{[1-(4-chlorophenyl)methylidene]amino}acetic acid tert-butyl ester | 166655-36-3

• 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-(4-chlorophenyl)methylidene]amino}acetic acid tert-butyl ester
• 英文别名: (4-chlorobenzylideneamino)acetic acid tert-butyl ester；N-(4-chlorophenyl)methyleneglycine t-butyl ester；(4-chlorobenzylidene)glycine tert-butyl ester；1,1-dimethylethyl-N-[(4-chlorophenyl)methylidine]glycinate；tert-butylglycinate p-chlorobenzaldehyde Schiff base；Glycine, N-[(4-chlorophenyl)methylene]-, 1,1-dimethylethyl ester；tert-butyl 2-[(4-chlorophenyl)methylideneamino]acetate
• CAS: 166655-36-3
• 化学式: C₁₃H₁₆ClNO₂
• 分子量: 253.729
• InChiKey: HSIDOHKQHALOQR-UHFFFAOYSA-N

物化性质

• 沸点：
  322.2±27.0 °C(Predicted)
• 密度：
  1.08±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  38.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  {[1-(4-chlorophenyl)methylidene]amino}acetic acid tert-butyl ester 在 盐酸 、 N,N-二甲基丙烯基脲 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙醚 、 正己烷 为溶剂， 生成 2-Amino-5-(tert-butyl-diphenyl-silanyl)-pent-4-ynoic acid tert-butyl ester
  参考文献：
  名称：

  Thiol Mediated Free Radical Cyclization of Alkenyl and Alkynyl Isocyanides

  摘要：

  Thiol-mediated free radical cyclizations of but-3-enyl and but-3-ynyl isocyanides of types 6-8 give new access to 3,5-disubstituted 2-(alkyl- and 2-(arylthio)pyrrolines 11, 12, and 18. When 2-mercaptoethanol is used with the same isocyanides the reaction results in pyroglutamates 16, 17, or 19. These cyclizations involve the formation of a new carbon-carbon bond through intramolecular addition of a carbon-centered thioimidoyl radical to a carbon-carbon multiple bond. Although cyclic products are usually obtained in high yields, in a few cases a competing radical degradation process leading to isothiocyanates was observed. Isocyanide 8a carrying an allyl(phenyl) sulfide moiety isomerizes to 2-(phenylthio)pyrroline 24 in a series of sequential steps.

  DOI：

  10.1021/jo00104a035
• 作为产物：
  描述：

  4-氯苯甲醛 、 甘氨酸叔丁酯盐酸盐 在 magnesium sulfate 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 生成 {[1-(4-chlorophenyl)methylidene]amino}acetic acid tert-butyl ester
  参考文献：
  名称：

  [3+3] 甲亚胺叶立德与腈亚胺的环加成反应合成 2,3,4,5-Tetrahydro-1,2,4-Triazine-5-Carboxylates

  摘要：

  建立了偶氮甲碱叶立德与腈亚胺的 [3+3] 环加成，以获取含有 1,2,4-三嗪的非天然环状氨基酸。在温和的反应条件下，以中等至优异的产率获得了一系列 2,3,4,5-四氢-1,2,4-三嗪-5-羧酸盐。

  DOI：

  10.1002/ejoc.202200768

文献信息

• Direct synthesis of pyrroles via 1,3-dipolar cycloaddition of azomethine ylides with ynones
  作者：Zheng Wang、Ying Shi、Xiaoyan Luo、De-Man Han、Wei-Ping Deng

  DOI：10.1039/c3nj00067b

  日期：——

  A direct and facile synthesis of multi-substituted pyrroles via AgOAc-catalyzed 1,3-dipolar cycloaddition of azomethine ylides with ynones is developed, providing the corresponding adducts in moderate to high yields (up to 89%).

  已开发了通过AgOAc催化的偶氮甲亚胺与炔酮的1,3-偶极环加成反应直接合成多取代吡咯的方法，可提供中等至高收率（最高89％）的相应加合物。
• Development of Catalytic Asymmetric 1,4-Addition and [3 + 2] Cycloaddition Reactions Using Chiral Calcium Complexes
  作者：Tetsu Tsubogo、Susumu Saito、Kazutaka Seki、Yasuhiro Yamashita、Shu̅ Kobayashi

  DOI：10.1021/ja8032058

  日期：2008.10.8

  4-addition and [3 + 2] cycloaddition reactions using chiral calcium species prepared from calcium isopropoxide and chiral bisoxazoline ligands have been developed. Glycine Schiff bases reacted with acrylic esters to afford 1,4-addition products, glutamic acid derivatives, in high yields with high enantioselectivities. During the investigation of the 1,4-addition reactions, we unexpectedly found that a [3

  已经开发了使用由异丙醇钙和手性双恶唑啉配体制备的手性钙物质的催化不对称 1,4-加成和 [3 + 2] 环加成反应。甘氨酸席夫碱与丙烯酸酯反应以高产率和高对映选择性提供 1,4-加成产物谷氨酸衍生物。在研究 1,4-加成反应期间，我们意外地发现 [3 + 2] 环加成发生在与巴豆酸酯衍生物的反应中，以高产率和高对映选择性提供取代的吡咯烷衍生物。基于这一发现，我们研究了不对称的 [3 + 2] 环加成，结果表明，获得了具有高非对映选择性和对映选择性的几种含有连续立体异构叔和季碳中心的旋光取代吡咯烷衍生物。此外，已经使用这种 [3 + 2] 环加成反应合成了丙型肝炎病毒 RNA 依赖性聚合酶抑制剂的光学活性吡咯烷核心和潜在的有效抗病毒剂。NMR 光谱分析和非线性效应实验中对映选择性的非放大观察表明，形成了具有阴离子配体的单体钙物质作为活性催化剂。提出了 [3 + 2] 环加成的逐步机制，包括 1
• Synthesis of the First Axially Dissymmetric,Cα,α-Disubstituted Glycine Containing a Crown Ether Receptor, and the Conformational Preferences of a Model Peptide
  作者：Jean-Paul Mazaleyrat、Yolaine Goubard、Maria-Vittoria Azzini、Michel Wakselman、Cristina Peggion、Fernando Formaggio、Claudio Toniolo

  DOI：10.1002/1099-0690(200204)2002:7<1232::aid-ejoc1232>3.0.co;2-i

  日期：2002.4

  esterification and Nα-Boc protection, gave (RS)-, (R)- and (S)-Boc-[HO]2-Bip-OMe. Cyclization with Cs2CO3/DMF and pentaethylene glycol ditosylate afforded the crown-carrier Cα,α-disubstituted glycines (RS)-Ia, (R)-Ia and (S)-Ia, possessing only axial dissymmetry. Although (R)-Ia and (S)-Ia are enantiomerically stable in solution at 110 °C, they were obtained with only 64% ee and 48% ee, respectively, because

  外消旋和对映体富集的 Nα-保护的甲基 6-amino-1,11-(20-crown-6)-6,7-dihydro-5H-dibenzo[a,c]cycloheptene-6-carboxylates (Boc-[20-C -6]-Bip-OMe) (RS)-Ia、(R)-Ia 和 (S)-Ia 是通过甘氨酸叔丁酯的 4-氯亚苄基衍生物的相转移二烷基化合成的，具有外消旋和拆分（两种对映异构体）2,2'-双（溴甲基）-6,6'-二甲氧基-1,1'-联苯用作烷化剂。将所得 (RS)-、(R)- 和 (S)-H-[MeO]2-Bip-OtBu 脱甲基化，然后进行酯化和 Nα-Boc 保护，得到 (RS)-、(R)- 和 ( S)-Boc-[H2O]2-Bip-OMe。用 Cs2CO3/DMF 和五乙二醇二甲苯磺酸环化得到仅具有轴向不对称性的冠载体 Cα,α-二取代甘氨酸 (RS)-Ia、(R)-Ia
• Asymmetric Construction of 3-Azabicyclo[3.1.0]hexane Skeleton with Five Contiguous Stereogenic Centers by Cu-Catalyzed 1,3-Dipolar Cycloaddition of Trisubstituted Cyclopropenes
  作者：Hua Deng、Wu-Lin Yang、Fei Tian、Wenjun Tang、Wei-Ping Deng

  DOI：10.1021/acs.orglett.8b01686

  日期：2018.7.6

  A highly diastereo- and enantioselective desymmetrization of prochiral cyclopropenes via a Cu(CH3CN)4BF4/Ph-Phosferrox complex catalyzed 1,3-dipolar cycloaddition of azomethine ylides was described. A variety of complex 3-azabicyclo[3.1.0]hexane derivatives bearing five contiguous stereogenic centers and two all-carbon quaternary stereogenic centers were directly synthesized as a single isomer in excellent

  描述了一种通过Cu（CH 3 CN）4 BF 4 / Ph-Phosferrox络合物催化的偶氮甲亚胺的1，3-偶极环加成反应的前手性环丙烯的高度非对映和对映选择性脱对称。可直接合成具有五个连续立体中心和两个全碳四元立体中心的多种复杂的3-氮杂双环[3.1.0]己烷衍生物，以优异的收率（高达99％）和对映选择性（97→99％）作为单个异构体ee）。值得注意的是，发现在该转化中环丙烯的各种官能团（CO 2 R，CN，CONMe 2和Ph）具有良好的耐受性。通过LiAlH 4可以方便地将环加合物转化为生物学上重要的GABA衍生物 还原和随后的水解。
• [EN] ACYL ISOINDOLINE DERIVATIVES AND ACYL ISOQUINOLINE DERIVATIVES AS ANTI-VIRAL AGENTS<br/>[FR] DERIVES D'ACYLE ISOINDOLINE ET D'ACYLE ISOQUINOLINE UTILISES COMME AGENTS ANTIVIRAUX
  申请人：GLAXO GROUP LTD

  公开号：WO2004096774A1

  公开（公告）日：2004-11-11

  Anti-viral agents of Formula (I) wherein: R3 represents aryl or heteroaryl; R4 represents one or two substituents independently selected from hydrogen, C 1-6alkyl, halo, ORA , C(O)NRBRC, C(O)RD, CO2H, CO2RD, NRBRC, NRE C(O)RD, NRECO2RD, NREC(O)NRFRG, NRESO2RD, SO2NRFRG, SO2RD, nitro, cyano, heterocyclyl, heteroaryl, aryl, arylalkyl heteroarylalkyl or CF3; R5 and R6 independently represent hydrogen, C1-6alkyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl; n represents 0 or 1; when n represents 0, R1 represents C(O)RH and R2 represents C1-6alkyl, heterocyclylalkyl, arylalkyl or heteroarylalkyl; when n represents 1, either i) R1 represents C(O)RH; R2 represents C1-6alkyl, heterocyclylalkyl, arylalkyl or heteroarylalkyl; and R7 and R8 independently represent hydrogen, C1-6alkyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl; or ii) R1 and R2 independently represent hydrogen, C1-6alkyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl; R7 represents C(O)RH; and R8 represents C1-6alkyl, heterocyclylalkyl, arylalkyl or heteroarylalkyl; RA represents hydrogen, C1-6alkyl, arylalkyl, heteroarylalkyl, aryl or heteroaryl; RB and RC independently represent hydrogen, C1-6alkyl, aryl or heteroaryl; or RB and RC together with the nitrogen atom to which they are attached form a 5 or 6 membered saturated cyclic group; RD is selected from the group consisting of C1-6alkyl, aryl, heteroaryl, arylalkyl, and heteroarylalkyl; RE represents hydrogen or C1-6alkyl; RF and RG are independently selected from the group consisting of hydrogen, C1-6alkyl, aryl, heteroaryl, arylalkyl, and heteroarylalkyl; or RF and RG together with the nitrogen atom to which they are attached form a 5 or 6 membered saturated cyclic group; RH represents hydroxy or NRBRC; and salts, solvates and esters thereof; provided that when RH is hydroxy, which is esterified to form -OR where R is selected from straight or branched chain alkyl, aralkyl, aryloxyalkyl, or aryl, then R is other than tert-butyl. Processes for their preparation and methods of using them in HCV treatment are provided.

  Formula（I）的抗病毒剂，其中：R3代表芳基或杂环芳基；R4代表一个或两个取代基，独立选择自氢、C1-6烷基、卤素、ORA、C（O）NRBRC、C（O）RD、CO2H、CO2RD、NRBRC、NREC（O）RD、NRECO2RD、NREC（O）NRFRG、NRESO2RD、SO2NRFRG、SO2RD、硝基、氰基、杂环烷基、杂环芳基、芳基、芳基烷基、杂环芳基烷基或CF3；R5和R6独立代表氢、C1-6烷基、芳基、杂环芳基、芳基烷基或杂环芳基烷基；n代表0或1；当n代表0时，R1代表C（O）RH，R2代表C1-6烷基、杂环烷基、芳基烷基或杂环芳基烷基；当n代表1时，要么i）R1代表C（O）RH；R2代表C1-6烷基、杂环烷基、芳基烷基或杂环芳基烷基；且R7和R8独立代表氢、C1-6烷基、芳基、杂环芳基、芳基烷基或杂环芳基烷基；或ii）R1和R2独立代表氢、C1-6烷基、芳基、杂环芳基、芳基烷基或杂环芳基烷基；R7代表C（O）RH；且R8代表C1-6烷基、杂环烷基、芳基烷基或杂环芳基烷基；RA代表氢、C1-6烷基、芳基烷基、杂环芳基烷基、芳基或杂环芳基；RB和RC独立代表氢、C1-6烷基、芳基或杂环芳基；或RB和RC与它们连接的氮原子一起形成5或6个成员饱和环；RD选自由C1-6烷基、芳基、杂环芳基、芳基烷基和杂环芳基烷基组成的群体；RE代表氢或C1-6烷基；RF和RG独立选择自氢、C1-6烷基、芳基、杂环芳基、芳基烷基和杂环芳基烷基组成的群体；或RF和RG与它们连接的氮原子一起形成5或6个成员饱和环；RH代表羟基或NRBRC；以及其盐、溶剂化合物和酯；但是当RH是羟基时，酯化形成-OR，其中R选择自直链或支链烷基、芳基烷基、芳氧基烷基或芳基，那么R不是叔丁基。提供了它们的制备方法以及在HCV治疗中使用它们的方法。