N-mesityl pyrrolidine | 210426-69-0

• 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: N-mesityl pyrrolidine
• 英文别名: 1-(2,4,6-Trimethylphenyl)pyrrolidine
• CAS: 210426-69-0
• 化学式: C₁₃H₁₉N
• 分子量: 189.301
• InChiKey: PYLLHSPAYXASHU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-mesityl pyrrolidine 在 palladium on activated charcoal 盐酸 、 硫酸 、 硝酸 、 ammonium formate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 17.0h， 生成 N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-pyrrolidinyl-2,4, 6-trimethylphenylaminocarbonyl)thiophene-3-sulfonamide
  参考文献：
  名称：

  Endothelin Antagonists:  Substituted Mesitylcarboxamides with High Potency and Selectivity for ET_A Receptors

  摘要：

  We have previously disclosed the discovery of 2,4-disubstituted anilinothiophenesulfonamides with potent ETA-selective endothelin receptor antagonism and the subsequent identification of sitaxsentan (TBC11251, 1) as a clinical development compound (Wu et al. J. Med. Chem. 1997, 40, 1682 and 1690). The orally active 1 has demonstrated efficacy in a phase II clinical trial of congestive heart failure (Givertz ct al. Circulation 1998, 98, Abstr. #3044) and was active in rat models of myocardial infarction (Podesser et al. Circulation. 1998, 98, Abstr. #2896) and acute hypoxia-induced pulmonary hypertension (Chen et al. FASEB J. 1996, 10 (3), A104). We now report that an additional substituent at the 6-position of the anilino ring further increases the potency of this series of compounds. It was also found that a wide range of functionalities at the 3-position of the 2,4,6-trisubstituted ring increased ETA selectivity by similar to 10-fold while maintaining in vitro potency, therefore rendering the compounds amenable to fine-tuning of pharmacological and toxicological profiles with enhanced selectivity. The optimal compound in this series was found to be TBC2576 (7u), which has similar to 10-fold higher ETA binding affinity than 1, high ETA/ETB selectivity, and a serum half-life of 7.3 h in rats, as well as in vivo activity.

  DOI：

  10.1021/jm9900063
• 作为产物：
  描述：

  1-mesitylpyrrolidine-2,5-dione 在 硼烷 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 以81%的产率得到N-mesityl pyrrolidine
  参考文献：
  名称：

  A Convenient Synthesis of HinderedN-Aryl Substituted Cyclic Amines

  摘要：

  An efficient and high yielding synthesis of N-substituted pyrrolidines and piperidines is described.

  DOI：

  10.1080/00397919808007182

文献信息

• Synthesis of β-Methylsulfonylated N-Heterocycles from Saturated Cyclic Amines with the Insertion of Sulfur Dioxide
  作者：Yan He、Jintao Yang、Qimeng Liu、Xinying Zhang、Xuesen Fan

  DOI：10.1021/acs.joc.0c02368

  日期：2020.12.4

  An efficient synthesis of β-methylsulfonylated N-heterocycles via FeCl3-catalyzed C(sp3)–H dehydrogenation and C(sp2)–H methylsulfonylation of inactivated cyclic amines with the promotion and participation of inorganic sodium metabisulfite and dicumyl peroxide (DCP) has been developed. Notably, bifunctional DCP acted not only as an oxidant to promote the dehydrogenation but also as a methyl radical

  FeCl 3催化的灭活环胺的C（sp 3）-H脱氢和C（sp 2）-H甲基磺酰化，并通过无机亚硫酸氢钠和过氧化二枯基的促进和参与，有效合成β-甲基磺酰化N-杂环。） 已经被开发出来。明显地，双官能DCP不仅充当促进脱氢的氧化剂，而且充当参与砜形成的甲基。通过该方案，以简便的一锅法获得了许多β-甲基磺酰化的四氢吡啶，四氢氮杂和吡咯。
• Dual C(sp³ )−H Bond Functionalization of N-Heterocycles through Sequential Visible-Light Photocatalyzed Dehydrogenation/[2+2] Cycloaddition Reactions
  作者：Guo-Qiang Xu、Ji-Tao Xu、Zhi-Tao Feng、Hui Liang、Zhu-Yin Wang、Yong Qin、Peng-Fei Xu

  DOI：10.1002/anie.201710523

  日期：2018.4.23

  through a sequential visible‐light photocatalyzed dehydrogenation/[2+2] cycloaddition procedure. As a complementary approach to the well‐established use of iminium ion and α‐amino radical intermediates, the elusive cyclic enamine intermediates were effectively generated by photoredox catalysis under mild conditions and efficiently captured by acetylene esters to form a wide array of bicyclic amino acid

  在这里，我们描述了一种温和的方法，用于通过顺序可见光光催化脱氢/ [2 + 2]环加成程序对饱和含氮杂环进行双C（sp 3）-H键官能化。作为完善使用亚胺离子和α-氨基自由基中间体的一种补充方法，难以捉摸的环状烯胺中间体是在温和条件下通过光催化氧化有效产生的，并被乙炔酯有效捕获，从而形成多种双环氨基酸衍生物，从而使两个邻位C（sp 3）-H键同时功能化。
• C(sp³)–H dehydrogenation and C(sp²)–H alkoxy carbonylation of inactivated cyclic amines towards functionalized N-heterocycles
  作者：Yan He、Fang Wang、Xinying Zhang、Xuesen Fan

  DOI：10.1039/c6cc10227a

  日期：——

  A novel and efficient synthesis of tetrahydropyridine-, dihydropyrrole-, and tetrahydroazepine-3-carboxylates via cascade reactions of cyclic amines with CO and alcohols is presented. To our knowledge, this should be the first example in which functionalized N-heterocycles were prepared through Pd-catalyzed C(sp3)-H dehydrogenation and C(sp2)-H carbonylation of cyclic amines.

  通过环胺与CO和醇的级联反应，提出了一种新颖而有效的四氢吡啶-，二氢吡咯-和四氢氮杂-3-羧酸酯的合成方法。据我们所知，这应该是第一个通过钯催化环胺的C（sp 3）-H脱氢和C（sp 2）-H羰基化制备N杂环的例子。
• B(C₆F₅)₃-Catalyzed Direct C3 Alkylation of Indoles and Oxindoles
  作者：Shyam Basak、Ana Alvarez-Montoya、Laura Winfrey、Rebecca L. Melen、Louis C. Morrill、Alexander P. Pulis

  DOI：10.1021/acscatal.0c01141

  日期：2020.4.17

  The direct C3 alkylation of indoles and oxindoles is a challenging transformation, and only a few direct methods exist. Utilizing the underexplored ability of triaryl boranes to mediate the heterolytic cleavage of α-nitrogen C–H bonds in amines, we have developed a catalytic approach for the direct C3 alkylation of a wide range of indoles and oxindoles using amine-based alkylating agents. We also employed

  吲哚和羟吲哚的直接C3烷基化是一项具有挑战性的转化，仅存在几种直接方法。利用未开发的三芳基硼烷介导胺中α-氮C–H键的杂合裂解的能力，我们开发了一种催化方法，可使用基于胺的烷基化剂直接对多种吲哚和羟吲哚进行C3烷基化。我们还在烷基化开环级联反应中采用了这种硼烷催化的策略。
• Dehydrogenative Aromatization and Sulfonylation of Pyrrolidines: Orthogonal Reactivity in Photoredox Catalysis
  作者：Krishnamoorthy Muralirajan、Rajesh Kancherla、Magnus Rueping

  DOI：10.1002/anie.201808427

  日期：2018.11.5

  were established. The mild reaction conditions make this approach an appealing and versatile strategy to functionalize/oxidize pyrrolidines whereby arylsulfonyl chlorides were identified to be both catalyst regeneration and sulfonylation reagents.

  建立了可见光氧化还原催化下N-杂环的氧化脱氢芳构化和选择性磺酰化反应。温和的反应条件使该方法成为使吡咯烷官能化/氧化的引人入胜且通用的策略，由此鉴定出芳基磺酰氯既是催化剂再生又是磺酰化试剂。