甲基2-异丙基-1,3-恶唑-4-羧酸酯 | 155884-24-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 甲基2-异丙基-1,3-恶唑-4-羧酸酯
• 英文名称: methyl 2-isopropyloxazole-4-carboxylate
• 英文别名: methyl 2-propan-2-yl-1,3-oxazole-4-carboxylate
• CAS: 155884-24-5
• 化学式: C₈H₁₁NO₃
• 分子量: 169.18
• InChiKey: KSSCLLNYZNLJFB-UHFFFAOYSA-N

物化性质

• 沸点：
  214.3±13.0 °C(Predicted)
• 密度：
  1.102±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  52.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  甲基2-异丙基-1,3-恶唑-4-羧酸酯 在 4-二甲氨基吡啶 、 sodium hydroxide 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 N-<1',1'-Bis(methoxycarbonyl)-2'-(phenylthio)ethyl>-2-isopropyloxazole-4-carboxamide
  参考文献：
  名称：

  Dimethyl amino[(phenylthio)methyl]malonate: a useful C-3 unit in a mild, direct synthesis of oxazole-4-carboxylates

  摘要：

  N-Acyl derivatives of the title compound undergo oxidative cyclization upon treatment with N-chlorosuccinimide in DMF to form dimethyl 4,5-dihydro(phenylthio)oxazole-4,4-dicarboxylates 4 which then are decarbomethoxylated with concomitant loss of thiophenoxide to form 2-substituted-4-carbomethoxy-5-unsubstituted oxazoles 1. The mildness and generality of this method has been demonstrated by the synthesis of a variety of examples, including a fragment used for a synthesis of calyculin A.

  DOI：

  10.1021/jo00073a040
• 作为产物：
  描述：

  甲基2-异丙基-4,5-二氢-1,3-恶唑-4-羧酸酯 在 过氧化苯甲酸叔丁酯 、 copper(I) bromide 作用下， 以 苯 为溶剂， 反应 12.0h， 以60%的产率得到甲基2-异丙基-1,3-恶唑-4-羧酸酯
  参考文献：
  名称：

  恶唑啉和噻唑啉氧化成恶唑和噻唑。Kharasch-Sosnovsky反应的应用。

  摘要：

  使用Kharasch-Sosnovsky反应的改进，将带有各种2-烷基取代基（手性和非手性）的恶唑啉和噻唑啉的氧化分别平滑地氧化为相应的恶唑和噻唑。成功实施此重要氧化反应的关键特征是使用Cu（I）和Cu（II）盐的混合物来增强中间俘虏性自由基的氧化作用24。氧化失败的原因是在C-4处缺少碳烷氧基的恶唑啉/噻唑啉。

  DOI：

  10.1021/jo9613491

文献信息

• [EN] MACROCYCLIC COMPOUNDS FOR MODULATING IL-17<br/>[FR] COMPOSÉS MACROCYCLIQUES POUR UNE MODULATION D'IL-17
  申请人：ENSEMBLE THERAPEUTICS CORP

  公开号：WO2013116682A1

  公开（公告）日：2013-08-08

  The invention relates generally to macrocyclic compounds of formula I and their therapeutic use. More particularly, the invention relates to macrocyclic compounds that modulate the activity of IL-17 and/or are useful in the treatment of medical conditions, such as inflammatory diseases and other IL-17-associated disorders.

  这项发明通常涉及公式I的大环化合物及其治疗用途。更具体地，该发明涉及调节IL-17活性的大环化合物，或者用于治疗炎症性疾病和其他与IL-17相关的疾病的大环化合物。
• Widely Exploited, Yet Unreported: Regiocontrolled Synthesis and the Suzuki-Miyaura Reactions of Bromooxazole Building Blocks
  作者：Vitalii V. Solomin、Dmytro S. Radchenko、Evgeniy Y. Slobodyanyuk、Oleksandr V. Geraschenko、Bohdan V. Vashchenko、Oleksandr O. Grygorenko

  DOI：10.1002/ejoc.201900032

  日期：2019.5.15

  An approach to synthesis of all isomeric bromooxazoles was optimized and its scope was extended to all three isomeric parents, as well as various alkyl‐ and aryl‐substituted bromooxazoles. The direct regiocontrolled lithiation followed by reaction with electrophilic bromine source was common and led exclusively to the target substituted 2‐, 4‐, and 5‐bromooxazoles on multigram scale. The utility of

  优化了所有异构体溴恶唑的合成方法，并将其范围扩展到所有三个异构体母体，以及各种烷基和芳基取代的溴恶唑。直接区位控制的锂化反应，随后与亲电溴源反应是很常见的现象，并且仅在毫克数范围内导致目标取代的2-，4-和5-溴恶唑。在平行合成条件下，Suzuki-Miyaura交叉偶联反应证明了在这项工作中获得的多功能构建基块的效用。
• MACROCYCLIC COMPOUNDS FOR MODULATING IL-17
  申请人：ENSEMBLE THERAPEUTICS CORPORATION

  公开号：US20150005319A1

  公开（公告）日：2015-01-01

  The invention relates generally to macrocyclic compounds of formula I and their therapeutic use. More particularly, the invention relates to macrocyclic compounds that modulate the activity of IL-17 and/or are useful in the treatment of medical conditions, such as inflammatory diseases and other IL-17-associated disorders.

  本发明涉及公式I的大环化合物及其治疗用途。更具体地，本发明涉及调节IL-17活性或用于治疗医疗情况（例如炎症性疾病和其他IL-17相关疾病）的大环化合物。
• Discovery of Ritonavir, a Potent Inhibitor of HIV Protease with High Oral Bioavailability and Clinical Efficacy
  作者：Dale J. Kempf、Hing L. Sham、Kennan C. Marsh、Charles A. Flentge、David Betebenner、Brian E. Green、Edith McDonald、Sudthida Vasavanonda、Ayda Saldivar、Norman E. Wideburg、Warren M. Kati、Lisa Ruiz、Chen Zhao、LynnMarie Fino、Jean Patterson、Akhteruzzaman Molla、Jacob J. Plattner、Daniel W. Norbeck

  DOI：10.1021/jm970636+

  日期：1998.2.1

  The structure-activity studies leading to the potent and clinically efficacious HIV protease inhibitor ritonavir are described. Beginning with the moderately potent and orally bioavailable inhibitor A-80987, systematic investigation of peripheral (P3 and P2') heterocyclic groups designed to decrease the rate of hepatic metabolism provided analogues with improved pharmacokinetic properties after oral dosing in rats. Replacement of pyridyl groups with thiazoles provided increased chemical stability toward oxidation while maintaining sufficient aqueous solubility for oral absorption, Optimization of hydrophobic interactions with the HIV protease active site produced ritonavir, with excellent in vitro potency (EC50 = 0.02 mu M) and high and sustained plasma concentrations after oral administration in four species. Details of the discovery and preclinical development of ritonavir are described.
• The oxidation of 2-oxazolines to 1,3-oxazoles
  作者：A.I. Meyers、Francis Tavares

  DOI：10.1016/s0040-4039(00)77149-8

  日期：1994.4

  Oxazolines are readily oxidized to 1,3-oxazoles using NBS/peroxide or light or, more efficiently, by the Kharasch-Sosnovsky Reaction.