1H-咪唑-4-甲腈 | 57090-88-7

• 物质功能分类: 医药中间体 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 1H-咪唑-4-甲腈
• 中文别名: 咪唑-4-甲腈；4-氰基咪唑；1H-咪唑-4-氰基
• 英文名称: 1H-imidazole-4-carbonitrile
• 英文别名: 4-cyanoimidazole；4-cyano-1H-imidazole；1H-imidazole-5-carbonitrile
• CAS: 57090-88-7
• 化学式: C₄H₃N₃
• mdl: MFCD00233358
• 分子量: 93.0879
• InChiKey: NWVGXXPWOYZODV-UHFFFAOYSA-N

物化性质

• 熔点：
  143.5-144.5 °C
• 沸点：
  388.1±15.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  7
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  52.5
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  室温且干燥

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 1H-Imidazole-4-carbonitrile
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: 1H-Imidazole-4-carbonitrile
CAS number: 57090-88-7

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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.
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: C4H3N3
Molecular weight: 93.1

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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

1H-咪唑-4-甲腈是一种重要的医药中间体。目前其制备方法仅在US2009/101921234A中有所揭示：通过4-咪唑甲酸酯、浓氨水和氯化铵反应生成4-酰胺咪唑，再与氰化剂反应形成1H-咪唑-4-甲腈。然而，其原料不易获得且价格昂贵，不适合工业化生产。为了适应市场需求，亟需开发一种原料易得、工艺简单、成本较低的1H-咪唑-4-甲腈制备方法。

制备 1.1 1H-咪唑-4-甲醛的制备

在500ml四口瓶中依次加入25.1g（0.254mol）4-羟甲基咪唑和125.5g甲醇，两者质量比为1:5。搅拌均匀后，在室温下缓慢加入66.3g（0.762mol）二氧化锰，4-羟甲基咪唑与二氧化锰的摩尔比为1:3。加料完毕后升温至70℃反应6小时，随后将反应液降温至25℃并过滤除去锰泥。滤液即为1H-咪唑-4-甲醛反应液（0.229mol），收率为90%，直接用于下一步。

1.2 4-甲肟基咪唑的制备

将步骤1所得1H-咪唑-4-甲醛反应液（0.229mol）搅拌降温至25℃，缓慢加入盐酸羟胺19.1g（0.275mol），两者摩尔比为1:1.2。控制温度30℃，室温下保温2小时后脱溶，得到粘稠状釜液4-甲肟基咪唑（0.227mol），收率为99%，直接用于下一步。

1.3 1H-咪唑-4-甲腈的制备

将步骤2所得粘稠状釜液4-甲肟基咪唑（0.227mol）加入69.5g乙酸酐（0.681mol），两者摩尔比为1:3。在100℃下保温反应1小时后减压蒸馏除去乙酸酐，随后控制温度≤30℃滴加25%的氢氧化钠水溶液调节pH至8.0。然后加入乙酸乙酯萃取两次，合并萃取层，再用25%氯化钠水溶液洗涤两次。洗涤后得到油层并减压蒸馏乙酸乙酯，最后在甲苯中脱水，析出大量固体，过滤得到17.6g含量97%的1H-咪唑-4-甲腈，收率为81%。

反应信息

• 作为反应物：
  描述：

  1H-咪唑-4-甲腈 在 ammonium hydroxide 、 氢气 作用下， 以 甲醇 为溶剂， 反应 15.0h， 生成 tert-butyl 2-(3-(((1H-imidazol-4-yl)methyl)amino)propanamido)-3-(benzo[d]thiazol-2-yl)-4,7-dihydrothieno[2,3-c]pyridine-6(5H)-carboxylate
  参考文献：
  名称：

  [EN] COMPOUNDS FOR THE MODULATION OF MYC ACTIVITY
  [FR] COMPOSÉS POUR LA MODULATION DE L'ACTIVITÉ DE MYC

  摘要：

  本发明提供了式（I）和式（II）的新化合物以及药学上可接受的盐、溶剂合物、水合物、互变异构体、立体异构体、同位素标记衍生物及其组合物。还提供了涉及这些化合物或组合物用于治疗或预防增生性疾病的方法和试剂盒，例如癌症（如乳腺癌、前列腺癌、淋巴瘤、肺癌、胰腺癌、卵巢癌、神经母细胞瘤或结肠直肠癌）、良性肿瘤、血管生成、炎症性疾病、纤维化（如多囊肾病）、自身炎症性疾病和自身免疫疾病的方法。

  公开号：

  WO2016197078A1
• 作为产物：
  描述：

  4-(三氟甲基)-1H-咪唑 在 ammonium hydroxide 作用下， 反应 8.0h， 以87%的产率得到1H-咪唑-4-甲腈
  参考文献：
  名称：

  A convenient procedure for the preparation of 4(5)-cyanoimidazoles

  摘要：

  DOI：

  10.1021/jo00366a037
• 作为试剂：
  描述：

  溴代异丁烷 、 4-溴苯甲酸乙酯 在 氯化镍二甲氧基乙烷 、 1H-咪唑-4-甲腈 、 三氟乙酸 、 sodium iodide 、 锌 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 16.0h， 以73%的产率得到ethyl 4-isobutylbenzoate
  参考文献：
  名称：

  新戊基溴化物与芳基溴化物的镍催化交叉亲电还原偶联。

  摘要：

  5-氰基咪唑通过筛选各种药物化合物文库，被确定为镍催化的交叉亲电子偶联的廉价配体。一种战略筛选方法导致了这种新型配体的发现，该配体已成功用于制备各种烷基化芳烃产品，并具有良好的高收率。此外，该配体的性质允许将还原性偶联的范围扩展至具有挑战性的底物，例如空间受阻的新戊基卤化物，已知这些底物产生在生物活性分子中普遍存在的基序。

  DOI：

  10.1021/acs.joc.0c00549

文献信息

• Broad spectrum antibiotics
  申请人：Pfizer Inc.

  公开号：US04025506A1

  公开（公告）日：1977-05-24

  6-[.alpha.-(Amidino- and imidoylaminoalkanoylamino)aracylamino]-penicillanic acids and synthetic methods for the preparation thereof.

  6-α-(酰胺基和亚胺基氨基烷酰氨基)阿拉伯氨基-青霉素酸及其制备的合成方法。
• FUSED MORPHOLINOPYRIMIDINES AND METHODS OF USE THEREOF
  申请人：FORUM Pharmaceuticals Inc.

  公开号：US20170044182A1

  公开（公告）日：2017-02-16

  The present disclosure relates to Fused Morpholinopyrimidines, pharmaceutical compositions comprising an effective amount of a Fused Morpholinopyrimidine and methods for using a Fused Morpholinopyrimidine in the treatment of a neurodegenerative disease, comprising administering to a subject in need thereof an effective amount of a Fused Morpholinopyrimidine.

  本公开涉及融合吗啉吡嘧啶类化合物，包括有效量的融合吗啉吡嘧啶类化合物的药物组合物，以及在治疗神经退行性疾病中使用融合吗啉吡嘧啶类化合物的方法，包括向需要的受试者施用有效量的融合吗啉吡嘧啶类化合物。
• SYNERGISTIC MODULATION OF FLT3 KINASE USING A FLT3 INHIBITOR AND A FARNESYL TRANSFERASE INHIBITOR
  申请人：Baumann Andrew Christian

  公开号：US20060281788A1

  公开（公告）日：2006-12-14

  The invention is directed to a method of inhibiting FLT3 tyrosine kinase activity or expression or reducing FLT3 kinase activity or expression in a cell or a subject comprising the administration of a farnesyl transferase inhibitor and a FLT3 kinase inhibitor selected from compounds of Formula I′: Included within the present invention is both prophylactic and therapeutic methods for treating a subject at risk of (or susceptible to) developing a cell proliferative disorder or a disorder related to FLT3.

  本发明涉及一种抑制FLT3酪氨酸激酶活性或表达或减少细胞或受试者中FLT3激酶活性或表达的方法，包括管理法尼基转移酶抑制剂和从公式I'的化合物中选择的FLT3激酶抑制剂。 本发明包括用于治疗处于发展细胞增殖障碍或与FLT3相关障碍风险（或易感性）的受试者的预防和治疗方法。
• METHOD OF INHIBITING C-KIT KINASE
  申请人：Illig R. Carl

  公开号：US20080051402A1

  公开（公告）日：2008-02-28

  A method of reducing or inhibiting kinase activity of C-KIT in a cell or a subject, and the use of such compounds for preventing or treating in a subject a cell proliferative disorder and/or disorders related to C-KIT using a compound of the present invention: or a solvate, hydrate, tautomer or pharmaceutically acceptable salt thereof. The present invention is further directed to methods for treating conditions such as cancers and other cell proliferative disorders.

  本发明提供了一种减少或抑制细胞或主体中C-KIT激酶活性的方法，以及使用本发明的化合物预防或治疗主体中的细胞增殖障碍和/或与C-KIT相关疾病的应用：或其溶剂化物、水合物、互变异构体或药用可接受盐。本发明进一步涉及治疗癌症和其他细胞增殖障碍等条件的方法。
• Synthesis and antibacterial activity of novel 4-pyrrolidinylthio carbapenems. Part III:
  作者：Hidenori Azami、David Barrett、Keiji Matsuda、Hideo Tsutsumi、Kenichi Washizuka、Minoru Sakurai、Satoru Kuroda、Fumiyuki Shirai、Toshiyuki Chiba、Toshiaki Kamimura、Masayoshi Murata

  DOI：10.1016/s0968-0896(99)00085-1

  日期：1999.8

  The synthesis and biological activity of a novel series of 2-alkyl-4-pyrrolidinylthio-beta-methylcarbapenems containing a variety of cationic heteroaromatic substituents is described. As a result of these studies, we uncovered a relationship between in vitro antibacterial activity and the length of the alkyl spacer part, and discovered FR20950 (1c), containing a two methylene spacer moiety and an imidazolio

  描述了含有各种阳离子杂芳族取代基的一系列新的2-烷基-4-吡咯烷基硫基-β-甲基卡巴南的合成和生物活性。这些研究的结果是，我们发现了体外抗菌活性与烷基间隔部分长度之间的关系，并发现了含有两个亚甲基间隔部分和一个咪唑基团的FR20950（1c），该基团具有均衡的抗菌谱活性，包括铜绿假单胞菌和耐甲氧西林的金黄色葡萄球菌（MRSA）。此外，FR20950表现出出色的尿液恢复能力，并且与比阿培南相比具有相对于肾脏脱氢肽酶-I（DHP-1）相当的稳定性。通过在咪唑环上引入取代基可以改善DHP-1的稳定性。