柯诺拉赞-d 3的合成  

Synthesis of Carenoprazan-d 3

作　　者：王悦秋[1] 王昌 梁大伟[1] WANG Yueqiu;WANG Chang;LIANG Dawei(Department of Pharmacy&Medical Laboratory,Ya′an Polytechnic College,Ya′an 625100,China;Key Laboratory of Structure-based Drug Design&Discovery of Ministry of Education,Shenyang Pharmaceutical University,Shenyang 110016,China)

机构地区：[1]雅安职业技术学院药学与检验学院,四川雅安625100 [2]沈阳药科大学基于靶点的药物设计与研究教育部重点实验室,辽宁沈阳110016

出　　处：《化学与生物工程》2023年第11期47-51,共5页Chemistry & Bioengineering

基　　金：雅安市应用技术研究与开发项目(21KJJH0080),雅安市高层次人才科技创新创业苗子工程重点项目(2021)。

摘　　要：以2-氟苯乙酮(2)为起始原料,经溴代、丙二腈取代、环合、脱氯得到5-(2-氟苯基)-1H-吡咯-3-甲腈(6),然后与1-(3-甲氧基丙氧基)苯磺酰氯(7)发生亲核取代反应得到5-(2-氟苯基)-1-((3-(3-甲氧基丙氧基)苯基)磺酰基)-1H-吡咯-3-甲腈(8),再经催化氢化、还原氨化得到柯诺拉赞-d 3(1),其结构经NMR和MS确证,7步总收率为14.1%,化学纯度为99.5%,同位素丰度为98.3%,可作为稳定同位素内标试剂用于临床药物代谢动力学研究。Using 2-fluorophenone(2)as a starting material,we firstly synthesized 5-(2-fluorophenyl)-1H-pyrrorole-3-carbonitrile(6)through bromination,malononitrile substitution,cyclization,and dechlorination.Then,we synthesized 5-(2-fluorophenyl)-1-((3-(3-methoxypropoxy)phenyl)sulfonyl)-1H-pyrrorole-3-carbonitrile(8)through nucleophilic substitution reaction of the compound 6 with 1-(3-methoxypropoxy)benzene sulfonyl chloride(7).Finally,we obtained Carenoprazan-d 3(1)by catalytic hydrogenation and reductive amination.The structure of Carenoprazan-d 3 is confirmed by NMR and MS.The total yield of seven steps is 14.1%.The chemical purity of Carenoprazan-d 3 is 99.5%,and the isotope abundance is 98.3%.Carenoprazan-d 3 can be used as a stable isotope internal standard reagent for clinical pharmacokinetic study.

关 键 词：氘代标记 柯诺拉赞 合成 

分 类 号：O625.752[理学—有机化学] R914.5[理学—化学]