cis-2,5-bis(methoxymethyl)pyrrolidine | 172823-19-7

• 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: cis-2,5-bis(methoxymethyl)pyrrolidine
• 英文别名: (2S,5R)-2,5-bis(methoxymethyl)pyrrolidine
• CAS: 172823-19-7
• 化学式: C₈H₁₇NO₂
• 分子量: 159.228
• InChiKey: HDXYTIYVVNJFLU-OCAPTIKFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  11
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  30.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  cis-2,5-bis(methoxymethyl)pyrrolidine 在 氧化亚氮 、 calcium hydroxide 作用下， 以 水 为溶剂， 20.0 ℃ 、1.72 MPa 条件下， 反应 120.0h， 以98%的产率得到calcium 1-((2R,5S)-2,5-bis(methoxymethyl)pyrrolidin-1-yl)diazen-1-ium-1,2-diolate
  参考文献：
  名称：

  Scalable Synthesis of Diazeniumdiolates: Application to the Preparation of MK-8150

  摘要：

  Synthetic diazeniumdiolate (DAZD)-based nitric oxide is utilized to modulate the nitric oxide (NO) concentration in cellular environments and to control physiological processes, yet chemists are still struggling to find efficient and scalable methodologies that will enable them to access sufficient quantities of the high-energy diazeniumdiolate intermediates for biological studies. Now, a general, scalable, safer, and high-yielding new methodology adaptable to the large-scale synthesis of DAZDs has been developed.

  DOI：

  10.1021/acs.orglett.9b01401
• 作为产物：
  描述：

  cis-N-benzyl-2,5-bis(methoxymethyl)pyrrolidine 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、2.03 MPa 条件下， 反应 6.0h， 生成 cis-2,5-bis(methoxymethyl)pyrrolidine
  参考文献：
  名称：

  Influence of 4- or 5-substituents on the pyrrolidine ring of 5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin derivatives on their inhibitory activities towards caspases-3 and -7

  摘要：

  A series of new 4- or 5-substituted pyrrolidine derivatives of 5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin bearing additional n-butyl or 4-fluorobutyl groups at the isatin nitrogen were prepared and their inhibitory activities have been tested against caspases-3 and -7, which are known to participate in the execution of the programmed cell death, called apoptosis. Several analogues fluorinated at the 4-position of the pyrrolidine ring were also synthesized since such inhibitors might be developed as F-18-radiotracers for molecular imaging of activated caspases in vivo by PET. Enantiomerically pure diastereomeric 4-fluoropyrrolidinyl derivatives inhibited the enzymes in the nanomolar scale, i.e.100-1000 times more efficient than the corresponding 4-methoxy analogues. The 4,4-difluorinated compound showed the best result with IC50 = 362 nM and 178 nM for the aforementioned caspases. In contrast, the 4-methoxy and 4-trifluoromethyl analogues exhibited less inhibition potencies for the enzymes in the mu M scale, whereas all 4-OPEG(4) (PEG(4) = tetraethyleneglycol) and 5-methoxymethyl derivatives were inactive. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.04.011

文献信息

• HIV protease inhibitors
  申请人：Wong Chi-Huey

  公开号：US06900238B1

  公开（公告）日：2005-05-31

  Combinatorial libraries of HIV and FIV protease inhibitors are characterized by α-keto amide or hydroxyethylamine core structures flanked by on one side by substituted pyrrolidines, piperidines, or azasugars and on the other side by phenylalanine, tyrosine, or substituted tyrosines. The libraries are synthesized via a one step coupling reaction. Highly efficacious drug candidates are identified by screening the libraries for binding and inhibitory activity against both HIV and FIV protease. Drug candidates displaying clinically useful activity against both HIV and FIV protease are identified as being potentially resistive against a loss of inhibitory activity due to development of resistant strains of HIV.

  HIV和FIV蛋白酶抑制剂的组合库以α-酮酰胺或羟乙基胺核心结构为特征，一侧为取代吡咯烷、哌啶或氮代糖，另一侧为苯丙氨酸、酪氨酸或取代酪氨酸。这些库是通过一步偶联反应合成的。通过筛选这些库，识别出对HIV和FIV蛋白酶的结合和抑制活性高效的药物候选化合物。对HIV和FIV蛋白酶都显示出临床有用活性的药物候选化合物被确定为潜在对抗由于HIV耐药株的发展而导致的抑制活性丧失。
• Restricted Stereochemistry of Solvation of Allylic Lithium Compounds:  Structural and Dynamic Consequences
  作者：Gideon Fraenkel、Joseph H. Duncan、Jinhai Wang

  DOI：10.1021/ja983047h

  日期：1999.1.1

  diethyl ether or THF solutions all these compounds exhibited one bond 13C, 7Li spin coupling of ∼8 Hz, a 1:1:1:1 13C NMR pattern indicating monomeric structures; all show ligand resonances to be magnetically nonequivalent and reveal C1, C3 13C NMR shifts of about 40 and 75 δ which lie between those for model delocalized 1 and localized species 2. These compounds are concluded to be examples of the heretofore

  已经制备了几种 1-硅烯丙基锂化合物，其中锂的潜在配体在 2 位被取代。它们是 [2-[[[cis-2,5-双(甲氧基甲基)-1-吡咯烷基]甲基]-1-(三甲基甲硅烷基)烯丙基]锂 (22), [2-[[cis-2,5-bis(甲氧基甲基）-1-吡咯烷基]甲基]-1-（二甲基乙基甲硅烷基）烯丙基]锂（23），[2-[[双（2-甲氧基乙基）氨基]甲基]-1-（二甲基乙基甲硅烷基）烯丙基]锂（24）， [2-[[双(2-甲氧基乙基)氨基]甲基]-1-(叔丁基二甲基甲硅烷基)烯丙基]锂(25)和[2-[2-[双(2-甲氧基乙基)氨基]-1,1 -二甲基乙基](乙基二甲基甲硅烷基)]烯丙基锂(26)。使用二乙醚或 THF 溶液，所有这些化合物都表现出一个 13C 键，~8 Hz 的 7Li 自旋耦合，1:1:1:1 13C NMR 模式表明单体结构；都显示配体共振在磁性上不等价并显示 C1，
• Stereochemistry of Solvation of Benzylic Lithium Compounds:  Structure and Dynamic Behavior
  作者：Gideon Fraenkel、Joseph H. Duncan、Kevin Martin、Jinhai Wang

  DOI：10.1021/ja990485v

  日期：1999.11.1

  been prepared. Ring 13C NMR shifts indicate that 12−15 have partially delocalized structures. Externally solvated allylic lithium compounds are found to be delocalized, and only some internally coordinated species are partially delocalized. Compound 15 exists as >95% of one stereoisomer of the two invertomers at Cα. This is in accord with a published ee of >98% in products of the reactions of 15 with

  几种仲苄基锂化合物，均外部配位，[α-（三甲基甲硅烷基）苄基]锂·PMDTA（12）和对叔丁基-α-（二甲基乙基甲硅烷基）苄基锂·TMEDA（13），以及内部配位，[α-（三甲基甲硅烷基）苄基]锂·PMDTA（12）和对叔丁基-α-（二甲基乙基甲硅烷基）苄基锂·TMEDA（13） -[[[[cis-2,5-双(甲氧基甲基)-1-吡咯烷基]甲基]二甲基甲硅烷基]-对叔丁基苄基]锂(14)和[α-[[[(S)-2-(甲氧基甲基) -1-吡咯烷基]甲基]二甲基甲硅烷基]苄基]锂（15）。环 13C NMR 位移表明 12-15 具有部分离域结构。发现外部溶剂化的烯丙基锂化合物是离域的，只有一些内部配位的物种部分离域。化合物 15 以超过 95% 的两种转化异构体的一种立体异构体形式存在于 Cα。这与公开的 15 与醛反应产物中的 ee 大于 98% 是一致的。所有四种化合物都显示出单键 13C-6Li
• VLA-4 INHIBITORY DRUG
  申请人：MACHINAGA Nobuo

  公开号：US20120157437A1

  公开（公告）日：2012-06-21

  This invention relates to a VLA-4 inhibitory drug, having good oral absorbability and exhibiting sufficient anti-inflammatory effects when administered orally, wherein an active ingredient is represented by formula (I), or a salt thereof: Q represents an optionally-substituted monocyclic or bicyclic nitrogen-containing heterocyclic group having a nitrogen atom as the bonding site; Y represents an oxygen atom or CH 2 ; W represents an optionally-substituted bicyclic aromatic hydrocarbon ring group or an optionally-substituted bicyclic aromatic heterocyclic group; A 1 represents a nitrogen atom or C—R 3d wherein R 3d represents a hydrogen atom, a halogen atom, a C1-8 alkoxy group or a C1-8 alkyl group; R 1 represents H or a C1-8 alkyl group; R 2 represents H, a halogen, a C1-8 alkoxy group, or an optionally-substituted benzyloxy group; and R 3a , R 3b and R 3c independently represent H, a halogen atom, a C1-8 alkoxy group or a C1-8 alkyl group.

  本发明涉及一种VLA-4抑制药物，具有良好的口服吸收性，并在口服给药时表现出足够的抗炎作用，其中活性成分由公式（I）或其盐表示：Q代表一个含氮杂环基团，可以是单环或双环，该基团上的氮原子可选地被取代；Y代表氧原子或CH2；W代表一个可选取代的双环芳香族碳氢环基团或可选取代的双环芳香族杂环基团；A1代表一个氮原子或C-R3d，其中R3d代表氢原子、卤素原子、C1-8烷氧基或C1-8烷基；R1代表氢原子或C1-8烷基；R2代表氢原子、卤素原子、C1-8烷氧基或可选取代的苄氧基；以及R3a、R3b和R3c分别独立地代表氢原子、卤素原子、C1-8烷氧基或C1-8烷基。
• VLA-4 inhibitory drug
  申请人：Machinaga Nobuo

  公开号：US20130065882A1

  公开（公告）日：2013-03-14

  This invention relates to a VLA-4 inhibitory drug, having good oral absorbability and exhibiting sufficient anti-inflammatory effects when administered orally, wherein an active ingredient is represented by formula (I), or a salt thereof: Q represents an optionally-substituted monocyclic or bicyclic nitrogen-containing heterocyclic group having a nitrogen atom as the bonding site; Y represents an oxygen atom or CH 2 ; W represents an optionally-substituted bicyclic aromatic hydrocarbon ring group or an optionally-substituted bicyclic aromatic heterocyclic group; A 1 represents a nitrogen atom or C—R 3d wherein R 3d represents a hydrogen atom, a halogen atom, a C1-8 alkoxy group or a C1-8 alkyl group; R 1 represents H or a C1-8 alkyl group; R 2 represents H, a halogen, a C1-8 alkoxy

  本发明涉及一种VLA-4抑制剂药物，具有良好的口服吸收性，并在口服给药时展现足够的抗炎效果，其中活性成分由公式（I）或其盐表示： Q代表一个可选取代的含氮杂环基团，其为单环或双环结构，其中氮原子为键合位点； Y代表一个氧原子或CH2； W代表一个可选取代的双环芳香烃环基团或可选取代的双环芳香杂环基团； A1代表一个氮原子或C-R3d，其中R3d代表氢原子、卤素原子、C1-8烷氧基团或C1-8烷基团； R1代表氢原子或C1-8烷基团； R2代表氢原子、卤素原子、C1-8烷氧基团或C1-8烷基团。