多奈哌齐杂质13(非对映体混合物) | 757173-38-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 中文名称: 多奈哌齐杂质13(非对映体混合物)
• 英文名称: AS2QT83Y3Z
• 英文别名: 2-[(1-benzylpyridin-1-ium-4-yl)methyl]-5,6-dimethoxy-2,3-dihydroinden-1-one
• CAS: 757173-38-9
• 化学式: C24H24NO3+
• 分子量: 374.5
• InChiKey: RCRQOFLAAVCAGE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  39.4
• 氢给体数：
  0
• 氢受体数：
  3

文献信息

• Novel Process for Production of Highly Pure Polymorph (I) Donepezil Hydrochloride
  申请人：Neu Jozsef

  公开号：US20080306271A1

  公开（公告）日：2008-12-11

  The present invention provides a novel, industrially realizable and economically preferable process for production of highly pure 1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methyl piperidine hydrochloride, i.e., donepezil hydrochloride shown in the following reaction scheme, in Polymorph (I) morphological crystal form. (I) In one of the key steps of the process, during the hydrogenation 5,6-dimethoxy 2-(pyridine-4-yhnethylene)indan- 1 -one hydrochloride is saturated using Pd carbon to get 4-[(5,6-dimethoxy- 1 -indanon)-2-yl]-methyl piperidine at more than 97% HPLC purity. In the crystallization step donepezil-hydrochloride is crystallized from an aqueous alcoholic solvent to get Polymorph (I) in at least 99.95% HPLC purity.

  本发明提供了一种新颖的、可在工业上实现的、经济上优选的过程，用于生产高纯度的1-苄基-4-[(5,6-二甲氧基-1-吲哚酮)-2-基]甲基哌啶盐酸盐，即多奈哌齐盐酸盐，以Polymorph (I)形态晶体形式呈现在以下反应方案中。在该过程的关键步骤之一中，在氢化过程中，使用Pd碳饱和5,6-二甲氧基2-(吡啶-4-基亚乙烯基)吲哚-1-酮盐酸盐以获得在97%以上的HPLC纯度下的4-[(5,6-二甲氧基-1-吲哚酮)-2-基]甲基哌啶。在结晶步骤中，多奈哌齐盐酸盐从水醇溶剂中结晶出来，以至少99.95%的HPLC纯度得到Polymorph (I)。
• PROCESS FOR THE PREPARATION OF DONEPEZIL AND INTERMEDIATE COMPOUNDS THEREOF AS WELL AS HYDRATES OF DONEPEZIL
  申请人：Manikowski Andrzej

  公开号：US20090137811A1

  公开（公告）日：2009-05-28

  The present invention relates to a new process for the preparation of intermediate compounds useful in the manufacture of donepezil, or a pharmaceutically-acceptable salt thereof, and also relates to processes for preparing donepezil and to the novel intermediates per se. In addition the invention relates to various hydrated forms of donepezil.

  本发明涉及一种新的制备中间体化合物的工艺，该中间体化合物可用于制造多奈哌齐或其药用可接受盐，并且还涉及制备多奈哌齐的工艺以及新的中间体化合物本身。此外，本发明还涉及多奈哌齐的各种水合形式。
• [EN] A PROCESS FOR THE PREPARATION OF DONEPEZIL HYDROCHLORIDE<br/>[FR] PROCESSUS DE PRÉPARATION DE CHLORHYDRATE DE DONÉPÉZIL
  申请人：ALEMBIC LTD

  公开号：WO2010070511A2

  公开（公告）日：2010-06-24

  The present invention relates to a process for the preparation of donepezil hydrochloride o formula (I) which comprises the steps of condensing a pyridinium bromide salt of formula (IV) with dimethoxy-indanone of formula (V) and reducing the resulting condensed bromide salt of formula (VI) in two steps. The present invention further relates to a di-ene intermediate of formula (VII).

  本发明涉及一种制备多奈哌齐盐酸盐的方法，其公式为(I)，包括以下步骤：将公式为(IV)的吡啶溴化物盐与公式为(V)的二甲氧基茚酮缩合，然后用两步还原法还原所得的缩合溴化物盐，本发明还涉及公式为(VII)的二烯中间体。
• PROCESS FOR MAKING DONEPEZIL
  申请人：Pospisilik Karel

  公开号：US20070135644A1

  公开（公告）日：2007-06-14

  A process for making donepezil using a new intermediate salt of formula (VIIIa), especially the tosylate, can achieve good yields.

  使用新的中间盐（尤其是甲磺酸盐）的公式（VIIIa）制备多奈哌齐的工艺可以获得良好的收率。
• OXIDISABLE PYRIDINE DERIVATIVES, THEIR PREPARATION AND USE AS ANTI-ALZHEIMER AGENTS
  申请人：INSA (INSTITUT NATIONAL DES SCIENNCES APPLIQUÉES) DE ROUEN

  公开号：US20150353493A1

  公开（公告）日：2015-12-10

  A compound of formula (I) in which the dotted lines indicate the presence of at least one double bond; n=0 to 4; R 3 and R 4 are H, or when n=1, R 3 and R 4 can also form together a double bond between the carbon atoms, and m=0, 1 or 2, Z is CH or N or Z is C and —CHR 3 — is ═CH— linked by the double bond to cyclopentanone; or −(−) m - is absent, and Z is NH, >N-alkyl, >N-phenyl, >N-benzyl or >N heteroaryl; R 8 is alkyl, aryl or heteroaryl which can be optionally substituted; EWG represents an electron withdrawing group selected from the group comprising COOR, COSR, CONRR′, CN, COR, CF 3 , SOR, SO 2 R, SONRR′, SO 2 NRR′, NO 2 , halogen, heteroaryl; and the pharmaceutical salts and stereisomers thereof. The compounds of formula (I) are potent in the treatment of neurodegenerative diseases such as Alzheimer's disease.

  式(I)的化合物中，虚线表示存在至少一个双键；n = 0至4；R3和R4为H，或当n = 1时，R3和R4也可以共同形成碳原子之间的双键，m = 0、1或2，Z为CH或N，或者Z为C，-CHR3-与环戊酮通过双键连接，或-(-)m-不存在，Z为NH，>N-烷基，>N-苯基，>N-苯甲基或> N杂环芳基；R8为烷基、芳基或杂环芳基，可以选择性地被取代；EWG代表从COOR、COSR、CONRR'、CN、COR、CF3、SOR、SO2R、SONRR'、SO2NRR'、NO2、卤素、杂环芳基中选择的电子吸引基；以及其药物盐和立体异构体。式(I)的化合物在治疗神经退行性疾病，如阿尔茨海默病方面具有很强的疗效。