3-氯-4'-甲基联苯 | 19482-19-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3-氯-4'-甲基联苯
• 英文名称: 3-chloro-4'-methylbiphenyl
• 英文别名: 3'-Chlor-4-methyl-biphenyl；1-chloro-3-(4-methylphenyl)benzene
• CAS: 19482-19-0
• 化学式: C₁₃H₁₁Cl
• 分子量: 202.683
• InChiKey: WAEKCHUPDOGQJY-UHFFFAOYSA-N

物化性质

• 熔点：
  41-42 °C
• 沸点：
  306.3±11.0 °C(Predicted)
• 密度：
  1.107±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  0

反应信息

• 作为反应物：
  描述：

  3-氯-4'-甲基联苯 在 盐酸 、 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 sodium hydride 作用下， 以 四氯化碳 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.75h， 生成 N-[3-[[4-(3-chlorophenyl)phenyl]methoxy]phenyl]piperidine-4-carboxamide;hydrochloride
  参考文献：
  名称：

  Biarylmethoxy isonipecotanilides as potent and selective inhibitors of blood coagulation factor Xa

  摘要：

  New chloro-substituted biarylmethoxyphenyl piperidine-4-carboxamides were synthesized and assayed in vitro as inhibitors of the blood coagulation enzymes factor Xa (fXa) and thrombin. An investigation of effects of the amidine and isopropyl groups attached at the piperidine nitrogen and 5-(halogenoaryl)isoxazol-3-yl groups as biaryl substituents led us to identify new compounds which proved to be selective fXa inhibitors, with inhibition constants in the low nanomolar range. The most potent compound 21e, that incorporates 2-Cl-thiophen-5-yl group as the P1 motif and 1-isopropylpiperidine P4 group, inhibited fXa with K-i value of 0.3 nM and very high selectivity over thrombin and some other tested serine proteases, achieving moderate levels of anticoagulant activity in the low micromolar range, as assessed by the prothrombin time clotting assay (PT2 = 3.30 mu M). Based on reliable docking simulations, molecular modeling provided a rationale for interpreting structure-activity relationships. The predicted binding modes highlighted the structural requirements for addressing the subsites S1 and S4 of the fXa enzyme. (C) 2010 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ejps.2010.11.010
• 作为产物：
  描述：

  对苄基三氟甲磺酸 、 3-氯苯甲酸钾 在 (±)-2,2 '-二(二-对甲苯基膦)-1,1 '-联萘 、 copper(I) oxide 、 1,10-菲罗啉 、 palladium(II) bromide 作用下， 以 N-甲基吡咯烷酮 为溶剂， 以59%的产率得到3-氯-4'-甲基联苯
  参考文献：
  名称：

  钯盐与芳基三氟甲磺酸酯的钯催化脱羧偶联合成联芳基和芳基酮

  摘要：

  已开发出一种双金属催化剂体系，该体系首次允许芳基和酰基羧酸盐与芳基三氟甲磺酸酯进行脱羧交叉偶联。与芳基卤化物相反，这些亲电试剂会产生非配位阴离子副产物，这些副产物不会干扰脱羧步骤，而脱羧步骤会导致亲核碳交联伙伴的产生。结果，可用于此转化的羧酸酯底物的范围从邻位取代或其他活化的衍生物扩展到广泛的邻位，间位和对位取代的芳族羧酸盐。优化了两种替代方案，一种方案涉及在存在铜的情况下加热基板I / 1,10-菲咯啉（10–15 mol％）和PdI 2 /膦（2–3 mol％）在NMP中作用1–24 h，另一项涉及Cu I / 1,10–菲咯啉（6–15 mol） ％）和NMP中的PdBr 2 / Tol-BINAP（2 mol％）使用微波加热5-10分钟。尽管大多数产品都可以通过标准加热来获得，但发现微波辐射特别有益于将未活化的羧酸酯与官能化的芳基三氟甲磺酸酯转化。通过48个示例演示了该转换的综合效

  DOI：

  10.1002/chem.200900892

文献信息

• [EN] GLUCAGON ANTAGONISTS<br/>[FR] ANTAGONISTES DE GLUCAGON
  申请人：METABASIS THERAPEUTICS INC

  公开号：WO2010019830A1

  公开（公告）日：2010-02-18

  Provided herein are compounds, including enantiomerically pure forms thereof, and pharmaceutically acceptable salts or co-crystals and prodrugs thereof which have glucagon receptor antagonist or inverse agonist activity. Further, provided herein are pharmaceutical compositions comprising the same as well as methods of treating, preventing, delaying the time to onset or reducing the risk for the development or progression of a disease or condition for which one or more glucagon receptor antagonist is indicated, including Type I and II diabetes, insulin resistance and hyperglycemia. Moreover, provided herein are methods of making or manufacturing compounds disclosed herein, including enantiomerically pure forms thereof, and pharmaceutically acceptable salts or Co- crystals and prodrugs thereof. Formula I

  本文提供了化合物，包括其对映体纯形式，以及具有胰高血糖素受体拮抗剂或逆向激动剂活性的药用盐或共晶体和前药。此外，本文提供了包括这些化合物的药物组合物，以及治疗、预防、延缓发病时间或减少一种或多种胰高血糖素受体拮抗剂适用的疾病或病情的发展或进展风险的方法，包括I型和II型糖尿病、胰岛素抵抗和高血糖。此外，本文提供了制备或生产本文披露的化合物的方法，包括其对映体纯形式，以及药用盐或共晶体和前药。公式I
• [EN] GLUCAGON ANTAGONISTS<br/>[FR] ANTAGONISTES DU GLUCAGON
  申请人：LIGAND PHARM INC

  公开号：WO2015191900A1

  公开（公告）日：2015-12-17

  Provided herein are compounds, including enantiomerically pure forms thereof, and pharmaceutically acceptable salts or co-crystals and prodrugs thereof which have glucagon receptor antagonist or inverse agonist activity. Further, provided herein are pharmaceutical compositions comprising the same as well as methods of treating, preventing, delaying the time to onset or reducing the risk for the development or progression of a disease or condition for which one or more glucagon receptor antagonist is indicated, including Type I and II diabetes, insulin resistance and hyperglycemia. Moreover, provided herein are methods of making or manufacturing compounds disclosed herein, including enantiomerically pure forms thereof, and pharmaceutically acceptable salts or co-crystals and prodrugs thereof.

  本文提供了化合物，包括其对映体纯形式，以及具有胰高血糖素受体拮抗剂或逆向激动剂活性的药用盐或共晶体及前药。此外，本文提供了包括这些化合物的药物组合物，以及治疗、预防、延缓发病时间或减少一种或多种胰高血糖素受体拮抗剂适用的疾病或症状的发展或进展风险的方法，包括I型和II型糖尿病、胰岛素抵抗和高血糖。此外，本文提供了制备或生产本文披露的化合物的方法，包括其对映体纯形式，以及药用盐或共晶体及前药。
• SUBSTITUTED CARBAMOYLCYCLOALKYL ACETIC ACID DERIVATIVES AS NEP
  申请人：KARKI Rajeshri Ganesh

  公开号：US20120122764A1

  公开（公告）日：2012-05-17

  The present invention provides a compound of formula I; or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , B, X, m and n are defined herein. The invention also relates to a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides pharmaceutical composition of compounds of the invention, and a combination of pharmacologically active agents and a compound of the invention.

  本发明提供了一种具有化学式I的化合物； 或其药学上可接受的盐，其中R 1 ，R 2 ，R 3 ，R 4 ，R 5 ，B，X，m和n在此处被定义。该发明还涉及制造该发明化合物的方法及其治疗用途。本发明进一步提供了该发明化合物的药物组合物，以及具有药理活性剂和该发明化合物的组合。
• Bisamino(diphosphonite) with dangling olefin functionalities: synthesis, metal chemistry and catalytic utility of Rh<scp>i</scp>and Pd<scp>ii</scp>complexes in hydroformylation and Suzuki–Miyaura reactions
  作者：Susmita Naik、Maruthai Kumaravel、Joel T. Mague、Maravanji S. Balakrishna

  DOI：10.1039/c3dt52400k

  日期：——

  Bisamino(diphosphonite), p-C6H4NP(OC6H4C3H5-o)2}2}2 (1), was prepared by reacting p-C6H4N(PCl2)2}2 with four equivalents of o-allylphenol in 85% yield. Compound 1 on treatment with [M(CO)4(HNC5H10)2] (M = Mo or W) gave cis-[M(CO)4}2p-C6H4N(P(OC6H4C3H5-o)2)2}2}] (2, M = Mo; 3, M = W). The reaction of 1 with [Fe(η5-C5H5)(CO)2]2 yielded the complex [Fe(η5-C5H5)(μ-CO)}2p-C6H4N(P(OC6H4C3H5-o)2)2}2}] (4)

  通过使p -C 6 H 4 N（PCl ）反应，制得双氨基（二膦酸酯）p -C 6 H 4 N P（OC 6 H 4 C 3 H 5 - o）2 } 2 } 2（1）。2）2 } 2具有四当量的邻烯丙基苯酚，产率为85％。用[M（CO）4（HNC 5 H 10）2 ]（M = Mo或W）处理的化合物1得到顺式-[M（CO）4 } 2 p -C 6 H 4 N（P（OC 6 H 4 C 3 H 5 - o）2）2 } 2 }]}（2，M = Mo; 3， M = W）。的反应1用的[Fe（η 5 -C 5 H ^ 5）（CO）2 ] 2，得到络合物[的Fe（η 5 -C 5 H ^ 5）（μ-CO）} 2 p -C6 H 4 N（P（OC 6 H 4 C 3 H 5 - o） 2） 2 } 2 }]（ 4）。用Fe（CO） 5处理1提供了单核络合物[Fe（CO） 3 }
• Cyrene as a Bio-Based Solvent for the Suzuki–Miyaura Cross-Coupling
  作者：Allan Watson、Kirsty Wilson、Jane Murray、Craig Jamieson

  DOI：10.1055/s-0036-1589143

  日期：2018.3

  reaction in the chemical industry. A large proportion of SM couplings employ dipolar aprotic solvents; however, current sustainability initiatives and increasingly stringent regulations advocate the use of alternatives that exhibit more desirable properties. Here we describe the scope and utility of the bio-derived solvent Cyrene™ in SM cross-couplings and evaluate its suitability as a reaction medium

  Suzuki-Miyaura (SM) 交叉偶联是化学工业中使用最广泛的 Pd 催化的 C-C 键形成反应。大部分 SM 偶联剂使用偶极非质子溶剂；然而，当前的可持续性举措和日益严格的法规提倡使用具有更理想特性的替代品。在这里，我们描述了生物衍生溶剂 Cyrene™ 在 SM 交叉偶联中的范围和效用，并评估其作为反应介质的适用性，以实现从发现到克级规模的这一基准转化。