5-((tertbutoxycarbonyl)amino)-2,2-dimethyl-1,3-dioxane-5-carboxylic acid | 654067-56-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 5-((tertbutoxycarbonyl)amino)-2,2-dimethyl-1,3-dioxane-5-carboxylic acid
• 英文别名: 5-(Tert-butoxycarbonylamino)-2,2-dimethyl-1,3-dioxane-5-carboxylic acid；2,2-dimethyl-5-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-dioxane-5-carboxylic acid
• CAS: 654067-56-8
• 化学式: C₁₂H₂₁NO₆
• 分子量: 275.302
• InChiKey: GLZDHEFXRNOEEY-UHFFFAOYSA-N

物化性质

• 熔点：
  166-169 °C (decomp)(Solv: ethyl acetate (141-78-6); hexane (110-54-3))
• 沸点：
  412.9±45.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  94.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-((tertbutoxycarbonyl)amino)-2,2-dimethyl-1,3-dioxane-5-carboxylic acid 在 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 乙酸铵 、 copper(l) iodide 、 caesium carbonate 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 乙醇 、 xylene 为溶剂， 反应 20.0h， 生成 {2,2-Dimethyl-5-[5-(4-oct-1-ynyl-phenyl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis of 4(5)-phenylimidazole-based analogues of sphingosine-1-phosphate and FTY720: Discovery of potent S1P1 receptor agonists

  摘要：

  The novel immunosuppressant FTY720 has been demonstrated to elicit immunomodulating effects via interaction with the G-protein coupled receptor S1P(1). FTY720 induced agonism at the S1P(3) receptor, however, has been shown to result in mild bradycardia, a minor side-effect of initial FTY720 therapy. This report describes the synthesis of several potent 4(5)-phenylimidazole-based SIP, receptor agonists that are accompanied by poor agonist activity at S1P(3). For instance, compound 20 displayed an EC50 = 4.7 +/- 1.3 nM at the S1P(1), receptor and EC50 = 780 +/- 1.3 nM at the SIP3 receptor using a [gamma-S-35]GTP-binding assay as compared to phospho-FTY720 (S1P(1): EC50 = 1.3 +/- 1.3 nM, S1P(3): EC50 = 2.0 +/- 2.4 nM). (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.05.097
• 作为产物：
  描述：

  5-氨基-2,2-二甲基-1,3-二恶烷-5-甲醇 在 sodium chlorite 、 sodium dihydrogenphosphate 、 2-甲基-2-丁烯 、 草酰氯 、 TEA 、 碳酸氢钠 、 二甲基亚砜 作用下， 以 四氢呋喃 、 二氯甲烷 、 叔丁醇 为溶剂， 反应 15.0h， 生成 5-((tertbutoxycarbonyl)amino)-2,2-dimethyl-1,3-dioxane-5-carboxylic acid
  参考文献：
  名称：

  Synthesis of 4(5)-phenylimidazole-based analogues of sphingosine-1-phosphate and FTY720: Discovery of potent S1P1 receptor agonists

  摘要：

  The novel immunosuppressant FTY720 has been demonstrated to elicit immunomodulating effects via interaction with the G-protein coupled receptor S1P(1). FTY720 induced agonism at the S1P(3) receptor, however, has been shown to result in mild bradycardia, a minor side-effect of initial FTY720 therapy. This report describes the synthesis of several potent 4(5)-phenylimidazole-based SIP, receptor agonists that are accompanied by poor agonist activity at S1P(3). For instance, compound 20 displayed an EC50 = 4.7 +/- 1.3 nM at the S1P(1), receptor and EC50 = 780 +/- 1.3 nM at the SIP3 receptor using a [gamma-S-35]GTP-binding assay as compared to phospho-FTY720 (S1P(1): EC50 = 1.3 +/- 1.3 nM, S1P(3): EC50 = 2.0 +/- 2.4 nM). (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.05.097

文献信息

• Oxoammonium salt/NaClO2: an expedient, catalytic system for one-pot oxidation of primary alcohols to carboxylic acids with broad substrate applicability
  作者：Masatoshi Shibuya、Takahisa Sato、Masaki Tomizawa、Yoshiharu Iwabuchi

  DOI：10.1039/b822944a

  日期：——

  A facile, green, one-pot oxidation of primary alcohols to carboxylic acids with broad substrate applicability has been developed by employing an expedient catalytic system consisting of 1-Me-AZADO+X−/NaClO2.

  通过采用一种便捷的催化体系，即1-甲基-AZADO+X−/NaClO2，研究人员开发了一种简易、环保、一步法将伯醇氧化为羧酸的方法，该方法具有广泛底物适用性。
• Decarbonylative Radical Coupling of α-Aminoacyl Tellurides: Single-Step Preparation of γ-Amino and α,β-Diamino Acids and Rapid Synthesis of Gabapentin and Manzacidin A
  作者：Masanori Nagatomo、Hayato Nishiyama、Haruka Fujino、Masayuki Inoue

  DOI：10.1002/anie.201410186

  日期：2015.1.26

  coupling method has been developed for the single‐step generation of various γ‐amino acids and α,β‐diamino acids from α‐aminoacyl tellurides. Upon activation by Et3B and O2 at ambient temperature, α‐aminoacyl tellurides were readily converted into α‐amino carbon radicals through facile decarbonylation, which then reacted intermolecularly with acrylates or glyoxylic oxime ethers. This mild and powerful

  已开发出一种新的基于自由基的偶联方法，可从α-氨酰基碲化物单步生成各种γ-氨基酸和α，β-二氨基酸。在室温下被Et 3 B和O 2活化后，α-氨基酰基碲化物很容易通过容易的脱羰作用转化为α-氨基碳原子团，然后与丙烯酸酯或乙醛氧基肟醚发生分子间反应。这种温和而有效的方法有效地整合到了加巴喷丁和天然产物（-）-甘露酸A的快速合成途径中。
• Compounds Active in Sphingosine 1-Phosphate Signaling
  申请人：Lynch R. Kevin

  公开号：US20070219163A1

  公开（公告）日：2007-09-20

  The present invention relates to S1P analogs that have activity as S1P receptor modulating agents and the use of such compounds to treat diseases associated with inappropriate S1P receptor activity. The compounds have the general structure: wherein R 11 is C 5 -C 18 alkyl or C 5 -C 18 alkenyl; Q is C 3 -C 6 optionally substituted cycloalkyl, C 3 -C 6 optionally substituted heterocyclic, C 3 -C 6 optionally substituted aryl C 3 -C 6 optionally substituted heteroaryl or —NH(CO)—; R 3 is H, C 1 -C 4 alkyl, (C 1 -C 4 alkyl)OH or (C 1 -C 4 alkyl)NH 2 ; R 23 is H or C 1 -C 4 alkyl, and R 15 is hydroxy, phosphonate, or wherein X and R 12 is O or S; or a pharmaceutically acceptable salt or tautomer thereof.

  本发明涉及具有S1P受体调节剂活性的S1P类似物，以及使用这些化合物治疗与不适当的S1P受体活性相关的疾病。这些化合物具有以下一般结构：其中R11是C5-C18烷基或C5-C18烯基；Q是C3-C6可选取代的环烷基，C3-C6可选取代的杂环基，C3-C6可选取代的芳基，C3-C6可选取代的杂芳基或—NH（CO）—；R3是H，C1-C4烷基，（C1-C4烷基）OH或（C1-C4烷基）NH2；R23是H或C1-C4烷基，R15是羟基，膦酸酯或其中X和R12是O或S；或其药学上可接受的盐或互变异构体。
• Orally available sphingosine 1-phosphate receptor agonists and antagonists
  申请人：Lynch R. Kevin

  公开号：US20070088002A1

  公开（公告）日：2007-04-19

  The present invention relates to S1P analogs that have activity as S1P receptor modulating agents and the use of such compounds to treat diseases associated with inappropriate S1P receptor activity. The compounds have the general structure (I) wherein R 11 is C 5 -C 18 alkyl or C 5 -C 18 alkenyl; Q is selected from the group consisting of C 3 -C 6 optionally substituted cycloalkyl, C 3 -C 6 optionally substituted heterocyclic, C 3 -C 6 optionally substituted aryl C 3 -C 6 optionally substituted heteroaryl and; R 2 is selected from the group consisting of H, C 1 -C 4 alkyl, (C 1 -C 4 alkyl)OH and (C 1 -C 4 alkyl)NH 2 ; R 23 is H or C 1 -C 4 alkyl, and R 15 is a phosphonate ester or a phosphate ester or a pharmaceutically acceptable salt or tautomer thereof.

  本发明涉及具有S1P受体调节剂活性的S1P类似物，并使用这些化合物治疗与不适当S1P受体活性相关的疾病。这些化合物具有一般结构（I），其中R11为C5-C18烷基或C5-C18烯基；Q选自C3-C6可选取代的环烷基、C3-C6可选取代的杂环、C3-C6可选取代的芳基、C3-C6可选取代的杂芳基；R2选自H、C1-C4烷基、（C1-C4烷基）OH和（C1-C4烷基）NH2；R23为H或C1-C4烷基，R15为磷酸酯或磷酸酯酯或其药学上可接受的盐或互变异构体。
• Chemical compounds
  申请人：Deng Hongfeng

  公开号：US20080070866A1

  公开（公告）日：2008-03-20

  The invention provides compounds of formula I and formula II, their preparation, and their use as pharmaceutically active immunosuppressive agents for the treatment of autoimmune disorders, organ transplant rejection, disorders associated with an activated immune system, as well as other disorders modulated by lymphopenia or S1P receptors.

  该发明提供了I式和II式化合物，它们的制备以及它们作为药物活性免疫抑制剂的用途，用于治疗自身免疫性疾病、器官移植排斥、与激活的免疫系统相关的疾病，以及其他受淋巴细胞减少或S1P受体调节的疾病。