甲基(4S)-2-异丙基-4,5-二氢-1,3-恶唑-4-羧酸酯 | 162739-76-6

• 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
• 中文名称: 甲基(4S)-2-异丙基-4,5-二氢-1,3-恶唑-4-羧酸酯
• 英文名称: methyl 2-isopropyl-2-oxazoline-4-carboxylate
• 英文别名: methyl (4S)-4,5-dihydro-2-(1-methylethyl)oxazole-4-carboxylate；(S)-2-iso-propyloxazoline-4-carboxylic acid methyl ester；methyl 2-isopropyl-4,5-dihydrooxazole-4-carboxylate；(S)-Methyl 2-isopropyl-4,5-dihydrooxazole-4-carboxylate；methyl (4S)-2-propan-2-yl-4,5-dihydro-1,3-oxazole-4-carboxylate
• CAS: 162739-76-6
• 化学式: C₈H₁₃NO₃
• 分子量: 171.196
• InChiKey: XCOCYBLYCISXHZ-LURJTMIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  47.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  甲基(4S)-2-异丙基-4,5-二氢-1,3-恶唑-4-羧酸酯 在 正丁基锂 、 三氯溴甲烷 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 copper(II) oxide 、 sodium hydroxide 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 正己烷 、 二氯甲烷 、 水 为溶剂， 反应 6.17h， 生成 3-(2-Propan-2-yl-1,3-oxazol-5-yl)thiophene-2-carbonitrile
  参考文献：
  名称：

  广泛开发但尚未报道：区域控制合成和溴恶唑结构单元的Suzuki-Miyaura反应

  摘要：

  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。

  DOI：

  10.1002/ejoc.201900032
• 作为产物：
  描述：

  N-isobutyryl-L-serine methyl ester 在 potassium phosphate 、 Trifluorosulfonic anhydride 、 二苯基亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 0.83h， 以79%的产率得到甲基(4S)-2-异丙基-4,5-二氢-1,3-恶唑-4-羧酸酯
  参考文献：
  名称：

  Discovery of Ritonavir, a Potent Inhibitor of HIV Protease with High Oral Bioavailability and Clinical Efficacy

  摘要：

  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.

  DOI：

  10.1021/jm970636+

文献信息

• Highly Enantio- and Regioselective Allylic Alkylations Catalyzed by Chiral [Bis(dihydrooxazole)]molybdenum Complexes
  作者：Frank Glorius、Markus Neuburger、Andreas Pfaltz

  DOI：10.1002/1522-2675(20011017)84:10<3178::aid-hlca3178>3.0.co;2-q

  日期：2001.10.17

  A series of chiral C-2-symmetric bis[dihydrooxazoles] with a trans-1,2-diaminocyclohexane backbone was synthesized. In view of the promising results obtained by Trost et al with related bis[pyridine] ligands, we tested these new ligands in the enantioselective molybdenum-catalyzed allylic alkylation of 1- and 3-monosubstituted allylic substrates. Enantiomer excesses of up to 98% and branched/linear ratios of up to 11 : 1 were obtained with (E)-3-(alkyl)allyl carbonates. (E)-3-Phenoxyallyl acetate gave a branclied/linear ratio of > 20:1 and an ee of 98%. Crystal structures of the free ligand 7a and of its tricarbonylmolybdenum(0) complex 28 are reported.
• Enantioselective Molybdenum-Catalyzed Allylic Alkylation Using Chiral Bisoxazoline Ligands
  作者：Frank Glorius、Andreas Pfaltz

  DOI：10.1021/ol990602r

  日期：1999.7.1

  [GRAPHICS]A series of chiral C-2-symmetric bisoxazolines with trans-1,2-diaminocyclohexane backbones was synthesized. In View of the promising results obtained by Trost with analogous bispyridine ligands, we tested our new ligands in the enantioselective molybdenum-catalyzed allylic alkylation of 1- and 3-monosubstituted allylic substrates, Enantiomeric excesses of up to 98% and branched/linear ratios of up to 11:1 were obtained with (E)-3-(n-alkyl)allyl carbonates. (E)-3-Phenoxyallyl acetate gave a branched/linear ratio of >20:1 and an ee of 98%.