N-[3,5-bis (trifluoromethyl)-benzyl]-N-(3-hydroxypropyl)amine | 183551-10-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-[3,5-bis (trifluoromethyl)-benzyl]-N-(3-hydroxypropyl)amine
• 英文别名: 3-[3,5-bis(trifluoromethyl)phenylmethylamino]-1-propanol；3-((3,5-bis(trifluoromethyl)benzyl)amino)propan-1-ol；3-[[3,5-bis(trifluoromethyl)benzyl]amino]-1-propanol；3-{[3,5-bis(trifluoromethyl)benzyl]amino}propan-1-ol；N-[3,5-bis (trifluoromethyl) benzyl]-N-(3-hydroxypropyl)amine；N-[3,5-bis(trifluoromethyl)benzyl]-N-(3-hydroxypropyl)amine；3-(3,5-Bis(trifluoromethyl)benzylamino)propanol；3-[[3,5-bis(trifluoromethyl)phenyl]methylamino]propan-1-ol
• CAS: 183551-10-2
• 化学式: C₁₂H₁₃F₆NO
• 分子量: 301.232
• InChiKey: GGKCSXZFEUHVBM-UHFFFAOYSA-N

物化性质

• 熔点：
  57-58 °C(Solv: ethyl ether (60-29-7); hexane (110-54-3))
• 沸点：
  271.7±40.0 °C(Predicted)
• 密度：
  1.317±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  32.3
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-[3,5-bis (trifluoromethyl)-benzyl]-N-(3-hydroxypropyl)amine 在 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 4.5h， 生成 5-[3,5-bis(trifluoromethyl)benzyl]-7-iodo-3,4,5,6-tetrahydro-2H-pyrido[2,3-b]-1,5-oxazocin-6-one
  参考文献：
  名称：

  FUSED BICYCLIC PYRIDINE DERIVATIVE AS TACHYKININ RECEPTOR ANTAGONIST

  摘要：

  公开号：

  EP1489083B1
• 作为产物：
  描述：

  3,5-双三氟甲基苄醇 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 生成 N-[3,5-bis (trifluoromethyl)-benzyl]-N-(3-hydroxypropyl)amine
  参考文献：
  名称：

  Amide-based atropisomers in tachykinin NK1-receptor antagonists: synthesis and antagonistic activity of axially chiral N-benzylcarboxamide derivatives of 2,3,4,5-tetrahydro-6H-pyrido[2,3-b][1,5]oxazocin-6-one

  摘要：

  A series of novel N-benzylcarboxamide derivatives of bicyclic compounds, 3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one and 2,3,4,5-tetrahydro-6H-pyrido[2,3-b][1,5]oxazocin-6-one, were synthesized by cyclization of N-benzyl-2-chloro-N-(2-hydroxyethyl)-and -(3-hydroxypropyl)-nicotinamides, respectively. Atropisomerism was observed in 5-[3,5-bis(trifluoromethyl)benzyl]-7-phenyl-2,3,4,5-tetrahydro-6H-pyrido[2,3-b][1,5]oxazocin-6-ones due to steric hindrance of the carboxamide moiety and restriction of its rotation. Cyclization of N-[3,5-bis(trifluoromethyl)benzyl]-2-chloro-N-[(2S)-3-hydroxy-2-methylpropyl]-5-methyl-4-phenylnicotinamide gave (3S)5-[3,5-bis(trifluoromethyl)benzyl]-3,8-dimethyl-7-phenyl-2,3,4,5-tetrahydro-6H-pyrido[2,3b][1,5]oxazocin-6-one, which exists predominantly in the thermodynamically stable aR-conformer in CDCl3. This compound showed excellent NK1-antagonistic activity with IC50 value (in vitro inhibition of [I-125]-Bolton-Hunter-substance P binding in human IM-9 cells) of 0.47 nM, which is ca. 200-fold more potent than that of its enantiomer, indicating that the atropisomer chirality affects NK1-receptor recognition. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2004.01.097

文献信息

• Enantioselective Radical Cyclization for Construction of 5-Membered Ring Structures by Metalloradical C–H Alkylation
  作者：Yong Wang、Xin Wen、Xin Cui、X. Peter Zhang

  DOI：10.1021/jacs.8b01662

  日期：2018.4.11

  use of unsaturated substrates. Guided by the concept of metalloradical catalysis, a different mode of radical cyclization that can employ saturated C-H substrates is demonstrated through the development of a Co(II)-based system for catalytic activation of aliphatic diazo compounds for enantioselective radical alkylation of various C(sp3)-H bonds. It allows for efficient construction of chiral pyrrolidines

  自由基环化代表了构建环状结构的强大策略。传统的自由基环化以自由基加成为关键步骤，需要使用不饱和底物。在金属自由基催化概念的指导下，通过开发基于Co(II)的系统，展示了一种可以使用饱和CH底物的不同自由基环化模式，该系统用于催化活化脂肪族重氮化合物，以实现各种C(sp3)的对映选择性自由基烷基化)-H键。它可以有效构建手性吡咯烷和其他有价值的五元环状化合物。这种自由基环化的替代策略提供了一种新的逆合成范例，通过 CH 和 C=O 元素的结合形成 CC 键，从容易获得的开链醛制备五元环状分子。
• Cyclic compounds, their prudiction and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US05770590A1

  公开（公告）日：1998-06-23

  Novel compounds of the following general formula or salts thereof. ##STR1## wherein Ring M is a heterocyclic ring having --N.dbd.C<, --CO--N< or --CS--N< as the partial structure --X . . . Y<; R.sup.a and R.sup.b are bonded to each other to form Ring A, or they are the same or different and represent, independently, a hydrogen atom or a substituent on the Ring M; Ring A and Ring B represent, independently, an optionally substituted homocyclic or heterocyclic ring, and at least one of them is optionally substituted heterocyclic ring; Rng C is optionally substituted homocyclic or heterocyclic ring; Rng Z is an optionally substituted ring; and n represents an integer of from 1 to 6, or a salt thereof, which has anexcellent tachykinin receptor antagonistic effect, and their production, and pharmaceutical compositions.

  具有以下通式的新化合物或其盐：##STR1##其中，环M是一个具有--N.dbd.C<、--CO--N<或--CS--N<作为部分结构--X . . . Y<的杂环环；R.sup.a和R.sup.b相互连接形成环A，或者它们相同或不同，独立地代表氢原子或环M上的取代基；环A和环B独立地代表可选择性取代的碳环或杂环，其中至少有一个是可选择性取代的杂环；环C是可选择性取代的碳环或杂环；环Z是可选择性取代的环；n代表1至6的整数，或其盐，具有优异的速激肽受体拮抗作用，以及它们的制备方法和药物组合物。
• Heterocyclic compounds, their production and use
  申请人：——

  公开号：US20020132817A1

  公开（公告）日：2002-09-19

  A compound represented by the formula: 1 wherein ring M is a heterocyclic ring wherein —X═Y< is one of —N═C<, —CO—N< or —CS—N<; R a and R b are bonded to each other to form Ring A, or they are the same or different and represent, independently, a hydrogen atom or a substituent on the Ring M; Ring A and Ring B represent, independently, an optionally substituted homocyclic or heterocyclic ring, with the proviso that at least one of them is an optionally substituted heterocyclic ring; Ring C is an optionally substituted homocyclic or heterocyclic ring; Ring Z is an optionally substituted nitrogen-containing heterocyclic ring; and n is an integer from 1 to 6, or a salt thereof has a tachykinin receptor antagonistic activity in vitro, and is useful for preventing or treating depression, anxiety, manic-depressive illness or psychopathy.

  一种由以下通式表示的化合物：1，其中环M为杂环环，其中—X═Y<为—N═C<、—CO—N<或—CS—N<之一；Ra和Rb彼此连接形成环A，或者它们相同或不同，独立地表示氢原子或环M上的取代基；环A和环B独立地表示可任选取代的碳环或杂环环，条件是至少一个为可任选取代的杂环环；环C为可任选取代的碳环或杂环环；环Z为可任选取代的含氮杂环环；n为1至6的整数，或其盐在体外具有速激肽受体拮抗活性，并可用于预防或治疗抑郁症、焦虑症、双相情感障碍或精神病。
• 2-Substituted-4-aryl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,5]oxazocin-5-one as a structurally new NK1 antagonist
  作者：Shigeki Seto、Asao Tanioka、Makoto Ikeda、Shigeru Izawa

  DOI：10.1016/j.bmcl.2004.12.089

  日期：2005.3

  The structurally novel pyrimido[4,5-b][1,5]oxazocine derivative 3, a hybrid compound of pyrido[4,3-b]- and [2,3-b]-1,5-oxazocine (1 and 2, respectively), was designed and synthesized. We examined the atropisomeric property and the NK1 antagonist activity of 3. Compound 3 was found to possess both a feature of 1, free rotation about the biaryl bond, and a feature of 2, potent in vivo activity.

  结构新颖的嘧啶并[4,5-b] [1,5]恶唑啉衍生物3，是吡啶并[4,3-b]-和[2,3-b] -1,5-恶唑嗪的杂化化合物（1和2），被设计和合成。我们检查了3的阻转异构性质和NK1拮抗剂活性。发现化合物3既具有1的特征，围绕联芳基键自由旋转，又具有2的特征，有效的体内活性。
• Design, synthesis, and evaluation of novel 2-substituted-4-aryl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,5]oxazocin-5-ones as NK1 antagonists
  作者：Shigeki Seto、Asao Tanioka、Makoto Ikeda、Shigeru Izawa

  DOI：10.1016/j.bmc.2005.06.015

  日期：2005.10

  guinea pigs (59.4% at 0.3 mg/kg iv and 62.8% at 3 mg/kg id). Furthermore, the effect of 3g on bladder function appeared to differ from that of tolterodine, another classical anti-pollakiuria agent, as determined by the distention-induced rhythmic bladder contraction assay using a urethane-anesthetized guinea pig model. Compound 3g is expected to be a promising agent for the treatment of urinary incontinence

  制备了一系列新颖的双环嘧啶衍生物，作为寻找旨在治疗尿失禁的NK1拮抗剂的一部分。其中3g，带有4-乙酰基哌嗪基和2-甲基苯基的嘧啶并[4,5-b] [1,5]恶唑啉衍生物，显示出有效的NK1拮抗剂活性，其K（B）值​​为为0.105 nM，显着增加了豚鼠的有效膀胱容量（0.3 mg / kg iv时为59.4％，id 3 mg / kg时为62.8％）。此外，使用尿烷麻醉的豚鼠模型，通过扩张诱导的节律性膀胱收缩试验确定了3g对膀胱功能的影响似乎与另一种经典的抗尿蛋白尿症托特罗定不同。化合物3g有望成为治疗尿失禁的有前途的药物。