4-(1,4-dioxaspiro<4.5>dec-8-yl)morpholine | 127562-53-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(1,4-dioxaspiro<4.5>dec-8-yl)morpholine
• 英文别名: 4-(1,4-dioxaspiro[4.5]decan-8-yl)morpholine；4-(1,4-dioxa-spiro[4.5]dec-8-yl)-morpholine
• CAS: 127562-53-2
• 化学式: C₁₂H₂₁NO₃
• 分子量: 227.304
• InChiKey: JDGLFTXYDPTSQZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  30.9
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2934999090

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 4-(1,4-Dioxaspiro[4.5]decan-8-yl)morpholine
Synonyms:

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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: 4-(1,4-Dioxaspiro[4.5]decan-8-yl)morpholine
CAS number: 127562-53-2

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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: C12H21NO3
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

反应信息

• 作为反应物：
  描述：

  4-(1,4-dioxaspiro<4.5>dec-8-yl)morpholine 在 盐酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 21.0h， 生成 (4-吗啉-4-基环己烯-1-基)三氟甲磺酸酯
  参考文献：
  名称：

  [EN] COMPOUNDS
  [FR] COMPOSÉS

  摘要：

  提供了抑制LRRK2激酶活性的新化合物，以及它们的制备方法、含有它们的组合物以及它们在治疗或预防与LRRK2激酶活性相关或以其为特征的疾病中的用途，例如帕金森病、阿尔茨海默病和肌萎缩侧索硬化症（ALS）。

  公开号：

  WO2018137593A1
• 作为产物：
  描述：

  吗啉 、 1,4-环己二酮单乙二醇缩酮 在 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 1,2-二氯乙烷 为溶剂， 生成 4-(1,4-dioxaspiro<4.5>dec-8-yl)morpholine
  参考文献：
  名称：

  钴催化环外烯烃的不对称异构化

  摘要：

  手性环状烯烃（1-甲基环己烯）是用于合成药物和天然产物的多功能构件。尽管这些结构基序很普遍，但开发有效的合成方法仍然是一个未解决的挑战。在此，我们报道了一种使用一系列新设计的手性钴催化剂对环外烯烃进行新型不对称异构化，从而可以直接构建具有多种功能的手性 1-甲基环己烯。该方法的合成效用通过对天然产物 β-红没药烯的简明和对映选择性合成突出。多种衍生化进一步证明了反应产物的多功能性。

  DOI：

  10.1021/jacs.1c11343

文献信息

• [EN] DIAZAINDOLE DERIVATIVES AND THEIR USE IN THE INHIBITION OF C-JUN N-TERMINAL KINASE<br/>[FR] DÉRIVÉS DE DIAZAINDOLE ET LEUR UTILISATION DANS L'INHIBITION DE KINASE C-JUN N-TERMINALE
  申请人：EISAI R&D MAN CO LTD

  公开号：WO2010015803A1

  公开（公告）日：2010-02-11

  The invention relates to diazaindole derivatives represented by the general formula (I): where A, E, G, R1, R2, R3 and R4 are defined herein, or pharmaceutically acceptable salts thereof, their use in the inhibition of c-Jun N-terminal kinase (JNK) activity, their use in medicine and particularly in the treatment of neurodegenerative disorders, inflammatory diseases, autoimmune diseases and/or organ failure. The invention also provides processes for the manufacture of said diazaindole derivatives and compositions containing them.

  本发明涉及由通用公式（I）表示的哒嗪吲哚衍生物：其中A、E、G、R1、R2、R3和R4在本说明书中定义，或其药用可接受的盐，它们用于抑制c-Jun N末端激酶（JNK）活性，它们用于医药领域，特别是在治疗神经退行性疾病、炎症性疾病、自身免疫性疾病和/或器官衰竭方面的应用。本发明还提供了制造所述哒嗪吲哚衍生物的方法以及包含它们的组合物。
• 1,5,7-TRISUBSTITUTED ISOQUINOLINE DERIVATIVES, PREPARATION THEREOF, AND USE THEREOF IN MEDICINES
  申请人：SHANGHAI HAIYAN PHARMACEUTICAL TECHNOLOGY CO., LTD.

  公开号：US20200262813A1

  公开（公告）日：2020-08-20

  The present disclosure relates to 1,5,7-trisubstituted isoquinoline derivatives, their preparation and pharmaceutical use. In particular, the present disclosure discloses a compound of formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate or prodrug thereof, and a preparation method and use thereof. The definitions of the groups in the formula can be found in the specification and claims.

  本公开涉及1,5,7-三取代异喹啉衍生物、其制备方法和药物用途。特别是，本公开披露了公式(I)的化合物或其药用可接受的盐、立体异构体、溶剂化物或前药，以及其制备方法和用途。公式的组的定义可以在说明书和权利要求中找到。
• INHIBITORS OF C-FMS KINASE
  申请人：Illig Carl R.

  公开号：US20070249608A1

  公开（公告）日：2007-10-25

  The invention is directed to compounds of Formula I: wherein Z, X, J, R 2 and W are set forth in the specification, as well as solvates, hydrates, tautomers and pharmaceutically acceptable salts thereof, that inhibit protein tyrosine kinases, especially c-fms kinase. Methods of treating autoimmune diseases; and diseases with an inflammatory component; treating metastasis from ovarian cancer, uterine cancer, breast cancer, prostate cancer, lung cancer, colon cancer, stomach cancer, hairy cell leukemia; and treating pain, including skeletal pain caused by tumor metastasis or osteoarthritis, or visceral, inflammatory, and neurogenic pain; as well as osteoporosis, Paget's disease, and other diseases in which bone resorption mediates morbidity including rheumatoid arthritis, and other forms of inflammatory arthritis, osteoarthritis, prosthesis failure, osteolytic sarcoma, myeloma, and tumor metastasis to bone with the compounds of Formula I, are also provided.

  该发明涉及以下式I的化合物：其中Z、X、J、R2和W如规范中所述，以及其溶剂合物、水合物、互变异构体和药用盐，能够抑制蛋白酪氨酸激酶，尤其是c-fms激酶。还提供了使用该化合物治疗自身免疫性疾病；有炎症成分的疾病；治疗卵巢癌、子宫癌、乳腺癌、前列腺癌、肺癌、结肠癌、胃癌、毛细胞白血病引起的转移；治疗疼痛，包括肿瘤转移或骨关节炎引起的骨骼疼痛，或内脏、炎症和神经源性疼痛；以及骨质疏松症、帕盖特氏病和其他骨吸收介导发病率的疾病，包括类风湿关节炎和其他形式的炎症性关节炎、骨关节炎、假体失败、溶骨性肉瘤、骨髓瘤和肿瘤转移至骨骼的方法。
• Synthesis of Diastereomeric 3,6-Diaminobicyclo[3.1.0]hexane Derivatives: A Stereocomplementary Approach
  作者：Elmar Vilsmaier、Joachim Fath、Gerhard Maas

  DOI：10.1055/s-1991-28406

  日期：——

  Diastereomeric (1α,3β,5α,6β)- and (1α,3α,5α,6β)-diaminobicyclo [3.1.0]hexane-6-carbonitriles 12 and 16 were synthesized with high stereoselectivity from 1,4-cyclohexanedione monoacetal 6 via chloroenamines 17 and 18, respectively. The sequence of reaction of 6 with a cyclic amine to give an enamine, chlorination with N-chlorosuccinimide and subsequent cyclopropanation with cyanide ion in the presence of a phase-transfer catalyst, cleavage of the acetal function followed by reductive amination, leads to 12. Changing the order of these synthetic steps allows an easy approach to 16. The configurations of 12 and 16 were established by 1H- and 13C-NMR data and an X-ray structural analysis of 16b.

  通过氯烯胺 17 和 18，分别以 1,4-环己二酮单乙醛 6 为原料，以高立体选择性合成了非对映的 (1δ±,3δ²,5δ±,6δ²)- 和 (1δ±,3δ±,5δ±,6δ²)- 二氨基双环 [3.1.0]己烷-6-甲腈 12 和 16。6 与环胺反应生成烯胺，与 N-氯代丁二酰亚胺发生氯化反应，随后在相转移催化剂存在下与氰离子发生环丙烷化反应，裂解缩醛功能，然后进行还原胺化反应，最终得到 12。改变这些合成步骤的顺序，就可以很容易地得到 16。通过 1H 和 13C-NMR 数据以及 16b 的 X 射线结构分析，确定了 12 和 16 的构型。
• USE OF 7-AZAINDOLES IN THE INHIBITION OF C-JUN N-TERMINAL KINASE
  申请人：GRACZYK Piotr Pawel

  公开号：US20100069358A1

  公开（公告）日：2010-03-18

  The present invention provides a compound of formula (I); or a pharmaceutically acceptable salt thereof in the inhibition of c-Jun N-terminal kinase (JNK) activity and particularly in the treatment of neurodegenerative disorders, inflammatory diseases and/or and autoimmune diseases. The invention also provides processes for the manufacture of said compounds of formula (I) or a pharmaceutically acceptable salt thereof and compositions containing them.

  本发明提供了一种化合物(I)或其药学上可接受的盐，用于抑制c-Jun N末端激酶（JNK）活性，特别是用于治疗神经退行性疾病、炎症性疾病和/或自身免疫性疾病。本发明还提供了制备该化合物(I)或其药学上可接受的盐的方法和含有它们的组合物。