(S)-2-(2-oxo-ethyl)-piperidine-1-carboxylic acid tert-butyl ester | 639458-43-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (S)-2-(2-oxo-ethyl)-piperidine-1-carboxylic acid tert-butyl ester
• 英文别名: 2-(2-oxo-ethyl)-piperidine-1-carboxylic acid tert-butyl ester；(S)-tert-butyl-2-(formylmethyl)piperidine-1-carboxylate；tert-butyl (S)-2-(formylmethyl)piperidine-1-carboxylate；tert-butyl (2S)-2-(2-oxoethyl)piperidine-1-carboxylate；(S)-tert-butyl 2-(2-oxoethyl)piperidine-1-carboxylate
• CAS: 639458-43-8
• 化学式: C₁₂H₂₁NO₃
• 分子量: 227.304
• InChiKey: VPUHJQDNBOTMSI-JTQLQIEISA-N

物化性质

• 沸点：
  318.1±15.0 °C(Predicted)
• 密度：
  1.035±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  (S)-2-(2-oxo-ethyl)-piperidine-1-carboxylic acid tert-butyl ester 在 三氟乙酸 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 为溶剂， 生成 (-)-allosedridine
  参考文献：
  名称：

  Short enantioselective synthesis of sedridines, ethylnorlobelols and coniine via reagent-based differentiation

  摘要：

  The preparation of collections of structurally diverse small molecules is a useful tool for studying biology and medicine with chemistry. Herein, we demonstrate the versatility of the pure enantiomers of 2-(2-oxo-ethyl)-piperidine-1-carboxylic acid tertbutyl ester to prepare the biological active alkaloids sedridine, allosedridine, methylsedridine, methylallosedridine, ethylnorlobelol, and coniine in two steps and in a stereoselective way via a reagent-based differentiation. The described syntheses are a demonstration of the versatility of 2-(2-oxo-ethyl)-piperidine-1-carboxylic acid tert-butyl esters as chiral building blocks. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2005.05.032
• 作为产物：
  描述：

  (S)-2-甲酰基-1-哌啶甲酸叔丁酯 在 盐酸 、 双(三甲基硅烷基)氨基钾 作用下， 以 四氢呋喃 、 水 、 丙酮 为溶剂， 反应 1.67h， 生成 (S)-2-(2-oxo-ethyl)-piperidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  l-脯氨酸衍生的含氮甾体系统：对14-氮杂类固醇的不对称方法†

  摘要：

  已经描述了在温和的反应条件下使用L-脯氨酸来访问14-氮杂类固醇的有效手性池方法。关键步骤涉及分子内的S N 2'环化反应，以在含氮的甾族结构中在Δ9 （11）位置携带不饱和键，以构建关键的C环。为了合成一些新的同类物，还观察到了A环上给电子基团和B环上的氧等杂原子对C环环化倾向的远程电子影响。

  DOI：

  10.1039/c3ra42272k

文献信息

• Enantioselective Approach to Quinolizidines: Total Synthesis of Cermizine D and Formal Syntheses of Senepodine G and Cermizine C
  作者：Nagarathanam Veerasamy、Erik C. Carlson、Nathan D. Collett、Mrinmoy Saha、Rich G. Carter

  DOI：10.1021/jo400324t

  日期：2013.5.17

  The formal syntheses of C5-epi-senepodine G and C5-epi-cermizine C have been accomplished through a novel diastereoselective, intramolecular amide Michael addition process. The total synthesis of cermizine D has been achieved through use of an organocatalyzed, heteroatom Michael addition to access a common intermediate. Additional key steps of this sequence include a matched, diastereoselective alkylation

  C的正式合成5 -外延-senepodine G和C 5 -外延-cermizine C 是通过一种新型的非对映选择性、分子内酰胺迈克尔加成过程完成的。cermizine D 的全合成是通过使用有机催化的杂原子迈克尔加成获得常见中间体来实现的。该序列的其他关键步骤包括使用碘甲基苯硫醚和砜-醛偶联/还原脱硫序列进行匹配的非对映选择性烷基化，以结合主要亚基。已经在功能密集的耦合伙伴上探索了 Hartwig 式 C-N 耦合的效用。已经研究了对 α,β-不饱和砜的非对映选择性共轭加成，这仅通过六步即可从市售起始材料中提供关键的砜中间体。N -Boc 保护的哌啶砜。
• Asymmetric synthesis of (+)-vertine and (+)-lythrine
  作者：Laëtitia Chausset-Boissarie、Roman Àrvai、Graham R. Cumming、Laure Guénée、E. Peter Kündig

  DOI：10.1039/c2ob25880c

  日期：——

  The total syntheses of the Lythracea alkaloids (+)-vertine and (+)-lythrine are described. Enantioenriched pelletierine is used as a chiral building block and engaged into a two step pelletierine condensation leading to two quinolizidin-2-one diastereomers in a 8 : 1 ratio. The major product is used in the synthesis of (+)-vertine via aryl–aryl coupling and ring closing metathesis to provide a Z-alkene α to the lactone carbonyl function. The same procedure was used for (+)-lythrine after base induced epimerization of the main quinolizidin-2-one diastereomer. Alternative classical ring closure strategies like macrolactonisation or aryl–aryl coupling failed.

  描述了(+)-vertine和(+)-lythrine这两种Lythracea生物碱的全合成过程。使用对映富集的pelletierine作为手性构建块，并通过两步pelletierine缩合反应，以8:1的比例生成两种喹啉环己二酮二异构体。主要产物通过芳基-芳基偶联和环闭合复分解反应合成(+)-vertine，提供了与内酯羰基功能团α位的Z-烯烃。对主要喹啉环己二酮二异构体进行碱诱导的异构化后，采用相同步骤合成了(+)-lythrine。传统的环闭合策略，如大环内酯化或芳基-芳基偶联都未能成功。
• [EN] COMPOUNDS AS MODULATORS OF ENDOPLASMIC RETICULUM AMINOPEPTIDASE 1 (ERAP1)<br/>[FR] COMPOSÉS EN TANT QUE MODULATEURS DE L'AMINOPEPTIDASE 1 DU RÉTICULUM ENDOPLASMIQUE (ERAP1)
  申请人：GREY WOLF THERAPEUTICS LTD

  公开号：WO2022064187A1

  公开（公告）日：2022-03-31

  A compound of formula (I-1), or a pharmaceutically acceptable salt or hydrate thereof, formula (I-1) wherein: ring A is a monocyclic 5, 6, or 7-membered heterocycloalkyl ring optionally substituted by one or more substituents selected from alkyl, CN, cycloalkyl, OH, alkoxy, halo, haloalkyl and heteroaryl, wherein said heteroaryl group is in turn optionally further substituted with one or more groups selected from halo and alkyl, and wherein one or two carbons in the 5, 6, or 7-membered heterocycloalkyl ring are optionally replaced by a group selected from O, NH, S and CO; L is a linker group which is a 2 to 7-membered saturated or unsaturated aliphatic group, wherein one or two carbon atoms in said group, other than the carbon atom directly bonded to ring A, are optionally replaced by a heteroatom-containing group selected from O, NH and S, and wherein when two carbon atoms are replaced, the heteroatom-containing groups are separated by at least two carbon atoms and the linker group is at least a 5- membered group;; the group X-Y is -NR23SO2- or -SO2NR23-; R1is H, CN or alkyl; R2is selected from COOH, tetrazolyl and C(O)NHSO2R24; R3is selected from H, halo and alkyl; R4is selected from H and halo; R6is H; R7is selected from H, CN, haloalkyl, halo, SO2-alkyl, SO2NR18R19, CONR20R21, heteroaryl and alkyl, wherein said heteroaryl group is optionally substituted by one or more substituents selected from alkyl, halo, alkoxy, CN, haloalkyl and OH; R8is selected from H, alkyl, haloalkyl and halo; R9is H, alkyl or halo; R18- R21and R23are each independently selected from H and alkyl; R24is selected from alkyl and cyclopropyl. Further aspects of the invention relate to such compounds for use in the field of immuno- oncology and related applications.

  化合物的结构式（I-1），或其药学上可接受的盐或水合物，结构式（I-1）其中：环A是一个单环的5、6或7-成员杂环烷基环，可选择地取代一个或多个取代基，所选取代基包括烷基、CN、环烷基、OH、烷氧基、卤素、卤代烷基和杂芳基，其中所述的杂芳基可进一步选择地取代一个或多个卤素和烷基基团，环中的5、6或7个杂环烷基环中的一个或两个碳原子可选择地被O、NH、S和CO中选择的一个基团所取代；L是一个连接基团，是一个2至7-成员的饱和或不饱和的脂肪族基团，其中除了直接与环A相结合的碳原子外，该基团中的一个或两个碳原子可选择地被O、NH和S中选择的含有杂原子的基团所取代，当两个碳原子被取代时，含有杂原子的基团之间至少被两个碳原子分开，连接基团至少是一个5-成员的基团；X-Y基团是-NR23SO2-或-SO2NR23-；R1是H、CN或烷基；R2选择自COOH、四唑基和C（O）NHSO2R24；R3选择自H、卤素和烷基；R4选择自H和卤素；R6是H；R7选择自H、CN、卤代烷基、卤素、SO2-烷基、SO2NR18R19、CONR20R21、杂芳基和烷基，其中所述的杂芳基可选择地被烷基、卤素、烷氧基、CN、卤代烷基和OH中选择的一个或多个取代基所取代；R8选择自H、烷基、卤代烷基和卤素；R9是H、烷基或卤素；R18-R21和R23各自独立地选择自H和烷基；R24选择自烷基和环丙基。该发明的进一步方面涉及用于免疫肿瘤学领域及相关应用的这类化合物。
• [EN] N-ACYL CYCLIC AMINE DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF<br/>[FR] DÉRIVÉ D'AMINE N-ACYLE CYCLIQUE OU SON SEL PHARMACEUTIQUEMENT ACCEPTABLE
  申请人：DAINIPPON SUMITOMO PHARMA CO

  公开号：WO2011111875A1

  公开（公告）日：2011-09-15

  The present invention provides compounds which show high effectiveness against positive symptoms, negative symptoms and cognitive dysfunction in schizophrenia and reduce conventional side-effect risks as well as have remarkable effects for central neurological diseases associated with cognitive dysfunction other than schizophrenia. N-Acyl cyclic amine derivatives of formula (1): wherein Ar1 and Ar2 are aryl or heteroaryl; V is nitrogen, or CR3; W1 is a single bond, -C(O)-, etc.; W2 is C1- alkylene; W3 is a single bond, methylene, -NH-, -CR4=CR5-, etc.; Ring Q is a group of formula (a) in which n is 0 or 1; m is 0 to 2; k is 1 to 3; Z is a single bond, methylene, oxygen, etc.; R1a, R1b and R1c are each, same or different, hydrogen, hydroxyl, halogen, cyano, C1-6 alkyl, etc.; or pharmaceutically acceptable salts thereof are provided.

  本发明提供了一种化合物，对于精神分裂症的阳性症状、阴性症状和认知功能障碍具有高效性，同时减少了传统的副作用风险，并对与精神分裂症以外的认知功能障碍相关的中枢神经系统疾病具有显著效果。提供了式（1）的N-酰基环胺衍生物，其中Ar1和Ar2是芳基或杂环芳基；V是氮或CR3；W1是单键，-C(O)-等；W2是C1-烷基；W3是单键，亚甲基，-NH-，-CR4=CR5-等；环Q是式（a）的一组，其中n为0或1；m为0到2；k为1到3；Z是单键，亚甲基，氧等；R1a、R1b和R1c分别是相同或不同的氢、羟基、卤素、氰基、C1-6烷基等；或其药用可接受盐。
• Enantioselective Synthesis of (+)-α-Conhydrine and (-)-Sedamine by L-Proline-Catalysed α-Aminooxylation
  作者：Tanveer Mahamadali Shaikh、Arumugam Sudalai

  DOI：10.1002/ejoc.201000169

  日期：——

  An efficient organocatalytic approach to the enantioslective synthesis of two important piperidine alkaloids, namely (+)-α-conhydrine (98 % ee) and (-)-sedamine (95 % ee), by L -proline-catalysed α-aminooxylation of aldehydes has been developed. The strategy involves an intramolecular cyclization to construct the piperidine core.

  一种有效的有机催化方法，通过 L-脯氨酸催化的醛的 α-氨基氧基化，对映选择性合成两种重要的哌啶生物碱，即 (+)-α-conhydrine (98% ee) 和 (-)-sedamine (95% ee)已经被开发出来。该策略涉及分子内环化以构建哌啶核心。