3-(1-(ethoxycarbonylmethyl)-2-oxo-3-pyrrolin-4-yl)-1-(ethoxycarbonylmethyl)-4-hydroxy-2-oxo-3-pyrroline | 105240-65-1

• 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: 3-(1-(ethoxycarbonylmethyl)-2-oxo-3-pyrrolin-4-yl)-1-(ethoxycarbonylmethyl)-4-hydroxy-2-oxo-3-pyrroline
• 英文别名: 1,1',5,5'-tetrahydro-4-hydroxy-2,2'-dioxo-[3,4'-bi-2H-pyrrole]-1,1'-diacetic acid diethyl ester；ethyl 2-[3-[1-(2-ethoxy-2-oxo-ethyl)-3-hydroxy-5-oxo-2H-pyrrol-4-yl]-5-oxo-2H-pyrrol-1-yl]acetate；ethyl 2-[3-[1-(2-ethoxy-2-oxoethyl)-3-hydroxy-5-oxo-2H-pyrrol-4-yl]-5-oxo-2H-pyrrol-1-yl]acetate
• CAS: 105240-65-1
• 化学式: C₁₆H₂₀N₂O₇
• 分子量: 352.344
• InChiKey: AOLFTJBMUXRGGK-UHFFFAOYSA-N

物化性质

• 沸点：
  571.8±50.0 °C(Predicted)
• 密度：
  1.398±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  113
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-(1-(ethoxycarbonylmethyl)-2-oxo-3-pyrrolin-4-yl)-1-(ethoxycarbonylmethyl)-4-hydroxy-2-oxo-3-pyrroline 在 氨 作用下， 以 甲醇 为溶剂， 反应 4.0h， 以80%的产率得到3-(1-(carbamoylmethyl)-2-oxo-3-pyrrolin-4-yl)-4-hydroxy-2-oxo-3-pyrroline-1-acetamide
  参考文献：
  名称：

  Potential Nootropic Agents: Synthesis of Some 1,4-Disubstituted 2-Oxopyrrolidines and Some Related Compounds

  摘要：

  4-(氨甲基)-1-苄基-2-氧代吡咯烷（VI）经过与（4-苄基哌嗪-1-基）羰基氯化物IIIb - IIId和（4-甲基哌嗪-1-基）羰基氯化物（IIIa）处理后转化为羧酰胺IVa - IVd。在乙腈中加水加热1-(乙氧羰基甲基)-2,4-二氧代吡咯烷（XIX）得到XVIIIa。与氨处理得到二酰胺XVIIIc，碱性水解XVIIIa得到二羧酸XVIIIb。4-(氨甲基)-1-(4-甲硫基苄基)-2-氧代吡咯烷（XII）通过4-(甲硫基)苄胺与顺丁二酸反应以及从得到的羧酸VII开始的一系列反应制备，包括酯化、还原和用氯化亚砜处理得到的醇IX，合成邻苯二甲酰亚胺衍生物XI和水解。胺XII加入4-氯苯基异氰酸酯形成XIII。制备的化合物进行了智力活性测试。

  DOI：

  10.1135/cccc19941126
• 作为产物：
  描述：

  (2,5-二氢-4-甲氧基-2-氧代-1H-吡咯-1-基)乙酸乙酯 在 Ru-carbon 盐酸 、 水 、 氢气 作用下， 以 溶剂黄146 为溶剂， 40.0 ℃ 、2.5 MPa 条件下， 反应 39.0h， 生成 3-(1-(ethoxycarbonylmethyl)-2-oxo-3-pyrrolin-4-yl)-1-(ethoxycarbonylmethyl)-4-hydroxy-2-oxo-3-pyrroline
  参考文献：
  名称：

  用四酸中间体高效合成外消旋4-羟基-2-氧-1-吡咯烷乙酰胺（奥西西坦）

  摘要：

  由（E）-4-氯-3-乙氧基丁-2-烯酸乙酯以消旋形式合成标题化合物1a，分五个步骤，总收率为43％。描述了最终产品的几种途径，但是最有效的途径涉及C（5）-未取代的四甲酸5b的氢化。这类化合物的不稳定性要求使用可以在非常酸性的水性条件下运行的催化剂，这种作用已被5％Ru / C催化剂成功填补。

  DOI：

  10.1002/hlca.19920750323

文献信息

• Bi-2H-pyrroli(di)nediones
  申请人：Ciba-Geigy Corporation

  公开号：US04758575A1

  公开（公告）日：1988-07-19

  Novel substituted tetrahydro-, hexahydro- and octahydro-[3,4'-bi-2H-pyrrole]-2,2'-diones of the formula ##STR1## in which each of R.sub.1 and R.sub.2 represents a carboxy-lower alkyl radical, or an unsubstituted carbamoyl-lower alkyl radical or a carbamoyl-lower alkyl radical which is N-mono- or N,N-di-substituted by lower alkyl, hydroxylower alkyl, lower alkoxy-lower alkyl, amino-lower alkyl, N-mono- or N,N-di-lower alkylamino-lower alkyl, or by N,N-alkyleneamino-lower alkyl optionally substituted (in the alkyleneamino radical) by lower alkoxycarbonyl and by oxo or hydroxy, or N,N-alkenyleneamino-lower alkyl optionally substituted (in the alkenyleneamino radical) by lower alkoxycarbonyl and optionally additionally by hydroxy, or N,N-(aza-, N'-lower alkylaza- or N'-lower alkanoylaza-, oxa- or thia)alkyleneamino-lower alkyl, each of which has from 4 to 8 ring members, carbamoyl-lower alkyl, N-mono- or N,N-di-lower alkylcarbamoyl-lower alkyl, 3- to 8-membered cycloalkyl, dicycloalkyl or tricycloalkyl, or by phenyl-lower alkyl which is unsubstituted or substituted in the phenyl moiety by lower alkyl, lower alkoxy, halogen and/or trifluoromethyl, or represents a carbamoyl-lower alkyl radical which is disubstituted by alkylene optionally substituted by lower alkoxycarbonyl and by oxo or hydroxy, or by alkenylene optionally substituted by lower alkoxycarbonyl and optionally additionally by hydroxy, or by aza-, N40 -lower alkylaza-or N'-lower alkanoylaza-, oxa- or thia-alkylene, each of which has from 3 to 7 chain members, each of R.sub.3, R.sub.4, R.sub.5 and R.sub.6 represents hydrogen or lower alkyl, or R.sub.3 and R.sub.4 together and/or R.sub.5 and R.sub.6 together represent a 4- to 8-membered alkylene radical, and each of R.sub.7, R.sub.8, R.sub.9 and R.sub.10 represents hydrogen, or R.sub.7 together with R.sub.8 and/or R.sub.9 together with R.sub.10 represent in each case an additional bond, and their salts, have nootropic activity and can be used as active ingredients in medicaments. They are manufactured, for example, as follows: in a compound of the formula ##STR2## in which R'.sub.1 represents a group that can be converted into a radical R.sub.1 and R'.sub.2 represents a radical R.sub.2 or a group that can be converted into the radical R.sub.2, or in a salt thereof, R'.sub.1 is converted into a group R.sub.1 and, optionally, a radical R'.sub.2 that can be converted into R.sub.2 is converted into a group R.sub.2.

  新型替代的四氢、六氢和八氢-[3,4'-双-2H-吡咯]-2,2'-二酮化合物的化学式如下：其中R.sub.1和R.sub.2分别表示一个羧基-较低烷基基团，或一个未取代的羰基-较低烷基基团或一个羰基-较低烷基基团，该基团通过较低烷基、羟基较低烷基、较低烷氧基-较低烷基、氨基-较低烷基、N-单取代或N,N-双取代的较低烷基氨基-较低烷基，或者通过N,N-烷基氨基-较低烷基（在烷基氨基基团中可选地取代）通过较低烷氧羰基和氧代或羟基，或者通过N,N-烯烃基氨基-较低烷基（在烯烃基氨基基团中可选地取代）通过较低烷氧羰基和可选地另外通过羟基，或者通过N,N-(氮杂、N'-较低烷基氮杂或N'-较低烷酰氮杂、氧代或硫代)烷基氨基-较低烷基，其中每个基团有4至8个环成员，羰基-较低烷基，N-单取代或N,N-双取代的较低烷基羰基-较低烷基，3至8个环状烷基，二环烷基或三环烷基，或者通过未取代或通过较低烷基、较低烷氧基、卤素和/或三氟甲基取代的苯基-较低烷基，或者表示一个通过烷基可选地取代的双取代羰基-较低烷基基团，通过较低烷氧羰基和氧代或羟基取代，或者通过烯烃可选地取代的烯基-较低烷基基团，可选地另外通过较低烷氧羰基和可选地通过羟基，或者通过氮杂、N40-较低烷基氮杂或N'-较低烷酰氮杂、氧代或硫代)烷基，其中每个基团有3至7个链成员，R.sub.3、R.sub.4、R.sub.5和R.sub.6分别表示氢或较低烷基，或者R.sub.3和R.sub.4一起和/或R.sub.5和R.sub.6一起表示一个有4至8个环成员的烷基基团，R.sub.7、R.sub.8、R.sub.9和R.sub.10分别表示氢，或者R.sub.7和R.sub.8一起和/或R.sub.9和R.sub.10一起分别代表一个额外的键，它们的盐具有智力促进活性，并可用作药物的活性成分。例如，它们的制备方法如下：在化合物的化学式中：其中R'.sub.1表示可转化为基团R.sub.1的基团，R'.sub.2表示基团R.sub.2或可转化为基团R.sub.2的基团，或者在其盐中，将R'.sub.1转化为基团R.sub.1，可选地，可转化为R.sub.2的基团R'.sub.2转化为基团R.sub.2。
• US4758575A
  申请人：——

  公开号：US4758575A

  公开（公告）日：1988-07-19
• US4789674A
  申请人：——

  公开号：US4789674A

  公开（公告）日：1988-12-06
• Potential Nootropic Agents: Synthesis of Some 1,4-Disubstituted 2-Oxopyrrolidines and Some Related Compounds
  作者：Vladimír Valenta、Jiří Urban、Jan Taimr、Zdeněk Polívka

  DOI：10.1135/cccc19941126

  日期：——

  4-(Aminomethyl)-1-benzyl-2-oxopyrrolidine (VI) was transformed by treatment with (4-benzhydrylpiperazin-1-yl)carbonyl chlorides IIIb - IIId and with (4-methylpiperazin-1-yl)carbonyl chloride (IIIa) to the carboxamides IVa - IVd. Heating of 1-(ethoxycarbonylmethyl)-2,4-dioxopyrrolidine (XIX) in acetonitrile in the presence of water afforded XVIIIa. Treatment with ammonia led to the diamide XVIIIc, while alkaline hydrolysis of XVIIIa gave the dicarboxylic acid XVIIIb. 4-(Aminomethyl)-1-(4-methylthiobenzyl)-2-oxopyrrolidine (XII) was prepared by the reaction of 4-(methylthio)benzylamine with itaconic acid and the following sequence of reactions starting from the obtained carboxylic acid VII including esterification, reduction and treatment the obtained alcohol IX with thionyl chloride, synthesis of phthalimido derivative XI and hydrazinolysis. Amine XII added to 4-chlorophenyl isocyanate formed XIII. The compounds prepared were tested for nootropic activity.

  4-(氨甲基)-1-苄基-2-氧代吡咯烷（VI）经过与（4-苄基哌嗪-1-基）羰基氯化物IIIb - IIId和（4-甲基哌嗪-1-基）羰基氯化物（IIIa）处理后转化为羧酰胺IVa - IVd。在乙腈中加水加热1-(乙氧羰基甲基)-2,4-二氧代吡咯烷（XIX）得到XVIIIa。与氨处理得到二酰胺XVIIIc，碱性水解XVIIIa得到二羧酸XVIIIb。4-(氨甲基)-1-(4-甲硫基苄基)-2-氧代吡咯烷（XII）通过4-(甲硫基)苄胺与顺丁二酸反应以及从得到的羧酸VII开始的一系列反应制备，包括酯化、还原和用氯化亚砜处理得到的醇IX，合成邻苯二甲酰亚胺衍生物XI和水解。胺XII加入4-氯苯基异氰酸酯形成XIII。制备的化合物进行了智力活性测试。
• An Efficient Synthesis of Racemic 4-Hydroxy-2-oxo-1-pyrrolidineacetamide (Oxiracetam) Using Tetramic-Acid Intermediates
  作者：David D. P. Laffan、Markus Bänziger、Lauren Duc、Andrew R. Evans、John F. McGarrity、Thomas Meul

  DOI：10.1002/hlca.19920750323

  日期：1992.5.6

  The title compund, 1a, has been synthesised in racemic form from ethyl (E)-4-chloro-3-ethoxybut-2-enoate in 43% overall yield in five steps. Several routes to the final product are described, but the most efficient involves hydrogenation of a C(5)-unsubstituted tetramic acid 5b. The instability of this class of compounds required the use of a catalyst which could operate under very acidic aqueous conditions

  由（E）-4-氯-3-乙氧基丁-2-烯酸乙酯以消旋形式合成标题化合物1a，分五个步骤，总收率为43％。描述了最终产品的几种途径，但是最有效的途径涉及C（5）-未取代的四甲酸5b的氢化。这类化合物的不稳定性要求使用可以在非常酸性的水性条件下运行的催化剂，这种作用已被5％Ru / C催化剂成功填补。