methyl (1-oxo-1,3-dihydro-2H-isoindol-2-yl)acetate | 96017-03-7

• 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: methyl (1-oxo-1,3-dihydro-2H-isoindol-2-yl)acetate
• 英文别名: N-(methoxycarbonylmethyl)-1-isoindolinone；methyl-2-(1-oxoisoindolin-2-yl)acetate；methyl 2-(1-oxo-2,3-dihydro-1H-isoindol-2-yl)acetate；methyl 2-(3-oxo-1H-isoindol-2-yl)acetate
• CAS: 96017-03-7
• 化学式: C₁₁H₁₁NO₃
• mdl: MFCD04124610
• 分子量: 205.213
• InChiKey: UWCZAKDBXHZFFX-UHFFFAOYSA-N

物化性质

• 熔点：
  125-127 °C
• 沸点：
  366.0±42.0 °C(Predicted)
• 密度：
  1.253±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.272
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl (1-oxo-1,3-dihydro-2H-isoindol-2-yl)acetate 在 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 tert-butyl 4-(2-(1-oxoisoindolin-2-yl)acetyl)piperazine-1-carboxylate
  参考文献：
  名称：

  Synthesis and Radiosynthesis of a Novel PET Fluorobenzyl Piperazine for Melanoma Tumour Imaging; [18F]MEL054

  摘要：

  2-{2-[4-(4-[18F]-氟苄基)哌嗪-1-基]-2-氧代乙基}异吲哚啉-1-酮（[18F]MEL054）是一种新的强效吲哚啉酮基黑色素粘合剂，设计用于靶向黑色素肿瘤。[18F]MEL054是通过两步放射合成法自动制备的，包括从4-甲酰基-N,N,N-三甲基苯胺三酸盐制备4-[18F]氟苯甲醛，然后与2-(2-氧代-2-哌嗪-1-乙基)异吲哚啉-1-酮进行还原烷基化反应。4-[18F]Fluorobenzaldehyde 是在 GE TRACERlab FXFN 模块上制备的，放射化学收率（RCY，未衰变校正）为 68 ± 8%，经 Sep-Pak Plus C18 滤芯纯化后洗脱到内部改进的 Nuclear Interface [18F]FDG 合成模块的反应器中，用于随后的还原烷基化反应。HPLC 纯化产生的[18F]MEL054 的收集 RCY 为 34 ± 9 %（非衰变校正），总制备时间（包括 Sep-Pak Plus C18 和 HPLC 纯化）不超过 105 分钟。[18F]MEL054的放射化学纯度大于99%，比放射性为71-119 GBq μmol-1，3小时后[18F]MEL054在生理盐水中保持稳定（98%）。

  DOI：

  10.1071/ch12489
• 作为产物：
  描述：

  甘氨酸甲酯盐酸盐 、 邻羧基苯甲醛 在 三乙酰氧基硼氢化钠 作用下， 以 乙腈 为溶剂， 以88%的产率得到methyl (1-oxo-1,3-dihydro-2H-isoindol-2-yl)acetate
  参考文献：
  名称：

  Synthesis and Radiosynthesis of a Novel PET Fluorobenzyl Piperazine for Melanoma Tumour Imaging; [18F]MEL054

  摘要：

  2-{2-[4-(4-[18F]-氟苄基)哌嗪-1-基]-2-氧代乙基}异吲哚啉-1-酮（[18F]MEL054）是一种新的强效吲哚啉酮基黑色素粘合剂，设计用于靶向黑色素肿瘤。[18F]MEL054是通过两步放射合成法自动制备的，包括从4-甲酰基-N,N,N-三甲基苯胺三酸盐制备4-[18F]氟苯甲醛，然后与2-(2-氧代-2-哌嗪-1-乙基)异吲哚啉-1-酮进行还原烷基化反应。4-[18F]Fluorobenzaldehyde 是在 GE TRACERlab FXFN 模块上制备的，放射化学收率（RCY，未衰变校正）为 68 ± 8%，经 Sep-Pak Plus C18 滤芯纯化后洗脱到内部改进的 Nuclear Interface [18F]FDG 合成模块的反应器中，用于随后的还原烷基化反应。HPLC 纯化产生的[18F]MEL054 的收集 RCY 为 34 ± 9 %（非衰变校正），总制备时间（包括 Sep-Pak Plus C18 和 HPLC 纯化）不超过 105 分钟。[18F]MEL054的放射化学纯度大于99%，比放射性为71-119 GBq μmol-1，3小时后[18F]MEL054在生理盐水中保持稳定（98%）。

  DOI：

  10.1071/ch12489

文献信息

• Photocatalyzed Decarboxylative Addition of N-Substituted Acetic Acids to Aldehydes
  作者：Bo Jin、Ariamala Gopalsamy、Bo Peng、Li Sha、Sharon Tentarelli、Lakshmaiah Gingipalli

  DOI：10.1021/acs.joc.2c01843

  日期：2023.2.3

  photoredox-catalyzed decarboxylative addition of N-substituted acetic acids to aldehydes to generate secondary alcohols under mild reaction conditions. Protic solvents were found to be critical to the successful implementation of this methodology. This strategy enables the formation of a novel C–C bond between aldehydes and N-substituted acetic acid derivatives of weakly nucleophilic and medicinally

  在此，我们报道了在温和的反应条件下，光氧化还原催化的 N-取代乙酸脱羧加成醛生成仲醇。发现质子溶剂对该方法的成功实施至关重要。该策略能够在醛和弱亲核性和医学相关杂芳基（如吲哚、吡咯、吲唑和氮杂吲哚）的 N-取代乙酸衍生物之间形成新的 C-C 键。
• Synthesis and in Vivo Evaluation of [¹²³I]Melanin-Targeted Agents
  作者：Maxine P. Roberts、Vu Nguyen、Mark E. Ashford、Paula Berghofer、Naomi A. Wyatt、Anwen M. Krause-Heuer、Tien Q. Pham、Stephen R. Taylor、Leena Hogan、Cathy D. Jiang、Benjamin H. Fraser、Nigel A. Lengkeek、Lidia Matesic、Marie-Claude Gregoire、Delphine Denoyer、Rodney J. Hicks、Andrew Katsifis、Ivan Greguric

  DOI：10.1021/acs.jmedchem.5b00777

  日期：2015.8.13

  study reports the synthesis, [I-123]radiolabeling, and biological profile of a new series of iodinated compounds for potential translation to the corresponding [I-131]radiolabeled compounds for radionuclide therapy of melanoma. Radiolabeling was achieved via standard electrophilic iododestannylation in 60-90% radiochemical yield. Preliminary SPECT imaging demonstrated high and distinct tumor uptake of all compounds, as well as high tumor-to-background ratios compared to the literature compound [I-123]4 (ICF01012). The most favorable compounds ([I-123]20, [I-123]23, [I-123] 41, and [I-123]53) were selected for further biological investigation. Biodistribution studies indicated that all four compounds bound to melanin containing tissue with low in vivo deiodination; [I-123]20 and [I-123]53 in particular displayed high and prolonged tumor uptake (13% ID/g at 48 h). [I-123]53 had the most favorable overall profile of the cumulative uptake over time of radiosensitive organs. Metabolite analysis of the four radiotracers found [I-123]41 and [I-123]53 to be the most favorable, displaying high and prolonged amounts of intact tracer in melanin containing tissues, suggesting melanin specific binding. Results herein suggest that compound [I-123]53 displays favorable in vivo pharrnacokinetics and stability and hence is an ideal candidate to proceed with further preclinical [I-131] therapeutic evaluation.
• High-yielding synthesis of 1-isoindolinone derivatives via palladium-catalysed cycloaminocarbonylation
  作者：Diána Marosvölgyi-Haskó、Attila Takács、Zsuzsanna Riedl、László Kollár

  DOI：10.1016/j.tet.2010.11.099

  日期：2011.2

  1-Isoindolinone derivatives were synthesised in high yields (up to 89%) by using 2-iodobenzyl bromide and 2-iodobenzylamine as bifunctional substrates in palladium-catalysed carbonylation. Depending on the N-nucleophiles, two types of compounds were synthesised with 2-iodobenzyl bromide: the use of primary amines, including amino acid methylesters, resulted in the formation of N-substituted 1-isoindolinones, while secondary amines react both with the benzyl bromide and iodoarene moieties resulting in the corresponding ortho-(N-piperidino/morpholinomethyl)-benzamides. The parent 1-isoindolinone was obtained in a facile, highly chemoselective intramolecular aminocarbonylation of 2-iodobenzylamine. The mechanistic details of the ring-closure reaction and the conditions leading to side-products are discussed as well. (C) 2010 Elsevier Ltd. All rights reserved.
• NEW, J. S.;YEVICH, J. P., J. HETEROCYCL. CHEM., 1984, 21, N 5, 1355-1360
  作者：NEW, J. S.、YEVICH, J. P.

  DOI：——

  日期：——
• Synthesis and Radiosynthesis of a Novel PET Fluorobenzyl Piperazine for Melanoma Tumour Imaging; [18F]MEL054
  作者：Stephen R. Taylor、Maxine P. Roberts、Naomi A. Wyatt、Tien Q. Pham、Daniela Stark、Thomas Bourdier、Peter Roselt、Andrew Katsifis、Ivan Greguric

  DOI：10.1071/ch12489

  日期：——

  2-2-[4-(4-[18F]-Fluorobenzyl)piperazin-1-yl]-2-oxoethyl}isoindolin-1-one ([18F]MEL054), is a new potent indolinone-based melanin binder designed to target melanotic tumours. [18F]MEL054 was prepared by an automated two-step radiosynthesis, comprising of the preparation of 4-[18F]fluorobenzaldehyde from 4-formyl-N,N,N-trimethylanilinium triflate, followed by reductive alkylation with 2-(2-oxo-2-piperazin-1-ylethyl)isoindolin-1-one. 4-[18F]Fluorobenzaldehyde was prepared on a GE TRACERlab FXFN module in 68 ± 8 % radiochemical yield (RCY, non-decay corrected), purified by a Sep-Pak Plus C18 cartridge and eluted into the reactor of an in-house modified Nuclear Interface [18F]FDG synthesis module for the subsequent reductive alkylation reaction. HPLC purification produced [18F]MEL054 in a collected RCY of 34 ± 9 % (non-decay corrected), the total preparation time (including Sep-Pak Plus C18 and HPLC purification) did not exceed 105 min. The radiochemical purity of [18F]MEL054 was greater than 99 % with a specific radioactivity of 71–119 GBq μmol–1 and [18F]MEL054 remained stable in saline solution (>98 %) after 3 h.

  2-2-[4-(4-[18F]-氟苄基)哌嗪-1-基]-2-氧代乙基}异吲哚啉-1-酮（[18F]MEL054）是一种新的强效吲哚啉酮基黑色素粘合剂，设计用于靶向黑色素肿瘤。[18F]MEL054是通过两步放射合成法自动制备的，包括从4-甲酰基-N,N,N-三甲基苯胺三酸盐制备4-[18F]氟苯甲醛，然后与2-(2-氧代-2-哌嗪-1-乙基)异吲哚啉-1-酮进行还原烷基化反应。4-[18F]Fluorobenzaldehyde 是在 GE TRACERlab FXFN 模块上制备的，放射化学收率（RCY，未衰变校正）为 68 ± 8%，经 Sep-Pak Plus C18 滤芯纯化后洗脱到内部改进的 Nuclear Interface [18F]FDG 合成模块的反应器中，用于随后的还原烷基化反应。HPLC 纯化产生的[18F]MEL054 的收集 RCY 为 34 ± 9 %（非衰变校正），总制备时间（包括 Sep-Pak Plus C18 和 HPLC 纯化）不超过 105 分钟。[18F]MEL054的放射化学纯度大于99%，比放射性为71-119 GBq μmol-1，3小时后[18F]MEL054在生理盐水中保持稳定（98%）。