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 Naratriptan hydrochloride;GG-548;GR-85548A;GR-85548(free base);Amerge;Naramig
Chemical Name N-Methyl-2-[3-(1-methylpiperidin-4-yl)-1H-indol-5-yl]ethanesulfonamide monohydrochloride
CAS 143388-64-1
Related CAS 121679-13-8 (free base), 121679-19-4 (HCl)
Formula C17H26ClN3O2S
Structure
Formula Weight 371.93267
Stage 上市-1997
Company GlaxoSmithKline (Originator), Sumitomo Pharmaceuticals (Licensee), Schwarz (Comarketer)
Activity/Mechanism Acute Attacks of Migraine, Treatment of, ANALGESIC AND ANESTHETIC DRUGS, Antimigraine Drugs, 5-HT1B Agonists, 5-HT1D Agonists
Syn. Route 1
Route 1
naratriptan can be obtained by several related ways:1) the reaction of 5-bromoindole (i) with 1-methylpiperidin-4-one (ii) by means of koh in methylated spirit (or methanol) at room temperature gives 5-bromo-3-(4-(hydroxy-1-methylpiperidin-4-yl)-1h-indole (iii) (1, 2), which is condensed with n-methylvinylsulfonamide (iv) by means of palladium acetate and tri-p-tolyl phosphine in hot (110 c) dmf to afford (e)-n-methyl-2-[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1h-indol-5-yl]vinylsulfonamide (v). finally, this compound is hydrogenated with h2 over pd/c in dmf/water/hcl, dmf/water/methanol/hcl, or water/methanesulfonic acid.2) the reaction of indole (i) with piperidone (ii) or with 4-hydroxy-1-methylpiperidine (vi) by means of koh in refluxing methylated spirit or 1-propanol gives 5-bromo-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1h-indole (vii), which is then condensed with n-methylvinylsufonamide (iv) as before, yielding the substituted sulfonamide (v), already obtained.3) the hydrogenation of the tetrahydropyridine (vii) with h2 over pto2 in methanol/hcl gives 5-bromo-3-(1-methylpiperidin-4-yl)-1h-indole (viii), which is finally condensed with n-methylvinylsulfonamide (iv) as before yielding n-methyl-2-[3-(1-methylpiperidin-4-yl)-1h-indol-5-yl]vinylsulfonamide (xi). finally, this compound is hydrogenated with h2 over pd/c in ethanol/dmf/hcl.4) the reaction of 5-bromoindole (i) with sulfonamide (iv) by means of palladium acetate as before gives 2-(1h-indol-3-yl)-n-methylvinylsulfonamide (ix), which is condensed with piperidone (ii) by means of refluxing koh as before, yielding the substituted tetrahydropyridine (v), already obtained.5) the condensation of sulfonamide (ix) with piperidone (ii), by means of koh at room temperature as before gives n-methyl-2-[3-(4-hydroxy-1-methylpiperidin-4-yl)-1h-indol-3-yl] vinylsulfonamide (x), which is dehydrated to tetrahydropyridine (v) with koh in refluxing methylated spirit.6) the cyclization of 2-(4-hydrazinophenyl)-n-methylethanesulfonamide (xii) with 2-(1-methylpiperidin-4-yl)acetaldehyde (xiii) by means of hcl in water.7) the reaction of 2-(1h-indol-5-yl)-n-methylethanesulfonamide (xiv) with piperidone (ii) by means of koh in refluxing methanol, yielding n-methyl-2-[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1h-indol-5-yl] ethylsulfonamide (xv), which is finally hydrogenated with h2 over pd/c in ethanol/dmf.
List of intermediates No.
5-fluoro-1-[6-(hydroxymethyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-2,4(1h,3h)-pyrimidinedione (ii)
4-(4-hydrazinophenyl)-4h-1,2,4-triazole (i)
(methoxymethyl)(triphenyl)phosphonium bromide (iii)
1-fluoro-3-[(e)-2-methoxyethenyl]benzene; (e)-2-(3-fluorophenyl)ethenyl methyl ether (iv)
3-(3-fluorophenyl)propanal (v)
3-(4-fluorophenyl)-2,5-dimethyl-1-(4-piperidinyl)-1h-indole (vi)
2-[4-[3-(4-fluorophenyl)-2,5-dimethyl-1h-indol-1-yl]-1-piperidinyl]acetonitrile (vii)
2-[4-[3-(4-fluorophenyl)-2,5-dimethyl-1h-indol-1-yl]-1-piperidinyl]-1-ethanamine (viii)
2-[(2-[4-[3-(4-fluorophenyl)-2,5-dimethyl-1h-indol-1-yl]-1-piperidinyl]ethyl)amino]acetonitrile (ix)
n-(2-aminoethyl)-n-(2-[4-[3-(4-fluorophenyl)-2,5-dimethyl-1h-indol-1-yl]-1-piperidinyl]ethyl)amine (x)
indole-3-acetic acid; 2-(1h-indol-3-yl)acetic acid; 3-indoleacetic acid (xi)
2-(1h-indol-3-yl)acetic acid ethyl ester (xii)
ethyl 2-[1-(4-fluorobenzyl)-1h-indol-3-yl]acetate (xiii)
2-[1-(4-fluorobenzyl)-1h-indol-3-yl]acetic acid (xiv)
4-pyridinamine; 4-aminopyridine (xv)
Reference 1:
    mealy, n.; castaner, j.; naratriptan. drugs fut 1996, 21, 5, 476.
Reference 2:
    oxford, a.w.; butina, d.; owen, m.r. (glaxo wellcome plc); indole derivs. au 8820692; ep 0303507; gb 2208646; jp 1989207288; us 4997841 .
Reference 3:
    blatcher, p.; carter, m.; hornby, r.; owen, m.r. (glaxo wellcome plc); process for the preparation of n-methyl-3-(1-methyl-4-piperidinyl)-1h-indole-5-ethanesulfonamide. wo 9509166 .

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盐酸那拉曲坦;英文名Naratriptan hydrochloride;GG-548;GR-85548A;GR-85548(free base);Amerge;Naramig;CAS[143388-64-1]

 
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
陕西地区醋酸价格下调
河北地区醋酸价格下跌
山东地区醋酸价格下调
华东地区醋酸价格下调
河北地区醋酸价格下调
华北地区醋酸价格下跌
陕西地区醋酸价格暂稳
江苏地区醋酸价格下调
河南地区醋酸价格下调
江苏地区醋酸价格下调
河南地区醋酸价格暂稳
江苏地区醋酸价格
河北地区醋酸价格
山东地区醋酸价格
华东地区BDO市场偏弱运行
华北地区BDO市场低位整理
华北地区醋酸价格
陕西地区醋酸价格
山东地区醋酸价格
华北地区顺酐市场行情整理
 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