(R)-2-[2-(4-methyl-piperidine-1-yl)-ethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester | 201039-14-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (R)-2-[2-(4-methyl-piperidine-1-yl)-ethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester
• 英文别名: (R)-2-[2-(4-methyl-piperidin-1-yl)ethyl]pyrrolidine-1-carboxylic acid, tert-butyl ester；tert-butyl (2R)-2-[2-(4-methylpiperidin-1-yl)ethyl]pyrrolidine-1-carboxylate
• CAS: 201039-14-7
• 化学式: C₁₇H₃₂N₂O₂
• 分子量: 296.453
• InChiKey: SFCQADLTXTVOSK-OAHLLOKOSA-N

物化性质

• 沸点：
  375.4±15.0 °C(Predicted)
• 密度：
  0.994±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-2-[2-(4-methyl-piperidine-1-yl)-ethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester 在 三氟乙酸 、 sodium hydroxide 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 0.5h， 生成 (R)-2-[2-(4-methyl-piperidin-1-yl)ethyl]pyrrolidine
  参考文献：
  名称：

  选择性 5-HT7 受体拮抗剂 SB-269970 的高效 Arndt-Eistert 合成

  摘要：

  摘要 该贡献描述了一种新的 Arndt-Eistert 方法，用于有效合成有效且选择性的 5-HT7-拮抗剂，(R)-3-(2-(2-(4-methylpiperidin-1-yl)-ethyl)pyrrolidine -1-磺酰基）苯酚 (SB-269970)，来自 D-脯氨酸。合成分10步进行，总产率为23%。

  DOI：

  10.1080/00397910902737155
• 作为产物：
  描述：

  (R)-叔丁基 2-(2-羟基乙基)吡咯烷-1-羧酸 在 吡啶 作用下， 以 乙腈 为溶剂， 反应 2.0h， 生成 (R)-2-[2-(4-methyl-piperidine-1-yl)-ethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  选择性 5-HT7 受体拮抗剂 SB-269970 的高效 Arndt-Eistert 合成

  摘要：

  摘要 该贡献描述了一种新的 Arndt-Eistert 方法，用于有效合成有效且选择性的 5-HT7-拮抗剂，(R)-3-(2-(2-(4-methylpiperidin-1-yl)-ethyl)pyrrolidine -1-磺酰基）苯酚 (SB-269970)，来自 D-脯氨酸。合成分10步进行，总产率为23%。

  DOI：

  10.1080/00397910902737155

文献信息

• Sulphonamide derivatives and their use in the treatment of CNS disorders
  申请人：SmithKline Beecham plc

  公开号：US06265408B1

  公开（公告）日：2001-07-24

  Sulphonamide compounds according to formula (I) or pharmaceutically acceptable salts thereof: wherein: Ar is naphthyl, phenyl or thienyl optionally substituted by one or more substituents selected from the group consisting of C1-6 alkyl optionally substituted by NR7R8, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkylthio, cyano, nitro, halogen, CF3, C2F5, NR7R8, CONR7R8, NR7COR8, S(O)pNR7R8, CHO, OCF3, SCF3, COR9, CH2OR9, CO2R9 or OR9 where p is 1 or 2 and R7, R8 and R9 are independently hydrogen or C1-6 alkyl. R1 and R2 are independently hydrogen or C1-6alkyl or together with the nitrogen atom to which they are attached form a 5- to 7-membered heterocyclic ring optionally substituted by Cl-6alkyl and optionally containing a further heteroatom selected from nitrogen, sulphur or oxygen, the nitrogen atom being substituted by hydrogen, C1-6 alkyl or cycloC3-7alkyl; R3 is hydrogen or C1-6 alkyl; X is oxygen, sulphur or a bond; n is 2 or 3; and m is 1 or 2; are provided. The present compounds are useful in the treatment of CNS disorders.

  化合物式（I）的磺胺化合物或其药学上可接受的盐： 其中：Ar是萘基，苯基或噻吩基，可选择地被来自C1-6烷基，其上可选地被NR7R8取代，C2-6烯基，C2-6炔基，C1-6烷基硫，氰基，硝基，卤素，CF3，C2F5，NR7R8，CONR7R8，NR7COR8，S（O）pNR7R8，CHO，OCF3，SCF3，COR9，CH2OR9，CO2R9或OR9的一个或多个取代基选自的取代基取代。 其中p为1或2，R7，R8和R9独立地为氢或C1-6烷基。 R1和R2独立地为氢或C1-6烷基，或与它们连接的氮原子一起形成一个5-至7-成员杂环环，可选择地被Cl-6烷基取代，并可选择地含有来自氮，硫或氧的进一步杂原子，该氮原子被氢，C1-6烷基或环C3-7烷基取代； R3为氢或C1-6烷基； X为氧，硫或键； n为2或3；和 m为1或2。 提供了目前化合物在治疗中枢神经系统疾病方面的用途。
• A Novel, Potent, and Selective 5-HT₇ Antagonist:  (<i>R</i>)-3-(2-(2-(4-Methylpiperidin-1-yl)ethyl)pyrrolidine-1-sulfonyl)phenol (SB-269970)
  作者：Peter J. Lovell、Steven M. Bromidge、Steven Dabbs、D. Malcolm Duckworth、Ian T. Forbes、Andrew J. Jennings、Frank D. King、Derek N. Middlemiss、Shirley K. Rahman、Damian V. Saunders、Lissa L. Collin、Jim J. Hagan、Graham J. Riley、David R. Thomas

  DOI：10.1021/jm991151j

  日期：2000.2.1
• Efficient Arndt–Eistert Synthesis of Selective 5-HT₇ Receptor Antagonist SB-269970
  作者：Christina Schjøth-Eskesen、Henrik Helligsø Jensen

  DOI：10.1080/00397910902737155

  日期：2009.8.20

  Abstract This contribution describes a novel Arndt–Eistert approach for the efficient synthesis of the potent and selective 5-HT7-antagonist, (R)-3-(2-(2-(4-methylpiperidin-1-yl)-ethyl)pyrrolidine-1-sulfonyl)phenol (SB-269970), from D-proline. The synthesis was carried out in 10 steps with an overall yield of 23%.

  摘要 该贡献描述了一种新的 Arndt-Eistert 方法，用于有效合成有效且选择性的 5-HT7-拮抗剂，(R)-3-(2-(2-(4-methylpiperidin-1-yl)-ethyl)pyrrolidine -1-磺酰基）苯酚 (SB-269970)，来自 D-脯氨酸。合成分10步进行，总产率为23%。
• Synthesis and biological evaluation of potential 5-HT7 receptor PET radiotracers
  作者：Julien Andries、Laetitia Lemoine、Didier Le Bars、Luc Zimmer、Thierry Billard

  DOI：10.1016/j.ejmech.2011.05.010

  日期：2011.8

  Brain serotonin 7 receptor (5-HT7) is involved in several mood disorders and drug candidates targeting this subtype are currently in development. Positron emission tomography (PET) is a molecular imaging modality offering great promise for accelerating the process from preclinical discovery to clinical phases. As no PET radiopharmaceutical has yet been used successfully to study the 5-HT7 receptor in vivo, our objective is to develop the first 5-HT7 fluorine-18 labeled radiotracer.Four structural analogs of SB269970, a specific 5-HT7 receptor antagonist, divided in FP3 series and FPMP series were synthesized. Their antagonist effects were investigated by cellular functional assay. Nitro-precursors of these analogs were radiolabeled via a [F-18(-)]nucleophilic substitution and in vitro autoradiographies were performed in rat brain.Chemical and radiochemical purities of fluorine radiotracers were >99% with specific activities in 40 -129 GBq/mu mole range. The four derivates presented antagonism potencies toward 5-HT7 receptors (PKB) between 7.8 and 8.8. The four PET radiotracers had suitable characteristic for 5-HT7 receptor probing in vitro even if the FP3 series seemed to be more specific for this receptor. These results encourage us to pursue in vivo studies. (C) 2011 Elsevier Masson SAS. All rights reserved.