文章摘要
丰巍伟,刘飞,徐云根,朱雪焱,张寅生.N-(三氘代甲氧羰基)-L-缬氨酸的合成*[J].药学与临床研究,2020,28(2):86~88
N-(三氘代甲氧羰基)-L-缬氨酸的合成*
Synthesis of ((Methoxy-d3)carbonyl)-L-valine*
投稿时间:2020-02-19  修订日期:2020-04-23
DOI:
中文关键词: N-(三氘代甲氧羰基)-L-缬氨酸  氘代达卡他韦  丙肝  合成
英文关键词: ((Methoxy-d3)carbonyl)-L-valine  Deudaclatasvir  HCV  Synthesis
基金项目:国家“重大新药创制”科技重大专项资助项目(No.2017ZX09201006010);江苏省博士后科研资助计划(No.2018K044A)
作者单位E-mail
丰巍伟 正大天晴药业集团股份有限公司 fengweiwei85@126.com 
刘飞 正大天晴药业集团股份有限公司 liufei@cttq.com 
徐云根 中国药科大学药学院  
朱雪焱 中国医药工业总院上海医药工业研究院  
张寅生 正大天晴药业集团股份有限公司  
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中文摘要:
      N-( 三氘代甲氧羰基)-L-缬氨酸(1)是氘代达卡他韦的关键中间体。以N-叔丁氧羰基-L-缬氨酸(3)为起始物料,4步合成目标产物(1),总收率58%(以氘代甲醇计,收率26%)。以L-缬氨酸甲酯(5’)为起始物料,2步合成化合物(1),总收率68%(以氘代甲醇计,收率30%)。该路线成本降低了约40%,同时大大降低了对环境的污染,适合工业化生产。
英文摘要:
      ((Methoxy-d3)carbonyl)-L-valine (1), the key intermediate of deudaclatasvir, was synthesized in four steps by using N-(tert-butoxycarbonyl)-L-valine (3)as the raw material, with a total yield of 58% (Calculated by methanol-d4, the yield was 26%). Starting ((Methoxy-d3)carbonyl)-L-valine (1), the key intermediate of deudaclatasvir, was synthesized in four steps by using N-(tert-butoxycarbonyl)-L-valine (3) as the raw material, with a total yield of 58% (calculated by methanol-d4, the yield was 26%). Starting from L-valine methyl ester (5’), the compound (1) was obtained in two steps with a total yield of 68% (calculated by methanol-d4, the yield was 30%). The cost of the route has been reduced by about 40% and the pollution to the environment has been greatly reduced, which is suitable for industrial production.
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