有机化学人才网 | 最新人才 | 最新职位 | 有机化学论坛 | 技术交易 | 药物合成 | 企业大全 | CAS大全 注册 | 登陆
   
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 4-MA
Chemical Name N,N-Diethyl-4-methyl-3-oxo-4-aza-5alpha-androstane-17beta-carboxamide
CAS 73671-86-0
Related CAS
Formula C24H40N2O2
Structure
Formula Weight 388.5986
Stage 未确定
Company
Activity/Mechanism  
Syn. Route 2
Route 1
the reaction of pregnenolone (i) with i2 and pyridine at 90 c gives (3beta-hydroxypregn-5-en-20-one-21-yl)pyridinium iodide (ii), which by treatment with sodium methoxide in refluxing methanol is converted into methyl 5-androsten-3beta-ol-17beta-carboxylate (iii). the meerwein-poundorf oxidation of (iii) with cyclohexanone (a) and aluminum isopropoxide in refluxing toluene yields methyl 4-androsten-3-one-17beta-carboxylate (iv), which is hydrolyzed with koh in refluxing methanol - water to the corresponding free acid (3-oxo-4-etienic acid) (v). the reaction of (v) with oxalyl chloride (b) and diethylamine in refluxing toluene affords 17beta-(n,n-diethylcarbamoyl)-4-androstene-3-one (vi), which is oxidized with o3 or with naio4 and kmno4 giving 17beta-(n,n-diethylcarbamoyl)-5-oxo-3,5-secoandrostan-3-oic acid (vii). the cyclization of (vii) with methylamine ethylene glycol at 180 c in a pressure vessel affords 17beta-(n,n-diethylcarbamoyl)-4-methyl-4-aza-5-androsten-3-one (viii), which is finally reduced with h2 over pt in acetic acid.the cyclization of the acid (vii) with nh3 in ethanol at 180 c in a pressure vessel gives 17beta-(n,n-diethylcarbamoyl)-4-aza-5-androsten-3-one (ix), which is reduced with h2 over pt in acetic acid yielding 17beta-(n,n-diethylcarbamoyl)-4-aza-5alpha-androstan-3-one (x). finally, this compound is methylated with ch3i by means of nah in toluene.
List of intermediates No.
(2r,3s)-1,1,1-trifluoro-4-methyl-3-nitro-2-pentanol (a)
3,5-dimethylisonicotinaldehyde (v)
(2s)-2-(acetamido)-3-methyl-3-sulfanylbutyric acid (iv)
1-(1,5-diisopropyl-1h-pyrazol-3-yl)-2-propen-1-one (b)
(7r,8r,9s,13s,14s,17s)-3-hydroxy-7-(9-hydroxynonyl)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6h-cyclopenta[a]phenanthren-17-yl acetate (i)
(7r,8r,9s,13s,14s,17s)-17-(acetoxy)-7-(9-hydroxynonyl)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6h-cyclopenta[a]phenanthren-3-yl benzoate (ii)
(7r,8r,9s,13s,14s,17s)-17-(acetoxy)-13-methyl-7-[9-[(methylsulfonyl)oxy]nonyl]-7,8,9,11,12,13,14,15,16,17-decahydro-6h-cyclopenta[a]phenanthren-3-yl benzoate (iii)
4,4,5,5,5-pentafluoropentylhydrosulfide; 4,4,5,5,5-pentafluoro-1-pentanethiol (vi)
(7r,8r,9s,13s,14s,17s)-17-(acetoxy)-13-methyl-7-[9-[(4,4,5,5,5-pentafluoropentyl)sulfanyl]nonyl]-7,8,9,11,12,13,14,15,16,17-decahydro-6h-cyclopenta[a]phenanthren-3-yl benzoate (vii)
(7r,8r,9s,13s,14s,17s)-13-methyl-7-[9-[(4,4,5,5,5-pentafluoropentyl)sulfanyl]nonyl]-7,8,9,11,12,13,14,15,16,17-decahydro-6h-cyclopenta[a]phenanthrene-3,17-diol (viii)
(4s,4as,5ar,12as)-9-[(2-bromoacetyl)amino]-4,7-bis(dimethylamino)-3,10,12,12a-tetrahydroxy-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydro-2-naphthacenecarboxamide (ix)
2-(tert-butylamino)acetyl chloride (x)
Reference 1:
    hillier, k.; blancafort, p.; serradell, m.n.; castaner, j.; 4-ma. drugs fut 1983, 8, 4, 323.
Reference 2:
    jobson, r.b.; johnston, d.b.r.; rasmusson, g.h.; reinhold, d.f.; utne, t. (merck & co., inc.); preparation of 4-aza-17-substituted-5 alpha -androstan-3-ones useful as 5 alpha -reductase inhibitors. us 4220775 .

Route 2
the oxidation of 3-oxo-4-etienic acid (v) with naio4 and kmno4 in tert-butanol - water gives 5-oxo-3,5-secoandrostane-3,17beta-dioic acid (xi), which is cyclized with methylamine in ethanol at 180 c in a pressure vessel yielding 17beta-carboxy-4-methyl-4-aza-5-androsten-3-one (xii). the hydrogenation of (xii) with h2 over pt in acetic acid affords 17beta-carboxy-4-methyl-4-azaandrostan-3-one (xiii), which is finally treated with oxalyl chloride (b) and diethylamine in toluene-thf.the amidation of (xiii) with oxalyl chloride (b) and nh3 in toluene-thf gives 17beta-carboxamide-4-methyl-4-azaandrostanone (xiv), which is alkylated with ethyl bromide and nah in toluene.the amidation of (xiii) with ethylamine and oxalyl chloride (b) in toluene-thf gives 17beta-(n-ethylcarbamoyl)-4-methyl-4-azaandrostan-3-one (xv), which is finally alkylated with ethyl bromide and nah in toluene.
List of intermediates No.
3,5-dimethyl-4-nitro-1-pyridiniumolate (xiii)
3,5-dimethylisonicotinaldehyde (v)
2-formylphenethyl benzoate (xi)
1-(1,5-diisopropyl-1h-pyrazol-3-yl)-2-propen-1-one (b)
(s)-(+)-2-amino-1-butanol; l-(+)-2-amino-1-butanol; (s)-2-amino-1-butanol (xii)
(2r)-2-ethyl-1-[(4-methylphenyl)sulfonyl]aziridine (xiv)
3-chlorothiophene; 3-thienyl chloride (xv)
Reference 1:
    hillier, k.; blancafort, p.; serradell, m.n.; castaner, j.; 4-ma. drugs fut 1983, 8, 4, 323.
Reference 2:
    jobson, r.b.; johnston, d.b.r.; rasmusson, g.h.; reinhold, d.f.; utne, t. (merck & co., inc.); preparation of 4-aza-17-substituted-5 alpha -androstan-3-ones useful as 5 alpha -reductase inhibitors. us 4220775 .

 
推荐VIP企业
宁波赛伦化工有限公司
无锡景耀生物科技有限公司
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
北京梅尔森医药技术开发有限公
热门文章
华东粗苯市场高位坚挺
宁波二甘醇市场震荡整理
华东二甘醇市场震荡
山西粗苯市场高位坚挺
华北市场苯乙烯市场淡稳观望
华东地区邻二甲苯价格平稳
华东港口丙烯腈市场报价暂稳
华北地区醋酐市场行情稳定
环氧乙烷市场高位运行为主
河北地区顺酐市场平稳
华中地区醋酐市场走势稳定
华南地区顺酐市场平稳
华南二甘醇市场窄幅整理
河北粗苯市场高位整理
山东地区顺酐市场价格暗降
宁波二甘醇市场小幅震荡
山西地区顺酐市场无价无市
华中地区醋酐市场走势稳定
华东地区醋酐市场行情稳定
华东地区邻二甲苯价格平稳
 友情链接
有机化学人才网  有机化学论坛
首页 | 会员级别 | 广告服务 | 建站服务 | 关于我们 | 联系我们 | 版权声明