methyl (S)-4-methoxycarbonyl-2-(1-pyrrolyl)butanoate | 116763-12-3

• 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 (S)-4-methoxycarbonyl-2-(1-pyrrolyl)butanoate
• 英文别名: dimethyl (2S)-2-(1H-pyrrol-1-yl)pentanedioate；(2S)-dimethyl 2-(1H-pyrrol-1-yl)glutarate；1,5-dimethyl (2S)-2-(1H-pyrrol-1-yl)pentanedioate；dimethyl (2S)-2-pyrrol-1-ylpentanedioate
• CAS: 116763-12-3
• 化学式: C₁₁H₁₅NO₄
• 分子量: 225.244
• InChiKey: GEADOYJXWOGGLV-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  16
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  57.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl (S)-4-methoxycarbonyl-2-(1-pyrrolyl)butanoate 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 0.25h， 以80%的产率得到methyl 8-oxo-5,6,7,8-tetrahydrohydroindolizine-5-carboxylate
  参考文献：
  名称：

  An enantiospecific entry to indolizidines by intramolecular acylation of N-pyrrole esters

  摘要：

  L-Glutamic diethyl ester hydrochloride was converted to its pyrrole derivative 22 by condensation with 2,5-dimethoxytetrahydrofuran in water. Cyclization of 22 with BBr3 afforded (5S)-5,6-dihydro-5-ethoxycarbonyl-8(7H)-indolizinone (23). Catalytic hydrogenation of 23 over Pd/C in acetic acid gave exclusively (5S,9R)-5-ethoxycarbonylindolizidine in an overall yield of 41%, whereas hydrogenation over Rh/Al2O3 in ethanol gave predominantly (5S,8S,9S)-5-ethoxycarbonyl-8-hydroxyindolizidine in 48.5% overall yield.

  DOI：

  10.1016/s0040-4039(00)76698-6
• 作为产物：
  描述：

  2,5-二甲氧基四氢呋喃 、 L-谷氨酸二甲酯盐酸盐 以 水 为溶剂， 反应 0.5h， 以23%的产率得到methyl (S)-4-methoxycarbonyl-2-(1-pyrrolyl)butanoate
  参考文献：
  名称：

  An enantiospecific entry to indolizidines by intramolecular acylation of N-pyrrole esters

  摘要：

  L-Glutamic diethyl ester hydrochloride was converted to its pyrrole derivative 22 by condensation with 2,5-dimethoxytetrahydrofuran in water. Cyclization of 22 with BBr3 afforded (5S)-5,6-dihydro-5-ethoxycarbonyl-8(7H)-indolizinone (23). Catalytic hydrogenation of 23 over Pd/C in acetic acid gave exclusively (5S,9R)-5-ethoxycarbonylindolizidine in an overall yield of 41%, whereas hydrogenation over Rh/Al2O3 in ethanol gave predominantly (5S,8S,9S)-5-ethoxycarbonyl-8-hydroxyindolizidine in 48.5% overall yield.

  DOI：

  10.1016/s0040-4039(00)76698-6

文献信息

• Stereoselective synthesis of 3,4‐dihydropyrrolo[1,2‐a]pyrazin‐1(2H)‐one derivatives as PIM kinase inhibitors inspired from marine alkaloids
  作者：Francesco Casuscelli、Elena Ardini、Nilla Avanzi、Alessandra Badari、Elena Casale、Teresa Disingrini、Daniele Donati、Antonella Ermoli、Eduard R. Felder、Arturo Galvani、Antonella Isacchi、Maria Menichincheri、Marisa Montemartini、Christian Orrenius、Claudia Piutti、Barbara Salom、Gianluca Papeo

  DOI：10.1002/chir.23501

  日期：2022.11

  We previously demonstrated that natural product-inspired 3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-ones derivatives delivered potent and selective PIM kinases inhibitors however with non-optimal ADME/PK properties and modest oral bioavailability. Herein, we describe a structure-based scaffold decoration and a stereoselective approach to this chemical class. The synthesis, structure–activity relationship

  我们之前证明了受天然产物启发的 3,4-二氢吡咯并[1,2-a]吡嗪-1(2H)-ones 衍生物可提供有效和选择性的 PIM 激酶抑制剂，但具有非最佳的 ADME/PK 特性和适度的口服生物利用度。在这里，我们描述了一种基于结构的支架装饰和这种化学类别的立体选择性方法。本文介绍了此类抑制剂化合物的合成、构效关系研究、手性分析和药代动力学数据。化合物20c对 PIM1 和 PIM2 表现出优异的效力，具有出色的激酶选择性和 PK 特性，可有效且剂量依赖性地促进 c-Myc 降解，并且似乎是有希望进一步开发的先导化合物。
• Kashima, Choji; Maruyama, Tatsuya; Harada, Kazuo, Journal of Chemical Research, Miniprint, 1988, # 2, p. 601 - 645
  作者：Kashima, Choji、Maruyama, Tatsuya、Harada, Kazuo、Hibi, Shigeki、Omote, Yoshimori

  DOI：——

  日期：——
• Bond, Timothy J.; Jenkins, Robert; Ridley, Andrew C., Journal of the Chemical Society. Perkin transactions I, 1993, # 19, p. 2241 - 2242
  作者：Bond, Timothy J.、Jenkins, Robert、Ridley, Andrew C.、Taylor, Paul C.

  DOI：——

  日期：——
• The synthesis of chiral 1-(1H-pyrrole) derivatives
  作者：Charles W. Jefford、Fabienne de Villedon de Naide、Krzysztof Sienkiewicz

  DOI：10.1016/0957-4166(96)00111-5

  日期：1996.4

  Enantiomerically pure primary amines possessing an epimerizable center, such as alpha-amino acids and their ester hydrochlorides, undergo condensation with tetrahydro-2,5-dimethoxyfuran 2 in acetic acid or acetic acid containing sodium acetate at 80 degrees C for 30 min. to give the corresponding 1-(1H-pyrrolyl) derivatives with partial racemization (9-18%). By replacing the solvent with a stirred mixture of aqueous acetic acid and 1,2-dichloroethane in the case of the acids and with water-1,2-dichloroethane for the ester hydrochlorides, repetition of the previous experiment gives the corresponding pyrroles in high yield and with complete retention of configuration, beta-Aminoalcohols are also efficiently converted to their 1-(1H-pyrrolyl) derivatives in a stirred, warm mixture of aqueous acetic acid and 1,2-dichloroethane. Copyright (C) 1996 Elsevier Science Ltd
• US9181258B2
  申请人：——

  公开号：US9181258B2

  公开（公告）日：2015-11-10