舒芬太尼杂质 | 72996-73-7

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 舒芬太尼杂质
• 英文名称: 4-(Methoxymethyl)-N-phenyl-1-<2-(2-thienyl)ethyl>-4-piperidinamine
• 英文别名: 1-[2-(thiophen-2-yl)ethyl]-4-methoxymethyl-4-phenylaminopiperidine；des-propionylsufentanil；despropionyl sufentanil；4-(methoxymethyl)-N-phenyl-1-(2-(thiophen-2-yl)ethyl)piperidin-4-amine；N-(2-Thien-2-ylethyl)-4-(phenylamino)-4-(methoxymethyl)piperidine；4-(methoxymethyl)-N-phenyl-1-(2-thiophen-2-ylethyl)piperidin-4-amine
• CAS: 72996-73-7
• 化学式: C₁₉H₂₆N₂OS
• 分子量: 330.494
• InChiKey: UBUDUWLTRRWLSI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  52.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  舒芬太尼杂质 在 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 5.0h， 生成 柠檬酸舒芬太尼
  参考文献：
  名称：

  阿芬太尼、舒芬太尼的制备方法及用于制备阿芬太尼、舒芬太尼的化合物

  摘要：

  本发明公开了阿芬太尼、舒芬太尼的制备方法及用于制备阿芬太尼、舒芬太尼的化合物，其中制备式V所示化合物的方法包括：使式IV所示化合物发生脱BOC反应，以便获得所述式V所示化合物，利用该方法能够方便、高效、安全地制备获得阿芬太尼、舒芬太尼合成的中间产物——式V所示化合物，进而，该式V所示化合物能够有效用于制备阿芬太尼、舒芬太尼。

  公开号：

  CN106336374A
• 作为产物：
  描述：

  2-噻吩乙醇 在 三乙胺 、 potassium iodide 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 1.0h， 生成 舒芬太尼杂质
  参考文献：
  名称：

  阿芬太尼、舒芬太尼的制备方法及用于制备阿芬太尼、舒芬太尼的化合物

  摘要：

  本发明公开了阿芬太尼、舒芬太尼的制备方法及用于制备阿芬太尼、舒芬太尼的化合物，其中制备式V所示化合物的方法包括：使式IV所示化合物发生脱BOC反应，以便获得所述式V所示化合物，利用该方法能够方便、高效、安全地制备获得阿芬太尼、舒芬太尼合成的中间产物——式V所示化合物，进而，该式V所示化合物能够有效用于制备阿芬太尼、舒芬太尼。

  公开号：

  CN106336374A

文献信息

• 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。
• Radioimmunoassay of the new opiate analgesics alfentanil and sufentanil. Preliminary pharmacokinetic profile in man
  作者：M Michiels、R Hendriks、J Heykants

  DOI：10.1111/j.2042-7158.1983.tb04275.x

  日期：2011.4.12

  The development of two analogous radioimmunoassay (RIA) procedures based on dextran-charcoal separation is described for the quantification of two fentanyl-like analgesics, alfentanil and sufentanil. Immunization of rabbits with conjugates of bovine serum albumin and carboxy-derivatives of the respective drugs resulted in the production of antisera capable of detecting less than 0.05 ng ml−1 of the parent analgesics with high specificity and almost no cross-reactivity with major metabolites. Excellent agreement was obtained between RIA—without prior extraction—and gas chromatography for alfentanil concentrations in human plasma. Because of sufentanil’s low therapeutic plasma levels, no comparison could be made between its RIA and an alternative assay, however, there was strong evidence for the specificity of the assay when applied directly to plasma. With these RIA methods preliminary information was obtained on plasma concentrations and elimination of alfentanil or sufentanil in patients given an intravenous bolus injection of 50 μg kg−1 of alfentanil, or 5 μg kg−1 of sufentanil. For both analgesics, the pharmacokinetic profile in man could be described by a three-compartment model. The terminal elimination half-life was 88 min for alfentanil and 140 min for sufentanil. Six hours after a therapeutic dose, plasma levels were in the order of 3 and 0.3 ng ml−1 for alfentanil and sufentanil respectively.

  本文介绍了基于右旋糖醇-木炭分离的两种类芬太尼类镇痛药物阿芬太尼和舒芬太尼的放射免疫测定（RIA）程序的开发。用牛血清白蛋白和相应药物的羧基衍生物偶联物免疫家兔，产生了能够检测到少于0.05 ng ml−1的原始镇痛药物的抗血清，具有高度的特异性，几乎没有与主要代谢物的交叉反应。在人类血浆中，阿芬太尼的RIA浓度与气相色谱的结果非常一致，无需先进行提取。由于舒芬太尼的治疗血浆水平较低，无法将其RIA与其他测定方法进行比较，但是在直接应用于血浆时，有强有力的证据证明了该测定方法的特异性。使用这些RIA方法，对给予50 μg kg−1阿芬太尼或5 μg kg−1舒芬太尼的患者的血浆中阿芬太尼或舒芬太尼的浓度和消除进行了初步的信息获取。对于两种镇痛药物，人体药代动力学特征可以用三室模型来描述。阿芬太尼的终末消除半衰期为88分钟，舒芬太尼为140分钟。治疗剂量6小时后，阿芬太尼和舒芬太尼的血浆水平分别为3和0.3 ng ml−1。

• [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。