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 Etiracetam;UCB-6474
Chemical Name (±)-2-(2-Oxopyrrolidin-1-yl)butyramide
CAS 33996-58-6
Related CAS
Formula C8H14N2O2
Structure
Formula Weight 170.21298
Stage II 期临床
Company UCB (Originator)
Activity/Mechanism Cognition Disorders, Treatment of, NEUROLOGIC DRUGS
Syn. Route 2
Route 1
reaction of (s)-2-aminobutyramide (i) with ethyl 4-bromobutyrate (ii) in the presence of triethylamine in toluene gives ethyl (s)-4-[1-(carbamoyl)propylamino]butyrate (iii), which is cyclized in toluene by means of 2-hydroxypyridine.compound (i) can also be condensed with 4-chlorobutyryl chloride (iv) either directly in the presence of tetrabutylammonium bromide (tbab) in dichloromethane, followed by in situ treatment with potassium hydroxide, or via the isolation of intermediate (s)-n-[1-(carbamoyl)propyl]-4-chlorobutyramide (v).an alternative procedure involves hydrolysis of racemic ethyl 2-(2-oxopyrrolidin-1-yl)butyrate (vi) with sodium hydroxide to give racemic 2-(2-oxopyrrolidin-1-yl)butyric acid (vii), which is resolved by fractional crystallization with (r)-(+)-alpha-methylbenzylamine in benzene, followed by acid-base treatment to give (s)-2-(2-oxopyrrolidin-1-yl)butyric acid (viii). compound (viii) is finally treated with ethyl chloroformiate and ammonia in dichloromethane.a third procedure involves ni-raney desulfurization of (s)-4-(methylthio)-2-(2-oxopyrrolidin-1-yl)butyramide (xi), prepared from (s)-2-amino-4-(methylthio)butyramide (ix) by reaction with 4-chlorobutyryl chloride (iv).compound (xi) can also be obtained by treatment of (ix) with ethyl 4-bromobutyrate (ii) to give ethyl (s)-4-[1-(carbamoyl)-3-(methylthio)propylamino]butyrate (x), which is cyclized in toluene by means of 2-hydroxypyridine.
List of intermediates No.
2,3,6,7-tetrahydrofuro[2,3-f][1]benzofuran
((3r)-2-[[(2r,3r,4s,11r,12s)-5-ethyl-3,4-dihydroxy-9-[[(2r,4r,5s)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2h-pyran-2-yl]oxy]-2,4,8,10,12,14-hexamethyl-7-oxo-6,15-dioxabicyclo[10.2.1]pentadec-1(14)-en-11-yl]oxy]-3-hydroxy-6-methyltetrahydro-2h-pyr (i)
(6r,7s,9s,11r,12r,13s)-14-ethyl-9-fluoro-4,6,7,12,13-pentahydroxy-3,5,7,9,11,13-hexamethyl-2,10-oxacyclotetradecanedione (ii)
1-[4-(2,4-difluorobenzoyl)-1-piperidinyl]-1-ethanone (iii)
(2,4-difluorophenyl)(4-piperidinyl)methanone (iv)
(2,4-difluorophenyl)(4-piperidinyl)methanone oxime (v)
3-(2-chloroethyl)-2-methyl-6,7,8,9-tetrahydro-4h-pyrido[1,2-a]pyrimidin-4-one (vi)
methyl (2s)-3-(1h-imidazol-4-yl)-2-[[(2r)-4-(4-morpholinyl)-2-(1-naphthylmethyl)-4-oxobutanoyl]amino]propanoate (vii-rac)
methyl (2s)-2-amino-3-(1h-imidazol-4-yl)propanoate (viii)
(2s)-2-[(tert-butoxycarbonyl)amino]-3-cyclohexylpropionic acid (ix)
tert-butyl (1s)-2-cyclohexyl-1-(hydroxymethyl)ethylcarbamate (x)
3-cyclohexylpropanoyl chloride (xi)
Reference 1:
    gobert, j.; geerts, j.-p.; bodson, g. (ucb sa); (s)-alpha-ethyl-2-oxopyrrolidineacetamide. au 8542530; ep 0162036; es 8608485; es 8704893; us 4696943; us 4837223 .
Reference 2:
    cossement, e.; motte, g.; geerts, j.-p.; gobert, j. (ucb sa); the preparation of s-alpha-ethyl-2-oxo-1-pyrrolidineacetamide. gb 2225322 .
Reference 3:
    castaner, j.; prous, j.; mealy, n.; levetiracetam. drugs fut 1994, 19, 2, 111.

Route 2
the condensation of pyrrolidin-2-one (i) with ethyl 2-bromobutyrate (ii) by means of nah or sodium ethoxide gives ethyl 2-(2-oxopyrrolidino)butyrate (iii), which is then treated with nh3 in methanol.
List of intermediates No.
3-(2-chloroethyl)-2-methyl-6,7,8,9-tetrahydro-4h-pyrido[1,2-a]pyrimidin-4-one (iii)
benzhydryl (6r,7s)-3-[[(aminocarbonyl)oxy]methyl]-7-hydroxy-7-[[(z)-1-methoxy-2-(2-thienyl)ethylidene]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate (i)
dimethyl 4-(acetamido)-6-chloroisophthalate (ii)
Reference 1:
    de angelis, l.; blancafort, p.; castaner, j.; serradell, m.n.; etiracetam. drugs fut 1981, 6, 9, 552.
Reference 2:
    strubbe, j.h.l.; linz, r.a. (ucb sa); new n-substd. lactams. de 2106418 .

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乙拉西坦;英文名Etiracetam;UCB-6474;CAS[33996-58-6]

 
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
华东地区邻苯市场行情上涨
华北地区醋酸价格
华北地区正丁醇市场行情
新型“超分子纳米囊”可减少农药
苯胺跌势难改
华东地区BDO市场僵持整理
诺普信等3家国内企业首登三氟苯
华东地区BDO市场持续僵持
华南地区苯酚市场窄幅上行
PTA止跌在眼前
华北苯酐市场行情
江苏地区顺酐市场行情整理
华东苯酐市场行情
山东地区三氯甲烷价格
山东地区辛醇市场行情
山东地区二氯甲烷市场价格动态
华东地区醋酸价格
河南地区醋酸价格
山东地区醋酸价格
浙江地区醋酸价格
 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