1-(2,2,2-trifluoroacetyl)piperidine-4-carbonyl chloride | 126501-71-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-(2,2,2-trifluoroacetyl)piperidine-4-carbonyl chloride
• 英文别名: N-(trifluoroacetyl)isonipecotyl chloride；N-trifluoroacetylisonipecotyl chloride；1-(2,2,2-trifluoroacetyl)piperidine-4-carboxylic acid chloride；1-(trifluoroacetyl)piperidine-4-carbonyl chloride；1-trifluoroacetyl-piperidine-4-carbonyl chloride；N-trifluoroacetyl-isonipecotoyl chloride
• CAS: 126501-71-1
• 化学式: C₈H₉ClF₃NO₂
• 分子量: 243.613
• InChiKey: CDFRRPLSDDDUND-UHFFFAOYSA-N

物化性质

• 沸点：
  321.6±42.0 °C(Predicted)
• 密度：
  1.422±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  37.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(2,2,2-trifluoroacetyl)piperidine-4-carbonyl chloride 在 titanium(IV) isopropylate 、 盐酸 、 sodium tetrahydroborate 、 三氯化铝 、 甲基溴化镁 、 potassium carbonate 、 1-羟基苯并三唑 、 对甲苯磺酸 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 乙酸乙酯 、 1,2-二氯乙烷 为溶剂， 反应 58.0h， 生成 [4-[4-[(4-Bromophenyl)-hydroxy-methyl]-1-piperidyl]-4-methyl-1-piperidyl]-(2,6-dimethylphenyl)methanone
  参考文献：
  名称：

  Synthesis, SAR, and Biological Evaluation of Oximino-Piperidino-Piperidine Amides. 1. Orally Bioavailable CCR5 Receptor Antagonists with Potent Anti-HIV Activity

  摘要：

  We previously reported the discovery of 4-[(Z)-(4-bromophenyl)(ethoxyimino)methyl]-1'-[(2,4-dimethyl-3-pyridinyl)carbonyl] -4'-methyl-1,4'-bipiperidine N-oxide 1 (SCH 351125) as an orally bioavailable human CCR5 antagonist for the treatment of HIV-1 infection. Herein, we describe in detail the discovery of 1 from our initial lead compound as well as the synthesis and SAR studies directed toward optimization of substitution at the phenyl, oxime, and right-hand side amide groups in the oximino-piperidino-piperidine series. Substitutions (4-Br, 4-CF3, 4-OCF3, 4-SO2Me, and 4-Cl) at the phenyl group are well-tolerated, and small alkyl substitutions (Me, Et, Pr-n, Pr-i, and cyclopropyl methyl) at the oxime moiety are preferred for CCR5 antagonism. The 2,6-dimethylnicotinamide N-oxide moiety is the optimal choice for the right-hand side. Several compounds in this series, including compound 1, exhibited excellent antiviral activity in vitro. Compound 1, which has a favorable pharmacokinetic profile in rodents and primates, excellent oral bioavailability, and potent antiviral activity against a wide range of primary HIV-1 isolates, is a potentially promising new candidate for treatment of HIV-1 infection.

  DOI：

  10.1021/jm0200815
• 作为产物：
  描述：

  在 氯化亚砜 作用下， 以 苯 为溶剂， 反应 2.0h， 生成 1-(2,2,2-trifluoroacetyl)piperidine-4-carbonyl chloride
  参考文献：
  名称：

  Conformation-activity relationship study of 5-HT3 receptor antagonists and a definition of a model for this receptor site

  摘要：

  A conformation-activity relationship study of 5-HT3 receptor antagonists was used to define a pharmacophore and receptor map to qualitatively account for their activity. The design and synthesis of specific keto-amino-indole derivatives that are potent 5-HT3 receptor antagonists gave some support to the model.

  DOI：

  10.1021/jm00168a011

文献信息

• Modulators of indoleamine 2,3-dioxygenase and methods of using the same
  申请人：Combs P. Andrew

  公开号：US20060258719A1

  公开（公告）日：2006-11-16

  The present invention is directed to modulators of indoleamine 2,3-dioxygenase (IDO), as well as compositions and pharmaceutical methods thereof.

  本发明涉及色氨酸2,3-二氧化酶（IDO）的调节剂，以及其组合物和药用方法。
• [EN] 1, 4-SUBSTITUTED PIPERIDINE DERIVATIVES<br/>[FR] DÉRIVÉS DE PIPÉRIDINE 1,4-SUBSTITUÉS
  申请人：CEPHALON INC

  公开号：WO2016205633A1

  公开（公告）日：2016-12-22

  Described herein are 1,4-substituted piperidine compounds according to Formula (I) that have demonstrated activity as fatty acid synthase inhibitors. Also described herein are pharmaceutical compositions containing the described 1,4-substituted piperidine compounds, and methods of treating diseases mediated by fatty acid synthase, by administering one or more of the compounds or pharmaceutical formulations described herein. Also described herein are methods of synthesizing the compounds described, including the described 1,4-substituted piperidine compounds and synthetic intermediates useful in those syntheses.

  本文描述了按照式（I）的1,4-取代哌啶化合物，这些化合物已经表现出作为脂肪酸合成酶抑制剂的活性。本文还描述了含有所述1,4-取代哌啶化合物的药物组合物，以及通过给予所述化合物或药物配方中的一个或多个来治疗由脂肪酸合成酶介导的疾病的方法。本文还描述了合成所述化合物的方法，包括所述的1,4-取代哌啶化合物和在这些合成中有用的合成中间体。
• SUBSTITUTED 5H-PYRIMIDO[5,4-B]INDOLES, METHOD FOR THE PRODUCTION THEREOF AND USE THEREOF FOR TREATING NON-SOLID MALIGNANT TUMORS OF THE BLOOD-PRODUCING SYSTEM
  申请人：Reichelt Claudia

  公开号：US20110021511A1

  公开（公告）日：2011-01-27

  The invention relates to compounds of general formula 1 to processes for the production thereof, to pharmaceutical preparations containing said compounds and/or physiologically compatible salts and/or solvates which can be produced therefrom as well as to the pharmaceutical use of said compounds, the salts or solvates thereof as inductors of apoptosis in the case of non-solid malignant tumors of the hematopoietic system, in particular in the case of leukemias and lymphomas, more particularly in the case of leukemic B lymphocytes.

  该发明涉及一般式1的化合物及其生产方法，包含所述化合物和/或可由其制备的生理兼容盐和/或溶剂的药物制剂，以及所述化合物、其盐或溶剂作为诱导非固体恶性血液系统肿瘤细胞凋亡的药物用途，特别是在白血病和淋巴瘤等情况下，更具体地说是在白血病B淋巴细胞的情况下。
• 1-Aminopyridinium Ylides as Monodentate Directing Groups for sp³ C–H Bond Functionalization
  作者：Ky Khac Anh Le、Hanh Nguyen、Olafs Daugulis

  DOI：10.1021/jacs.9b06643

  日期：2019.9.18

  1-Aminopyridinium ylides are efficient directing groups for palladium-catalyzed β-arylation and alkylation of sp3 C-H bonds in carboxylic acid derivatives. The efficiency of these directing groups depends on the substitution at the pyridine moiety. The unsubstituted pyridine-derived ylides allow functionalization of primary C-H bonds, while methylene groups are unreactive in the absence of external

  1-氨基吡啶鎓叶立德是钯催化的 β-芳基化和羧酸衍生物中 sp3 CH 键烷基化的有效导向基团。这些导向基团的效率取决于吡啶部分的取代。未取代的吡啶衍生的叶立德允许初级 CH 键的功能化，而亚甲基在没有外部配体的情况下是不反应的。在没有外部配体的情况下，含 4-吡咯烷并吡啶的叶立德能够在无环亚甲基中进行 CH 官能化，从而与氨基喹啉导向基团的效率相媲美。已经进行了初步的机械研究。已分离出一种环钯中间体，并通过 X 射线晶体学对其进行表征，并研究了其反应性。
• N-Heterocyclic Carbene Ligand-Enabled C(sp³)−H Arylation of Piperidine and Tetrahydropyran Derivatives
  作者：Shengqing Ye、Weibo Yang、Timothy Coon、Dewey Fanning、Tim Neubert、Dean Stamos、Jin-Quan Yu

  DOI：10.1002/chem.201600191

  日期：2016.3.24

  PdII‐catalyzed C(sp3)−H arylation of saturated heterocycles with a wide range of aryl iodides is enabled by an N‐heterocyclic carbene (NHC) ligand. A C(sp3)−H insertion step by the PdII/NHC complex in the absence of ArI is demonstrated experimentally for the first time. Experimental data suggests that the previously established NHC‐mediated Pd0/PdII catalytic manifold does not operate in this reaction

  N杂环卡宾（NHC）配体可实现Pd II催化的饱和杂环与各种芳基碘的C（sp 3）-H芳基化反应。首次通过实验证明了在不存在ArI的情况下，Pd II / NHC络合物的AC（sp 3）-H插入步骤。实验数据表明，先前建立的NHC介导的Pd 0 / Pd II催化歧管在该反应中不起作用。该转化为使药学上相关的哌啶和四氢吡喃环系统多样化提供了一种新方法。