Alpha-溴代-4-吗啡啉苯乙酮 | 210832-85-2

• 物质功能分类: 医药中间体
• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: Alpha-溴代-4-吗啡啉苯乙酮
• 中文别名: Α-溴代-4-吗啡啉苯乙酮；α-溴代-4-吗啡啉苯乙酮；2-溴-1-(4-吗啉苯基)乙酮；2-溴-1-(4-吗啉苯基)-1-乙酮
• 英文名称: 2-bromo-1-(4-morpholinophenyl)ethan-1-one
• 英文别名: 2-Bromo-1-(4-morpholinophenyl)ethanone；2-bromo-1-(4-morpholin-4-ylphenyl)ethanone
• CAS: 210832-85-2
• 化学式: C₁₂H₁₄BrNO₂
• 分子量: 284.153
• InChiKey: OUGMZFJPRSTGMJ-UHFFFAOYSA-N

物化性质

• 熔点：
  112 °C

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险品标志：
  C
• 安全说明：
  S26,S36/37/39,S45
• 危险类别码：
  R34
• 海关编码：
  2934999090

SDS

Name:	2-Bromo-1-(4-morpholinophenyl)-1-ethanone 97% Material Safety Data Sheet
Synonym:
CAS:	210832-85-2

Section 1 - Chemical Product MSDS Name:2-Bromo-1-(4-morpholinophenyl)-1-ethanone 97% Material Safety Data Sheet
Synonym:

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
210832-85-2	2-Bromo-1-(4-morpholinophenyl)-1-ethan	97%	unlisted

Hazard Symbols: C
Risk Phrases: 34

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Causes burns.
Potential Health Effects
Eye:
Causes eye burns.
Skin:
Causes skin burns.
Ingestion:
Causes gastrointestinal tract burns.
Inhalation:
Causes chemical burns to the respiratory tract.
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:
Do not induce vomiting. Get medical aid immediately. Wash mouth out with 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.
Extinguishing Media:
Use foam, dry chemical, or carbon dioxide.

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Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Vacuum or sweep up material and place into a suitable disposal container.

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Section 7 - HANDLING and STORAGE
Handling:
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:
Store in a cool, dry place. Store in a tightly closed container.
Corrosives area.

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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# 210832-85-2: 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: Solid
Color: Not available.
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 118 - 119 deg C
Autoignition Temperature: Not available.
Flash Point: Not available.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water:
Specific Gravity/Density:
Molecular Formula: C12H14BrNO2
Molecular Weight: 284.15

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Not available.
Conditions to Avoid:
Incompatible materials.
Incompatibilities with Other Materials:
Strong oxidizing agents.
Hazardous Decomposition Products:
Nitrogen oxides, carbon monoxide, carbon dioxide, hydrogen bromide, bromine.
Hazardous Polymerization: Has not been reported

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 210832-85-2 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
2-Bromo-1-(4-morpholinophenyl)-1-ethanone - Not listed by ACGIH, IARC, or NTP.

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Section 12 - ECOLOGICAL INFORMATION

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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: CORROSIVE SOLID, N.O.S.*
Hazard Class: 8
UN Number: 1759
Packing Group: III
IMO
Shipping Name: CORROSIVE SOLID, N.O.S.
Hazard Class: 8
UN Number: 1759
Packing Group: III
RID/ADR
Shipping Name: CORROSIVE SOLID, N.O.S.
Hazard Class: 8
UN Number: 1759
Packing group: III

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Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: C
Risk Phrases:
R 34 Causes burns.
Safety Phrases:
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 37/39 Wear suitable 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# 210832-85-2: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 210832-85-2 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 210832-85-2 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

制备

1. 中间体 4-吗啉苯基乙酮的制备

   取50克4-氟苯乙酮，溶于350毫升二甲基亚砜（DMSO）中（约7~8倍质量体积比），搅拌均匀，形成无色溶液。常温下缓慢滴加78.8克（0.9摩尔）的吗啡啉，滴毕后升温至120℃回流反应。溶液逐渐变为淡黄色。反应3~4小时，并用薄层色谱（TLC）监测反应终点，确保反应完全。待反应结束后冷却至室温，将反应液慢慢倾倒入大量冰水中，搅拌，析出黄色固体。抽滤收集滤饼，用水洗两次，干燥后得到黄色固体63克，收率为85%。

2. 中间体 2,2-二溴-1-(4-吗啉苯基)乙酮的制备

   将30克（0.15摩尔）4-吗啉苯基乙酮和210毫升浓硫酸（约7~8倍质量体积比），加入到装有机械搅拌和温度计的500毫升三颈瓶中，搅拌使其溶解。将反应液冷却至0℃，在此温度下缓慢滴入7.8毫升溴素，控制温度在0℃。滴毕后室温下继续反应约6小时，并用TLC监测反应是否完全。随后将反应液倒入大量冰水中，析出黄绿色固体并搅拌直至冰溶解。抽滤收集滤饼，用水洗至中性，干燥后得到黄绿色固体47克，收率为88%。

反应信息

• 作为反应物：
  描述：

  Alpha-溴代-4-吗啡啉苯乙酮 在 氢氧化钾 、 溶剂黄146 作用下， 以 乙醇 、 水 为溶剂， 反应 7.5h， 生成 3-Hydroxy-7,8-dimethyl-2-(4-morpholinophenyl)quinoline-4-carboxylic acid
  参考文献：
  名称：

  P-选择素拮抗剂喹啉水杨酸的合成及生物学评价。

  摘要：

  白细胞炎症和组织损伤部位的募集涉及白细胞沿内皮壁滚动，然后白细胞牢固粘附，最后白细胞跨细胞连接转运到下面的组织中。初始滚动步骤由包含活性部分的白细胞糖蛋白（如唾液酸化的Lewisx（sLex））与在内皮细胞上表达的P-选择蛋白的相互作用介导。因此，借助于小分子P-选择蛋白拮抗剂抑制这种相互作用是治疗炎性疾病如关节炎的有吸引力的策略。惠氏化学文库的高通量筛选确定了喹啉水杨酸类化合物（1）作为P-选择素的拮抗剂，其体外和基于细胞的测定方法的功效远远优于sLex。通过迭代药物化学，我们鉴定出具有改善的P-选择素活性，减少的二氢Orate脱氢酶抑制作用和可接受的CYP谱的类似物。铅化合物36在类风湿关节炎的大鼠AIA模型中有效。

  DOI：

  10.1021/jm0602256
• 作为产物：
  描述：

  2,2-二溴-1-(4-吗啉-4-基苯基)乙酮 在 (EtO)2HPO 作用下， 以 四氢呋喃 为溶剂， 以91%的产率得到Alpha-溴代-4-吗啡啉苯乙酮
  参考文献：
  名称：

  P-选择素拮抗剂喹啉水杨酸的合成及生物学评价。

  摘要：

  白细胞炎症和组织损伤部位的募集涉及白细胞沿内皮壁滚动，然后白细胞牢固粘附，最后白细胞跨细胞连接转运到下面的组织中。初始滚动步骤由包含活性部分的白细胞糖蛋白（如唾液酸化的Lewisx（sLex））与在内皮细胞上表达的P-选择蛋白的相互作用介导。因此，借助于小分子P-选择蛋白拮抗剂抑制这种相互作用是治疗炎性疾病如关节炎的有吸引力的策略。惠氏化学文库的高通量筛选确定了喹啉水杨酸类化合物（1）作为P-选择素的拮抗剂，其体外和基于细胞的测定方法的功效远远优于sLex。通过迭代药物化学，我们鉴定出具有改善的P-选择素活性，减少的二氢Orate脱氢酶抑制作用和可接受的CYP谱的类似物。铅化合物36在类风湿关节炎的大鼠AIA模型中有效。

  DOI：

  10.1021/jm0602256
• 作为试剂：
  描述：

  Alpha-溴代-4-吗啡啉苯乙酮 、 t-butyl 2-([(3-fluoroanilino)carbothioyl]amino)ethylcarbamate 在 Alpha-溴代-4-吗啡啉苯乙酮 作用下， 生成
  参考文献：
  名称：

  THERAPEUTIC AGENT FOR CHRONIC OBSTRUCTIVE PULMONARY DISEASE

  摘要：

  本发明涉及一种通过给予下式表示的5元环化合物的预防和/或治疗慢性阻塞性肺疾病的方法：或其药学上可接受的盐或其前药物，其中X代表氧原子或硫原子; R1代表氢原子、取代或未取代的烷基或类似物; R2代表氢原子、取代或未取代的烷基或类似物; Y1代表单键、取代或未取代的脂肪基或类似物; 波浪线表示（E）或（Z）配位; R3代表氢原子、取代或未取代的芳基或类似物; Y2代表取代或未取代的脂肪基或烯基; R4代表氢原子、取代或未取代的烷酰基或类似物; R5代表氢原子或取代或未取代的烷基。

  公开号：

  EP1875915A1

文献信息

• Switching Reversibility to Irreversibility in Glycogen Synthase Kinase 3 Inhibitors: Clues for Specific Design of New Compounds
  作者：Daniel I. Perez、Valle Palomo、Concepción Pérez、Carmen Gil、Pablo D. Dans、F. Javier Luque、Santiago Conde、Ana Martínez

  DOI：10.1021/jm1016279

  日期：2011.6.23

  halomethylketone moiety to reversible inhibitors turned them into irreversible inhibitors with IC50 values in the nanomolar range. Overall, the results point out that these compounds might be useful pharmacological tools to explore physiological and pathological processes related to signaling pathways regulated by GSK-3 opening new avenues for the discovery of novel GSK-3 inhibitors.

  开发针对中枢神经系统（CNS）疾病的激酶靶向疗法是一项巨大的挑战。糖原合酶激酶3（GSK-3）在严重的中枢神经系统未满足疾病中具有巨大潜力，它是针对不同疾病的临床试验中的抑制剂之一。根据我们基于GSK-3结合位点残基Cys199的增强反应性的假设，我们在这里检查苯基卤代甲基酮作为不可逆抑制剂的适用性。我们的数据证实卤代甲基酮单元对于抑制活性是必不可少的。此外，在可逆抑制剂中添加卤代甲基酮部分可将其转变为具有IC 50的不可逆抑制剂值在纳摩尔范围内。总体而言，结果指出这些化合物可能是探索与GSK-3调节的信号通路相关的生理和病理过程的有用药理工具，为发现新型GSK-3抑制剂开辟了新途径。
• Design, Synthesis, and Biological Evaluation of N,N-Disubstituted-4-Arylthiazole-2-Methylamine Derivatives as Cholesteryl Ester Transfer Inhibitors
  作者：Xinran Wang、Xuehua Lin、Xuanqi Xu、Wei Li、Lijuan Hao、Chunchi Liu、Dongmei Zhao、Maosheng Cheng

  DOI：10.3390/molecules22111925

  日期：——

  Cholesteryl ester transfer protein (CETP) has been identified as a potential target for cardiovascular disease (CVD) for its important role in the reverse cholesteryl transfer (RCT) process. In our previous work, compound 5 was discovered as a moderate CETP inhibitor. The replacement of the amide linker by heterocyclic aromatics and then a series of N,N-substituted-4-arylthiazole-2-methylamine derivatives

  胆固醇酯转移蛋白 (CETP) 因其在反向胆固醇转移 (RCT) 过程中的重要作用而被确定为心血管疾病 (CVD) 的潜在靶标。在我们之前的工作中，化合物 5 被发现是一种温和的 CETP 抑制剂。利用构象限制策略设计了用杂环芳烃取代酰胺接头，然后设计了一系列 N,N-取代-4-芳基噻唑-2-甲胺衍生物。合成了 36 种化合物并评估了它们的 CETP 抑制活性。构效关系研究表明，电子供体基团取代了环 A，环 B 的 4 位上的吸电子基团对效力至关重要。在这些化合物中，化合物30表现出优异的CETP抑制活性（IC50=0.79±0。
• Design, synthesis, in vitro and in silico investigation of aldose reductase inhibitory effects of new thiazole-based compounds
  作者：Belgin Sever、Mehlika Dilek Altıntop、Yeliz Demir、Gülşen Akalın Çiftçi、Şükrü Beydemir、Ahmet Özdemir

  DOI：10.1016/j.bioorg.2020.104110

  日期：2020.9

  In the current study, new 4-aryl-2-[2-((3,4-dihydro-2H-1,5-benzodioxepine-7-yl)methylene)hydrazinyl]thiazole derivatives (1–12) were synthesized and screened for their inhibitory effects on AR which was purified by diverse chromatographic methods with a yield of 1.40% and a specific activity of 2.00 EU/mg. All compounds were determined as promising AR inhibitors with the Ki values in the range of 0

  醛糖还原酶（AR）催化多元醇途径中依赖NADPH的葡萄糖还原为山梨糖醇，这在糖尿病并发症的发展中起重要作用，包括白内障，视网膜病变，肾病和神经病。AR被认为是治愈这些长期糖尿病并发症的重要目标，因此，开发新的AR抑制剂是现代药物化学中的重要方法。在当前的研究中，新的4-芳基-2- [2-（（（3,4-二氢-2 H -1,5-苯并二氧杂庚烷-7-基）亚甲基）肼基]噻唑衍生物（1 – 12合成）并筛选其对AR的抑制作用，其通过多种色谱方法纯化，收率为1.40％，比活性为2.00EU / mg。与槲皮素相比，所有化合物均被确定为有前途的AR抑制剂，其K i值在0.018±  0.005μM -3.746± 1.321μM范围内（K i = 7.025±1.780μM）。尤其是，检测到的最多的是4-（4-氰基苯基）-2- [2-（（（3,4-二氢-2 H -1,5-苯并二氧杂庚-7-基）亚甲基）肼
• Synthesis and Evaluation of New Thiazolyl Hydrazone Derivatives as Potential Anticancer Agents
  作者：Zafer Asım Kaplancıklı、Belgin Sever、Mehlika Dilek Altıntop、Ozlem Atlı、Merve Baysal、Ahmet Ozdemir

  DOI：10.2174/1570180814666161104161711

  日期：2017.6.6

  Background: In recent years, thiazole derivatives incorporated with hydrazone moiety have attracted a great deal of interest due to their pivotal role in the field of current cancer research. Methods: In the present study, new thiazolyl hydrazone derivatives were synthesized via the reaction of 1-(4-phenylcyclohexylidene)thiosemicarbazide with 2-bromoacetophenone derivatives. MTT assay was performed to assess

  背景：近年来，掺入部分的噻唑衍生物由于在当前癌症研究领域中起着关键作用而引起了人们的极大兴趣。 方法：本研究通过1-（4-苯基环己叉基）硫代氨基脲与2-溴苯乙酮衍生物的反应合成了新的噻唑基衍生物。进行MTT测定以评估化合物对A549人肺腺癌，HepG2人肝肝细胞癌和C6大鼠神经胶质瘤细胞系的细胞毒性作用。使用NIH / 3T3小鼠胚胎成纤维细胞系研究了化合物的选择性。 结果：发现4-（4-甲基磺酰基苯基）-2-（2-（4-苯基环己叉基）肼基）噻唑（7）是最有希望的抗HepG2细胞系抗癌剂，与顺铂相比，IC50值为0.316 mM。 （IC50 ＝ 0.091mM）。化合物2和6还对HepG2细胞系表现出细胞毒性作用，IC50值分别为0.81 mM和0.79 mM。此外，化合物2、6和7对NIH / 3T3细胞系没有任何细胞毒性。 结论：特别地，由于化合物7对HepG2细胞系具有选择性的抗肿
• ALKALOID AMINOESTER DERIVATIVES AND MEDICINAL COMPOSITIONS THEREOF
  申请人：AMARI Gabriele

  公开号：US20110311458A1

  公开（公告）日：2011-12-22

  The present invention relates to alkaloid aminoester compounds which act as muscarinic receptor antagonists, processes for their preparation, compositions comprising them, and therapeutic uses thereof.

  本发明涉及作为毒蕈碱受体拮抗剂的生物碱氨基酸酯化合物、它们的制备方法、包含它们的组合物及其治疗用途。