1-tert-butyl 2-methyl 2-(3-hydroxypropyl)pyrrolidine-1,2-dicarboxylate | 201209-02-1

• 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: 1-tert-butyl 2-methyl 2-(3-hydroxypropyl)pyrrolidine-1,2-dicarboxylate
• 英文别名: 2-(3-hydroxypropyl)pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester；1-(Tert-butyl) 2-methyl 2-(3-hydroxypropyl)pyrrolidine-1,2-dicarboxylate；1-O-tert-butyl 2-O-methyl 2-(3-hydroxypropyl)pyrrolidine-1,2-dicarboxylate
• CAS: 201209-02-1
• 化学式: C₁₄H₂₅NO₅
• 分子量: 287.356
• InChiKey: QTBBFQJUNQVAGJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-tert-butyl 2-methyl 2-(3-hydroxypropyl)pyrrolidine-1,2-dicarboxylate 在 草酰氯 、 碳酸氢铵 、 二甲基亚砜 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 生成 1-tert-butyl 2-methyl 2-(2'-(2'',5''-dioxoimidazolidin-4''-yl)ethyl)pyrrolidine-1,2-dicarboxylate
  参考文献：
  名称：

  Synthesis and evaluation of C8-substituted 4.5-spiro lactams as Glycogen Phosphorylase a inhibitors

  摘要：

  An effective synthesis of 4.5-spiro lactams 28/29, has been completed in nine steps with an overall yield of 5.8%. The 4.5-spiro lactams were made from 2-allyl-Cbz-Pro-OMe 21, which was converted into the corresponding alcohol 22 via a hindered borane reaction with (2-methylbutyl)(2)borane. Subsequent Swern oxidation of 22 gave novel aldehyde 23. Aldehyde 23 was treated under Bucherer-Bergs reaction conditions to give hydantoin 26, which was opened to the corresponding amino acid 30 using di-tert-butyl dicarbonate and DMAP followed by hydrolysis. Treatment of amino acid 30 with acidic methanol gave 4.5-spiro lactams 28/29. Only 4.5-spiro lactam 29 displayed moderate activity against GPa with an IC50 of 241 mu M. (c) 2012 Published by Elsevier Ltd.

  DOI：

  10.1016/j.tet.2012.12.004
• 作为产物：
  描述：

  L-脯氨酸甲酯盐酸盐 在 硼烷四氢呋喃络合物 、 双氧水 、 2-甲基-丁烯 、 三乙胺 、 sodium hydroxide 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 1.5h， 生成 1-tert-butyl 2-methyl 2-(3-hydroxypropyl)pyrrolidine-1,2-dicarboxylate
  参考文献：
  名称：

  Synthesis and evaluation of C8-substituted 4.5-spiro lactams as Glycogen Phosphorylase a inhibitors

  摘要：

  An effective synthesis of 4.5-spiro lactams 28/29, has been completed in nine steps with an overall yield of 5.8%. The 4.5-spiro lactams were made from 2-allyl-Cbz-Pro-OMe 21, which was converted into the corresponding alcohol 22 via a hindered borane reaction with (2-methylbutyl)(2)borane. Subsequent Swern oxidation of 22 gave novel aldehyde 23. Aldehyde 23 was treated under Bucherer-Bergs reaction conditions to give hydantoin 26, which was opened to the corresponding amino acid 30 using di-tert-butyl dicarbonate and DMAP followed by hydrolysis. Treatment of amino acid 30 with acidic methanol gave 4.5-spiro lactams 28/29. Only 4.5-spiro lactam 29 displayed moderate activity against GPa with an IC50 of 241 mu M. (c) 2012 Published by Elsevier Ltd.

  DOI：

  10.1016/j.tet.2012.12.004

文献信息

• NITROGEN-CONTAINING SPIROCYCLIC COMPOUNDS AND PHARMACEUTICAL USES THEREOF
  申请人：Noji Satoru

  公开号：US20110136778A1

  公开（公告）日：2011-06-09

  A compound of the following general formula [I]: wherein each symbol has the same meaning as defined herein, or a pharmaceutically acceptable salt thereof, or a solvate thereof, and a pharmaceutical use of the same in treating organ transplant rejection, graft versus host reaction after transplantation, autoimmune disease, allergic disease and chronic myeloproliferative disease.

  以下通用公式[I]的化合物：其中每个符号具有本文中定义的相同含义，或其药用可接受盐，或其溶剂化合物，并且其在治疗器官移植排斥、移植后移植物抗宿主反应、自身免疫疾病、过敏疾病和慢性骨髓增生性疾病中的药用。
• Spirobicyclic diamines 1: synthesis of proline-derived spirolactams via thermal intramolecular ester aminolysis
  作者：Fintan Kelleher、Sinead Kelly

  DOI：10.1016/j.tetlet.2006.03.021

  日期：2006.5

  Proline-derived [4.4]-spirolactams have been synthesised in good yields by a reductive-amination reaction followed by thermal cyclisation of the resulting amine onto the proline ester group in refluxing toluene. The synthesis of the corresponding [4.5]-spirolactams by the same method gave much reduced yields.

  脯氨酸衍生的[4.4]-螺内酰胺通过还原胺化反应，然后在回流的甲苯中将所得胺热环化到脯氨酸酯基上，以高收率合成。用相同的方法合成相应的[4.5]-螺内酰胺，产率大大降低。
• Regioselective synthesis of bridged azabicyclic compounds using radical translocations/cyclisations of methyl 2-alkynyl-1-(o-iodobenzoyl)pyrrolidine-2-carboxylates: a formal total synthesis of (±)-epibatidine
  作者：Masazumi Ikeda、Yasuhiro Kugo、Yukari Kondo、Taro Yamazaki、Tatsunori Sato

  DOI：10.1039/a705226j

  日期：——

  toluene gave, regioselectively, the 7-azabicyclo[2.2.1]heptane 19, 8-azabicyclo[3.2.1]octane 23, and 9-azabicyclo[4.2.1]nonane 26, respectively. The method has been applied to a formal total synthesis of (±)-epibatidine.

  已经研究了Bu 3 SnH介导的2-炔基-1-（邻碘苯甲酰基）吡咯烷-2-羧酸甲酯的自由基易位/环化。2- [3-（三甲基甲硅烷基）丙-2-炔基] -8,2- [4-（三甲基甲硅烷基）丁-3-炔基] -14和2- [5-（三甲基甲硅烷基）戊-4-炔基] -吡咯烷衍生物18，在沸腾的甲苯中在偶氮异丁腈存在下用氢化三丁基锡处理后，区域选择性地得到7-氮杂双环[2.2.1]庚烷19、8-氮杂双环[3.2.1]辛烷23和9-氮杂双环[ 4.2.1]壬烷26。该方法已应用于（±）-表哌丁啶的正式全合成。
• Nitrogen-containing spirocyclic compounds and pharmaceutical uses thereof
  申请人：Noji Satoru

  公开号：US08609647B2

  公开（公告）日：2013-12-17

  A compound of the following general formula [I]: wherein each symbol has the same meaning as defined herein, or a pharmaceutically acceptable salt thereof, or a solvate thereof, and a pharmaceutical use of the same in treating organ transplant rejection, graft versus host reaction after transplantation, autoimmune disease, allergic disease and chronic myeloproliferative disease.

  以下是通式[I]的化合物，其中每个符号的含义如下定义，或其药学上可接受的盐，或其溶剂化物，以及其在治疗器官移植排斥、移植后移植物抗宿主反应、自身免疫性疾病、过敏性疾病和慢性增生性疾病中的药物用途。
• NITROGEN-CONTAINING SPIRO-RING COMPOUND AND MEDICINAL USE OF SAME
  申请人：Japan Tobacco, Inc.

  公开号：EP2460806A1

  公开（公告）日：2012-06-06

  A compound of the following general formula [I]: wherein each symbol has the same meaning as defined herein, or a pharmaceutically acceptable salt thereof, or a solvate thereof, and a pharmaceutical use of the same in treating organ transplant rejection, graft versus host reaction after transplantation, autoimmune disease, allergic disease and chronic myeloproliferative disease.

  以下通式[I]的化合物： 其中各符号的含义与本文所定义的相同，或其药学上可接受的盐，或其溶液，以及其在治疗器官移植排斥反应、移植后移植物与宿主反应、自身免疫性疾病、过敏性疾病和慢性骨髓增生性疾病中的药物用途。