Tert-butyl (4-(3-methoxyphenyl)but-3-yn-1-yl)carbamate | 905293-03-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: Tert-butyl (4-(3-methoxyphenyl)but-3-yn-1-yl)carbamate
• 英文别名: tert-butyl N-[4-(3-methoxyphenyl)but-3-ynyl]carbamate
• CAS: 905293-03-0
• 化学式: C₁₆H₂₁NO₃
• 分子量: 275.348
• InChiKey: KPQVIAXTJQFMQB-UHFFFAOYSA-N

物化性质

• 沸点：
  420.3±30.0 °C(Predicted)
• 密度：
  1.08±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Tert-butyl (4-(3-methoxyphenyl)but-3-yn-1-yl)carbamate 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 20.0 ℃ 、344.74 kPa 条件下， 生成 [4-(3-Methoxy-phenyl)-butyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Design, Synthesis, and Structure−Activity Relationships of Novel 2-Substituted Pyrazinoylguanidine Epithelial Sodium Channel Blockers:  Drugs for Cystic Fibrosis and Chronic Bronchitis

  摘要：

  Amiloride (1), the prototypical epithelial sodium channel (ENaC) blocker, has been administered with limited success as aerosol therapy for improving pulmonary function in patients with the genetic disorder cystic fibrosis. This study was conducted to synthesize and identify more potent, less reversible ENaC blockers, targeted for aerosol therapy and possessing minimal systemic renal activity. A series of novel 2-substituted acylguanidine analogues of amiloride were synthesized and evaluated for potency and reversibility on bronchial ENaC. All compounds tested were more potent and less reversible at blocking sodium-dependent shortcircuit current than amiloride. Compounds 30-34 showed the greatest potency on ENaC with IC50 values below 10 nM. A regioselective difference in potency was found (compounds 30, 39, and 40), whereas no stereospecific (compounds 33, 34) difference in potency on ENaC was displayed. Lead compound 32 was 102-fold more potent and 5-fold less reversible than amiloride and displayed the lowest IC50 value ever reported for an ENaC blocker.

  DOI：

  10.1021/jm051134w
• 作为产物：
  描述：

  3-碘苯甲醚 、 N-BOC-丁氰-4-胺 在 copper(l) iodide 二乙胺 、 三苯基膦 、 palladium dichloride 作用下， 生成 Tert-butyl (4-(3-methoxyphenyl)but-3-yn-1-yl)carbamate
  参考文献：
  名称：

  Design, Synthesis, and Structure−Activity Relationships of Novel 2-Substituted Pyrazinoylguanidine Epithelial Sodium Channel Blockers:  Drugs for Cystic Fibrosis and Chronic Bronchitis

  摘要：

  Amiloride (1), the prototypical epithelial sodium channel (ENaC) blocker, has been administered with limited success as aerosol therapy for improving pulmonary function in patients with the genetic disorder cystic fibrosis. This study was conducted to synthesize and identify more potent, less reversible ENaC blockers, targeted for aerosol therapy and possessing minimal systemic renal activity. A series of novel 2-substituted acylguanidine analogues of amiloride were synthesized and evaluated for potency and reversibility on bronchial ENaC. All compounds tested were more potent and less reversible at blocking sodium-dependent shortcircuit current than amiloride. Compounds 30-34 showed the greatest potency on ENaC with IC50 values below 10 nM. A regioselective difference in potency was found (compounds 30, 39, and 40), whereas no stereospecific (compounds 33, 34) difference in potency on ENaC was displayed. Lead compound 32 was 102-fold more potent and 5-fold less reversible than amiloride and displayed the lowest IC50 value ever reported for an ENaC blocker.

  DOI：

  10.1021/jm051134w

文献信息

• Synthesis of Pyrrolidine Derivatives by a Platinum/Brønsted Acid Relay Catalytic Cascade Reaction
  作者：Alicia Galván、Jonás Calleja、Francisco J. Fañanás、Félix Rodríguez

  DOI：10.1002/chem.201405776

  日期：2015.2.16

  A new catalytic reaction for the synthesis of pyrrolidine derivatives is presented. The method implies the coupling of N‐Boc‐protected alkynamine derivatives and appropriate alkenes or alkynes in a process catalysed by a platinum/triflic acid catalytic binary system. This reaction is believed to proceed through a cascade process implying an initial platinum‐catalysed cycloisomerization of the alkynamine

  提出了一种新的合成吡咯烷衍生物的催化反应。该方法暗示了N的耦合在铂/三氟甲磺酸催化的二元体系催化的过程中，由Boc保护的炔胺衍生物和适当的烯烃或炔烃。该反应被认为是通过级联过程进行的，这意味着乙炔胺衍生物的初始铂催化的环异构化，然后是三氟甲磺酸促进的烯烃或炔烃的亲核加成，并捕获了由Boc基团形成的阳离子。在该反应中不仅使用简单的烯烃和炔烃，而且还使用了烯丙基三甲基硅烷和炔丙基三甲基硅烷。特别地，当使用烯丙基三甲基硅烷作为烯烃对应物时，得到包含三甲基硅烷基团的令人感兴趣的双环化合物。然而，碳键。
• Simultaneous Generation and Subsequent Cycloaddition of <i>ortho</i> -Quinonemethides and Cyclic Enecarbamates Promoted by a Gold/Lewis Acid Catalytic System
  作者：Patricia Fernández、Pedro Alonso、Francisco J. Fañanás、Félix Rodríguez

  DOI：10.1002/ejoc.201800679

  日期：2018.8.7

  A gold/BF3 catalytic system promotes the transformation of simple 3‐butynamines and 2‐(hydroxymethyl)phenol derivatives into cyclic enamines and ortho‐quinone methide derivatives. The subsequent formal [4+2]‐cyclization reaction between these two intermediates gives rise to hexahydrochromeno[2,3‐b]pyrrole derivatives.

  金/ BF 3催化体系促进简单的3-丁炔胺和2-（羟甲基）苯酚衍生物转化为环烯胺和邻醌甲基化物衍生物。这两个中间体之间随后的正式的[4 + 2]-环化反应产生了六氢色素[2,3- b ]吡咯衍生物。
• Gold(I)-Catalyzed Generation of the Two Components of a Formal [4+2] Cycloaddition Reaction for the Synthesis of Tetracyclic Pyrano[2,3,4-<i>de</i> ]chromenes
  作者：Tamara Arto、Francisco J. Fañanás、Félix Rodríguez

  DOI：10.1002/anie.201602948

  日期：2016.6.13

  diene derivatives for reactions with different dienophiles. Herein, we describe the behavior of ortho‐alkynylsalicylaldehydes, a particular case of ortho‐alkynylbenzaldehydes. The gold‐catalyzed cycloisomerization of ortho‐alkynylsalicylaldehydes delivers an unusual heterodiene derivative that reacts with electron‐rich alkenes through a formal [4+2] cycloaddition. In this reaction, both the diene and

  邻炔基苯甲醛已广泛用于通过金催化的环异构化反应生成异iso烯衍生物。这些异chrome烯衍生物已被用作正式的二烯衍生物，用于与不同的亲二烯体的反应。在这里，我们描述的行为邻-alkynylsalicylaldehydes，特定情况下邻-alkynylbenzaldehydes。邻位金催化的环异构化炔基水杨醛醛可提供一种不寻常的杂二烯衍生物，该杂二烯衍生物可通过形式为[4 + 2]的环加成反应与富电子烯烃发生反应。在该反应中，二烯和亲二烯体都是通过适当的炔胺或炔醇的金催化的环异构化反应原位生成的。该反应用于合成复杂四环吡喃并[2,3,4-去]从两个非常简单的原料（一种色烯邻-alkynylsalicylaldehyde和alkynamine或炔醇）与完整的原子经济性，并用的键，周期选择性形成，并立体中心。
• Design, Synthesis, and Structure−Activity Relationships of Novel 2-Substituted Pyrazinoylguanidine Epithelial Sodium Channel Blockers:  Drugs for Cystic Fibrosis and Chronic Bronchitis
  作者：Andrew J. Hirsh、Bruce F. Molino、Jianzhong Zhang、Nadezhda Astakhova、William B. Geiss、Bruce J. Sargent、Brian D. Swenson、Alexander Usyatinsky、Michael J. Wyle、Richard C. Boucher、Rick T. Smith、Andra Zamurs、M. Ross Johnson

  DOI：10.1021/jm051134w

  日期：2006.7.1

  Amiloride (1), the prototypical epithelial sodium channel (ENaC) blocker, has been administered with limited success as aerosol therapy for improving pulmonary function in patients with the genetic disorder cystic fibrosis. This study was conducted to synthesize and identify more potent, less reversible ENaC blockers, targeted for aerosol therapy and possessing minimal systemic renal activity. A series of novel 2-substituted acylguanidine analogues of amiloride were synthesized and evaluated for potency and reversibility on bronchial ENaC. All compounds tested were more potent and less reversible at blocking sodium-dependent shortcircuit current than amiloride. Compounds 30-34 showed the greatest potency on ENaC with IC50 values below 10 nM. A regioselective difference in potency was found (compounds 30, 39, and 40), whereas no stereospecific (compounds 33, 34) difference in potency on ENaC was displayed. Lead compound 32 was 102-fold more potent and 5-fold less reversible than amiloride and displayed the lowest IC50 value ever reported for an ENaC blocker.