4-(氨基甲基)-4-羟基哌啶-1-甲酸叔丁酯 | 392331-66-7

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 4-(氨基甲基)-4-羟基哌啶-1-甲酸叔丁酯
• 中文别名: 4-氨基甲基-4-羟基-1-哌啶羧酸-1,1-二甲基乙酯；1-Boc-4-(氨甲基)-4-羟基哌啶
• 英文名称: tert-butyl 4-(aminomethyl)-4-hydroxypiperidine-1-carboxylate
• 英文别名: t-butyl 4-(aminomethyl)-4-hydroxypiperidine-1-carboxylate；4-(aminomethyl)-4-hydroxypiperidine-1-carboxylic acid tert-butyl ester
• CAS: 392331-66-7
• 化学式: C₁₁H₂₂N₂O₃
• 分子量: 230.307
• InChiKey: XYWCDAFPRBDRER-UHFFFAOYSA-N

物化性质

• 沸点：
  341.0±27.0 °C(Predicted)
• 密度：
  1.124

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  75.8
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933399090
• 危险性防范说明：
  P261,P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H332,H335
• 储存条件：
  存储条件：2-8°C，避光，并保存在惰性气体中。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
tert-Butyl 4-(aminomethyl)-4-hydroxypiperidine-1-carboxylate
Product Name:
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H315: Causes skin irritation
H319: Causes serious eye irritation
H335: May cause respiratory irritation
P261: Avoid breathing dust/fume/gas/mist/vapours/spray
Wear protective gloves/protective clothing/eye protection/face protection
P280:
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing
P304+P340: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing
P405: Store locked up

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Section 3. Composition/information on ingredients.
tert-Butyl 4-(aminomethyl)-4-hydroxypiperidine-1-carboxylate
Ingredient name:
CAS number: 392331-66-7

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Section 4. First aid measures
Immediately wash skin with copious amounts of water for at least 15 minutes while removing
Skin contact:
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.
Ingestion:

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Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

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Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

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Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Storage: Store in closed vessels, refrigerated.

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Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

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Section 9. Physical and chemical properties
Not specified
Appearance:
Boiling point: No data
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C11H22N2O3
Molecular weight: 230.3

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Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide, nitrogen oxides.

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Section 11. Toxicological information
No data.

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Section 12. Ecological information
No data.

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Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

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Section 14. Transportation information
Non-harzardous for air and ground transportation.

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Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

该化合物4-(氨基甲基)-4-羟基哌啶-1-甲酸叔丁酯主要用于有机合成和作为医药中间体。

反应信息

• 作为反应物：
  描述：

  4-(氨基甲基)-4-羟基哌啶-1-甲酸叔丁酯 在 dimethyl sulfide borane 、 potassium tert-butylate 、 potassium carbonate 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 、 异丙醇 为溶剂， 反应 64.0h， 生成 1-氧杂-4,9-二氮杂螺[5.5]十一烷-9-甲酸叔丁酯
  参考文献：
  名称：

  HETEROCYCLIC SPIRO COMPOUNDS AS MAGL INHIBITORS

  摘要：

  本发明部分提供具有下式I的杂环螺化合物： 以及它们的药用盐；其制备过程；用于其制备的中间体；以及包含这些化合物或盐的药物组合物，以及它们用于治疗MAGL介导的疾病和障碍，例如疼痛、炎症性障碍、抑郁症、焦虑症、阿尔茨海默病、代谢障碍、中风或癌症的使用。

  公开号：

  US20180208608A1
• 作为产物：
  描述：

  1-噁-6-氮杂螺[2.5]辛烷-6-羧酸-1,1-二甲基乙酯 在 氨 作用下， 以 甲醇 为溶剂， 反应 16.0h， 以74%的产率得到4-(氨基甲基)-4-羟基哌啶-1-甲酸叔丁酯
  参考文献：
  名称：

  EST73502 的发现，一种双 μ-阿片受体激动剂和 σ1 受体拮抗剂，用于治疗疼痛的临床候选药物

  摘要：

  一系列新的 4-烷基-1-氧杂-4,9-二氮杂螺[5.5]十一烷衍生物的合成和药理活性，作为 σ 1受体 (σ 1 R) 和 μ-阿片受体 (MOR) 的有效双配体）被报道。对初始 4-芳基类似物的先导优化程序提供了具有所需功能性和良好选择性和 ADME 特性的 4-烷基衍生物。化合物14u (EST73502) 在单次和重复给药后在急性和慢性疼痛动物模型中显示出 MOR 激动作用和 σ 1 R 拮抗作用以及有效的镇痛活性，与 MOR 激动剂羟考酮相当。与羟考酮相反， 14u产生镇痛活性，并减少阿片类药物引起的相关不良事件，如肠道运输抑制和纳洛酮诱发的阿片戒断行为症状。这些结果证明，MOR 的双重激动和 σ 1 R 拮抗可能是获得有效且更安全的镇痛药的有用策略，并且是选择14u作为治疗疼痛的临床候选药物的基础。

  DOI：

  10.1021/acs.jmedchem.0c01127
• 作为试剂：
  描述：

  1-噁-6-氮杂螺[2.5]辛烷-6-羧酸-1,1-二甲基乙酯 、 ammonium hydroxide 在 4-(氨基甲基)-4-羟基哌啶-1-甲酸叔丁酯 作用下， 以 甲醇 为溶剂， 反应 7.0h， 生成 4-(氨基甲基)-4-羟基哌啶-1-甲酸叔丁酯
  参考文献：
  名称：

  Quinazoline analogs as receptor tyrosine kinase inhibitors

  摘要：

  本发明提供了Formula I的喹唑啉类似物：其中A与双环环上的5、6、7或8位置中的至少一个碳原子键合，并且该环被最多两个独立的R3基团取代。本发明还包括使用Formula I化合物作为I型受体酪氨酸激酶抑制剂和治疗癌症等增生性疾病的方法。

  公开号：

  US20050043334A1

文献信息

• Synthesis and Antibacterial Activity of Anacardic Acid Derivatives
  作者：Subhakara Reddy Nallamilli、V. Ravi Kumar、V. Himabindu、B. Ram、Srinivas Rao Aalapati

  DOI：10.2174/157018011796235167

  日期：2011.8.1

  New anacardic acid derivatives (6a -6u) were prepared from commercially available anacardic acid and tested for Gram positive and Gram negative activities. Most compounds were found to be active compared to ampicillin.

  新型槚如酸衍生物（6a-6u）是从市售的槚如酸制备而得，并对其实现了革兰氏阳性及阴性活性测试。多数化合物相较于氨苄青霉素表现出了活性。
• [EN] INDAZOLE COMPOUNDS AS 5-HT4 RECEPTOR AGONISTS<br/>[FR] COMPOSÉS D'INDAZOLE EN TANT QU'AGONISTES DE RÉCEPTEUR DE 5-HT4
  申请人：SUVEN LIFE SCIENCES LTD

  公开号：WO2015092804A1

  公开（公告）日：2015-06-25

  The present invention relates to novel indazole compounds of the Formula (I), wherein, R1 is alkyl or cycloalkyl; (Formula II) including their stereoisomers and their pharmaceutically acceptable salts. This invention also relates to methods of making such compounds and pharmaceutical compositions comprising such compounds. The compounds of this invention are useful in the treatment of various disorders that are related to 5-Hydroxytryptamine 4 (5-HT4) receptor agonists

  本发明涉及一种新型吲唑化合物，其化学式为（I），其中R1为烷基或环烷基；（化学式II），包括其立体异构体和药学上可接受的盐。本发明还涉及制备这种化合物的方法和包含这种化合物的药物组合物。本发明的化合物在治疗与5-羟色胺4（5-HT4）受体激动剂相关的各种疾病中是有用的。
• Identification and Structure-Guided Development of Pyrimidinone Based USP7 Inhibitors
  作者：Colin R. O’Dowd、Matthew D. Helm、J. S. Shane Rountree、Jakub T. Flasz、Elias Arkoudis、Hugues Miel、Peter R. Hewitt、Linda Jordan、Oliver Barker、Caroline Hughes、Ewelina Rozycka、Eamon Cassidy、Keeva McClelland、Ewa Odrzywol、Natalie Page、Stephanie Feutren-Burton、Scarlett Dvorkin、Gerald Gavory、Timothy Harrison

  DOI：10.1021/acsmedchemlett.7b00512

  日期：2018.3.8

  potential involvement in oncogenic pathways as well as possible roles in both metabolic and immune disorders in addition to viral infections. Potent, novel, and selective inhibitors of USP7 have been developed using both rational and structure-guided design enabled by high-resolution cocrystallography. Initial hits were identified via fragment-based screening, scaffold-hopping, and hybridization exercises

  泛素特异性蛋白酶7（USP7，HAUSP）由于在调节Mdm2水平（进而调节p53）中的作用，已成为药物发现中的引人注目的靶标。由于USP7可能参与致癌途径以及除病毒感染外在代谢和免疫疾病中的可能作用，因此人们对USP7的兴趣也越来越高。USP7的强效，新型和选择性抑制剂已通过高分辨率共结晶技术的合理设计和结构指导设计得到开发。最初的命中是通过基于片段的筛选，支架跳跃和杂交练习来确定的。描述了两个不同的子系列以及相关的结构-活性关系趋势，以及旨在开发适用于体内化合物的初步努力实验。总体而言，这些发现将有助于进一步研究USP7的更广泛的生物学作用。
• New oxybenzamide derivatives useful for inhibiting factor Xa or VIIa
  申请人：——

  公开号：US20020198195A1

  公开（公告）日：2002-12-26

  The present invention relates to compounds comprising the following formula: R 0 —Q—X—Q′—W—U—V—G—M  (I) These compounds are useful as pharmacologically active compounds. They exhibit an antithrombotic effect and are suitable, for example, for the therapy and prophylaxis of cardiovascular disorders such as thromboembolic diseases or restenoses. These compounds are reversible inhibitors of the blood clotting enzymes factor Xa (FXa) and/or factor VIIa (FVIIa), and can generally be used to treat, prevent, or cure conditions in which an undesired activity of factor Xa and/or factor VIIa is present, or where inhibition of factor Xa and/or factor VIIa is intended. The invention further relates to processes for the preparation of these compounds, methods of their use (e.g., as active ingredients in pharmaceuticals), and pharmaceutical preparations comprising them.

  本发明涉及包含以下公式的化合物： R 0 —Q—X—Q′—W—U—V—G—M  (I) 这些化合物作为药物活性化合物是有用的。它们展现出抗血栓作用，并适用于例如治疗和预防心血管疾病，如血栓栓塞性疾病或再狭窄。这些化合物是血液凝固酶因子Xa（FXa）和/或因子VIIa（FVIIa）的可逆性抑制剂，通常可用于治疗、预防或治愈存在因子Xa和/或因子VIIa不期望活性的情况，或旨在抑制因子Xa和/或因子VIIa的情况。本发明还涉及制备这些化合物的方法、它们的使用方法（例如，作为药品中的活性成分）以及包含它们的药物制剂。
• Discovery and Preclinical Characterization of Usmarapride (SUVN-D4010): A Potent, Selective 5-HT₄Receptor Partial Agonist for the Treatment of Cognitive Deficits Associated with Alzheimer’s Disease
  作者：Ramakrishna Nirogi、Abdul Rasheed Mohammed、Anil Karbhari Shinde、Shankar Reddy Gagginapally、Durga Malleshwari Kancharla、Srinivasa Rao Ravella、Narsimha Bogaraju、Vanaja Reddy Middekadi、Ramkumar Subramanian、Raghava Choudary Palacharla、Vijay Benade、Nageswararao Muddana、Renny Abraham、Rajesh Babu Medapati、Jagadeesh Babu Thentu、Venkat Reddy Mekala、Surendra Petlu、Bujji Babu Lingavarapu、Sivasekhar Yarra、Narendra Kagita、Vinod Kumar Goyal、Santosh Kumar Pandey、Venkat Jasti

  DOI：10.1021/acs.jmedchem.1c00703

  日期：2021.8.12

  A series of oxadiazole derivatives were synthesized and evaluated as 5-hydroxytryptamine-4 receptor (5-HT4R) partial agonists for the treatment of cognitive deficits associated with Alzheimer’s disease. Starting from a reported 5-HT4R antagonist, a systematic structure–activity relationship was conducted, which led to the discovery of potent and selective 5-HT4R partial agonist 1-isopropyl-3-5-[1-(3-methoxypropyl)

  合成并评估了一系列恶二唑衍生物作为 5-羟色胺-4 受体 (5-HT 4 R) 部分激动剂，用于治疗与阿尔茨海默病相关的认知缺陷。从报道的 5-HT 4 R 拮抗剂开始，进行了系统的构效关系，从而发现了有效和选择性的 5-HT 4 R 部分激动剂 1-异丙基-3-5-[1-(3 -甲氧基丙基）哌啶-4-基]-[1,3,4]恶二唑-2-基}-1H-吲唑草酸盐（Usmarapride，12l）。它在认知模型中表现出平衡的理化-药代动力学特性，具有强大的非临床功效。它还显示出改善疾病的潜力，因为它增加了神经保护性可溶性淀粉样前体蛋白 α 水平，以及剂量依赖性靶标参与和功效与口服暴露的相关性。1 期临床研究已完成，预计有效浓度已达到，没有任何重大安全问题。实现长期安全性研究的第 2 阶段已经完成，无需担心进一步开发。