4-(2-氨乙基)四氢吡喃 | 65412-03-5

• 物质功能分类: 医药中间体 - 吡喃类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧烷类
• 中文名称: 4-(2-氨乙基)四氢吡喃
• 中文别名: 2-(四氢-2H-吡喃-4-基)乙胺
• 英文名称: 4-(2-aminoethyl)tetrahydropyran
• 英文别名: 2-(tetrahydro-2H-pyran-4-yl)ethan-1-amine；2-(tetrahydro-2H-pyran-4-yl)ethanamine；2-(tetrahydro-pyran-4-yl)-ethylamine；2-tetrahydropyran-4-ylethanamine；2-(oxan-4-yl)ethanamine
• CAS: 65412-03-5
• 化学式: C₇H₁₅NO
• mdl: MFCD02179433
• 分子量: 129.202
• InChiKey: BZMADPOGYCRPAI-UHFFFAOYSA-N

物化性质

• 沸点：
  88-89°C 13mm
• 密度：
  0.931±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  9
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  35.2
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26,S36/37/39
• 危险类别码：
  R36/37/38
• 海关编码：
  2932999099
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  保持冷静

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 4-(2-Aminoethyl)tetrahydropyran
Synonyms: 2-(Tetrahydropyran-4-yl)ethylamine

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H315: Causes skin irritation
H318: Causes serious eye damage
H335: May cause respiratory irritation
P261: Avoid breathing dust/fume/gas/mist/vapours/spray
P280: Wear protective gloves/protective clothing/eye protection/face protection
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing

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Section 3. Composition/information on ingredients.
Ingredient name: 4-(2-Aminoethyl)tetrahydropyran
CAS number: 65412-03-5

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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.
Storage: Store in closed vessels.

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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
No data
Boiling point:
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C7H15NO
Molecular weight: 129.2

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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

概述

4-(2-氨乙基)四氢吡喃是新药贝福普兰的主要原料之一，直接影响到倍福普兰的成本、规模以及后续的推广应用。现有技术中，关于4-(2-氨乙基)四氢吡喃的合成方法包括：方法1是以吡喃酮和氰甲基磷酸二乙酯反应生成；方法2采用四氢-2H-吡喃-4-丙酸与叠氮化钠反应生成；方法3是4-氯四氢吡喃与氰乙酸甲酯反应生成。

制备方法 1. 反应步骤

步骤一：

以4-氯四氢吡喃、氰乙酸甲酯和叔丁醇钾为原料，按照摩尔比0.9:1投料，并溶解于100ml甲苯中。在50℃下搅拌反应12小时后，升温至110℃继续反应12小时。反应完成后，用300ml水洗涤三次，有机相减压浓缩，得到油状物2-氰基-2-(四氢-4-吡喃基)乙酸甲酯113.6g（0.62mol）。

步骤二：

将2-氰基-2-(四氢-4-吡喃基)乙酸甲酯113.6g、水10.8ml和氯化钠10.8g加入烧瓶中，再加入540ml二甲基亚砜。在150℃下搅拌反应8小时后进行蒸馏，并用1000ml水搅拌，通过乙醚萃取四次收集有机相。分别用水和饱和食盐水洗涤有机相，干燥脱色后蒸馏得到油状物(四氢-4-吡喃基)-乙腈75g（0.60mol）。

步骤三：

在加氢釜中加入(四氢-4-吡喃基)乙腈75g、Pd/C2.5g和400ml乙醇，置换三次后进行加氢反应。控制压力1MPa，温度25℃下搅拌反应12小时。反应完毕过滤，滤液转移至烧瓶中减压蒸馏得到4-(2-氨乙基)四氢吡喃油状物65.8g（0.51mol）。所得产品收率为76.1%，纯度为98.5%。

反应信息

• 作为反应物：
  描述：

  4-(2-氨乙基)四氢吡喃 在 palladium 10% on activated carbon 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 3.0h， 生成 4-(1,3-benzoxazol-2-yl)-1-N-[2-(oxan-4-yl)ethyl]benzene-1,2-diamine
  参考文献：
  名称：

  AGENT FOR TREATMENT OR PREVENTION OF DISEASES ASSOCIATED WITH ACTIVITY OF NEUROTROPHIC FACTORS

  摘要：

  公开号：

  EP2436683B1
• 作为产物：
  描述：

  4-氰基甲基四氢吡喃 在 palladium on activated charcoal 、 氢气 作用下， 以 乙醇 为溶剂， 25.0 ℃ 、1.0 MPa 条件下， 反应 12.0h， 以76.1%的产率得到4-(2-氨乙基)四氢吡喃
  参考文献：
  名称：

  一种4-(2-氨乙基)四氢吡喃的合成方法

  摘要：

  本发明属于化学药物中间体的合成技术领域，具体涉及一种药物贝福普兰中间体4‑(2‑氨乙基)四氢吡喃的合成方法。该方法包括如下步骤：（1）4‑氯四氢吡喃与氰乙酸甲酯反应得到2‑氰基‑2‑（四氢‑4‑吡喃基）乙酸甲酯；（2）2‑氰基‑2‑（四氢‑4‑吡喃基）乙酸甲酯脱酯得到（四氢‑4‑吡喃基）‑乙腈；（3）(四氢‑4‑吡喃基）‑乙腈 C加氢反应得到4‑(2‑氨乙基)四氢吡喃。该方法采用4‑氯四氢吡喃，氰乙酸甲酯为原料，该方法反应时间短，成本较低，原料易得，无剧毒管制及不稳定的化学原料，安全有效，产率较高，杂质较少。

  公开号：

  CN106083787B
• 作为试剂：
  描述：

  6-(2-fluoro-4-formyl-phenoxy)-nicotinamide 、 4-(2-氨乙基)四氢吡喃 在 4-(2-氨乙基)四氢吡喃 作用下， 以71.3的产率得到Ondelopran
  参考文献：
  名称：

  Diaryl ethers as opioid receptor antagonist

  摘要：

  公开了化合物的公式（I），其中变量X1至X10，R1至R7包括R3'，E，v，y，z，A和B如所述，或其药学上可接受的盐，溶剂化物，对映体，外消旋体，非对映异构体或其混合物，用于治疗，预防或改善肥胖症和相关疾病。

  公开号：

  US07381719B2

文献信息

• Novel Affinity Ligands for Chromatography Using Combinatorial Chemistry
  作者：Tor Regberg、Charlotta Lindquist、Ake Pilotti、Christel Ellstrom、Lars Fagerstam、Ann Eckersten、Yasuro Shinohara、Steven L. Gallion、Joseph C. Hogan

  DOI：10.2174/138620711795222482

  日期：2011.5.1

  Spatially addressable combinatorial libraries were synthesized by solution phase chemistry and screened for binding to human serum albumin. Members of arylidene diamide libraries were among the best hits found, having submicromolar binding affinities. The results were analyzed by the frequency with which particular substituents appeared among the most potent compounds. After immobilization of the ligands either through the oxazolone or the amine substituent, characterization by surface plasmon resonance showed that ibuprofen affected the binding kinetics, but phenylbutazone did not. It is therefore likely that these compounds bind to Site 2 in sub domain IIIA of human serum albumin (HSA).

  通过溶液相化学合成了空间可寻址的组合库，并对其与人体血清白蛋白的结合能力进行了筛选。在发现的优秀结合分子中，有一类是芳亚基二酰胺类化合物，它们具有亚微摩尔级别的结合亲和力。通过对这些最强效化合物中特定取代基出现的频率进行分析，得出了结果。通过醛酮或胺取代基将配体固定化后，利用表面等离子体共振技术进行表征，结果显示布洛芬影响了结合动力学，而保泰松则没有。因此，这些化合物很可能结合在人血清白蛋白（HSA）亚域IIIA的第2位点上。
• Quinoline derivatives as H3R inverse agonists
  申请人：McArthur Gatti Silvia

  公开号：US20060084679A1

  公开（公告）日：2006-04-20

  The present invention relates to compounds of formula I: and pharmaceutically acceptable salts thereof as well as to pharmaceutical compositions comprising these compounds and to methods for their preparation. The compounds are useful for the treatment and/or prevention of diseases which are associated with the modulation of H3 receptors.

  本发明涉及以下式I的化合物： 以及其药用盐，以及包含这些化合物的药物组合物，以及其制备方法。这些化合物可用于治疗和/或预防与H3受体调节相关的疾病。
• BENZIMIDAZOLE AND IMADAZOPYRIDINE CARBOXIMIDAMIDE COMPOUNDS
  申请人：Gilead Sciences, Inc.

  公开号：US20160333009A1

  公开（公告）日：2016-11-17

  The present disclosure provides indoleamine 2,3-dioxygenase 1 (IDOL) inhibitors of Formula I: or pharmaceutically acceptable salts thereof, in which X, L, n, m, R 1 , R 2a , R 2b , R n , R m , and R t are as defined herein, as well as pharmaceutical compositions that include a compound of Formula I, or pharmaceutically acceptable salts thereof, and methods of using the same to treat conditions mediated by IDO1.

  本公开提供了式I的吲哌酮2,3-二氧化酶1（IDOL）抑制剂： 或其药学上可接受的盐，其中X、L、n、m、R 1 、R 2a 、R 2b 、R n 、R m 和R t 如本文所定义，以及包括式I化合物的药物组合物，或其药学上可接受的盐，并使用这些方法来治疗由IDO1介导的疾病。
• [EN] THERAPEUTIC COMPOUNDS: PYRIDINE AS SCAFFOLD<br/>[FR] COMPOSES THERAPEUTIQUES DANS LESQUELS LA PYRIDINE EST UTILISEE COMME SQUELETTE
  申请人：ASTRAZENECA AB

  公开号：WO2005115986A1

  公开（公告）日：2005-12-08

  Compounds of formulas I, IA, and IB or IC or pharmaceutically acceptable salts thereof: wherein A, A1, A2, A3, A4, R2, R3, R4 and n are as defined in the specifications well as salts and pharmaceutical compositions including the compounds are prepared. They are useful in therapy, in particular in the management of pain.

  其中A、A1、A2、A3、A4、R2、R3、R4和n的化合物的公式I、IA和IB或IC或其药学上可接受的盐：其中A、A1、A2、A3、A4、R2、R3、R4和n的定义如规范中所述，以及包括这些化合物的盐和药物组合物已经准备好。它们在治疗中很有用，特别是在疼痛管理中。
• [EN] RESPIRATORY SYNCYTIAL VIRUS INHIBITORS<br/>[FR] INHIBITEURS DU VIRUS RESPIRATOIRE SYNCYTIAL
  申请人：MEDIVIR AB

  公开号：WO2015065336A1

  公开（公告）日：2015-05-07

  Compounds of Formula (I): wherein R1, R2 and R3 are defined herein, are useful as inhibitors of RSV.

  式(I)的化合物：其中R1、R2和R3如本文所定义，可用作RSV的抑制剂。