(+/-)-N,N-diisopropyl-3-(2-hydroxy-5-methylphenyl)-3-phenyl-propanamide | 897314-72-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (+/-)-N,N-diisopropyl-3-(2-hydroxy-5-methylphenyl)-3-phenyl-propanamide
• 英文别名: (N,N-diisopropyl-3-phenyl-3-(2-hydroxy-5-methylphenyl)propionamide)；3-(2-hydroxy-5-methyl-phenyl)-N,N-diisopropyl-3-phenyl-propionamide；N,N-diisopropyl-3-phenyl-3-(2-hydroxy-5-methylphenyl)propionamide；3-(2-hydroxy-5-methylphenyl)-3-phenyl-N,N-di(propan-2-yl)propanamide
• CAS: 897314-72-6
• 化学式: C₂₂H₂₉NO₂
• 分子量: 339.478
• InChiKey: CRCFRTHJZDPVLI-UHFFFAOYSA-N

物化性质

• 沸点：
  491.9±45.0 °C(Predicted)
• 密度：
  1.055±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (+/-)-N,N-diisopropyl-3-(2-hydroxy-5-methylphenyl)-3-phenyl-propanamide 在 lithium aluminium tetrahydride 、 溶剂黄146 作用下， 以 乙醚 为溶剂， 反应 96.0h， 生成 托特罗定
  参考文献：
  名称：

  A process for the preparation of tolterodine

  摘要：

  公开号：

  EP1693361B1
• 作为产物：
  描述：

  N,N-diisopropyl-3-phenyl-3-p-tolyloxy-propionamide 在 PPA 、 sodium hydroxide 作用下， 以 水 为溶剂， 反应 4.5h， 生成 (+/-)-N,N-diisopropyl-3-(2-hydroxy-5-methylphenyl)-3-phenyl-propanamide
  参考文献：
  名称：

  Process for the preparation of tolterodine

  摘要：

  一种用于制备托特罗定（即(R)-N,N-二异丙基-3-(2-羟基-5-甲基苯基)-3-苯丙胺）的新型方法，以其外消旋形式为基础，并提供了制备该化合物的中间体。

  公开号：

  US20060189827A1

文献信息

• [EN] PROCESS FOR THE PREPARATION OF N,N-DIISOPROPYL-3-(2-HYDROXY-5-METHYLPHENYL)- 3-PHENYL PROPYLAMINE AND ITS SALTS STARTING FROM A NOVEL INTERMEDIATE<br/>[FR] PROCÉDÉ POUR LA PRÉPARATION DE N,N-DIISOPROPYL-3-(2-HYDROXY-5-MÉTHYLPHÉNYL)-3-PHÉNYLPROPYLAMINE ET DE SES SELS À PARTIR D'UN NOUVEL INTERMÉDIAIRE
  申请人：CAMBREX PROFARMACO MILANO S R L

  公开号：WO2012098044A1

  公开（公告）日：2012-07-26

  The invention concerns an improved process for the preparation of tolterodine (N,N-diisopropyl-3-(2-hydroxy-5-methylphenyl)-3-phenyl propyl amine) and its salts, in particular for the preparation of the tartrate salt, and more particularly for the (+)-(R) enantiomer of tolterodine L-tartrate, starting from a novel intermediate, N,N-diisopropyl-3-(2-hydroxy-5-methylphenyl)-3- phenyl-2-propenamide, which can be used as pure Z or E isomer or as a mixture of Z and E isomers. When the target is the preparation of the enantiomer (R)-(+)-(N,N- diisopropyl-3-(2-hydroxy-5-methylphenyl)-3-phenylpropylamine) and diastereomeric crystallization of suitable compound is applied, the present invention covers also the use of racemisation of undesired (S)-(-)- (N,N-diisopropyl-3-(2-hydroxy-5-methylphenyl)-3 -phenyl propylamine) enantiomer and its recycle in the process.

  该发明涉及一种改进的制备托特罗定（N,N-二异丙基-3-(2-羟基-5-甲基苯基)-3-苯基丙胺）及其盐的过程，特别是制备酒石酸盐，更具体地是制备托特罗定L-酒石酸盐的（+）-(R)对映体的过程，从一种新型中间体N,N-二异丙基-3-(2-羟基-5-甲基苯基)-3-苯基-2-丙烯酰胺开始，该中间体可用纯Z或E异构体或Z和E异构体混合物形式使用。当目标是制备对映体(R)-(+)-(N,N-二异丙基-3-(2-羟基-5-甲基苯基)-3-苯基丙胺)并且适当化合物的二对映体结晶被应用时，该发明还涵盖了对不需要的(S)-(-)-(N,N-二异丙基-3-(2-羟基-5-甲基苯基)-3-苯基丙胺)对映体的消旋化及其在过程中的再循环的用途。
• Process for the preparation of N,N-diisopropyl-3-(2-hydroxy-5-methylphenyl)- 3-phenyl propylamine and its salts starting from a novel intermediate
  申请人：Cambrex Profarmaco Milano S.r.l.

  公开号：EP2476665A1

  公开（公告）日：2012-07-18

  The invention concerns an improved process for the preparation of tolterodine (N,N-diisopropyl-3-(2-hydroxy-5-methylphenyl)-3-phenyl propylamine) and its salts, in particular for the preparation of the tartrate salt, and more in particular for the (+)-(R) enantiomer of tolterodine L-tartrate, starting from a novel intermediate, N,N-diisopropyl-3-(2-hydroxy-5-methylphenyl)-3-phenyl-2-propenamide which can be used as pure Z or E isomer or as a mixture of Z and E isomers.

  这项发明涉及一种改进的制备替洛特定（N，N-二异丙基-3-(2-羟基-5-甲基苯基)-3-苯基丙胺）及其盐的过程，特别是制备酒石酸盐，更特别是从一种新的中间体N，N-二异丙基-3-(2-羟基-5-甲基苯基)-3-苯基-2-丙烯酰胺开始制备(+)-(R)对映体替洛特定L-酒石酸盐，该中间体可用作纯Z或E异构体，也可用作Z和E异构体的混合物。
• PROCESS FOR PREPARING TOLTERODINE AND THE L-TARTRATE THEREOF
  申请人：Wang Gang

  公开号：US20110306792A1

  公开（公告）日：2011-12-15

  The present invention relates to a process for preparing tolterodine and the L-tartrate thereof. The preparation consists of the following steps: A) ammonolysis reaction between diisopropylamine and compound 2 (3,4-dihydro-6-methyl-4-phenyl-2H-benzopyran-2-one) activated by an activator to afford the amide 3; B) reduction of the amide by a reductant to give compound 1, i.e., racemic tolterodine free base; C) Resolution of the tolterodine free base to afford tolterodine L-tartrate. The present route is very short and suitable for industrial production.

  本发明涉及一种制备托吡酯及其L-酒石酸盐的方法。制备过程包括以下步骤：A）用活化剂促进二异丙胺和化合物2（3,4-二氢-6-甲基-4-苯基-2H-苯并吡喃-2-酮）的氨解反应，得到酰胺3；B）用还原剂还原酰胺，得到化合物1，即外消旋托吡酯自由碱；C）分离托吡酯自由碱，得到托吡酯L-酒石酸盐。该制备路线非常简短，适合工业生产。
• [EN] PROCESS FOR PREPARATION OF TOLTERODINE AND ITS L-TARTRATE<br/>[FR] PROCÉDÉ DE PRÉPARATION DE TOLTÉRODINE ET SON L-TARTRATE
  申请人：2Y CHEM LTD

  公开号：WO2010078703A1

  公开（公告）日：2010-07-15

  The invention provides a process for the preparation of Tolterodine and its L-tartrate.  The preparation is as follows, A) after diisopropyl amine is activated by activator, it is reacted with 3,4-dihydro-6-methyl-4-phenylchroman-2-one to obtain N,N-diisopropyl-3-phenyl-3-(2-hydroxy-5-methylphenyl)-propionamide; or after diisopropyl amine and 3,4-dihydro-6-methyl-4-phenyl-chroman-2-one are actived by Lewis acid, they take aminolysis to obtain N,N-diisopropyl-3-phenyl-(2-hydroxy-5-methylphenyl)-propionamide; B) N,N-diisopropyl-3-phenyl-(2-hydroxy-5-methylphenyl)-propionamide is reduced by reductant to obtain the free base of (±)-Tolterodine; C) the free base of (±)-Tolterodine was resolved by L-(+)-tartaric acid to give L-(+)-Tolterodine tartrate. The process has the advantages of simple procedure, low cost, high yield, easy to operate, simple post-treatment, steady quality of the product, and suitable for industrial production.

  本发明提供了一种制备托吡酯及其L-酒石酸盐的方法。其制备方法如下：A)将二异丙基胺经活化剂活化后，与3,4-二氢-6-甲基-4-苯基色酮反应，得到N,N-二异丙基-3-苯基-3-(2-羟基-5-甲基苯基)-丙酰胺；或者将二异丙基胺和3,4-二氢-6-甲基-4-苯基色酮经路易斯酸活化后，进行氨解反应，得到N,N-二异丙基-3-苯基-(2-羟基-5-甲基苯基)-丙酰胺；B)将N,N-二异丙基-3-苯基-(2-羟基-5-甲基苯基)-丙酰胺经还原剂还原，得到(±)-托吡酯的自由碱；C)将(±)-托吡酯的自由碱用L-(+)-酒石酸分离得到L-(+)-托吡酯酒石酸盐。该方法具有程序简单、成本低、产率高、易于操作、后处理简单、产品质量稳定、适用于工业生产等优点。
• USE OF 5HT2A INVERSE AGONISTS FOR TREATING PSYCHOSIS
  申请人：Axovant Sciences GmbH

  公开号：US20190046506A1

  公开（公告）日：2019-02-14

  Disclosed herein are methods of using a 5-HT 2A serotonin receptor inverse agonist for the prophylaxis and/or treatment of psychosis or psychotic symptoms in an individual comprising administering to said individual in need thereof a therapeutically effective amount of said 5-HT 2A serotonin receptor inverse agonist.