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 Irbesartan;BMS-186295;SR-47436;Avapro;Karvea;Aprovel
Chemical Name 2-Butyl-1-[2-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]spiro[2-imidazoline-4,1-cyclopentane]-5-one
CAS 138402-11-6
Related CAS
Formula C25H28N6O
Structure
Formula Weight 428.54151
Stage 上市-1997
Company Sanofi-synthélabo (Originator), Bristol-Myers Squibb (Licensee), Shionogi (Licensee)
Activity/Mechanism CARDIOVASCULAR DRUGS, Diabetic Nephropathy, Agents for, ENDOCRINE DRUGS, Heart Failure Therapy, Hypertension, Treatment of, Treatment of Diabetic Complications, Angiotensin AT1 Antagonists
Syn. Route 1
Route 1
the reaction of cyclopentanone (i) with sodium cyanide, nh3 and nh4cl in hot methanol/water gives 1-aminocyclopentanecarbonitrile (ii), which is partially hydrolyzed with concentrated h2so4 to the corresponding amide (iii). the acylation of (iii) with pentanoyl chloride (iv) by means of triethylamine in thf yields 1-(pentanamido)cyclopentane-1-carboxamide (v), which, without isolation, is cyclized by means of koh in refluxing methanol/water to afford 2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one (vi). this compound (vi) can also be obtained by cyclization of 1-aminocyclopentanecarboxylic acid ethyl ester (vii) with pentanimidic ethyl ester (viii) by means of acetic acid in refluxing xylene. the condensation of (vi) with 4-(bromomethyl)biphenyl-2-carbonitrile (ix) by means of nah in dmf gives 4-(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-ylmethyl)biphenyl-2-carbonitrile (x). cyclization of (x) with tributyltin azide in refluxing xylene, followed by reaction with trityl chloride in dmf, affords 2-butyl-3-[2-[1-(triphenylmethyl)tetrazol-5-yl]biphenyl-4-ylmethyl]-1,3-diazaspiro[4.4]non-1-en-4-one (xi). finally, this compound is hydrolyzed to irbesartan with hcl in methanol/thf. the final cyclization of (x) with tributyltin azide or sodium azide also directly gives irbesartan.
List of intermediates No.
tert-butyl 4-[3-[(3r)-3-([[(1s)-3-methoxy-3-oxo-1-(3-pyridinyl)propyl]amino]carbonyl)piperidinyl]-3-oxopropyl]-1-piperidinecarboxylate (i)
1-(3,4-dichlorophenyl)cyclobutanecarbonitrile (ii)
1-[1-(3,4-dichlorophenyl)cyclobutyl]-1-ethanone (iii)
2-bromo-1-[1-(3,4-dichlorophenyl)cyclobutyl]-1-ethanone (iv)
1-[[amino(imino)methyl]sulfanyl]-3-(dimethylamino)propane (v)
n,n-dimethyl-n-(3-sulfanylpropyl)amine sodium salt (vi)
bis[(1r,2s,5r)-2-isopropyl-5-methylcyclohexyl] (1s,2s)-1,2-cyclopropanedicarboxylate (vii)
(1s,2s)-2-([[(1r,2s,5r)-2-isopropyl-5-methylcyclohexyl]oxy]carbonyl)cyclopropanecarboxylic acid (viii)
(1r,2s,5r)-2-isopropyl-5-methylcyclohexyl (1s,2s)-2-(chlorocarbonyl)cyclopropanecarboxylate (xi)
9-(iodomethyl)-9h-xanthene (x)
tert-butyl (3s)-2,6-dioxopiperidinylcarbamate (ix)
Reference 1:
    casas, a.; merlos, m.; castaner, j.; irbesartan. drugs fut 1997, 22, 5, 481.
Reference 2:
    bernhart, c.; breliere, j.-c.; clement, j.; nisato, d.; perreaut, p. (sanofi-synthélabo ); heterocyclic n-substd. derivs., their preparation and the pharmaceutical compsns. containing them. ep 0454511; fr 2659967; fr 2665702; jp 1992506222; jp 1998279566; us 5270317; wo 9114679 .
Reference 3:
    caron, a.; chantreux, d.; bouloumie, c. (sanofi-synthelabo ); method for the preparation of a tetrazole deriv. under two crystalline forms and novel crystalline form of this deriv. ep 0708103 .
Reference 4:
    bernhart, c.a.; perreaut, p.m.; ferrari, b.p.; et al.; a new series of imidazolones: highly specific and potent nonpeptide at1 angiotensin ii receptor antagonists. j med chem 1993, 36, 22, 3371-80.
Reference 5:
    bernhart, c.; clement, j.; ferrari, b.; et al.; spiro-dihydro-imidazolones, a new class of non-peptide angiotensin ii receptor antagonists. 12th int symp med chem (sept 13-17, basel) 1992, abst p-084.a..

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厄贝沙坦;英文名Irbesartan;BMS-186295;SR-47436;Avapro;Karvea;Aprovel;CAS[138402-11-6]

 
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
呋虫胺和烯啶虫胺继续扩作
华南地区环氧丙烷市场稳定
华东地区丁二烯市场盘整
苯胺跌势难改
醋酸市场供需平衡
华北地区醋酸价格整体上调
山东地区环氧丙烷市场稳定
吡丙醚和氟啶虫酰胺继续扩作
嘧菌胺获欧盟批准开展再评审,但
丰山集团正式挂牌,发行首日秒封
丙炔氟草胺领军“其他PPO抑制
PTA 回调为主
新型“超分子纳米囊”可减少农药
损失或超6千万!这家上市公司被
红太阳子公司南京生化完成增资工
装置集中检修 丁酮强势上涨难持
关于农药登记有关行政许可办理系
华南地区正丁醇市场行情
46家农药上市公司半年报披露,
新增一家毒氟磷制剂登记企业
 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