1-(carbethoxy)-4-(phenylamino)-4-piperidine carboxanilide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 1-(carbethoxy)-4-(phenylamino)-4-piperidine carboxanilide
• 英文别名: 1-(carbethoxy)-4-(phenylamino)-4-piperidinecarboxanilide；Ethyl 4-anilino-4-(phenylcarbamoyl)piperidine-1-carboxylate
• 化学式: C₂₁H₂₅N₃O₃
• 分子量: 367.448
• InChiKey: ZMLYLJUSLYZLGL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  70.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(carbethoxy)-4-(phenylamino)-4-piperidine carboxanilide 在 sodium hydroxide 、 水 、 异丙醇 作用下， 155.0 ℃ 、482.64 kPa 条件下， 反应 96.0h， 生成 N-phenyl-α-(4-piperidino)glycine
  参考文献：
  名称：

  WO2007/87164

  摘要：

  公开号：
• 作为产物：
  描述：

  哌啶酮 、 苄基三乙基氯化铵 在 sodium hydroxide 、 苯胺 作用下， 以 四氢呋喃 、 氯仿 、 水 、 乙酸乙酯 为溶剂， 生成 1-(carbethoxy)-4-(phenylamino)-4-piperidine carboxanilide
  参考文献：
  名称：

  Preparation of piperidine derivatives

  摘要：

  一种哌啶衍生物，如舒芬太尼，是通过将哌啶酮与一种初级胺缩合而形成的，从而形成4-氨基-4-羧基氨基哌啶的过程中产生的。

  公开号：

  US05489689A1

文献信息

• Process for preparing remifentanil, intermediates thereof, use of said intermediates and processes for their preparation
  申请人：KERN PHARMA, S.L.

  公开号：EP1867635A1

  公开（公告）日：2007-12-19

  A process for preparing remifentanil by conversion of the nitrile group of a cyanopiperidinyl propanoate derivative to an ester group. Advantageously, with this process the number of steps for preparing remifentanil from commercial products is significantly reduced, compared to the processes known in the art.

  通过将氰基哌啶丙酸酯衍生物的腈基转化为酯基来制备雷米芬太尼的方法。优点是，与已知的工艺相比，使用这种方法从商业产品制备雷米芬太尼的步骤数量大大减少。
• Process for the Preparation of Sufentanil Base and Related Compounds
  申请人：ORR Brian

  公开号：US20120071659A1

  公开（公告）日：2012-03-22

  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。
• 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。