(1alpha,5alpha,6alpha)-3-氮杂双环[3.1.0]己烷-3,6-二甲酸 3-叔丁酯 | 927679-54-7

• 物质功能分类: 医药中间体 - 杂环化合物
• 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: (1alpha,5alpha,6alpha)-3-氮杂双环[3.1.0]己烷-3,6-二甲酸 3-叔丁酯
• 中文别名: (1alpha,5alpha,6alpha)-3-氮杂双环[3.1.0]己烷-3,6-二甲酸3-叔丁酯；(1α,5α,6α)-3-氮杂双环[3.1.0]己烷-3,6-二羧酸-3-(1,1-二甲基乙基)酯；(1ALPHA,5ALPHA,6ALPHA)-3-氮杂双环[3.1.0]己烷-3,6-二甲酸3-叔丁酯
• 英文名称: (1R,5S)-3-(tert-butoxycarbonyl)-3-azadicyclo[3.1.0]hexane-3-carboxylic acid
• 英文别名: (1S,5R)-3-tert-butoxycarbonyl-3-azabicyclo[3.1.0]hexane-6-carboxylic acid；(1R,5S)-3-(tert-butoxycarbonyl)-3-azabicyclo[3.1.0]hexane-6-carboxylic acid；(1R,5S,6R)-3-(tert-butoxycarbonyl)-3-azabicyclo[3.1.0]hexane-6-carboxylic acid；(1S,5R)-3-[(2-methylpropan-2-yl)oxycarbonyl]-3-azabicyclo[3.1.0]hexane-6-carboxylic acid
• CAS: 927679-54-7
• 化学式: C₁₁H₁₇NO₄
• 分子量: 227.26
• InChiKey: GYEQQDCMLKKYGG-DHBOJHSNSA-N

物化性质

• 沸点：
  355.9±35.0 °C(Predicted)
• 密度：
  1.276

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: (1R,5S,6R)-3-BOC-3-azabicyclo[3.1.0]hexane-6-carboxylic acid
Synonyms: (1R,5S,6R)-3-(tert-Butoxycarbonyl)-3-azabicyclo[3.1.0]hexane-6-carboxylic acid

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

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Section 3. Composition/information on ingredients.
Ingredient name: (1R,5S,6R)-3-BOC-3-azabicyclo[3.1.0]hexane-6-carboxylic acid
CAS number: 927679-54-7

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Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
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.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

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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.
Store in closed vessels, refrigerated.
Storage:

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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
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C11H17NO4
Molecular weight: 227.3

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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

简介

3-氮杂双环[3.1.0]己烷类衍生物是一种氮杂环化合物，这一类分子具有独特的生物活性，并常被用作医药和农药结构单元。含氮化合物易于进行结构修饰，因此可以很方便地引入各种基团，赋予其不同的性能。

制备

国内外对3-氮杂双环[3.1.0]己烷的合成已有不少报道。该分子主要由一个五元氮杂环和一个三元环构成，因此在制备过程中需要构建这两个环状结构。五元环通常基于顺式-1,2-二取代环丙烷进行构建；而三元环则可通过共轭五元环与卡宾或硫叶立德的反应来实现。

以较为廉价的富马酸二乙酯和氯乙酸乙酯为起始原料，合成(1α,5α,6α)-3-氮杂双环[3.1.0]己烷-3,6-二甲酸3-叔丁酯。这一过程中通过碱催化下的迈克尔加成反应构建了环丙烷结构，文献报道的产率达到80%。后续各步骤条件温和且产率较高。

在制备I-3时，按照文献报道，在同时存在酯基和酰胺键的情况下，可以通过选择性还原酰胺键而保留酯基，产率高达90%。整个合成路线中，第一步反应的产率为80%，其他各步均超过85%，符合大规模工业生产的要求。

反应信息

• 作为反应物：
  描述：

  (1alpha,5alpha,6alpha)-3-氮杂双环[3.1.0]己烷-3,6-二甲酸 3-叔丁酯 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以61.6%的产率得到tert-butyl (1R,5S)-6-(hydroxymethyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate
  参考文献：
  名称：

  嘧啶类化合物及其用途

  摘要：

  本发明提出了嘧啶类化合物及其用途，具体地，本发明提出了一种有效抑制ATX的新化合物，其为下式所示化合物，或者下式示化合物的互变异构体、立体异构体、水合物、溶剂化物、药学可接受的盐或前药：

  公开号：

  CN113943275A

文献信息

• [EN] ANTIBACTERIAL 8-PHENYLAMINO-3-(PYRAZOL-4-YL)IMIDAZO[1,2-A]PYRAZINE DERIVATIVES<br/>[FR] DÉRIVÉS ANTIBACTÉRIENS DE 8-PHÉNYLAMINO-3-(PYRAZOL-4-YL)IMIDAZO[1,2-A]PYRAZINE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2021219578A1

  公开（公告）日：2021-11-04

  The invention provides novel imidazopyrazine derivatives having the general formula (I), wherein X and R3 to R9 are as described herein or pharmaceutically acceptable salts thereof, wherein X and R3 to R9 are as defined herein. Further provided are pharmaceutical compositions including the compounds, processes of manufacturing the compounds and methods of using the compounds as medicaments, in particular methods of using the compounds as antibiotics for the treatment or prevention of bacterial infections and resulting diseases.

  这项发明提供了具有一般式(I)的新型咪唑吡嗪衍生物，其中X和R3至R9如本文所述或其药学上可接受的盐，其中X和R3至R9如本文所定义。还提供了包括这些化合物的药物组合物、制造这些化合物的方法以及将这些化合物用作药物的方法，特别是将这些化合物用作抗生素治疗或预防细菌感染及由此导致的疾病的方法。
• BIHETEROARYL COMPOUNDS AND USES THEREOF
  申请人：GENENTECH, INC.

  公开号：US20140328805A1

  公开（公告）日：2014-11-06

  The present invention provides for compounds of Formula I and embodiments and salts thereof for the treatment of diseases (e.g., neurodegenerative diseases). R 1 , R 2 , R 3 , X 1 , X 2 , A and Cy variable in Formula all have the meaning as defined herein.

  本发明提供了一种公式I的化合物及其衍生物和盐，用于治疗疾病（例如，神经退行性疾病）。在公式中，R1、R2、R3、X1、X2、A和Cy变量的含义如本文所定义。
• 一种含氮杂环衍生物及其制备
  申请人：四川海思科制药有限公司

  公开号：CN112778274B

  公开（公告）日：2022-02-15

  本发明公开一种式(I)所示的含氮杂环化合物及其立体异构体、溶剂化物、代谢产物、药学上可接受的盐、共晶或者前药以及其药物组合物、制备方法，以及在由自分泌运动因子介导的疾病的预防和治疗中的用途。
• NOVEL PYRROLIDINE DERIVED BETA 3 ADRENERGIC RECEPTOR AGONISTS
  申请人：Edmondson Scott D.

  公开号：US20120157432A1

  公开（公告）日：2012-06-21

  The present invention provides compounds of Formula (I), pharmaceutical compositions thereof, and method of using the same in the treatment or prevention of diseases mediated by the activation of β3-adrenoceptor.

  本发明提供公式（I）的化合物、其制药组合物以及使用该化合物治疗或预防通过激活β3-肾上腺素受体介导的疾病的方法。
• AMINOPYRIMIDINE COMPOUNDS AS INHIBITORS OF T790M CONTAINING EGFR MUTANTS
  申请人：Bryan Marian C.

  公开号：US20160016948A1

  公开（公告）日：2016-01-21

  This invention relates to novel compounds which are inhibitors of T790M containing EGFR mutants, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy for the prevention or treatment of cancer.

  本发明涉及一种新型化合物，它们是T790M含有EGFR突变体的抑制剂，包括含有它们的制药组合物、它们的制备过程以及它们在预防或治疗癌症的治疗中的使用。