(4-(phenylamino)-1-(2-(thiophen-2-yl)ethyl)piperidin-4-yl)methanol | 164790-59-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (4-(phenylamino)-1-(2-(thiophen-2-yl)ethyl)piperidin-4-yl)methanol
• 英文别名: N-(2-thien-2-ylethyl)-4-(phenylamino)-4-(hydroxymethyl)piperidine；[4-anilino-1-(2-thiophen-2-ylethyl)piperidin-4-yl]methanol
• CAS: 164790-59-4
• 化学式: C₁₈H₂₄N₂OS
• 分子量: 316.467
• InChiKey: QXWYCZZCKVKIHV-UHFFFAOYSA-N

物化性质

• 沸点：
  476.2±40.0 °C(Predicted)
• 密度：
  1.184±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  63.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4-(phenylamino)-1-(2-(thiophen-2-yl)ethyl)piperidin-4-yl)methanol 在 叔丁醇 sodium hydride 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 二乙二醇二甲醚 、 水 、 mineral oil 为溶剂， 反应 20.67h， 生成 舒芬太尼
  参考文献：
  名称：

  Process for the Preparation of Sufentanil Base and Related Compounds

  摘要：

  本公开涉及一种改进的制备各种哌啶衍生物的方法。更具体地说，本公开涉及一种改进的制备舒芬太尼碱（1）和相关化合物的方法，该方法利用更具成本效益和/或更少危险的试剂，包括一种分散物，其包含约50%至约70%的重量（基于分散物总重量）的碱金属氢化物，如氢化钠，并且消除了昂贵和/或耗时的纯化技术的需求。

  公开号：

  US20120071659A1
• 作为产物：
  描述：

  1-(2-(噻吩-2-基)乙基)哌啶-4-醇 在 草酰氯 、 dimsylsodium 、 triethyloxonium fluoroborate 、 二甲基亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (4-(phenylamino)-1-(2-(thiophen-2-yl)ethyl)piperidin-4-yl)methanol
  参考文献：
  名称：

  Concise and Versatile Syntheses of N-Arylalkylpiperidines as Potential Intermediates for 4-Anilidopiperidine Analgesics

  摘要：

  N-Arylalkylpiperidones and N-arylalkylspiroepoxypiperidine as potential intermediates for 4-anilidopiperidine analgesics and their structural analogues have been efficiently synthesized from the simple arylalkylamines by two and three step sequences respectively.

  DOI：

  10.3987/com-97-8056

文献信息

• Methods for the syntheses of alfentanil sufentanil and remifentanil
  申请人：——

  公开号：US20040138461A1

  公开（公告）日：2004-07-15

  Synthetic pathways are disclosed for synthesizing derivatives or analogs of fentanyl. Specifically set out are pathways for synthesizing alfentanil, sufentanil and remifentanil. The disclosed methods require fewer steps and produce a greater yield of product than methods reported in the prior art. The pathways to all these compounds begin with a common pathway of condensing a piperidone with a primary amine so as to form a 4-amino carboxyamino-piperidine, wherein N of said piperidone is a —N—COO—(CH 2 ) n CH 3 , alkylating an N of said primary amine which was condensed with said piperidone thereby producing an N-alkyl-anilide, and hydrolyzing said —COO—(CH 2 ) n CH 3? group of said 4-amino-4-carboxyamino-piperidine following the condensation reaction so as to form a piperidine hydrolysis product. This product can then be convened to remifentanil in a 4 step reaction. Also, this hydrolysis product can be treated with a hydride to yield a 4-hydroxymthyl-piperidine which can be converted to alfentanil in 3 further steps, to sufentanil in 3 more steps, or to a variety of remifentanil analogs in two steps.

  本文披露了合成芬太尼衍生物或类似物的合成途径。具体介绍了合成阿芬太尼、舒芬太尼和瑞芬太尼的途径。所披露的方法需要的步骤更少，产物收率比先前报道的方法更高。所有这些化合物的途径都始于将哌啶酮与一种一级胺缩合，从而形成4-氨基羧氨基哌啶，其中所述哌啶酮的N为—N—COO—(CH2)nCH3，烷基化所述与所述哌啶酮缩合的所述一级胺的N，从而产生一种N-烷基酰胺，然后水解所述缩合反应的4-氨基-4-羧氨基哌啶中的所述—COO—(CH2)nCH3?基团，从而形成哌啶水解产物。然后，可以通过4步反应将该产物转化为瑞芬太尼。此外，该水解产物可以用氢化物处理，产生4-羟甲基哌啶，可以通过3个进一步的步骤将其转化为阿芬太尼，通过3个更多的步骤将其转化为舒芬太尼，或者通过两个步骤将其转化为各种瑞芬太尼类似物。
• [EN] NEW METHODS FOR THE SYNTHESES OF ALFENTANIL, SUFENTANIL AND REMIFENTANIL<br/>[FR] NOUVELLES METHODES DE SYNTHESE D'ALFENTANIL, DE SUFENTANIL ET DE REMIFENTANIL
  申请人：MALLINCKRODT INC

  公开号：WO2001040184A2

  公开（公告）日：2001-06-07

  Synthetic pathways are disclosed for synthesizing derivatives or analogs of fentanyl. Specifically set out are pathways for synthesizing alfentanil, sufentanil and remifentanil. The disclosed methods require fewer steps and produce a greater yield of product than methods reported in the prior art. The pathways to all these compounds begin with a common pathway of condensing a piperidone with a primary amine so as to form a 4-amino-4-carboxyamino-piperidine, wherein N of said piperidone is a -N-COO-(CH2)nCH3, alkylating an N of said primary amine which was condensed with said piperidone thereby producing an N-alkyl-anilide, and hydrolyzing said -COO-(CH2)nCH3 group of said 4-amino-4-carboxyamino-piperidine following the condensation reaction so as to form a piperidine hydrolysis product. This product can then be converted to remifentanil in a 4 step reaction. Also, this hydrolysis product can be treated with a hydride to yield a 4-hydroxymethyl-piperidine which can be converted to alfentanil in 3 further steps, to sufentanil in 3 more steps, or to a variety of remifentanil analogs in two steps.

  揭示了合成芬太尼衍生物或类似物的合成途径。具体列出了合成阿芬太尼、舒芬太尼和瑞芬太尼的途径。所揭示的方法需要较少的步骤，并且产量比先前报道的方法更高。所有这些化合物的途径都始于将哌啶酮与一种一级胺缩合以形成4-氨基-4-羧基氨基哌啶的共同途径，其中所述哌啶酮的N为-N-COO-（CH2）nCH3，烷基化所述与所述哌啶酮缩合的所述一级胺的N，从而产生一种N-烷基酰胺，以及在缩合反应后水解所述4-氨基-4-羧基氨基哌啶的所述-COO-（CH2）nCH3基团，从而形成哌啶水解产物。然后，该产物可以通过4步反应转化为瑞芬太尼。此外，可以用还原剂处理该水解产物以产生4-羟甲基哌啶，然后通过3个进一步的步骤将其转化为阿芬太尼，通过另外3个步骤将其转化为舒芬太尼，或通过2个步骤将其转化为各种瑞芬太尼类似物。
• New methods for the synthesis of alfentanil, sufentanil, and remifentanil
  申请人：Mathew Jacob

  公开号：US20060149071A1

  公开（公告）日：2006-07-06

  Synthetic pathways are disclosed for synthesizing derivatives or analogs of fentanyl. Specifically set out are pathways for synthesizing alfentanil, sufentanil and remifentanil. The disclosed methods require fewer steps and produce a greater yield of product than methods reported in the prior art.

  本文披露了合成芬太尼衍生物或类似物的合成途径。具体列出了合成阿芬太尼、舒芬太尼和瑞芬太尼的途径。披露的方法所需步骤较少，产量比先前报道的方法更高。
• Process for the preparation of sufentanil base and related compounds
  申请人：Orr Brian

  公开号：US08946433B2

  公开（公告）日：2015-02-03

  The present disclosure generally related to an improved process for the preparation of various piperidine derivatives. More particularly, the present disclosure related to an improved process for preparing sufentanil base (1) and related compounds, which advantageously utilizes more cost effective and/or less hazardous reagents, including a dispersion comprising between about 50% and about 70% by weight (based on the total weight of the dispersion) of an alkali metal hydride, such as sodium hydride, as well as eliminates the need for expensive and/or time consuming purification techniques.

  本公开涉及一种改进的制备各种哌啶衍生物的方法。更具体地，本公开涉及一种改进的制备舒芬太尼基础物质（1）及其相关化合物的方法，该方法利用成本更低廉和/或更少危险性的试剂，包括一种分散体，其中包含约50%至约70%重量（基于分散体的总重量）的碱金属氢化物，例如氢化钠，并且消除了昂贵和/或耗时的纯化技术的需要。
• METHODS FOR THE SYNTHESES OF ALFENTANIL, SUFENTANIL AND REMIFENTANIL
  申请人：MALLINCKRODT INC.

  公开号：EP1246801B1

  公开（公告）日：2006-09-20