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 Nivadipine;Nilvadipine;CL-287389;SK&F-102362;FK-235;FR-34235;Escor;Nivadil
Chemical Name 2-Cyano-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 5-isopropyl 3-methyl ester
CAS 75530-68-6
Related CAS
Formula C19H19N3O6
Structure
Formula Weight 385.37978
Stage 上市-1989
Company Fujisawa (Originator), Fujisawa Deutschland (Originator)
Activity/Mechanism CARDIOVASCULAR DRUGS, Hypertension, Treatment of, Calcium Channel Blockers
Syn. Route 3
Route 1
1) the synthesis of deuterated nilvadipine has been reported:the selective hydrolysis of nilvadipine (i) with lithium iodide and pyridine gives the monolithium salt (ii), which is then treated with perdeuterated methanol and 2-bromo-1-methylpyridinium bromide and dimethylaniline in dmf.
List of intermediates No.
ethyl (2e,4e)-5-[4-[(ethoxycarbonyl)oxy]-3-methoxyphenyl]-2,4-pentadienoate (i)
(2e,4e)-5-(4-hydroxy-3-methoxyphenyl)-2,4-pentadienoic acid (ii)
ethyl (e)-4-(diethoxyphosphoryl)-2-butenoate (iii)
Reference 1:
    okumura, k.; satoh, y.; shiokawa, y.; studies on nilvadipine. iv. synthesis of deuterated and optically active isopropyl 2-cyano-3-methoxycarbonyl-4-(3-nitrophenyl)-6-methyl-1,4-dihydropyridine-5-carboxylate (nilvadipine). chem pharm bull 1994, 42, 4, 950.

Route 2
2) the optical isomers of nilvidapine have also been synthesized:the selective hydrolysis of nilvadipine (i) with formic acid gives the monocarboxylic acid (ii), which is treated with (-)-cinconidine, yielding the corresponding salt (iv) as a diastereomeric mixture, which is separated by fractional crystallization to give, after hydrolysis with hcl, 2-cyano-3-(methoxycarbonyl)-6-methyl-4(r)-(3-nitrophenyl)-1,4-dihydropy ridine-5-carboxylic acid (va) and 2-cyano-3-(methoxycarbonyl)-6-methyl-4(s)-(3-nitrophenyl)-1,4-dihydropy ridine-5-carboxylic acid (vb) as pure optical isomers. both compounds are esterified by conversion to the corresponding acyl chlorides with pcl5 and esterification with isopropyl alcohol.
List of intermediates No.
5-[4-(ethoxycarbonyl)-3-methoxyphenyl]-2(e),4(e)-pentadienoic acid ethoxycarbonyl anhydride (i)
2-[4-(benzhydryloxy)-1-piperidinyl]ethylamine; 2-[4-(benzhydryloxy)-1-piperidinyl]-1-ethanamine (ii)
ethyl 4-hydroxy-1-piperidinecarboxylate (iv)
2-[2-[4-(benzhydryloxy)-1-piperidinyl]ethyl]-1h-isoindole-1,3(2h)-dione (va)
benzhydryl 4-bromo-3-oxobutanoate (vb)
Reference 1:
    okumura, k.; satoh, y.; shiokawa, y.; studies on nilvadipine. iv. synthesis of deuterated and optically active isopropyl 2-cyano-3-methoxycarbonyl-4-(3-nitrophenyl)-6-methyl-1,4-dihydropyridine-5-carboxylate (nilvadipine). chem pharm bull 1994, 42, 4, 950.

Route 3
the condensation of isopropyl acetoacetate (i) with 3-nitrobenzaldehyde (ii) gives isopropyl 2-(3-nitrobenzylidene)acetoacetate (iii), which is cyclized with methyl 3-amino-4,4-dimethoxycrotonate (iv) at 100 c yielding 5-isopropyl-3-methyl-2-(dimethoxymethyl)-6-methyl-4-(3-nitropheny)-1,4-dihydropyridine-3,5-dicarboxylate (v). the hydrolysis of the acetal group of (v) with hcl in acetone affords the corresponding 2-formyl derivative (vi), which is finally treated with hydroxylamine and acetic anhydride in acetic acid at 100 c.
List of intermediates No.
ethyl 2-cyano-2-(1-methyl-4-piperidinylidene)acetate (iii)
n-(2-aminoethyl)-n-methylcarbamic acid tert-butyl ester; tert-butyl 2-aminoethyl(methyl)carbamate (ii)
(2,3,5-trichlorophenyl)methanol (i)
benzyl (2s,3s,4r,5s)-3-azido-5-methoxy-4-[[(4-methylphenyl)sulfonyl]oxy]tetrahydro-2-furancarboxylate (iv)
benzyl (2s,3s,4r,5r)-3-azido-5-hydroxy-4-[[(4-methylphenyl)sulfonyl]oxy]tetrahydro-2-furancarboxylate (v)
benzyl (2s,3s,4r,5s)-3-azido-5-hydroxy-4-[[(4-methylphenyl)sulfonyl]oxy]tetrahydro-2-furancarboxylate (vi)
Reference 1:
    satu, y. (fujisawa pharmaceutical co., ltd.); 1,4-dihydropyridine derivatives and pharmaceutical method of the same. be 0879263; de 2940833; fr 2438654; gb 2036722; us 4284634; us 4338322 .
Reference 2:
    blancafort, p.; castaner, j.; serradell, m.n.; fr-34,235. drugs fut 1983, 8, 9, 776.

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尼伐地平;英文名Nivadipine;Nilvadipine;CL-287389;SK&F-102362;FK-235;FR-34235;Escor;Nivadil;CAS[75530-68-6]

 
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
利用 iPS 细胞治疗脊髓损伤
Bavencio 组合疗法用于
默沙东 Keytruda 剑指
广东省已核发58张农药生产许可
我国首次集中批准一批火龙果用药
杀线虫农药产品的登记情况和展望
四大环保风暴即将来袭!江苏率先
罗氏向 FDA 递交 Kadc
前列腺癌药物苯扎鲁胺达到 AR
欧盟批准武田霍奇金淋巴瘤药物
停产整治!安道麦老厂区排污不达
赛诺菲砍掉 38 个研发项目,
江苏地区醋酸价格下调
河南地区醋酸价格暂稳
华北地区醋酸价格
国光股份募集资金投资项目变更实
山东地区醋酸价格
江苏地区醋酸价格
华北地区顺酐市场行情整理
陕西地区醋酸价格暂稳
 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