1-甲基六氢氮杂卓-4-酮盐酸盐 | 19869-42-2

• 物质功能分类: 化学试剂 - 有机试剂 - 脂肪酮(含烯醇)
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂环庚烷
• 中文名称: 1-甲基六氢氮杂卓-4-酮盐酸盐
• 中文别名: N-甲基-4-氮杂卓酮盐酸盐；N-甲基氮卓-4-酮盐酸盐；1-甲基六氢-4H-氮杂卓-4-酮盐酸盐；1-甲基氮卓-4-酮盐酸盐；1-甲基六氢-4H-氮杂卓-4-酮；1-甲基-六氢氮杂卓-4-酮盐酸盐；N-甲基六氢氮杂卓-4-酮盐酸盐；盐酸氮卓斯汀中间体(七元环)；1-甲基六氢氮卓基-4-酮盐酸盐
• 英文名称: 1-methylazepan-4-one hydrochloride
• 英文别名: 1-methylazepan-4-one;hydrochloride
• CAS: 19869-42-2
• 化学式: C₇H₁₃NO*ClH
• mdl: MFCD07779465
• 分子量: 163.647
• InChiKey: BHSJZGRGJYULPA-UHFFFAOYSA-N

物化性质

• 熔点：
  115-120°C
• 沸点：
  97-100°C
• 溶解度：
  可溶于氯仿（轻微、加热）、DMSO（轻微）

计算性质

• 辛醇/水分配系数(LogP)：
  0.46
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.857
• 拓扑面积：
  20.3
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933990090
• 危险类别：
  IRRITANT
• 安全说明：
  S24/25
• 危险性防范说明：
  P261,P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H332,H335
• 储存条件：
  适宜在室温和干燥的环境中存放。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 1-Methylhexahydroazepin-4-one, HCl
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: 1-Methylhexahydroazepin-4-one, HCl
CAS number: 19869-42-2

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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: C7H13NO.ClH
Molecular weight: 163.6

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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, hydrogen chloride.

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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

N-甲基六氢氮杂卓-4-酮盐酸盐的概述

N-甲基六氢氮杂卓-4-酮盐酸盐是一种化工原料，也可用作化工医药中间体。它主要用于合成抗哮喘药物——盐酸氮卓斯汀。

制备过程 第一步

将18克N-甲基-2-吡咯烷酮加入到37毫升浓盐酸中搅拌回流5小时。冷却后，减压蒸馏除去盐酸至干，得到的固体物用50毫升冷丙酮溶解、搅动并冷却。结晶析出后，通过冷冻使其完全析出，过滤并用15毫升丙酮洗涤两次，抽干后干燥，最终获得24.2克产品，总收率为88.2%。

第二步

在外浴温度控制在-5℃至0℃的情况下，向150毫升无水甲醇中滴加氯化亚砜40毫升，并保持反应液内温不超过-3℃。约3小时内完成滴加，随后加入第一步获得的产物20克，室温下反应12小时。减压浓缩甲醇后，母液搅拌均匀，备用。

第三步

在25℃条件下，将22克丙烯酸甲酯和20克三乙胺溶解于150毫升无水甲醇中，并加热至回流状态。随后，在搅拌下滴加第二步所得的母液，约1小时内完成滴加。升温至回流4小时后过滤，滤液减压蒸干；剩余物为浅黄色双酯(c)。

第四步

向80毫升二甲苯中加入10克叔丁醇钾搅拌并回流半小时后，均匀地分批加入10克步骤(3)中的双酯(c)，边滴加边蒸除副产物叔丁醇。2小时内完成滴加，继续回流反应3小时。冷却至10℃后，在搅拌下慢慢加入25克碎冰与25毫升浓盐酸的混合物，搅拌20分钟后静置。分出有机层并用浓盐酸20毫升和去离子水19毫升提取一次，合并有机层。

第五步

将上述有机层加热回流约6小时后，加入约50克冰块与萃取剂二氯甲烷100毫升，并在冷冻条件下使用液碱调pH值至12.5。继续搅拌20分钟后静置分层。水相再用30毫升二氯甲烷提取一次，合并有机层后用水10毫升反洗一次。使用无水硫酸钠干燥上述混合物。

第六步

步骤(5)中干燥后的有机层通过水浴减压蒸馏除去二氯甲烷。然后向剩余的母液中加入30毫升异丙醇溶解，冷却至10℃后用盐酸异丙醇调pH值到1.0～2之间，并静置结晶。在0℃下进行减压干燥处理，最终获得土黄色N-甲基六氢氮杂卓-4-酮盐酸盐7.2克，收率为95.64%（基于双酯计算），熔点为165.8～166.4℃，纯度达99%。

反应信息

• 作为反应物：
  描述：

  1-甲基六氢氮杂卓-4-酮盐酸盐 在 氢氧化钾 、 sodium tetrahydroborate 、 苯甲酰肼 、 盐酸 作用下， 以 水 为溶剂， 生成 (±)-4-hydrazinyl-1-methylazepane hydrogenchloride
  参考文献：
  名称：

  Crystalline form of azelastine

  摘要：

  阿齐拉斯汀的多形态I的化学式(I)，其制备过程包括以下步骤：a)从异丁基甲基酮溶液中结晶化阿齐拉斯汀；b)分离出在上一步骤中出现的阿齐拉斯汀的多形态I；c)从所得的阿齐拉斯汀多形态I中去除有机溶剂，并将其用作抗组胺药。

  公开号：

  EP2072510A1
• 作为产物：
  描述：

  氮杂环庚烷-2,5-二酮 在 potassium carbonate 、 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 反应 32.0h， 生成 1-甲基六氢氮杂卓-4-酮盐酸盐
  参考文献：
  名称：

  一种制备N-甲基氮卓-4-酮盐酸盐的方法

  摘要：

  本发明公开一种制备N‑甲基氮卓‑4‑酮盐酸盐的方法。该方法以4‑肟环已酮为原料，在Beckmann重排条件下得到氮杂环庚烷‑2,5‑二酮，接着与乙二醇缩合生成缩酮，经红铝还原酰胺，再甲基化，在盐酸条件下脱掉乙二醇最终得到N‑甲基氮卓‑4‑酮盐酸盐。本发明提供一种安全可靠高效的合成途径，原料价格便宜，反应条件温和，不需要使用易爆的重氮甲烷，也不需要丙烯酸甲酯这种易聚合且高致癌的化学试剂，本方法更适合工业大规模生产。

  公开号：

  CN112920120B

文献信息

• [EN] METHOD FOR INHIBITION OF DEUBIQUITINATING ACTIVITY<br/>[FR] MÉTHODE D'INHIBITION DE L'ACTIVITÉ DE DÉSUBIQUITINATION
  申请人：VIVOLUX AB

  公开号：WO2013058691A1

  公开（公告）日：2013-04-25

  A compound of the general structure (I) is capable of abrogating the deubiquitinating (DUB) activity of the 19S RP DUBs. The compound can be used for treating cancer, in particular of cancer refractory to treatment by state-of-the-art chemotherapy. Also disclosed are corresponding methods of treatment and a pharmaceutical composition comprising the compound.

  一种具有一般结构（I）的化合物能够废除19S RP DUBs的去泛素化（DUB）活性。该化合物可用于治疗癌症，特别是对于无法通过最先进化疗治疗的癌症。还公开了相应的治疗方法和包含该化合物的药物组合物。
• [EN] TRICYCLIC PSYCHOPLASTOGENS AND USES THEREOF<br/>[FR] PSYCHOPLASTOGÈNES TRICYCLIQUES ET LEURS UTILISATIONS
  申请人：DELIX THERAPEUTICS INC

  公开号：WO2021252691A1

  公开（公告）日：2021-12-16

  Disclosed herein are compounds, compositions, and methods for promoting neuronal growth and/or improving neuronal structure with the compounds and compositions disclosed herein. Also described are methods of treating diseases or disorders that are mediated by the loss of synaptic connectivity and/or plasticity, such as neurological diseases and disorders, with non-hallucinogenic psychoplastogens.

  本文披露了一些化合物、组合物和方法，用于促进神经元生长和/或改善神经元结构，所述化合物和组合物。还描述了使用非致幻性精神塑形剂治疗由突触连接丧失和/或可塑性介导的疾病或障碍的方法，如神经系统疾病和障碍。
• [EN] AZEPINO-INDOLES AND OTHER HETEROCYCLES FOR TREATING BRAIN DISORDERS<br/>[FR] AZÉPINO-INDOLES ET AUTRES HÉTÉROCYCLES POUR TRAITER DES TROUBLES DU CERVEAU
  申请人：UNIV CALIFORNIA

  公开号：WO2020176599A1

  公开（公告）日：2020-09-03

  The present invention provides azepino-indoles and other heterocycles and methods of using the compounds for treating brain disorders.

  本发明提供了氮杂环戊二酮吲哚类化合物和其他杂环化合物，以及利用这些化合物治疗脑部疾病的方法。
• Microwave-Assisted Synthesis of Nitro-Substituted Tetrahydropyrido­azepines
  作者：Wilfried Braje、Thomas Schultz、Sean Turner

  DOI：10.1055/s-0029-1218678

  日期：2010.4

  The microwave-assisted condensation of azepan-4-ones with 3,5-dinitro-1-methylpyridin-2-one in the presence of ammonia was found to be a highly efficient method for the synthesis of nitro-substituted tetrahydropyridoazepines. Variation of the substituent at the amino group enables the regioselective synthesis of tetrahydropyrido[3,2-c]azepines and tetrahydropyrido[2,3-d]azepines.

  氨存在下，与3,5-二硝基-1-甲基吡啶-2-酮进行微波辅助缩合反应，被发现是合成硝基取代四氢吡啶并氮杂酮的一种高效方法。氨基上取代基的变化使得能够区域选择性地合成四氢吡啶并[3,2-c]氮杂酮和四氢吡啶并[2,3-d]氮杂酮。
• [EN] AZEPINO [4, 5-B] INDOLES AND METHODS OF USE<br/>[FR] AZÉPINO[4,5-B]INDOLES ET PROCÉDÉS POUR LEUR UTILISATION
  申请人：MEDIVATION TECHNOLOGIES INC

  公开号：WO2010051503A1

  公开（公告）日：2010-05-06

  This disclosure relates to new azepino[4,5-b]indole compounds that may be used to modulate a histamine receptor in an individual. Novel compounds are described, including new 1, 2,3,4,5, 6-tetrahydroazepino[4,5-b]indoles. Pharmaceutical compositions are also provided.

  这份披露涉及新的azepino[4,5-b]indole化合物，可用于调节个体中的组胺受体。描述了新的化合物，包括新的1, 2, 3, 4, 5, 6-六氢azepino[4,5-b]indoles。还提供了药物组合物。