2-(1H-吡咯-1-基)丙二酸二乙酯 | 67451-43-8

• 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: 2-(1H-吡咯-1-基)丙二酸二乙酯
• 英文名称: 2-(pyrrol-1-yl)malonic acid diethyl ester
• 英文别名: (1-Pyrryl)malonic acid,diethylester；pyrrol-1-yl-malonic acid diethyl ester；(1-Pyrryl)malonic acid, diethylester；diethyl 2-(1H-pyrrol-1-yl)malonate；diethyl 2-pyrrol-1-ylpropanedioate
• CAS: 67451-43-8
• 化学式: C₁₁H₁₅NO₄
• mdl: MFCD00052825
• 分子量: 225.244
• InChiKey: DUAOPKFJIPCUNK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.454
• 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：

  2-(1H-吡咯-1-基)丙二酸二乙酯 在 sodium hydride 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 35.5h， 生成 2-[4-Ethoxycarbonyl-1,3-dioxo-2-(2-phenylethyl)pyrrolo[1,2-a]pyrazin-4-yl]acetic acid
  参考文献：
  名称：

  Novel, Highly Potent Aldose Reductase Inhibitors:  (R)-(−)-2-(4-Bromo-2-fluorobenzyl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine- 4-spiro-3‘-pyrrolidine-1,2‘,3,5‘-tetrone (AS-3201) and Its Congeners

  摘要：

  A series of novel tetrahydropyrrolo[1,2-a]pyrazine derivatives were synthesized and evaluated as aldose reductase inhibitors (ARIs) on the basis of their abilities to inhibit porcine lens aldose reductase (AR) in vitro and to inhibit sorbitol accumulation in the sciatic nerve of streptozotocin-induced diabetic rats in vivo. Of these compounds, spirosuccinimide-fused tetrahydropyrrolo[1,2-a]pyrazine-1,3-dione derivatives showed significantly potent AR inhibitory activity. In the in vivo activity of these derivatives, 2-(4-bromo-2-fluorobenzyl)-1,2,3,4-tetrahydropyrrolo- [1,2-a][1,2a]pyrazine-4-spiro-3'-pyrrolidine-1,2',3,5'-tetrone (23t) (SX-3030) showed the best oral activity. The enantiomers of 23t were synthesized, and the biological activities were evaluated. It was found that AR inhibitory activity resides in the (-)-enantiomer 43 (AS-3201), which was 10 times more potent in inhibition of the AR (IC50 = 1.5 x 10(-8) M) and 500 times more potent in the in vivo activity (ED50 = 0.18 mg/kg/day for 5 days) than the corresponding (+)enantiomer 44 (SX-3202): From these results, AS-3201 was selected as the candidate for clinical development. The absolute configuration of AS-3201 was also established to be (R)-form by single-crystal X-ray analysis. In this article we report the preparation and structure-activity relationship (SAR) of tetrahydropyrrolopyrazine derivatives including a novel ARI, AS-3201.

  DOI：

  10.1021/jm9802968
• 作为产物：
  描述：

  2,5-二甲氧基四氢呋喃 、 氨基丙二酸二乙酯盐酸盐 在 sodium acetate 作用下， 以 溶剂黄146 为溶剂， 以77%的产率得到2-(1H-吡咯-1-基)丙二酸二乙酯
  参考文献：
  名称：

  有效利用不需要的异构体的非原位对映体聚合方法：具有多个手性中心的底物的立体化学聚合和脱羧副产物的再循环

  摘要：

  摘要 外消旋原料的酶介导动力学拆分是制备对映体富集化合物的一种有价值且方便的工具。为了克服常规动力学拆分中50％的收率限制，已经开发了多种对映体收敛方法。在简要介绍了最近开发的“原位脱氨法”和“非原位对映体收敛方法”之后，我们提出了独特的非原位对映体收敛方法来解决两个困难的情况：1）乙基（3 R，4 S，5 R）shimate，非对映异构体（3 R *，4 S *，5 S*）包含多个手性中心的底物应用于酶催化的乙酰化反应中，并且酶催化的产物和未反应的底物均通过部分立体化学转化转化为（3 R，4 S，5 R）-shi草酸乙酯。2）详细描述了雷尼司他前体的酶催化的动力学拆分和脱羧副产物的外消旋底物的再生。由于在后者的研究中，酯基水解后产物自发脱羧，因此外消旋底物的原位再生非常困难。我们成功地安装乙氧羰基由副产品易地 顺序衍生化以克服50％的产量限制。 1对映收敛方法的简短回顾 2具有多个手性中心的基质的拆分

  DOI：

  10.1055/s-0035-1561620

文献信息

• Pyrrole cephalosporin derivatives
  申请人：Yeda Research and Development Co., Ltd.

  公开号：US04148998A1

  公开（公告）日：1979-04-10

  New pyrrole derivatives of cephalosporin compounds have been prepared which are useful as antibiotics.

  头孢菌素化合物的新吡咯烷衍生物已经制备出来，可用作抗生素。
• Tetrahydropyrrolo[1,2-a]pyrazine-4-spiro-3'-pyrrolidine derivatives,
  申请人：Dainippon Pharmaceutical Co., Ltd.

  公开号：US05258382A1

  公开（公告）日：1993-11-02

  Tetrahydropyrrolo[1,2-a]pyrazine-4-spiro-3'-pyrrolidine derivatives of the formula: ##STR1## wherein R.sup.1 and R.sup.2 are independently hydrogen, halogen, trifluoromethyl, alkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms, or nitro, and R.sup.3 is hydrogen, halogen or alkyl having 1 to 6 carbon atoms, and pharmaceutically acceptable salts thereof, processes for preparation thereof, and pharmaceutical composition containing the same. Said compounds and their salts show excellent aldose reductase inhibitory activity and are useful for the prevention and treatment of diabetic complications.

  Tetrahydropyrrolo[1,2-a]pyrazine-4-spiro-3'-pyrrolidine衍生物的化学式为：##STR1##其中R.sup.1和R.sup.2独立地为氢、卤素、三氟甲基、具有1至6个碳原子的烷基、具有1至6个碳原子的烷氧基或硝基，R.sup.3为氢、卤素或具有1至6个碳原子的烷基，以及其药学上可接受的盐，制备方法和含有这些化合物的药物组合物。这些化合物及其盐显示出优秀的醛糖还原酶抑制活性，可用于预防和治疗糖尿病并发症。
• Diastereodivergent synthesis of bispirooxindoles <i>via</i> asymmetric Friedel–Crafts/aldol cascade reaction: co-catalyst effects on diastereoselective outcomes
  作者：Nai-Kai Li、Wei-Tai Fan、Jun-Qi Zhang、Bing-Bing Sun、Jun-Bo Chen、Xing-Wang Wang

  DOI：10.1039/c7cc09489b

  日期：——

  A combination of metal- and organo-catalysts sequentially catalyzing the Friedel–Crafts/aldol tandem reaction between 3-pyrrolyl-oxindoles and isatin-derived β,γ-unsaturated α-ketoesters has been reported, which leads to two types of diastereomeric enantio-enriched bispirooxindoles with three quaternary stereocentres and synthetically valuable functional groups in high yields with excellent enantioselectivity

  据报道，金属和有机催化剂相继催化3-吡咯基-氧吲哚与伊斯丁衍生的β，γ-不饱和α-酮酸酯之间的Friedel-Crafts /羟醛串联反应，导致两种类型的非对映体对映体。具有三个季铵立体中心和合成有价值的官能团的高产量的双螺毒素类化合物，具有出色的对映选择性和非对映选择性。
• Succinic acid diester derivative, process for production thereof, and use of the derivative in the production of pharmaceutical preparation
  申请人：Inagaki Takashi

  公开号：US20100076203A1

  公开（公告）日：2010-03-25

  The present invention provides with a process of preparing an optically active succinimide derivative, which is a key intermediate for production of ranirestat. A compound (3) is easily prepared by treating the derivative of succinic acid diester of the formula (2): wherein R 1 is an amino group protected with a group removed by hydrogenolysis or a tert-butoxycarbonylamino group and R 2 is an ethyl group optionally substituted with one or two methyl group(s) at α-position, provided that R 2 is not a tert-butyl group when R 1 is a tert-butoxycarbonylamino group; with alkali metal alkoxide and the compound (3) can be an important intermediate for production of ranirestat.

  本发明提供了一种制备光学活性琥珀酰亚胺衍生物的方法，该衍生物是生产拉尼瑞斯塔的关键中间体。通过处理公式（2）的琥珀酸二酯衍生物，可以轻松制备化合物（3）：其中R1是通过氢解去除的保护氨基或叔丁氧羰基氨基，R2是在α位上可选地取代一个或两个甲基的乙基基团，但当R1是叔丁氧羰基氨基时，R2不能是叔丁基基团。使用碱金属醇盐处理化合物（3），可以得到生产拉尼瑞斯塔的重要中间体。
• SUCCINIC ACID DIESTER DERIVATIVE, PROCESS FOR PRODUCTION THEREOF, AND USE OF THE DERIVATIVE IN THE PRODUCTION OF PHARMACEUTICAL PREPARATION
  申请人：INAGAKI Takashi

  公开号：US20110046373A1

  公开（公告）日：2011-02-24

  The present invention provides with a process of preparing an optically active succinimide derivative, which is a key intermediate for production of ranirestat. A compound (3) is easily prepared by treating the derivative of succinic acid diester of the formula (2): wherein R 1 is an amino group protected with a group removed by hydrogenolysis or a tert-butoxycarbonylamino group and R 2 is an ethyl group optionally substituted with one or two methyl group(s) at α-position, provided that R 2 is not a tert-butyl group when R 1 is a tert-butoxycarbonylamino group; with alkali metal alkoxide and the compound (3) can be an important intermediate for production of ranirestat.

  本发明提供了一种制备光学活性琥珀酰亚胺衍生物的方法，该衍生物是生产拉尼瑞斯塔的关键中间体。化合物（3）可以通过处理以下式子的琥珀酸二酯衍生物而轻松制备出来：其中R1是通过氢解去除的保护氨基或叔丁氧羰基氨基，R2是乙基基团，在α-位置上可以选择性地取代一个或两个甲基基团，但当R1是叔丁氧羰基氨基时，R2不能是叔丁基基团；用碱金属醇盐处理。化合物（3）可以是生产拉尼瑞斯塔的重要中间体。