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
Keytruda 与阿西替尼联
亮剑!四家涉嫌违法环评机构将被
欧盟因心血管风险宣布暂停芬司匹
抗真菌药氟康唑或可推高孕妇流产
广东省已核发58张农药生产许可
Intercept 脂肪肝药物
喜讯!久易丙硫菌唑相关产品获农
Bavencio 组合疗法用于
德国拜耳向雅本化学颁发“伙伴关
默沙东 Keytruda 未能
华北地区顺酐市场行情整理
华东地区己二酸市场小幅下行
我国首次集中批准一批火龙果用药
山东地区木薯乙醇市场变动不大
山东地区木薯乙醇市场变动不大
山东地区木薯乙醇市场行情
山东地区二氯甲烷市场价格上调
陕西地区醋酸价格
华东地区醋酸价格下调
山东地区醋酸价格下调
 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