帕拉米韦杂质42 | 251327-01-2

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 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
• 中文名称: 帕拉米韦杂质42
• 英文名称: methyl (4R)-4-[(tert-butyloxycarbonyl)amino]cyclopent-1-ene-1-carboxylate
• 英文别名: methyl (R)-4-((tert-butoxycarbonyl)amino)cyclopent-1-enecarboxylate；(R)-methyl 4-(tert-butoxycarbonylamino)cyclopent-1-enecarboxylate；methyl (4R)-4-{[(tert-butoxy)carbonyl]amino}cyclopent-1-ene-1-carboxylate；methyl (4R)-4-[(2-methylpropan-2-yl)oxycarbonylamino]cyclopentene-1-carboxylate
• CAS: 251327-01-2
• 化学式: C₁₂H₁₉NO₄
• 分子量: 241.287
• InChiKey: BPVUUOLKMLXVJR-SECBINFHSA-N

物化性质

• 沸点：
  340.6±42.0 °C(Predicted)
• 密度：
  1.11±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

制备方法与用途

本品为帕拉米韦的杂质，主要用于作为标准品和对照品。

反应信息

• 作为反应物：
  描述：

  帕拉米韦杂质42 在 4-二甲氨基吡啶 、 三异丙基亚磷酸酯 、 palladium diacetate 、 臭氧 、 sodium sulfate 、 对甲苯磺酰肼 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 甲苯 为溶剂， 生成 methyl (2R,3aR,6aR)-2-[bis[(2-methylpropan-2-yl)oxycarbonyl]amino]-2,3,4,5,6,6a-hexahydro-1H-pentalene-3a-carboxylate
  参考文献：
  名称：

  Novel 2-aminooctahydrocyclopentalene-3a-carboxamides as potent CCR2 antagonists

  摘要：

  Novel CCR2 antagonists with a novel 2-aminooctahydrocyclopentalene-3a-carboxamide scaffold were designed. SAR studies led to a series of potent compounds. For example, compound 51 had a good PK profile in both dog and monkey, and exhibited excellent efficacy when dosed orally in an inflammation model in hCCR2 KI mice. In addition, an asymmetric synthesis to the core structures was developed. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.069
• 作为产物：
  描述：

  (1R,4S)- N-BOC-4-氨基环戊-2-烯甲酸 在 氯化亚砜 、 potassium carbonate 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 28.83h， 生成 帕拉米韦杂质42
  参考文献：
  名称：

  一种手性反式-N-BOC-1-氨基环戊烷-3-甲酸的制备方法

  摘要：

  本发明提供了一种手性反式‑N‑BOC‑1‑氨基环戊烷‑3‑甲酸的制备方法，所述制备方法包括以下步骤：(1)将(1R,4S)‑4‑((叔丁氧基羰基)氨基)环戊‑2‑烯甲酸与甲醇混合酯化，得到化合物1；(2)将化合物1与碱、二碳酸二叔丁酯混合反应，得到化合物2；(3)将化合物2与碳酸钾混合反应，得到化合物3；(4)将化合物3与硼氢化钠、催化剂混合反应，得到化合物4；(5)将化合物4与碱混合水解，得到所述手性反式‑N‑BOC‑1‑氨基环戊烷‑3‑甲酸。本发明提供的制备方法相比现有技术，反应步骤、工序明显减少，整体过程更加简单，总收率更高，大幅降低了生产成本，适合工业化生产。

  公开号：

  CN117756677A

文献信息

• [EN] OCTAHYDRO-CYCLOPENTAPYRROLYL ANTAGONISTS OF CCR2<br/>[FR] ANTAGONISTES OCTAHYDRO-CYCLOPENTAPYRROLYL ANTI-CCR2
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2014014901A1

  公开（公告）日：2014-01-23

  The present invention comprises compounds of Formula (I). Formula (I) wherein: R1, R2, R3, R4, R5, Z1 and Z2 are as defined in the specification. The invention also comprises a method of preventing, treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is type II diabetes, obesity and asthma. The invention also comprises a method of inhibiting CCR2 activity in a mammal by administration of a therapeutically effective amount of at least one compound of Formula (I).

  本发明包括式(I)的化合物。其中：R1、R2、R3、R4、R5、Z1和Z2如规范中所定义。该发明还包括一种预防、治疗或改善综合症、疾病或疾病的方法，其中所述综合症、疾病或疾病是II型糖尿病、肥胖和哮喘。该发明还包括通过给哺乳动物施用至少一种式(I)化合物的治疗有效量来抑制CCR2活性的方法。
• Regio- and Stereoselective Synthesis of Functionalized Cyclopentene Derivatives via Mizoroki–Heck Reactions
  作者：Alexander Wetzel、Joakim Bergman、Peter Brandt、Mats Larhed、Jonas Brånalt

  DOI：10.1021/acs.orglett.7b00325

  日期：2017.4.7

  Mizoroki–Heck alkenylations and arylations of protected aminocyclopentenes, prepared in a few steps from Vince lactam, afforded functionalized cyclopentenes in high yields and stereoselectivities. DFT calculations were performed to rationalize the high diastereoselectivities. Functionalized cyclopentene products were transformed into valuable chiral building blocks, such as cyclic γ-amino acids and carbocyclic

  Pd（0）催化的从Vince内酰胺制备的受保护的氨基环戊烯的Mizoroki-Heck烯基化和芳基化（从文斯内酰胺制备）仅需几步即可提供高产率和立体选择性的官能化环戊烯。进行DFT计算以合理化高非对映选择性。功能化的环戊烯产物被转化为有价值的手性构件，例如环状γ-氨基酸和碳环核苷前体。
• OCTAHYDRO-CYCLOPENTAPYRROLYL ANTAGONISTS OF CCR2
  申请人：Janssen Pharmaceutica NV

  公开号：US20140024646A1

  公开（公告）日：2014-01-23

  The present invention comprises compounds of Formula (I). wherein: R 1 , R 2 , R 3 , R 4 , R 5 , Z 1 and Z 2 are as defined in the specification. The invention also comprises a method of preventing, treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is type II diabetes, obesity and asthma. The invention also comprises a method of inhibiting CCR2 activity in a mammal by administration of a therapeutically effective amount of at least one compound of Formula (I).

  本发明涉及公式（I）的化合物，其中：R1、R2、R3、R4、R5、Z1和Z2如规范中所定义。本发明还涉及一种预防、治疗或改善综合症、失调或疾病的方法，其中所述综合症、失调或疾病是II型糖尿病、肥胖症和哮喘。本发明还涉及一种通过给哺乳动物注射公式（I）至少一种化合物的治疗有效剂量来抑制CCR2活性的方法。
• Octahydro-cyclopentapyrrolyl antagonists of CCR2
  申请人：Janssen Pharmaceutica NV

  公开号：US09024017B2

  公开（公告）日：2015-05-05

  The present invention comprises compounds of Formula (I). wherein: R1, R2, R3, R4, R5, Z1 and Z2 are as defined in the specification. The invention also comprises a method of preventing, treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is type II diabetes, obesity and asthma. The invention also comprises a method of inhibiting CCR2 activity in a mammal by administration of a therapeutically effective amount of at least one compound of Formula (I).

  本发明涉及式（I）的化合物，其中：R1、R2、R3、R4、R5、Z1和Z2如规范中所定义。本发明还涉及一种预防、治疗或改善综合症、障碍或疾病的方法，其中所述的综合症、障碍或疾病是2型糖尿病、肥胖症和哮喘。本发明还涉及通过给哺乳动物施用至少一种式（I）化合物的治疗有效量来抑制CCR2活性的方法。
• Modular Synthesis of Cyclopropane‐Fused <i>N</i> ‐Heterocycles Enabled by Underexplored Diazo Reagents
  作者：Matthieu J. R. Richter、Frédéric J. Zécri、Karin Briner、Stuart L. Schreiber

  DOI：10.1002/anie.202203221

  日期：2022.9.19

  Modular synthesis of cyclopropane-fused N-heterocycles from readily available amines was achieved. Key to the disclosed strategy was the development and implementation of reactive α-diazo acylating agents, providing access to structurally and functionally diverse products. Application of the method is showcased in the concise syntheses of therapeutic agents milnaciprane and amitifadine.

  从容易获得的胺中实现了环丙烷稠合的N-杂环的模块化合成。所公开策略的关键是反应性α-重氮酰化剂的开发和实施，提供结构和功能多样化的产品。该方法在治疗药物米那普兰和阿米替发定的简明合成中得到应用。