3-(1-甲氧基羰基哌啶-4-基)丙酸 | 157649-29-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 3-(1-甲氧基羰基哌啶-4-基)丙酸
• 英文名称: 3-(1-methoxycarbonylpiperidin-4-yl)propionic acid
• 英文别名: 3-[N-(methoxycarbonyl)-piperidin4-yl]proprionic acid；3-(1-methoxycarbonyl-4-piperidinyl)propionic acid；4-Piperidinepropanoic acid, 1-(methoxycarbonyl)-；3-(1-methoxycarbonylpiperidin-4-yl)propanoic acid
• CAS: 157649-29-1
• 化学式: C₁₀H₁₇NO₄
• 分子量: 215.249
• InChiKey: VFYIKWMHUOXSDY-UHFFFAOYSA-N

物化性质

• 沸点：
  362.0±15.0 °C(Predicted)
• 密度：
  1.170±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(1-甲氧基羰基哌啶-4-基)丙酸 在 三氯化铝 、 氯化亚砜 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 16.5h， 生成 1-(2-acetyl-2,3,4,5-tetrahydro-1H-2-benzazepin-8-yl)-3-(1-methoxycarbonylpiperidine-4-yl)propan-1-one
  参考文献：
  名称：

  Regioselective Friedel–Crafts acylation of 2,3,4,5-tetrahydro-1H-2-benzazepine and related nitrogen heterocycles

  摘要：

  It is revealed that NH-protected 2,3,4,5-tetrahydro-1H-2-benzazepine 4 is acylated on C-8 with greater than 95% regioselectivity. This regioselectivity has been applied to the synthesis of 3-(1-benzylpiperidin-4-yl)-1-(2,3,4,5-tetrahydro-1H-2-benzazepin-8-yl)propan-1-one 3a, an inhibitor of acetylcholinesterase (AChE). The regioselectivities of the acylation of the following nitrogen heterocycles have also been studied: 4-formyl-2,3,4,5-tetrahydro-1,4-benzoxazepine 6, 2,3,4,5-tetrahydro-1H-2-benzazepin-3-one 7, 2,3,4,5-tetrahydro-1H-3-benzazepin-2-one 8, 7,11b,12,13-tetrahydro-5H-isoindolo[2,1-b][2] benzazepin-7-one 9 and 6,7,9,13b-tetrahydro-5H-isoindolo[1,2-a][2]benzazepin-9-one 10. A molecular orbital (MO) calculation on the Lewis acid coordinated substrates has been used for predicting regioselectivity.

  DOI：

  10.1039/p19940002993
• 作为产物：
  描述：

  4-哌啶丙酸 、 氯甲酸甲酯 在 盐酸 作用下， 生成 3-(1-甲氧基羰基哌啶-4-基)丙酸
  参考文献：
  名称：

  Processes and intermediates for preparing 5,

  摘要：

  本发明涉及一种制备具有以下式子的化合物的方法：##STR1## 其中，i）在碱的存在下在高温下加热具有以下式子的化合物：##STR2## 其中，R.sup.3为R.sup.4或苄基，R.sup.4为R.sup.5 C(.dbd.O)、R.sup.5 C(.dbd.O)或R.sup.5 SO.sub.2，R.sup.5为（C.sub.1-C.sub.6）烷基或（C.sub.6-C.sub.10）芳基（C.sub.1-C.sub.6）烷基；但是当所得产物中R.sup.3为R.sup.4时，该产物需要进行ii）进一步处理，即在高温下用水矿酸处理，然后再用a）苄基化试剂在碱的存在下处理或b）苯甲醛在还原剂和酸的存在下处理。

  公开号：

  US05916902A1

文献信息

• Tricyclic condensed heterocyclic compounds, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US05527800A1

  公开（公告）日：1996-06-18

  A novel compound of the formula: ##STR1## wherein Ar represents an optionally substituted tricyclic condensed benzene ring group which includes at least one heterocyclic ring as a component ring; n represents an integer from 2 to 10; R.sup.1 represents H or an optionally substituted hydrocarbon group, which may be different from one another in the repetition of n; and Y represents an optionally substituted 4-piperidinyl, 1-piperazinyl or 4-benzyl-1-piperidinyl group, or a salt thereof, inhibiting excellent cholinesterase inhibitory activity and monoamine reuptake inhibitory activity, thus being useful as therapeutic and/or prophylactic medicaments of senile dementia.

  一种化合物的式子：##STR1## 其中Ar代表一个可选择取代的三环融合苯环基团，其中至少包含一个杂环环作为组成环；n代表一个从2到10的整数；R.sup.1代表H或一个可选择取代的烃基团，可能在n的重复中彼此不同；Y代表一个可选择取代的4-哌啶基、1-哌嗪基或4-苄基-1-哌啶基团，或其盐，抑制优异的胆碱酯酶抑制活性和单胺再摄取抑制活性，因此可用作治疗和/或预防老年性痴呆症的药物。
• Process for the preparation of donepezil
  申请人：CHEMAGIS LTD

  公开号：US20040048893A1

  公开（公告）日：2004-03-11

  The invention provides a process for the preparation of a compound of the formula 6 comprising the hydrolysis and decarboxylation of a compound of the formula 5 according to the reaction: 1 wherein R and R 2 independently a C 1 -C 4 alkyl group or an aralkyl group.

  该发明提供了一种配方6的化合物制备过程，包括根据反应：1对配方5的化合物进行水解和脱羧，其中R和R2分别是C1-C4烷基或芳基烷基。
• Tetracyclic condensed heterocyclic compounds and their use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US05620973A1

  公开（公告）日：1997-04-15

  A novel compound of the formula ##STR1## wherein Ar represents a tetracyclic fused heterocyclic group which may be substituted; R.sup.1 represents H or a hydrocarbon group which may be substituted; Y represents an amino or nitrogen-containing saturated heterocyclic group which may be substituted, its salt, inhibiting excellent cholinesterase inhibitory activity and monoamine uptake inhibitory activity, thus being useful as therapeutic and/or prophylactic medicaments of senile dementia.

  该化合物的式子为##STR1## 其中Ar代表一个四环融合的杂环基团，可以被取代；R.sup.1代表氢或一个可以被取代的碳氢基团；Y代表一个氨基或含氮的饱和杂环基团，可以被取代，它的盐具有优异的胆碱酯酶抑制活性和单胺摄取抑制活性，因此可用作治疗和/或预防老年性痴呆的药物。
• 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)。
• Processes for Preparing Donepezil
  申请人：Kharatkar Raju Mahadev

  公开号：US20100105916A1

  公开（公告）日：2010-04-29

  A process for preparing highly pure donepezil, particularly donepezil hydrochloride, is provided comprising hydrogenating compound 1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-ylidene]methyl-piperidine or its hydrochloride salt with a noble metal catalyst or a derivative thereof, in the presence of at least one additive, wherein the additive contains at least one heteroatom, e.g., a sulfur, phosphorous, or nitrogen heteroatom.

  提供了一种制备高纯度多奈哌齐（尤其是盐酸多奈哌齐）的方法，包括在至少一种添加剂的存在下，使用贵金属催化剂或其衍生物对化合物1-苄基-4-[(5,6-二甲氧基-1-茚酮)-2-基亚甲基]-哌啶或其盐酸盐进行氢化反应，其中该添加剂包含至少一个杂原子，例如硫、磷或氮杂原子。