cis-2,6-dimethylmorpholine | 6485-55-8

• 物质功能分类: 有机原料 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: cis-2,6-dimethylmorpholine
• 英文别名: (2R,6S)-2,6-dimethylmorpholine；(2S,6R)-2,6-dimethylmorpholine；2,6-dimethylmorpholine；2,6-cis-dimethylmorpholine；rac-(2R,6S)-2,6-dimethylmorpholine
• CAS: 6485-55-8
• 化学式: C₆H₁₃NO
• mdl: MFCD00078428
• 分子量: 115.175
• InChiKey: HNVIQLPOGUDBSU-OLQVQODUSA-N

物化性质

• 熔点：
  -85 °C
• 沸点：
  140-142 °C
• 密度：
  0.93
• 闪点：
  41 °C
• 溶解度：
  氯仿（少量溶解）、二氯甲烷（少量溶解）、甲醇（少量溶解）
• LogP：
  -0.15 at 25℃

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  8
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险等级：
  3
• 危险品标志：
  C
• 安全说明：
  S26,S36/37/39
• 危险类别码：
  R10,R41,R21,R37/38
• 海关编码：
  2934999090
• 危险品运输编号：
  UN 1993
• 危险类别：
  3
• RTECS号：
  QE1750000
• 包装等级：
  III
• 危险性防范说明：
  P210,P233,P240,P241+P242+P243,P280,P302+P352+P312+P361+P364,P305+P351+P338+P310,P370+P378,P403+P235,P405,P501
• 危险性描述：
  H225,H311,H318
• 储存条件：
  flammable area

SDS

Name:	cis-2 6-Dimethylmorpholine 97% Material Safety Data Sheet
Synonym:
CAS:	6485-55-8

Section 1 - Chemical Product MSDS Name:cis-2 6-Dimethylmorpholine 97% Material Safety Data Sheet
Synonym:

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
6485-55-8	cis-2,6-Dimethylmorpholine	97%	229-353-0

Hazard Symbols: C
Risk Phrases: 10 21/22 34

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Flammable. Harmful in contact with skin and if swallowed. Causes burns.Moisture sensitive.
Potential Health Effects
Eye:
Causes eye burns.
Skin:
Harmful if absorbed through the skin. Causes skin burns.
Ingestion:
Harmful if swallowed. Causes gastrointestinal tract burns.
Inhalation:
Causes chemical burns to the respiratory tract. Inhalation may be fatal as a result of spasm, inflammation, edema of the larynx and bronchi, chemical pneumonitis and pulmonary edema. May cause burning sensation, coughing, wheezing, laryngitis, shortness of breath, headache, nausea, and vomiting.
Chronic:
Not available.

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Section 4 - FIRST AID MEASURES
Eyes: Immediately flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid immediately.
Skin:
Get medical aid immediately. Immediately flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes.
Ingestion:
Get medical aid immediately. Do NOT induce vomiting. If conscious and alert, rinse mouth and drink 2-4 cupfuls of milk or water.
Inhalation:
Get medical aid immediately. Remove from exposure and move to fresh air immediately. If not breathing, give artificial respiration. If breathing is difficult, give oxygen.
Notes to Physician:
Treat symptomatically and supportively.

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Section 5 - FIRE FIGHTING MEASURES
General Information:
As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear. Will burn if involved in a fire.
Extinguishing Media:
Use water spray, dry chemical, carbon dioxide, or chemical foam.

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Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Cover with sand, dry lime or soda ash and place in a closed container for disposal. Remove all sources of ignition. Use a spark-proof tool. Isolate area and deny entry.

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Section 7 - HANDLING and STORAGE
Handling:
Use spark-proof tools and explosion proof equipment. Do not breathe dust, vapor, mist, or gas. Do not get in eyes, on skin, or on clothing. Use only in a chemical fume hood.
Storage:
Keep away from sources of ignition. Store in a cool, dry place.
Store in a tightly closed container. Flammables-area. Store below 35C.

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Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION
Engineering Controls:
Facilities storing or utilizing this material should be equipped with an eyewash facility and a safety shower. Use adequate ventilation to keep airborne concentrations low.
Exposure Limits CAS# 6485-55-8: Personal Protective Equipment Eyes: Not available.
Skin:
Wear appropriate protective gloves to prevent skin exposure.
Clothing:
Wear appropriate protective clothing to prevent skin exposure.
Respirators:
Follow the OSHA respirator regulations found in 29 CFR 1910.134 or European Standard EN 149. Use a NIOSH/MSHA or European Standard EN 149 approved respirator if exposure limits are exceeded or if irritation or other symptoms are experienced.

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Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Liquid
Color: clear colorless
Odor: Not available.
pH: 11.8 (100 g/l (20C))
Vapor Pressure: 7mbar @20 deg C
Viscosity: 5.3 mPa.s @20 deg C
Boiling Point: 140 - 142 deg C @760mmHg
Freezing/Melting Point: -85 deg C
Autoignition Temperature: 280 deg C ( 536.00 deg F)
Flash Point: 41 deg C ( 105.80 deg F)
Explosion Limits, lower: 1.6 Vol %
Explosion Limits, upper: 12.9 Vol %
Decomposition Temperature:
Solubility in water: Miscible.
Specific Gravity/Density: 0.930
Molecular Formula: C6H13NO
Molecular Weight: 115.18

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable under normal temperatures and pressures.
Conditions to Avoid:
Incompatible materials, ignition sources, exposure to moist air or water.
Incompatibilities with Other Materials:
Acids.
Hazardous Decomposition Products:
Carbon monoxide, oxides of nitrogen, carbon dioxide.
Hazardous Polymerization: Has not been reported.

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 6485-55-8 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
cis-2,6-Dimethylmorpholine - Not listed by ACGIH, IARC, or NTP.

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Section 12 - ECOLOGICAL INFORMATION
Other No information available.

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Section 13 - DISPOSAL CONSIDERATIONS
Dispose of in a manner consistent with federal, state, and local regulations.

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Section 14 - TRANSPORT INFORMATION

IATA
Shipping Name: AMINES, LIQUID, CORROSIVE, FLAMMABLE, N.O.S.*
Hazard Class: 8 (3)
UN Number: 2734
Packing Group: II
IMO
Shipping Name: AMINES, LIQUID, CORROSIVE, FLAMMABLE, N.O.S.
Hazard Class: 8 (3)
UN Number: 2734
Packing Group: II
RID/ADR
Shipping Name: AMINES, LIQUID, CORROSIVE, FLAMMABLE, N.O.S.
Hazard Class: 8 (3)
UN Number: 2734
Packing group: II

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Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: C
Risk Phrases:
R 10 Flammable.
R 21/22 Harmful in contact with skin and if
swallowed.
R 34 Causes burns.
Safety Phrases:
S 16 Keep away from sources of ignition - No
smoking.
S 23 Do not inhale gas/fumes/vapour/spray.
S 26 In case of contact with eyes, rinse immediately
with plenty of water and seek medical advice.
S 36/37/39 Wear suitable protective clothing, gloves
and eye/face protection.
S 45 In case of accident or if you feel unwell, seek
medical advice immediately (show the label where
possible).
WGK (Water Danger/Protection)
CAS# 6485-55-8: 1
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 6485-55-8 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 6485-55-8 is not listed on the TSCA inventory.
It is for research and development use only.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

简介

顺式-2,6-二甲基吗啉是抗肿瘤药物索尼吉布(Sonidegib)的重要中间体。一种现有方法是在浓硫酸的存在下，通过高温脱水环合二异丙醇胺，然后在高真空条件下分馏顺反异构体。

背景

2,6-二甲基吗啉作为一种重要的农药和医药中间体，在合成杀菌剂克菌啉、吗菌啉、丙菌啉、丁苯吗啉及抗真菌药盐酸阿莫罗芬等时不可或缺。对于丙菌啉而言，顺式异构体对病菌的抑制活性明显高于反式异构体，而混合的顺反异构体会降低整体活性。通常在医药领域中，丙菌啉指的是顺式异构体。

应用

顺式-2,6-二甲基吗啉作为一种有机合成中间体和医药中间体，在实验室研发和化工医药合成过程中具有广泛应用，可用于合成阿莫罗芬。

反应信息

• 作为反应物：
  描述：

  cis-2,6-dimethylmorpholine 在 4-二甲氨基吡啶 、 potassium phosphate monohydrate 、 铁粉 、 氯化铵 作用下， 以 水 为溶剂， 反应 42.17h， 生成 sonidegib
  参考文献：
  名称：

  使用水中Pd的ppm级催化，对环境负责的3罐，5步合成抗肿瘤剂Sonidegib

  摘要：

  Sonidegib的当前工业方法利用了浪费的有机溶剂，并依赖于高含量的濒临灭绝的Pd。该抗癌药现在只需3个罐，就可以在5个步骤中合成，而且ppm的Pd催化剂含量也可以在环境温度下在水中完成。

  DOI：

  10.1039/c9gc03495a
• 作为产物：
  描述：

  二异丙醇胺 在 硫酸 、 sodium hydroxide 作用下， 以 水 为溶剂， 生成 cis-2,6-dimethylmorpholine
  参考文献：
  名称：

  顺式-2,6-二甲基吗啉的纯化方法

  摘要：

  本申请公开了一种顺式‑2,6‑二甲基吗啉的纯化方法，包括提供顺式‑2,6‑二甲基吗啉、反式‑2,6‑二甲基吗啉、顺式‑2,5‑二甲基吗啉和反式‑2,5‑二甲基吗啉的混合物，在酯类溶剂中将所述混合物与羧酸反应，析晶，得到顺式‑2,6‑二甲基吗啉羧酸盐，其中在所述混合物中所述顺式‑2,6‑二甲基吗啉的含量≥80摩尔％，将所述顺式‑2,6‑二甲基吗啉羧酸盐用碱性物质水解，得到顺式‑2,6‑二甲基吗啉。本申请方法的原料易得，原料选择范围更广泛，工艺简便，成本低，所用试剂对环境友好，成品纯度高，能够满足药用和其他领域的使用要求。

  公开号：

  CN110950818B
• 作为试剂：
  描述：

  4-溴-3-甲基苯甲酸甲酯 在 palladium bis[bis(diphenylphosphino)ferrocene] dichloride 、 potassium carbonate 、 cis-2,6-dimethylmorpholine 作用下， 以 二甲基亚砜 、 甲苯 为溶剂， 反应 96.5h， 生成 4-(4-甲酰基-2-甲基苯基)-3-甲基苯甲醛
  参考文献：
  名称：

  扩展的环四苯偶姻

  摘要：

  环苯偶姻是光电子和多孔材料制备中感兴趣的形状持久性大环化合物。使用N杂环卡宾催化的安息香缩合合成了衍生自联苯，萘和甲苯骨架的新环四安息香。他们的制备具有与在氰化物催化的母体四环安息香中制备的观察到的不同的区域选择性。已经获得了两种新的环四苯偶姻乙酸酯的晶体结构。甲苯基环四苯偶姻的炔基被Co 2（CO）6部分合成后官能化。

  DOI：

  10.1021/acs.orglett.0c04014

文献信息

• [EN] 2-QUINOLONE DERIVED INHIBITORS OF BCL6<br/>[FR] INHIBITEURS DE BCL6 DÉRIVÉS DE 2-QUINOLONE
  申请人：CANCER RESEARCH TECH LTD

  公开号：WO2018215798A1

  公开（公告）日：2018-11-29

  The present invention relates to compounds of formula I that function as inhibitors of BCL6(B- cell lymphoma 6) activity: Formula I wherein X1, X2, X3, R1, R2, R3, R4 and R5 are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer,as well as other diseases or conditions in which BCL6 activity is implicated.

  本发明涉及作为BCL6（B细胞淋巴瘤6）活性抑制剂的I式化合物：式中X1、X2、X3、R1、R2、R3、R4和R5分别如本文所定义。本发明还涉及制备这些化合物的方法，包括含有它们的药物组合物，以及它们在治疗增生性疾病（如癌症）以及其他BCL6活性所涉及的疾病或病况中的用途。
• SUBSTITUTED BRIDGED UREA ANALOGS AS SIRTUIN MODULATORS
  申请人：GLAXOSMITHKLINE LLC

  公开号：US20150152108A1

  公开（公告）日：2015-06-04

  The present invention relates to novel substituted bridged urea compounds, corresponding related analogs, pharmaceutical compositions and methods of use thereof. Sirtuin-modulating compounds of the present invention may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders, which include, but are not limited to, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. The present invention also related to compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.

  本发明涉及新型取代桥式脲化合物，相应的相关类似物，药物组合物以及其使用方法。本发明的抑制素调节化合物可用于延长细胞寿命，并治疗和/或预防各种疾病和疾病，包括但不限于与衰老或压力、糖尿病、肥胖、神经退行性疾病、心血管疾病、血液凝块疾病、炎症、癌症和/或潮红有关的疾病或疾病，以及那些会受益于增加线粒体活性的疾病或疾病。本发明还涉及包含抑制素调节化合物与另一治疗剂组合的组合物。
• [EN] SUBSTITUTED BRIDGED UREA ANALOGS AS SIRTUIN MODULATORS<br/>[FR] ANALOGUES D'URÉE PONTÉS SUBSTITUÉS EN TANT QUE MODULATEURS DE SIRTUINE
  申请人：GLAXOSMITHKLINE IP NO 2 LTD

  公开号：WO2016079709A1

  公开（公告）日：2016-05-26

  The present invention relates to novel substituted bridged urea analog compounds of Formula (I) or pharmaceutically acceptable salts thereof, corresponding pharmaceutical compositions, processes for making and use of such compounds, alone or in combination with other therapeutic agents, as Sirtuin Modulators useful for increasing lifespan of a cell, and for use in treating and/or preventing a wide variety of diseases and disorders, which include, but are not limited to, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity.

  本发明涉及一种新型的取代桥式脲类似物化合物，其化学式为（I）或其药学上可接受的盐，相应的药物组合物，制备这种化合物的方法以及单独使用或与其他治疗剂联合使用的这些化合物作为Sirtuin调节剂，可用于增加细胞寿命，并用于治疗和/或预防各种疾病和紊乱，包括但不限于与衰老或压力、糖尿病、肥胖、神经退行性疾病、心血管疾病、血液凝块紊乱、炎症、癌症和/或潮红有关的疾病或紊乱，以及那些会受益于增加线粒体活性的疾病或紊乱。
• [EN] COMPOUNDS INHIBITING LEUCINE-RICH REPEAT KINASE ENZYME ACTIVITY<br/>[FR] COMPOSÉS INHIBANT L'ACTIVITÉ ENZYMATIQUE DE LA KINASE À MOTIFS RÉPÉTÉS RICHES EN LEUCINE
  申请人：MERCK SHARP & DOHME

  公开号：WO2014137723A1

  公开（公告）日：2014-09-12

  The present invention is directed to indazole compounds which are potent inhibitors of LRRK2 kinase and useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which LRRK-2 kinase is involved.

  本发明涉及吲唑类化合物，这些化合物是LRRK2激酶的有效抑制剂，并且在治疗或预防LRRK2激酶参与的疾病，如帕金森病中有用。该发明还涉及包含这些化合物的药物组合物，以及在预防或治疗LRRK-2激酶参与的这类疾病中使用这些化合物和组合物。
• [EN] COMPOUNDS INHIBITING LEUCINE-RICH REPEAT KINASE ENZYME ACTIVITY<br/>[FR] COMPOSÉS INHIBANT L'ACTIVITÉ ENZYMATIQUE DE LA KINASE À SÉQUENCE RÉPÉTÉE RICHE EN LEUCINE
  申请人：MERCK SHARP & DOHME

  公开号：WO2014134774A1

  公开（公告）日：2014-09-12

  Disclosed are indazole compounds which are potent inhibitors of LRRK2 kinase and useful in the treatment or prevention of diseases in which LRRK2 kinase is involved. Also disclosed are pharmaceutical compositions in the prevention or treatment of such diseases in which LRRK2 kinase is involved.

  揭示了一种indazole化合物，它们是LRRK2激酶的有效抑制剂，并且在涉及LRRK2激酶的疾病的治疗或预防中有用。还揭示了在涉及LRRK2激酶的这类疾病的预防或治疗中使用的药物组合物。

表征谱图