5-溴-1-(1,1-二甲基乙基)-1H-吡咯-1,2-二羧酸-2-甲酯 | 924708-81-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 中文名称: 5-溴-1-(1,1-二甲基乙基)-1H-吡咯-1,2-二羧酸-2-甲酯
• 中文别名: 1-BOC-5-溴-2-吡咯甲酸乙酯
• 英文名称: methyl 5-bromo-1-(tert-butoxycarbonyl)-1H-pyrrole-2-carboxylate
• 英文别名: 1-(tert-butyl) 2-methyl 5-bromo-1H-pyrrole-1,2-dicarboxylate；1-Tert-butyl 2-methyl 5-bromo-1H-pyrrole-1,2-dicarboxylate；1-O-tert-butyl 2-O-methyl 5-bromopyrrole-1,2-dicarboxylate
• CAS: 924708-81-6
• 化学式: C₁₁H₁₄BrNO₄
• 分子量: 304.14
• InChiKey: SCHZUSCPCITFOF-UHFFFAOYSA-N

物化性质

• 沸点：
  349.7±45.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  57.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-溴-1-(1,1-二甲基乙基)-1H-吡咯-1,2-二羧酸-2-甲酯 在 四(三苯基膦)钯 N-溴代丁二酰亚胺(NBS) 、 四丁基碘化铵 、 sodium carbonate 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 26.0h， 生成 dimethyl 3,4-dibromo-5-(4-methoxyphenyl)-1H-pyrrole-1,2-dicarboxylate
  参考文献：
  名称：

  Regioselective Couplings of Dibromopyrrole Esters

  摘要：

  研究了几种 4,5- 和 3,4- 二溴吡咯-2-羧酸酯的铃木偶联反应的区域选择性。一般来说，在较缺电子的位点（分别为 C5 和 C3）进行初始偶联时，可以实现区域选择性。与此同时，转化率往往不高（40-60%），试图将反应推向更高的转化率往往会导致竞争性二偶联。

  DOI：

  10.1055/s-2006-950305
• 作为产物：
  描述：

  2,5-二溴-1H-吡咯-1-羧酸-1,1-二甲基乙酯 、 氯甲酸甲酯 在 正丁基锂 作用下， 以 乙醚 为溶剂， 反应 1.5h， 以81%的产率得到5-溴-1-(1,1-二甲基乙基)-1H-吡咯-1,2-二羧酸-2-甲酯
  参考文献：
  名称：

  Modular Synthesis of Lamellarins via Regioselective Assembly of 3,4,5-Differentially Arylated Pyrrole-2-carboxylates

  摘要：

  A modular synthesis of lamellarins via 3,4,5-differentially arylated pyrrole-2-carboxylate intermediates has been developed. The key reactions employed are Br-Li exchange-methoxycarbonylation of 2,5-dibromo-1-(tert-butoxycarbonyl)-1H-pyrrole (1) followed by palladium-catalyzed iterative Suzuki-Miyaura coupling of the pyrrole core. The 3,4,5-triarylpyrrole 4 thus synthesized was readily converted to 5,6-saturated lamellarin L (2) and 5,6-unsaturated lamellarin N (3) via lactonization followed by annulation of the pyrrole nitrogen and lateral aromatic ring at C5 using 2-bromoethyl phenyl sulfide or bromoacetaldehyde dimethyl acetal as two-carbon homologation agents. In principle, this strategy allows the production of diverse lamellarins in short steps with high yields using readily accessible arylboronic acids as aromatic modules.

  DOI：

  10.1021/jo402181w

文献信息

• Nickel-Catalyzed Decarboxylative Cross-Coupling of Bicyclo[1.1.1]pentyl Radicals Enabled by Electron Donor–Acceptor Complex Photoactivation
  作者：Viktor C. Polites、Shorouk O. Badir、Sebastian Keess、Anais Jolit、Gary A. Molander

  DOI：10.1021/acs.orglett.1c01558

  日期：2021.6.18

  The use of bicyclo[1.1.1]pentanes (BCPs) as para-disubstituted aryl bioisosteres has gained considerable momentum in drug development programs. Carbon–carbon bond formation via transition-metal-mediated cross-coupling represents an attractive strategy to generate BCP–aryl compounds for late-stage functionalization, but these typically require reactive organometallics to prepare BCP nucleophiles on

  使用双环 [1.1.1] 戊烷 (BCP) 作为对-二取代芳基生物等排体在药物开发计划中获得了相当大的动力。通过过渡金属介导的交叉偶联形成碳-碳键代表了一种有吸引力的策略来生成用于后期功能化的 BCP-芳基化合物，但这些通常需要反应性有机金属来根据需要从 [1.1.1] 螺旋桨制备 BCP 亲核试剂。在这项研究中，报道了通过光活性电子供体-受体复合物的作用，用（杂）芳基溴化物合成和 Ni 催化的 BCP 氧化还原活性酯的官能化。
• Discovery of novel and potent heterocyclic carboxylic acid derivatives as protein tyrosine phosphatase 1B inhibitors
  作者：Sujay Basu、Uppuleti Viplava Prasad、Dinesh A. Barawkar、Siddhartha De、Venkata P. Palle、Suraj Menon、Meena Patel、Sachin Thorat、Umesh P. Singh、Koushik Das Sarma、Yogesh Waman、Sanjay Niranjan、Vishal Pathade、Ashwani Gaur、Satyanarayana Reddy、Shariq Ansari

  DOI：10.1016/j.bmcl.2012.02.070

  日期：2012.4

  novel heterocyclic carboxylic acid based protein tyrosine phosphatase 1B (PTP1B) inhibitors with hydrophobic tail have been synthesized and characterized. Structure–activity relationship (SAR) optimization resulted in identification of several potent, selective (over the highly homologous T-cell protein tyrosine phosphatase, TCPTP) and metabolically stable PTP1B inhibitors. Compounds 7a, 19a and 19c showed

  合成和表征了一系列具有疏水尾基的新型基于杂环羧酸的蛋白质酪氨酸磷酸酶1B（PTP1B）抑制剂。结构-活性关系（SAR）的优化导致鉴定出几种有效的，选择性的（通过高度同源的T细胞蛋白酪氨酸磷酸酶，TCPTP）和代谢稳定的PTP1B抑制剂。化合物7a，19a和19c在小鼠中表现出良好的细胞通透性和药代动力学特性，具有中等至非常好的口服（％F  = 13–70）生物利用度。
• Modular Synthesis of Lamellarins via Regioselective Assembly of 3,4,5-Differentially Arylated Pyrrole-2-carboxylates
  作者：Masashi Komatsubara、Teppei Umeki、Tsutomu Fukuda、Masatomo Iwao

  DOI：10.1021/jo402181w

  日期：2014.1.17

  A modular synthesis of lamellarins via 3,4,5-differentially arylated pyrrole-2-carboxylate intermediates has been developed. The key reactions employed are Br-Li exchange-methoxycarbonylation of 2,5-dibromo-1-(tert-butoxycarbonyl)-1H-pyrrole (1) followed by palladium-catalyzed iterative Suzuki-Miyaura coupling of the pyrrole core. The 3,4,5-triarylpyrrole 4 thus synthesized was readily converted to 5,6-saturated lamellarin L (2) and 5,6-unsaturated lamellarin N (3) via lactonization followed by annulation of the pyrrole nitrogen and lateral aromatic ring at C5 using 2-bromoethyl phenyl sulfide or bromoacetaldehyde dimethyl acetal as two-carbon homologation agents. In principle, this strategy allows the production of diverse lamellarins in short steps with high yields using readily accessible arylboronic acids as aromatic modules.
• Regioselective Couplings of Dibromopyrrole Esters
  作者：Scott Handy、Yanan Zhang

  DOI：10.1055/s-2006-950305

  日期：2006.11

  The regioselectivity of the Suzuki couplings of several 4,5- and 3,4-dibromopyrrole-2-carboxylate esters has been studied. In general, regioselectivity can be achieved for initial coupling at the more electron-deficient site (C5 and C3, respectively). At the same time, conversions are often modest (40-60%) and attempts to force the reactions to higher conversions often lead to competitive dicoupling.

  研究了几种 4,5- 和 3,4- 二溴吡咯-2-羧酸酯的铃木偶联反应的区域选择性。一般来说，在较缺电子的位点（分别为 C5 和 C3）进行初始偶联时，可以实现区域选择性。与此同时，转化率往往不高（40-60%），试图将反应推向更高的转化率往往会导致竞争性二偶联。