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 Bifonazole;Bay-h-4502;Azolmen;Amycor;Mycospor
Chemical Name (±)-1-(p,alpha-Diphenylbenzyl)imidazole;(±)-1-[alpha-(4-Biphenylyl)benzyl]imidazole;(±)-1-[(1,1-Biphenyl)-4-ylphenylmethyl]-1H-imidazole
CAS 60628-96-8
Related CAS 60629-09-6 (monoHCl), 60629-08-5 (sulfate)
Formula C22H18N2
Structure
Formula Weight 310.40216
Stage 上市-1983
Company Bayer (Originator), Lipha (Not Determined), Menarini (Licensee)
Activity/Mechanism Antifungal Agents, ANTIINFECTIVE THERAPY
Syn. Route 2
Route 1
the reduction of 4-phenylbenzophenone (i) with nabh4 in ethanol gives 4-phenylbenzhydrol (ii), which is then condensed with imidazole (iii) by means of socl2 in acetonitrile.
List of intermediates No.
(3r,4s)-1-(4-methoxyphenyl)-4-[(e)-1-propenyl]-3-[(triisopropylsilyl)oxy]-2-azetidinone (iii)
(4s)-4-benzyl-3-[2-(4-fluorophenyl)acetyl]-1,3-oxazolidin-2-one (i)
2,4,6-triisopropylbenzenesulfonyl azide (ii)
Reference 1:
    regel, e.; draber, w.; buechel, k.h.; plempel, m. (bayer ag); alpha-(4-biphenylyl)-benzylazolium salts and their use for combating microorganisms. be 0859041; de 2643563; fr 2365559; gb 1535148; jp 53044568; nl 7710489; us 4243670 .
Reference 2:
    regel, e.; draber, w.; buechel, k.h.; plempel, m. (bayer ag); substituted azol-1-ylmethanes. be 0836924; ca 1059134; ch 619454; dd 124729; de 2461406; fr 2295747; gb 1469617; jp 51091260; nl 7514940; us 4118487 .
Reference 3:
    regel, e.; draber, w.; buechel, k.h.; plempel, m. (bayer ag); combating crop damaging fungi with alpha-(4-biphenylyl)-benzyl-azolium salts. de 2714290; jp 53121941; us 4251540 .
Reference 4:
    serradell, m.n.; blancafort, p.; castaner, j.; bifonazole. drugs fut 1982, 7, 2, 87.

Route 2
the condensation of (s)-1-(4-bromophenyl)-1-phenylmethylamine (s)-(i) with phenylboronic acid (ii) by means of pd(oac)2, pph3 and na2co3 in propanol/water gives the corresponding biphenyl derivative (s)-(iii), which is condensed with 3-bromopropanal dimethylacetal (iv) by means of k2co3 in dmf yielding the secondary amine (s)-(v). the reaction of (s)-(v) with refluxing butyl formate (vi) affords the formamide (s)-(vii), which is cyclized with ammonium acetate in acetic acid to furnish the (s)-enantiomer of the target compound.the corresponding (r)-enantiomer has been obtained by the same reaction sequence but starting from (r)-1-(4-bromophenyl)-1-phenylmethylamine (r)-(i).
List of intermediates No.
(4ar,6r,7r,7as)-6-(6-amino-9h-purin-9-yl)-2,7-dihydroxytetrahydro-4h-2lambda(5)-furo[3,2-d][1,3,2]dioxaphosphinin-2-one (ii)
4-[(2s,3r)-3-[(3s)-3-(acetoxy)-3-(4-fluorophenyl)propyl]-1-(4-fluorophenyl)-4-oxoazetidinyl]phenyl acetate (iv)
benzyl (2s)-1-((2s)-2-[[(2s,4s)-4-hydroxy-2,5-dimethyl-3-oxohexanoyl]amino]-4-methylpentanoyl)-2-pyrrolidinecarboxylate (s-i)
benzyl (2s)-1-[(2s,5s,7s,11s,12r,15s,16r,19s)-11-[[tert-butyl(dimethyl)silyl]oxy]-2-isobutyl-7-isopropyl-19-(4-methoxybenzyl)-5,16,20-trimethyl-15-[[(2r)-4-methyl-2-(methylamino)pentanoyl]amino]-12-[(1s)-1-methylpropyl]-4,6,9,14,18,21-hexaoxo-23-phenyl-8,17,22-trioxa-3,13,20-triazatricos-1-anoyl]-2-pyrrolidinecarboxylate (s-iii)
(2r)-n-[(3s,6r,7s,10r,11s,15s,17s,20s,25as)-11-[[tert-butyl(dimethyl)silyl]oxy]-20-isobutyl-15-isopropyl-3-(4-methoxybenzyl)-2,6,17-trimethyl-10-[(1s)-1-methylpropyl]-1,4,8,13,16,18,21-heptaoxodocosahydro-15h-pyrrolo[2,1-f][1,15,4,7,10,20]dioxatetraazacyclotricosin-7-yl]-4-methyl-2-(methylamino)pentanamide (s-v)
(2r)-n-[(3s,6r,7s,10r,11s,15s,17s,20s,25as)-11-hydroxy-20-isobutyl-15-isopropyl-3-(4-methoxybenzyl)-2,6,17-trimethyl-10-[(1s)-1-methylpropyl]-1,4,8,13,16,18,21-heptaoxodocosahydro-15h-pyrrolo[2,1-f][1,15,4,7,10,20]dioxatetraazacyclotricosin-7-yl]-4-methyl-2-(methylamino)pentanamide (vi)
(2s)-2-(benzyloxy)propionic acid (s-vii)
(2s)-1-[(2s)-2-(benzyloxy)propanoyl]-2-pyrrolidinecarboxylic acid (r-i)
(2s,4s)-4-(benzyloxy)-2,5-dimethyl-3-oxohexanoic acid (r-iii)
2-(trimethylsilyl)ethyl (2s)-2-amino-4-methylpentanoate (r-v)
2-(trimethylsilyl)ethyl (2s)-2-[[(2s,4s)-4-hydroxy-2,5-dimethyl-3-oxohexanoyl]amino]-4-methylpentanoate (r-vii)
Reference 1:
    botta, m.; et al.; chiral azole derivatives.4.enantiomers of bifonazole and related antifungal agents. synthesis, configuration assignment, and biological evaluation. j org chem 2000, 65, 15, 4736.

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联苯苄唑;英文名Bifonazole;Bay-h-4502;Azolmen;Amycor;Mycospor;CAS[60628-96-8]

 
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
华东地区己二酸市场小幅下行
黑龙江粗苯价格暂稳
华东地区邻苯市场行情维稳
江西地区二氯甲烷价格暂稳
华北地区邻苯市场行情暂稳
东北地区邻苯市场行情暂稳
山东地区粗苯价格暂稳
华南地区己二酸行情弱势走低
山东地区三氯甲烷价格
江苏地区粗苯价格暂稳
山东地区二氯甲烷市场价格下调
江苏地区二氯甲烷价格下调
浙江地区二氯甲烷价格下调
PTA止跌在眼前
华东地区丁二烯市场价格盘整为主
DOP价格继续下行
华东地区BDO市场平稳整理
华南地区顺酐市场行情整理
江苏地区顺酐市场行情整理
山东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