利匹韦林Z异构体盐酸 | 500287-94-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 利匹韦林Z异构体盐酸
• 英文名称: 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile
• 英文别名: 4-[[4-[[4-[(Z)-2-cyanoethenyl]-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile；4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile (Z)；(Z) 4-[[4-[[4-(2cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile；Rilpivirine, (Z)-；4-[[4-[4-[(Z)-2-cyanoethenyl]-2,6-dimethylanilino]pyrimidin-2-yl]amino]benzonitrile
• CAS: 500287-94-5
• 化学式: C₂₂H₁₈N₆
• 分子量: 366.425
• InChiKey: YIBOMRUWOWDFLG-ARJAWSKDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  97.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-(4-(4-(羟基甲基)-2,6-二甲基苯基氨基)嘧啶-2-基氨基)苯甲腈 在 manganese(IV) oxide 、 potassium tert-butylate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 29.0h， 生成 利匹韦林Z异构体盐酸
  参考文献：
  名称：

  Synthesis of Novel Diarylpyrimidine Analogues and Their Antiviral Activity against Human Immunodeficiency Virus Type 1

  摘要：

  This paper reports the synthesis and the antiviral properties of new diarylpyrimidine (DAPY) compounds as nonnucleoside reverse transcriptase inhibitors (NNRTIs). The synthesis program around this new DAPY series was further optimized to produce compounds displaying improved activity against a panel of eight clinically relevant single and double mutant strains of human immunodeficiency virus type 1 (HIV-1).

  DOI：

  10.1021/jm040838n

文献信息

• Pharmaceutical compositions comprising a basic drug compound, a surfactant, and a physiologically tolerable water soluble acid
  申请人：Vandecruys Roger Petrus Gerebern

  公开号：US09192577B2

  公开（公告）日：2015-11-24

  The invention provides a novel pharmaceutical composition comprising a basic respectively acidic drug compound, a surfactant and a physiologically tolerable water-soluble acid respectively base characterized in that the acid respectively base:drug compound ratio is at least 1:1 by weight.

  这项发明提供了一种新型的药物组合物，包括一种碱性或酸性药物化合物、表面活性剂和一种生理耐受的水溶性酸或碱，其特点在于酸或碱与药物化合物的比例至少为1:1（按重量计）。
• [EN] PROCESSES FOR THE PREPARATION OF 4-[[4-[[4-(2-CYANOETHENYL)-2,6-DIMETHYLPHENYL]AMINO]-2-PYRIMIDINYL]AMINO]BENZONITRILE<br/>[FR] PROCEDES DE PREPARATION DE 4-[[4-[[4-(2-CYANOETHENYL)-2,6-DIMETHYLPHENYL]AMINO]-2-PYRIMIDINYL]AMINO]BENZONITRILE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2004016581A1

  公开（公告）日：2004-02-26

  Processes for the preparation of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile of formula (I), a N-oxide, a pharmaceutically acceptable acid addition salt, a quaternary amine or a stereochemically isomeric form thereof are provided, said processes comprise a) reacting 4-(2-cyanoethenyl)-2,6-dimethylbenzenamine with an intermediate of formula (III) in the presence of a suitable solvent; b) reacting an intermediate of formula (IV) with acrylonitrile in the presence of a suitable palladium catalyst, a suitable base and a suitable solvent; c) dehydrating the corresponding amide of the compound of formula (I).

  提供制备4-[[4-[[4-(2-氰乙烯基)-2,6-二甲基苯基]氨基]-2-嘧啶基]氨基]苯甲腈的配方(I)的过程，包括与N-氧化物、药学上可接受的酸附加盐、季铵盐或其立体化异构形式的过程，所述过程包括a)在适当的溶剂存在下将4-(2-氰乙烯基)-2,6-二甲基苯胺与配方(III)的中间体反应；b)在适当的钯催化剂、适当的碱和适当的溶剂存在下将配方(IV)的中间体与丙烯腈反应；c)脱水化配方(I)化合物的相应酰胺。
• [EN] A METHOD OF PRODUCING HIGHLY PURE RILPIVIRINE AND ITS SALTS<br/>[FR] PROCÉDÉ DE PRODUCTION DE RILPIVIRINE EXTRÊMEMENT PURE ET DE SES SELS
  申请人：ZENTIVA KS

  公开号：WO2016116074A1

  公开（公告）日：2016-07-28

  A method of preparing Rilpivirine of formula I, or a suitable salt thereof, comprising a reaction of a hydrogen halide of the aniline derivative of formula II with chloropyrimidine of formula III in methyl isobutyl ketone and in the presence of a polar additive.

  一种制备式I的Rilpivirine或其适宜盐的方法，包括在甲基异丁基酮中，在极性添加剂的存在下，通过将式II的苯胺衍生物的氢卤化物与式III的氯吡咯烷反应。
• [EN] IMPROVED PROCESS FOR PREPARATION OF RILPIVIRINE AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF<br/>[FR] PROCÉDÉ AMÉLIORÉ POUR LA PRÉPARATION DE RILPIVIRINE ET DE SELS PHARMACEUTIQUEMENT ACCEPTABLES DE CELLE-CI
  申请人：LAURUS LABS PRIVATE LTD

  公开号：WO2013179105A1

  公开（公告）日：2013-12-05

  Disclosed is an improved process for the preparation of rilpivirine hydrochloride. The process comprises a) reacting 3-(4-amino-3,5-dimethyl phenyl)-acrylonitrile hydrochloride and 4-[(4-chloropyrimidin-2-yl) amino] benzonitrile in the presence of a phase transfer catalyst followed by saltification with an acid and b) converting the rilpivirine acid addition salt into rilpivirine hydrochloride salt.

  本发明公开了一种改进的利托那韦盐酸盐制备工艺。该工艺包括a) 在相转移催化剂的存在下，反应3-(4-氨基-3,5-二甲基苯基)-丙烯腈盐酸盐和4-[(4-氯嘧啶-2-基)氨基]苯腈，然后与酸盐化；b) 将利托那韦酸加盐转化为利托那韦盐酸盐。
• SALT OF 4-[[4-[[4-(2-CYANOETHENYL)-2,6-DIMETHYLPHENYL]AMINO]-2-PYRIMIDINYL]AMINO]BENZONITRILE
  申请人：GUILLEMONT Jérôme Emile Georges

  公开号：US20110008434A1

  公开（公告）日：2011-01-13

  The present invention relates to a pharmaceutical composition comprising as active ingredient the hydrochloric acid salt of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethyl-phenyl]amino]-2-pyrimidinyl]amino]benzonitrile and to processes for their preparation.

  本发明涉及一种药物组合物，其活性成分为4-[[4-[[4-(2-氰基乙烯基)-2,6-二甲基苯基]氨基]-2-嘧啶基]氨基]苯腈的盐酸盐，并涉及其制备方法。