(2S)-5-氧代哌啶-2-羧酸 | 146467-21-2

• 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: (2S)-5-氧代哌啶-2-羧酸
• 英文名称: (S)-5-oxo-2-piperidinecarboxylic acid
• 英文别名: piperidine-5-one-2S-carboxylic acid；5-oxo-L-pipecolic acid；(2S)-5-oxopiperidin-1-ium-2-carboxylate
• CAS: 146467-21-2
• 化学式: C₆H₉NO₃
• 分子量: 143.142
• InChiKey: YXHXRACVAHDTEL-YFKPBYRVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.9
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S)-5-氧代哌啶-2-羧酸 在 吡啶 、 2,6-二甲基吡啶 、 氯磺酸 、 disodium hydrogenphosphate 、 葡萄糖 、 三氟甲磺酸酐 、 palladium 10% on activated carbon 、 甲酸铵 、 potassium carbonate 、 三乙胺 、 柠檬酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 104.17h， 生成 Avibactam; 硫酸单[(1R,2S,5R)-2-(氨基羰基)-7-氧代-1,6-氮杂双环[3.2.1]辛-6-基]酯
  参考文献：
  名称：

  β内酰胺酶抑制剂阿维巴坦的合成方法

  摘要：

  本发明涉及一种β内酰胺酶抑制剂阿维巴坦的合成方法，属于β内酰胺酶抑制剂的制备技术领域。本发明包括以下步骤：(1)以化合物2为原料，与R1NH2反应生成化合物3；(2)在有机溶剂中，化合物3与生物催化剂在葡萄糖或蔗糖的存在下生成化合物4；(3)化合物4和三氟乙酸酐反应生成化合物5；(4)化合物5和R2ONH2反应生成化合物6；(5)化合物6在碱性条件下水解生成化合物7；(6)化合物7和三光气反应生成化合物8；(7)在有机溶剂中，化合物8在催化剂存在下与甲酸铵反应生成化合物9，催化剂为Pd/C体系；(8)化合物9与磺化剂反应生成产物1。本发明工艺稳定，收率高，操作简单安全，生产成本低。

  公开号：

  CN106699756B
• 作为产物：
  描述：

  6-重氮-5-氧代-L-正亮氨酸 在 Ru(CO)(TPPS) 作用下， 以 水 为溶剂， 反应 6.0h， 以73%的产率得到(2S)-5-氧代哌啶-2-羧酸
  参考文献：
  名称：

  Chemical reactivity of 6-diazo-5-oxo-l-norleucine (DON) catalyzed by metalloporphyrins (Fe,Ru)

  摘要：

  The transfer of the metallocarbene derived from N- and O-protected 6-diazo-5-oxo-L-norleucine (DON) catalyzed by metalloporphyrins undergoes dimerization, cyclopropanation. N-H and S-H insertion reactions, respectively. An efficient and direct synthesis of 5-oxo-L-pipecolic acid from DON is described from unprotected 6-diazo-5-oxo-L-norleucine. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2010.04.080

文献信息

• Method of preparing 5R-[(benzyloxy) amino] piperidine-2S-carboxylic acid or a derivative thereof
  申请人：XINFA PHARMACEUTICAL CO., LTD

  公开号：US11142499B1

  公开（公告）日：2021-10-12

  The present application relates to methods of preparing 5R-[(benzyloxy) amino] piperidine-2S-carboxylic acid or its derivatives in an environment-friendly way. The method uses L-glutamic acid as a starting material, which is first subjected to esterification reaction in the presence of an acidic reagent, and then reacted successively with 2-haloacetate and N-protecting agent, or with N-protecting agent and 2-haloacetate under a basic condition to obtain compound IV; then, the obtained compound IV is subjected to intramolecular condensation into a ring under the action of a strong base to obtain N-protecting group piperidine-5-one-2S-carboxylate (V).

  本申请涉及以环保方式制备5R-[(苄氧基)氨基]哌啶-2S-羧酸或其衍生物的方法。该方法以L-谷氨酸为起始原料，首先在酸性试剂存在下进行酯化反应，然后与2-卤代醋酸酯和N-保护试剂连续反应，或在碱性条件下与N-保护试剂和2-卤代醋酸酯反应以获得化合物IV；然后，所得的化合物IV在强碱作用下进行分子内缩合形成环，得到N-保护基哌啶-5-酮-2S-羧酸酯(V)。
• Novel tyloindicines and related processes, pharmaceutical compositions and methods
  申请人：Baker C. David

  公开号：US20050222418A1

  公开（公告）日：2005-10-06

  The invention provides novel tyloindicines analogues and related processes, pharmaceutical compositions, and methods. The novel tyloindicines are useful in a wide variety of antiviral, antineoplastic, antibacterial, and anti-inflammatory applications. Preferred embodiments of the instant invention include the novel tyloindicine designated herein as compound IT-3 (NSC-716802). Compounds of the instant invention have exhibited potent antiviral and anticancer activity in vitro. The invention further provides novel methods of treating neoplastic, bacterial, viral, and anti-inflammatory disorders using tyloindicines including the novel tyloindicine analogues of the instant invention. The invention also provides novel syntheses of tyloindicines including the novel tyloindicines analogues of the instant invention.

  本发明提供了新型的tyloindicines类似物及其相关的过程、药物组合物和方法。这些新型的tyloindicines在广泛的抗病毒、抗肿瘤、抗菌和抗炎症应用中非常有用。本发明的首选实施例包括在此指定为化合物IT-3（NSC-716802）的新型tyloindicine。本发明的化合物在体外展现出强大的抗病毒和抗癌活性。此外，本发明还提供了使用tyloindicines治疗肿瘤、细菌、病毒和抗炎症疾病的新方法，包括本发明的新型tyloindicine类似物。本发明还提供了tyloindicines的新合成方法，包括本发明的新型tyloindicine类似物。
• METHOD FOR PREPARING 5R-BENZYLOXYAMINOPIPERIDIN-2S-CARBOXYLIC ACID OR DERIVATIVE THEREOF
  申请人：Xinfa Pharmaceutical Co., Ltd

  公开号：EP3733648A1

  公开（公告）日：2020-11-04

  The present application relates to methods of preparing 5R-[(benzyloxy) amino] piperidine-2S-carboxylic acid or its derivatives in an environment-friendly way. The method uses L-glutamic acid as a starting material, which is first subjected to esterification reaction in the presence of an acidic reagent, and then reacted successively with 2-haloacetate and N-protecting agent, or with N-protecting agent and 2-haloacetate under a basic condition to obtain compound IV; then, the obtained compound IV is subjected to intramolecular condensation into a ring under the action of a strong base to obtain N-protecting group piperidine-5-one-2S-carboxylate (V). The obtained compound V is used for preparing 5R-[(benzyloxy) amino] piperidine-2S-carboxylic acid (or ester thereof) through one of the routes below: Route 1: compound V is subjected to removal of protecting group, condensation with benzyloxyamine hydrochloride, imine reduction-chiral resolution, neutralization, and hydrolysis; Route 2: compound V is subjected to hydrolysis, removal of protecting group, condensation with benzyloxyamine hydrochloride, imine reduction-chiral resolution, and neutralization; Route 3: compound V is subjected to condensation with benzyloxyamine hydrochloride, imine reduction-chiral resolution, removal of protecting group, neutralization, and hydrolysis. All of the routes above may be implemented by a "one-pot" method.

  本申请涉及以环保方式制备 5R-[（苄氧基）氨基]哌啶-2S-羧酸或其衍生物的方法。该方法以 L-谷氨酸为起始原料，先在酸性试剂存在下进行酯化反应，然后依次与 2-卤乙酸酯和 N-保护剂反应，或在碱性条件下与 N-保护剂和 2-卤乙酸酯反应，得到化合物 IV；然后将得到的化合物 IV 在强碱作用下进行分子内缩合成环，得到 N-保护基团哌啶-5-酮-2S-羧酸（V）。得到的化合物 V 可通过以下途径之一用于制备 5R-[（苄氧基）氨基]哌啶-2S-羧酸（或其酯类）：路线 1：将化合物 V 除去保护基团，与盐酸苄氧基胺缩合，亚胺还原-手性解析，中和，水解； 路线 2：将化合物 V 水解，除去保护基团，与盐酸苄氧基胺缩合，亚胺还原-手性解析，中和； 路线 3：将化合物 V 与盐酸苄氧基胺缩合，亚胺还原-手性解析，除去保护基团，中和，水解。上述所有路线均可通过 "一锅法 "实现。
• SIMPLE PREPARATION METHOD FOR AVIBACTAM
  申请人：Xinfa Pharmaceutical Co., Ltd

  公开号：EP3766869A1

  公开（公告）日：2021-01-20

  The present invention provides a simple process of preparing avibactam. Piperidine-5-one-2S-carboxylate II as the raw material is subjected to condensation reaction with O-protecting hydroxylamine hydrochloride; the resulting compound is subjected to reduction and chiral resolution to obtain 5R-substituted oxyaminopiperidine-2S-carboxylic acid V in a basic condition; then, the compound of formula V is subjected to urea cyclization, acyl chlorination, and amidation with phosgene, solid phosgene, or diphosgene in a "one-pot" process, and then subjected to deprotection, sulfation, and tetrabutylammonium salt formation reaction to obtain (2S,5R)-2-carbamoyl-7-oxo-1,6-diazabicyclo[3.2.1]octan-6-yl]oxy}sulfonyl tetra-n-butyl ammonium salt VII, and finally, the compound of formula VII is subjected to ion exchange to obtain avibactam I. The present invention has a simple preparing scheme, ease of operation, inexpensive starting materials, and a low cost; besides, the present invention discharges less waste water, waste gas, and waste residuals, such that it is environment friendly; the yields of its respective steps are high, which facilitate industrial production of avibactam.

  本发明提供了一种制备阿维菌素的简单工艺。以哌啶-5-酮-2S-羧酸 II 为原料，与 O-保护羟胺盐酸盐进行缩合反应，得到的化合物在碱性条件下进行还原和手性解析，得到 5R 取代氧氨基哌啶-2S-羧酸 V；然后，将式 V 的化合物与光气、固体光气或二光气以 "一锅 "工艺进行脲环化、酰基氯化和酰胺化，然后进行脱保护、硫化和四丁基铵盐形成反应，得到 (2S,5R)-2-氨基甲酰基-7-氧代-1,6-二氮杂双环[3.本发明制备方案简单，操作方便，起始原料价格低廉，成本低；废水、废气、废渣排放少，对环境友好；各步骤收率高，有利于阿维菌素的工业化生产。
• Simple process for preparing avibactam
  申请人：XINFA PHARMACEUTICAL CO., LTD

  公开号：US11208417B2

  公开（公告）日：2021-12-28

  The present invention provides a simple process of preparing avibactam. Piperidine-5-one-2S-carboxylate II as the raw material is subjected to condensation reaction with O-protecting hydroxylamine hydrochloride; the resulting compound is subjected to reduction and chiral resolution to obtain 5R-substituted oxyaminopiperidine-2S-carboxylic acid V in a basic condition; then, the compound of formula V is subjected to urea cyclization, acyl chlorination, and amidation with phosgene, solid phosgene, or diphosgene in a “one-pot” process, and then subjected to deprotection, sulfation, and tetrabutylammonium salt formation reaction to obtain (2S,5R)-2-carbamoyl-7-oxo-1,6-diazabicyclo[3.2.1]octan-6-yl]oxy}sulfonyl tetra-n-butyl ammonium salt VII, and finally, the compound of formula VII is subjected to ion exchange to obtain avibactam I.

  本发明提供了一种制备阿维菌素的简单工艺。以哌啶-5-酮-2S-羧酸 II 为原料，与 O-保护羟胺盐酸盐进行缩合反应，得到的化合物在碱性条件下进行还原和手性解析，得到 5R 取代氧氨基哌啶-2S-羧酸 V；然后，将式 V 的化合物与光气、固体光气或二光气以 "一锅 "工艺进行脲环化、酰基氯化和酰胺化，然后进行脱保护、硫化和四丁基铵盐形成反应，得到 (2S,5R)-2-氨基甲酰基-7-氧代-1,6-二氮杂双环[3.2.1]辛烷-6-基]氧基}磺酰基四正丁基铵盐 VII，最后将式 VII 的化合物进行离子交换，得到阿维菌素 I。