate that condenses with 6,7-didehydro-19-nortestosterone (iv) to provide the adduct (v). cleavage of the silyl ether group of (v) with hoac/water in thf gives alcohol (vi), which is esterified with ac2o and pyridine, yielding the corresponding diacetate (vii). aromatization of enone (vii) with cubr2 and libr in refluxing acetonitrile affords phenol (viii), which is selectively hydrolyzed with naoh in methanol to provide the primary alcohol (ix). the selective esterification of the phenolic oh group of (ix) with benzoyl chloride and naoh in acetone/water furnishes the aryl benzoate (x).
List of intermediates No.
(e)-2-isopropyl-3-[4-methoxy-3-(3-methoxypropoxy)phenyl]-2-propenoic acid (i)
2-(1,3-dioxo-1,3-dihydro-2h-isoindol-2-yl)acetyl chloride (ii)
ethyl 4-(1,3-dioxo-1,3-dihydro-2h-isoindol-2-yl)-3-oxobutanoate (iii)
diethyl 2-[2-(1,3-dioxo-1,3-dihydro-2h-isoindol-2-yl)acetyl]succinate (iv)
ethyl 2-bromoacetate (v)
diethyl 2-[2-(1,3-dioxo-1,3-dihydro-2h-isoindol-2-yl)acetyl]succinate (vi)
2,2-dimethyl-1,3-dioxane-4,6-dione (vii)
ethyl 4-(1,3-dioxo-1,3-dihydro-2h-isoindol-2-yl)-3-oxobutanoate (viii)
diethyl 2-[2-(1,3-dioxo-1,3-dihydro-2h-isoindol-2-yl)acetyl]succinate (ix)
methyl phenyl sulfone; methyl(dioxo)phenyl-lambda~6~-sulfane (x)
Reference 1:
    castaner, j.; dsouza, n.; levin, m.; fulvestrant. drugs fut 2001, 26, 9, 841.
Reference 2:
    bowler, j.; tait, b.s. (astrazeneca plc); steroid derivs.. ep 0138504; jp 1985097995; us 4659516 .

Route 2
by reaction of primary oh group of (x) with mesyl chloride and tea in dichloromethane gives the mesylate (xi). compound (xi) is condensed with 4,4,5,5,5-pentafluoropentanethiol (xii) by means of nah in thf to yield the thioether (xiii), which is submitted to basic hydrolysis of the ester groups by means of naoh in meoh/water to afford the corresponding dihydroxy compound (xiv). finally, this compound is oxidized with sodium metaperiodate to provide fulvestrant.
List of intermediates No.
methyl phenyl sulfone; methyl(dioxo)phenyl-lambda~6~-sulfane (x)
ethyl 2-{[tert-butyl(dimethyl)silyl]oxy}acetate (xi)
1-{[tert-butyl(dimethyl)silyl]oxy}-3-(phenylsulfonyl)acetone (xii)
ethyl 5-{[tert-butyl(dimethyl)silyl]oxy}-4-oxo-3-(phenylsulfonyl)pentanoate (xiii)
ethyl 5-{[tert-butyl(dimethyl)silyl]oxy}-4-oxopentanoate (xiv)
Reference 1:
    castaner, j.; dsouza, n.; levin, m.; fulvestrant. drugs fut 2001, 26, 9, 841.
Reference 2:
    bowler, j.; tait, b.s. (astrazeneca plc); steroid derivs.. ep 0138504; jp 1985097995; us 4659516 .

来源:药化网

作者:药化小编

摘要:本文合成路线介绍的是药物中文名氟维司群;英文名Fulvestrant;ZD-9238;ZM-182780;ZD-182780;ICI-182780;Faslodex;CAS[129453-61-8]

 
推荐VIP企业
无锡景耀生物科技有限公司
杭州卢普生物科技有限公司
宁波赛伦化工有限公司
苏州昊赛生物科技有限公司
北京嘉盛扬医药科技有限公司
上海泽涵生物医药科技有限公司
河北固安三利化工公司
郑州凯普瑞生物技术有限公司
上海药谷药业有限公司
兰州康寓信生物科技有限公司
湖北朗昕生化药业有限公司
武汉福鑫化工有限公司
嘉兴市英南化工有限公司
苏州迪飞医药科技有限公司
北京富安凯科技有限公司
上海盛中医药化工有限公司
连云港天和化学有限公司
南京晨瑞医药科技有限公司
南京苏如化工有限公司
常州瑞盛化工有限公司
热门文章
江苏地区粗苯价格暂稳
山东地区粗苯价格暂稳
华东地区丁二烯市场弱势盘整
浙江省化学农药使用量连续7年持
兴发集团实现草甘膦副产物高效高
华北地区BDO市场弱势延续
中国农民礼赞!——写在第一个“
我国化工园区第一个国家标准已获
红太阳/丰山集团等8家农药生产
农业农村部农药检定所征求《农药
刘学:浅析农药登记后再评价工作
2018年秋播小麦种子药剂处理
内蒙古元正精细化工高效氟吡甲禾
华南地区己二酸行情持稳
华东地区丁二烯市场价格走低
噻虫嗪比吡虫啉更适合小麦拌种
中国农药供应的历程、特点和主要
丁香菌酯等农药产品入选《201
国内百草枯登记证已到期,需寻求
华东地区己二酸市场小幅整理
 友情链接
有机化学人才网  
首页 | 广告服务 | 建站服务 | 关于我们 | 联系我们 | 版权声明