4-(4',5'-dihydro-4',4'-dimethyl-Δ²-oxazolin-2-yl)-3,5-dimethylisoxazole | 93599-35-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑啉类
• 英文名称: 4-(4',5'-dihydro-4',4'-dimethyl-Δ²-oxazolin-2-yl)-3,5-dimethylisoxazole
• 英文别名: 4-(4,4-dimethyl-5H-1,3-oxazol-2-yl)-3,5-dimethyl-1,2-oxazole
• CAS: 93599-35-0
• 化学式: C₁₀H₁₄N₂O₂
• 分子量: 194.233
• InChiKey: RVOSZECDUXHWKF-UHFFFAOYSA-N

物化性质

• 熔点：
  76-78 °C
• 沸点：
  310.1±42.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  47.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(4',5'-dihydro-4',4'-dimethyl-Δ²-oxazolin-2-yl)-3,5-dimethylisoxazole 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 4.0h， 生成
  参考文献：
  名称：

  4-Isoxazolyl-1,4-dihydropyridines exhibit binding at the multidrug-resistance transporter

  摘要：

  The 4-isoxazolyl-dihydropyridines (IDHPs) exhibit inhibition of the multidrug-resistance transporter (MDR-1), and exhibit an SAR distinct from their activity at voltage gated calcium channels (VGCC). Among the four most active IDHPs, three were branched at C-5 of the isoxazole, including the most active analog, 1k. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.09.022
• 作为产物：
  描述：

  3,5-二甲基异噁唑-4-甲酰氯 在 氯化亚砜 作用下， 以 氯仿 为溶剂， 生成 4-(4',5'-dihydro-4',4'-dimethyl-Δ²-oxazolin-2-yl)-3,5-dimethylisoxazole
  参考文献：
  名称：

  Metalation of isoxazolyloxazolines, a facile route to functionally complex isoxazoles: utility, scope, and comparison to dianion methodology

  摘要：

  DOI：

  10.1021/jo00350a047

文献信息

• The direct synthesis of 2-Oxazolines from carboxylic esters using lanthanide chloride as catalyst
  作者：Peiwen Zhou、Jason E. Blubaum、Christopher T. Burns、Nicholas R. Natale

  DOI：10.1016/s0040-4039(97)01641-9

  日期：1997.10

  Using catalytic amounts of lanthanide III (Ln = La, Sm) chlorides and amino alkoxides as reagents, an one-pot direct synthesis for 2-oxazolines, in good yield, from carboxylic esters has been developed.

  使用催化量的镧系元素III（Ln = La，Sm）氯化物和氨基醇盐作为试剂，已经开发了从羧酸酯一锅直接合成高收率的2-恶唑啉的方法。
• A facile synthesis of functionally complex isoxazole derivatives
  作者：N.R. Natale、Chorng-Shyr Niou

  DOI：10.1016/0040-4039(84)80036-2

  日期：——

  takes place initially and selectively on the C-5′-alkyl group. Subsequent metalation also proceeds at this position. Selective deprotection of the oxazoline was accomplished without disturbing the isoxazole ring.

  2（4'-异恶唑基）的金属化-Δ 2 -oxazolines发生起初有选择地在C-5'-烷基。随后的金属化也在该位置进行。在不干扰异恶唑环的情况下完成了对恶唑啉的选择性脱保护。
• Metalation and Electrophilic Quenching of C-4 Functionalized Isoxazoles; VIII. Preparation of Derivatives of 5-Thioalkylisoxazoles
  作者：T. N. Balasubramaniam、Yousef R. Mirzaei、N. R. Natale

  DOI：10.1055/s-1990-27099

  日期：——

  The lateral metalation and electrophilic quenching of isoxazoles bearing electron withdrawing groups in the 4-position 1 with disulfides, represents a selective, direct and synthetically useful entry to the thioalkyl derivatives 2 (nine examples). One exception to the formation of monothioalkyl major products was observed for the dianion of 4-[(2-hydroxymethyl-1-pyrrolidinyl)carbonyl]-3,5-dimethylisoxazole (1i) which was found to produce the 5-[bis(phenylthio)methyl]isoxazole derivative 3i as the major isolated product (66%). Oxidation of 2a with 3-chloroperoxybenzoic acid (MCPBA) proceeds selectively at sulfur in the presence of both isoxazole and oxazoline nitrogens to give the corresponding sulfoxide 4a (56%) or sulfone 5a (72%), respectively.

  在 4-位 1 上带有吸电子基团的异恶唑与二硫化物的横向金属化和亲电子猝灭代表了硫代烷基衍生物 2 的选择性、直接和合成上有用的进入（九个例子）。 对于 4-[(2-羟甲基-1-吡咯烷基)羰基]-3,5-二甲基异恶唑 (1i) 的二阴离子，观察到形成单硫代烷基主要产物的一个例外，发现它会产生 5-[双(苯硫基) )甲基]异恶唑衍生物 3i 作为主要分离产物 (66%)。在异恶唑和恶唑啉氮存在下，用 3-氯过苯甲酸 (MCPBA) 选择性地对硫进行氧化，分别得到相应的亚砜 4a (56%) 或砜 5a (72%)。
• Regiospecific Control of Additions of 4-Substituted 3,5-Dimethylisoxazoles to α,β Unsaturated Carbonyls
  作者：J. R. Stenzel

  DOI：10.1055/s-1997-1315

  日期：1997.9

  Transmetalation of C-5-lithiomethylisoxazoles with the lower-order cuprate reagent lithium thienylcyanocuprate (Li[ThCuCN]) in THF results in exclusive conjugate addition to α,β-unsaturated carbonyls. In contrast, transmetalation with samarium tris(hexamethyldisilazide) (Sm[HMDS]3) in diethyl ether directs 1,2-carbonyl addition. In both cases, optimum results were realized with a 4,5-dihydro-4,4-dimethyl-Δ 2-oxazoline substituent at the C-4 position of the isoxazole.

  用低阶铜氧化物试剂噻吩基氰基杯酸锂（Li[ThCuCN]）在四氢呋喃中对 C-5-lithiomethylisoxazoles 进行反金属反应，可使其与δ、δ²-不饱和羰基发生共轭加成反应。相反，在二乙醚中用三(六甲基二硅氮化物)钐（Sm[HMDS]3）进行反金属化则可直接进行 1,2-羰基加成。在这两种情况下，异噁唑 C-4 位上的 4,5-二氢-4,4-二甲基-δ 2-噁唑啉取代基都能产生最佳结果。
• Lipophilic 4-Isoxazolyl-1,4-dihydropyridines:  Synthesis and Structure−Activity Relationships
  作者：Nicholas R. Natale、Mark E. Rogers、Richard Staples、David J. Triggle、Aleta Rutledge

  DOI：10.1021/jm980439q

  日期：1999.8.1

  A series of 4-isoxazolyl-1,4-dihydropyridines bearing lipophilic side chains at the C-5 position of the isoxazole ring have been prepared. The calcium channel antagonistic activity of these compounds has been evaluated. A hypothetical model for binding of these compounds in the calcium channel. is proposed, and the validity of this model is evaluated based on the. SAR of this series of calcium binding, especially for the two most active derivatives, 1a,g. The solid-state structure for the most active compound, 1a, has also been determined, and its important features are reported.