N-[(4-fluorophenyl)methyl]-N,1-dimethylpiperidin-4-amine

• 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-[(4-fluorophenyl)methyl]-N,1-dimethylpiperidin-4-amine
• 化学式: C₁₄H₂₁FN₂
• 分子量: 236.33
• InChiKey: UGFLYMWKHHABKT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  6.5
• 氢给体数：
  0
• 氢受体数：
  3

文献信息

• [EN] A PRODUCTION METHOD OF 1-(4-FLUOROBENZYL)-3-(4-ISOBUTOXYBENZYL)-1-(1-METHYLPIPERIDIN- 4— YL)UREA AND ITS DEUTERATED ANALOGS NOT CONTAINING DIMERIC IMPURITIES<br/>[FR] PROCÉDÉ DE PRODUCTION DE 1-(4-FLUOROBENZYL)-3-(4-ISOBUTOXYBENZYL)-1-(1-MÉTHYLPIPÉRIDIN-4-YL)URÉE ET DE SES ANALOGUES DEUTÉRÉS NE CONTENANT PAS D'IMPURETÉS SOUS FORME DE DIMÈRES
  申请人：ZENTIVA KS

  公开号：WO2017036432A1

  公开（公告）日：2017-03-09

  The invention relates to an improved production method of 1-(4-fluorobenzyl)-3-(4-- isobutoxybenzyl)-1-(1— methylpiperidin-4-yl)urea of formula I, known under the generic name of pimavanserin. The method consists of two steps, namely a reaction of N-(4- fluorobenzyl)-l-methylpiperidine-4-amine with cyanic acid, the next step being a reaction of the obtained compound from the first step, 1-(4-fluorobenzyl)-1-(1-methylpiperidin-4-yl)urea and 4-isobutoxybenzaldehyde or with its precursors. Pimavanserin is an inverse agonist of the serotonin 5-HT2A receptor and is currently in the tartrate form in stage III of clinical trial for the treatment of psychosis in patients suffering from Parkinson's disease and has potential to become part of the therapy of other psychotic conditions.

  本发明涉及一种改进的1-(4-氟苯基)-3-(4-异丁氧基苯基)-1-(1-甲基哌啶-4-基)脲式I的生产方法，通用名称为匹马万辛。该方法包括两个步骤，即N-(4-氟苯基)-1-甲基哌啶-4-胺与氰酸反应，下一步是将第一步得到的化合物，1-(4-氟苯基)-1-(1-甲基哌啶-4-基)脲和4-异丁氧基苯甲醛或其前体反应。匹马万辛是血清素5-HT2A受体的反向激动剂，目前处于临床试验III期的酒石酸盐形式，用于治疗帕金森病患者的精神病症状，并有潜力成为其他精神病症状治疗的一部分。
• [EN] PROCESS FOR THE PREPARATION OF A PHARMACEUTICAL AGENT<br/>[FR] PROCÉDÉ DE PRÉPARATION D'UN AGENT PHARMACEUTIQUE
  申请人：ZAKL FARMACEUTYCZNE POLPHARMA S A

  公开号：WO2020212268A1

  公开（公告）日：2020-10-22

  This invention relates to a process for the preparation of pimavanserin comprising: (i) providing an acid addition salt of pimavanserin; (ii) dissolving the acid addition salt of pimavanserin in an aqueous solvent to form an aqueous solution; (ill) washing the aqueous solution obtained in step (ii) with an organic solvent; and (iv) adding a base to the washed aqueous solution to form pimavanserin. The invention also relates to a process for the preparation of an acid addition salt of pimavanserin additionally comprising step (v) of converting pimavanserin into an acid addition salt of pimavanserin. The invention also relates to pimavanserin or an acid addition salt thereof obtainable by the process, and to the use of pimavanserin hydrochloride, pimavanserin hydrogen sulfate or pimavanserin acetate for preparing pimavanserin or an acid addition salt thereof.

  本发明涉及一种制备匹马万辛的方法，包括：（i）提供匹马万辛的酸盐加合物；（ii）将匹马万辛的酸盐加合物溶解在水溶剂中形成水溶液；（iii）用有机溶剂洗涤步骤（ii）中获得的水溶液；以及（iv）向洗涤后的水溶液中加入碱以形成匹马万辛。本发明还涉及一种制备匹马万辛的酸盐加合物的方法，还包括将匹马万辛转化为匹马万辛的酸盐加合物的步骤（v）。本发明还涉及通过该方法获得的匹马万辛或其酸盐加合物，以及使用匹马万辛盐酸盐、匹马万辛硫酸氢盐或匹马万辛醋酸盐制备匹马万辛或其酸盐加合物的用途。
• [EN] A PHARMACEUTICAL INTERMEDIATE<br/>[FR] INTERMÉDIAIRE PHARMACEUTIQUE
  申请人：ZAKL FARMACEUTYCZNE POLPHARMA S A

  公开号：WO2020234383A1

  公开（公告）日：2020-11-26

  This invention relates to4-(4-fluorobenzylamino)-1-methylpiperidine trihydrateand a process for the preparation of 4-(4-fluorobenzylamino)-1-methylpiperidine trihydrate comprising treating 4-(4- fluorobenzylamino)-1-methylpiperidine with water. The invention also relates toa process for the preparation of pimavanserin comprising reacting 4-(4- fluorobenzylamino)-1-methylpiperidine trihydrate with 1-isobutoxy-4-(isocyanatomethyl)benzene; toa process for the preparation of a pimavanserin acid addition salt comprising reacting 4-(4- fluorobenzylamino)-1-methylpiperidine trihydrate with 1-isobutoxy-4-(isocyanatomethyl)benzene and converting pimavanserin into a pimavanserinacid additionsalt, pimavanserin and pimavanserin acid addition salts obtainable by the process, and to the use of 4-(4-fluorobenzylamino)-1-methylpiperidine trihydrate for preparing pimavanserin or an acid additionsalt thereof.

  本发明涉及4-(4-氟苯甲基氨基)-1-甲基哌啶三水合物及其制备方法，包括将4-(4-氟苯甲基氨基)-1-甲基哌啶与水处理。本发明还涉及一种制备匹马万辛的方法，包括将4-(4-氟苯甲基氨基)-1-甲基哌啶三水合物与1-异丁氧基-4-(异氰酸甲基)苯反应；一种制备匹马万辛酸盐加合物的方法，包括将4-(4-氟苯甲基氨基)-1-甲基哌啶三水合物与1-异丁氧基-4-(异氰酸甲基)苯反应，并将匹马万辛转化为匹马万辛酸盐加合物，以及通过该方法可获得的匹马万辛、匹马万辛酸盐加合物，以及使用4-(4-氟苯甲基氨基)-1-甲基哌啶三水合物制备匹马万辛或其酸盐加合物的用途。
• [EN] PROCESS FOR THE PREPARATION OF 1-(4-FLUOROBENZYL)-3-(4-ISOBUTOXYBENZYL)-1-(1- METHYLPIPERIDIN-4-YL)UREA AND SALTS THEREOF<br/>[FR] PROCÉDÉ POUR LA PRÉPARATION DE LA 1-(4-FLUOROBENZYL)-3-(4-ISOBUTOXYBENZYL)-1-(1-MÉTHYLPIPÉRIDIN-4-YL)URÉE ET DE SES SELS
  申请人：JUBILANT GENERICS LTD FORMERLY A DIVISION OF JUBILANT LIFE SCIENCES LTD

  公开号：WO2019008595A1

  公开（公告）日：2019-01-10

  The present invention relates to an efficient process for the preparation of 1-(4-fluorobenzyl)-3-(4-isobutoxybenzyl)-1-(1- methylpiperidin-4-yl)urea and pharmaceutically acceptable salts thereof involving use of novel intermediates.

  本发明涉及一种高效制备1-(4-氟苯甲基)-3-(4-异丁氧基苯甲基)-1-(1-甲基哌啶-4-基)脲及其药学上可接受的盐的方法，其中涉及使用新颖的中间体。
• A PRODUCTION METHOD OF 1-(4-FLUOROBENZYL)-3-(4-ISOBUTOXYBENZYL)-1-(1-METHYLPIPERIDIN- 4 YL)UREA AND ITS DEUTERATED ANALOGS NOT CONTAINING DIMERIC IMPURITIES
  申请人：Zentiva, K.S.

  公开号：EP3344603B1

  公开（公告）日：2020-09-30