瑞替加滨的合成

祁金龙1,张 超1,吴 茵2,刘保霞1,张海林1*

主办:上海医药工业研究院
   中国药学会
   中国化学制药工业协会
ISSN 1001-8255   CN 31-1243/R   ZYGZEA
中国医药工业杂志 ›› 2013, Vol. 44 ›› Issue (3) : 223-225.
化学药物与合成技术 Chemical Drug & Synthetic Technology

瑞替加滨的合成

作者信息 +

Synthesis of Retigabine

Author information +
History +

摘要

对硝基苯胺经酰化、硝基还原、氨基保护、硝化、氨基脱保护,与对氟苯甲醛缩合得到N-[ 2- 硝基-4-( 4- 氟苯亚甲胺基) 苯基] 氨基甲酸乙酯,再用Pd/C 催化氢化同时还原硝基和亚胺得到抗癫痫药瑞替加滨,总收率约44%。

Abstract

Retigabine, an anti-epileptic agent, was synthesized from 4-nitroaniline by acylation, reduction of nitro group, protection of amino group, nitration, deprotection of amino group, and then condensation with 4-fluorobenzaldehyde to give ethyl N-[4-[(4-fluorobenzylidene)amino]-2-nitrophenyl]carbamate, followed by Pd/Ccatalyzed reduction of both nitro group and Schiff's base simultaneously with an overall yield about 44%.

关键词

瑞替加滨 / 抗癫痫药 / 合成

Key words

retigabine / anti-epileptic agent / synthesis

引用本文

导出引用
祁金龙1,张 超1,吴 茵2,刘保霞1,张海林1*. 瑞替加滨的合成. 中国医药工业杂志. 2013, 44(3): 223-225
QI Jinlong1, ZHANG Chao1, WU Yin2, LIU Baoxia1, ZHANG Hailin1*. Synthesis of Retigabine. Chinese Journal of Pharmaceuticals. 2013, 44(3): 223-225

参考文献

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[7] Va s a n t h a B, Hema n t h a HP, S u r e s h b a b u VV. 1 -Propanephosphonic acid cyclic anhydride (T3P) as an efficient promoter for the Lossen rearrangement: application to the synthesis of urea and carbamate derivatives [J] . Synthesis, 2010, 17: 2990-2996.

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[10] Sobanov AA, Zolotukhin AV, Galkina IV, et al. Kinetics and mechanism of the Pudovik reaction in the azomethine series: Ⅲ . Acid-catalyzed hydrophosphorylation of imines [J]. Russ J Gen Chem, 2006, 76(3): 421-429.

[11] Serra MJ, Duran LE, Boschillado J. Diethyl 4-( 4-fluorobenzylamino)-1,2-phenylenedicarbamate, and salts thereof: WO, 2011012659 [P]. 2011-02-03.

基金

国家“973”计划(2007CB512102)、国家自然科学基金重点项目(30730031)

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