5-氨基-1-甲基-1H-吲唑 | 50593-24-3

• 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 - 苯并吡唑类
• 中文名称: 5-氨基-1-甲基-1H-吲唑
• 中文别名: 1-甲基-5-氨基-1H-吲唑
• 英文名称: 1-methyl-1H-indazol-5-amine
• 英文别名: 5-amino-1-methyl-1H-indazole；1-methyl-5-aminoindazole；1-methyl-1H-indazol-5-ylamine；5-Amino-1-methyl-indazol；1-methyl-5-amino-1H-indazole；1-methylindazol-5-amine
• CAS: 50593-24-3
• 化学式: C₈H₉N₃
• mdl: MFCD03305455
• 分子量: 147.18
• InChiKey: PYOFNPHTKBSXOM-UHFFFAOYSA-N

物化性质

• 熔点：
  142-144°C
• 沸点：
  321.6±15.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.125
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  室温且干燥环境下使用。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 1-Methyl-1h-indazol-5-amine
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-Methyl-1h-indazol-5-amine
CAS number: 50593-24-3

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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: C8H9N3
Molecular weight: 147.2

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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

用途

5-氨基-1-甲基-1H-吲唑主要用于制备具有(杂)芳基的腙类化合物，并用于治疗与tau蛋白相关的疾病。此外，该化合物还被用作合成二氢异吲哚-1H-吡唑罗[3,4-d]嘧啶酮类化合物的重要中间体，后者作为Wee1抑制剂应用于激酶相关疾病的治疗。

应用前景

5-氨基-1-甲基-1H-吲唑是一种关键的医药中间体，在构建活性药物分子母核方面发挥重要作用。在小分子化学药物合成、筛选等领域展现出广阔的应用前景。含有吲唑环结构的活性药物分子，作为潜在的蛋白激酶抑制剂，在癌症、心血管疾病、心脏疾病、免疫缺陷、青光眼、糖尿病和炎症等多种疾病的治疗中具有重要应用价值。

制备

5-氨基-1-甲基-1H-吲唑可通过2-氨基-5-硝基甲苯为原料进行制备。具体步骤如下：

1. 将55克2-氨基-5-硝基甲苯溶解于2.5升冰乙酸中，冷却至所需温度，在不超过25℃的条件下加入25克亚硝酸钠和60毫升水配成的溶液。
2. 反应生成黄色沉淀后过滤除去，反应液放置3天后减压浓缩。
3. 将剩余物用200毫升水搅打成糊状，过滤并用水洗涤滤饼，干燥后用甲醇重结晶。此过程可得到42-47克5-硝基吲唑，收率约为72%-80%。

接下来是进一步的反应步骤：

1. 在三口反应瓶中加入N,N-二甲基甲酰胺和5-硝基吲唑，搅拌30分钟。在0℃下缓慢滴加碘甲烷，并在室温条件下继续反应。
2. 使用薄层色谱检测反应进度，待反应完全后，用乙酸乙酯洗涤并水洗3～4次。有机相经无水硫酸镁干燥后过滤浓缩，得到5-硝基-1-甲基-1H-吲唑。

最后的步骤为：

1. 将5-硝基-1-甲基-1H-吲唑加入2升单口瓶中，并用甲醇溶解。在搅拌下加入Pd/C(10克，Pd∶C=10∶1)，排除空气后通入氢气。
2. 室温搅拌4小时直至反应完全。抽滤去除Pd/C，将滤液蒸除溶剂得到固体粗品，再用500毫升乙酸乙酯溶解，并用水洗涤有机相两次。经无水硫酸钠干燥后，除去溶剂并以正己烷处理残余物，最终获得目标化合物5-氨基-1-甲基-1H-吲唑。

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  1-甲基-5-硝基-1H-吲唑	1-methyl-5-nitro-1H-indazole	5228-49-9	C8H7N3O2	177.162
  5-硝基吲唑	5-nitroindazole	5401-94-5	C7H5N3O2	163.136

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  5-碘-1-甲基-1H-吲唑	5-iodo-1-methyl-1H-indazole	1072433-59-0	C8H7IN2	258.061
  ——	(R)-methyl 2-hydroxy-3-(1-methyl-1H-indazol-5-ylamino)propanoate	945928-50-7	C12H15N3O3	249.269
  1-甲基-1H-吲唑-5-醇	1-methyl-1H-indazol-5-ol	756839-14-2	C8H8N2O	148.164
  ——	benzyl (1-methyl-1H-indazol-5-yl)carbamate	945928-65-4	C16H15N3O2	281.314
  ——	2-[(1-Methylindazol-5-yl)amino]benzoic acid	132283-39-7	C15H13N3O2	267.287
  ——	1-methyl-1H-indazole-5-sulfonyl chloride	1097730-93-2	C8H7ClN2O2S	230.675

反应信息

• 作为反应物：
  描述：

  5-氨基-1-甲基-1H-吲唑 在 硫酸 、 铜 作用下， 以 戊醇 为溶剂， 反应 11.0h， 生成 3-methylpyrazolo<4,3-a>acridin-9(10H)-one
  参考文献：
  名称：

  Boyer, Gerard; Galy, Jean-Pierre; Faure, Robert, Journal of Chemical Research, Miniprint, 1990, # 11, p. 2601 - 2615

  摘要：

  DOI：
• 作为产物：
  描述：

  1-甲基-5-硝基-1H-吲唑 在 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 为溶剂， 生成 5-氨基-1-甲基-1H-吲唑
  参考文献：
  名称：

  发现1-（1H-吲唑-4-基）-3-（（1-苯基-1H-吡唑-5-基）甲基）尿素作为有效和热中性TRPV1拮抗剂。

  摘要：

  研究了一系列1-吲唑-3-（1-苯基吡唑-5-基）甲基脲作为h TRPV1拮抗剂。系统地研究了吲唑A区和3-三氟甲基/叔丁基吡唑C区的结构-活性关系，以优化对辣椒素活化的拮抗作用。其中，拮抗剂26，50和51显示具有高度有效的拮抗作用ķ我（CAP） = 0.4-0.5纳米。此外，在小鼠体内的研究表明，这些衍生物均拮抗辣椒素诱导的体温过低，与它们的体外相符活动，并且他们自己没有诱发热疗。在福尔马林模型中，51以剂量依赖性方式显示出抗伤害感受活性。

  DOI：

  10.1016/j.bmcl.2020.127548

文献信息

• [EN] PYRROLOTRIAZINES AS ALK AND JAK2 INHIBITORS<br/>[FR] PYRROLOTRIAZINES EN TANT QU'INHIBITEURS D'ALK ET DE JAK2
  申请人：CEPHALON INC

  公开号：WO2010071885A1

  公开（公告）日：2010-06-24

  The present invention provides a compound of formula (I) or a salt form thereof, wherein Q1, Q2, Q3, and Q4 are as defined herein. The compound of formula (I) has ALK and/or JAK2 inhibitory activity, and may be used to treat proliferative disorders.

  本发明提供了一种式（I）的化合物或其盐形式，其中Q1、Q2、Q3和Q4如本文所定义。式（I）的化合物具有ALK和/或JAK2抑制活性，并可用于治疗增殖性疾病。
• Uniting Amide Synthesis and Activation by P^III/P^V–Catalyzed Serial Condensation: Three-Component Assembly of 2-Amidopyridines
  作者：Jeffrey M. Lipshultz、Alexander T. Radosevich

  DOI：10.1021/jacs.1c07608

  日期：2021.9.15

  An organophosphorus (PIII/PV redox) catalyzed method for the three-component condensation of amines, carboxylic acids, and pyridine N-oxides to generate 2-amidopyridines via serial dehydration is reported. Whereas amide synthesis and functionalization usually occur under divergent reaction conditions, here a phosphetane catalyst (together with a mild bromenium oxidant and terminal hydrosilane reductant)

  报道了一种有机磷（P III /P V氧化还原）催化胺、羧酸和吡啶N-氧化物三组分缩合通过连续脱水生成 2-氨基吡啶的方法。虽然酰胺合成和官能化通常发生在不同的反应条件下，但此处显示膦烷催化剂（与温和的溴氧化剂和末端氢硅烷还原剂一起）在自动串联催化级联中以化学选择性驱动这两个步骤。在单一有机催化活性中间体的作用下制备和官能化酰胺的能力为高效和模块化制备药物靶标提供了新的可能性。
• Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 (MAPKAP-K2) as an Antiinflammatory Target: Discovery and in Vivo Activity of Selective Pyrazolo[1,5-<i>a</i>]pyrimidine Inhibitors Using a Focused Library and Structure-Based Optimization Approach
  作者：Tomomi Kosugi、Dale R. Mitchell、Aiko Fujino、Minoru Imai、Mika Kambe、Shinji Kobayashi、Hiroaki Makino、Yohei Matsueda、Yasuhiro Oue、Kanji Komatsu、Keiichiro Imaizumi、Yuri Sakai、Satoshi Sugiura、Osami Takenouchi、Gen Unoki、Yuko Yamakoshi、Vicky Cunliffe、Julie Frearson、Richard Gordon、C. John Harris、Heidi Kalloo-Hosein、Joelle Le、Gita Patel、Donald J. Simpson、Brad Sherborne、Peter S. Thomas、Naotaka Suzuki、Midori Takimoto-Kamimura、Ken-ichiro Kataoka

  DOI：10.1021/jm300411k

  日期：2012.8.9

  A novel class of mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP-K2) inhibitors was discovered through screening a kinase-focused library. A homology model of MAPKAP-K2 was generated and used to guide the initial SAR studies and to rationalize the observed selectivity over CDK2. An X-ray crystal structure of a compound from the active series bound to crystalline MAPKAP-K2 confirmed

  通过筛选激酶集中的文库，发现了一类新型的促分裂原活化蛋白激酶活化蛋白激酶2（MAPKAP-K2）抑制剂。MAPKAP-K2的同源性模型已生成，可用于指导最初的SAR研究并合理化所观察到的对CDK2的选择性。结合到晶体MAPKAP-K2的活性系列化合物的X射线晶体结构证实了预测的结合模式。这使得能够发现一系列吡唑并[1,5- a ]嘧啶衍生物，它们在抗内毒素休克的小鼠模型中作为抗TNF-α剂具有良好的体外细胞效价和体内功效。
• [EN] FURO[3,2-d]PYRIMIDINE COMPOUNDS<br/>[FR] COMPOSÉS DE FURO[3,2-D]PYRIMIDINE
  申请人：ABBOTT LAB

  公开号：WO2012048222A1

  公开（公告）日：2012-04-12

  The present invention is directed to novel compounds of Formula (I), pharmaceutically acceptable salts, biologically active metabolites, pro-drugs, racemates, enantiomers, diastereomers, solvates and hydrates thereof wherein the variables are defined as herein. The compounds of Formula (I) are useful as kinase inhibitors and as such would be useful in treating certain conditions and diseases, especially inflammatory conditions and diseases and proliferative disorders and conditions, for example, cancers.

  本发明涉及式(I)的新化合物、药用可接受的盐、生物活性代谢物、前药、外消旋混合物、对映异构体、非对映异构体、溶剂合物和水合物，其中变量如本文所述定义。式(I)的化合物作为激酶抑制剂是有用的，因此可用于治疗某些状况和疾病，特别是炎症状况和疾病以及增殖性障碍和状况，例如癌症。
• [EN] OXAZOLIDINONE HYDROXAMIC ACID COMPOUNDS FOR THE TREATMENT OF BACTERIAL INFECTIONS<br/>[FR] COMPOSÉS D'ACIDE OXAZOLIDINONE-HYDROXAMIQUE POUR LE TRAITEMENT D'INFECTIONS BACTÉRIENNES
  申请人：NOVARTIS AG

  公开号：WO2015066413A1

  公开（公告）日：2015-05-07

  This invention pertains generally to treating bacterial infections using organic compounds of Formula I. In certain aspects, the invention pertains to treating infections caused by Gram-negative bacteria. (I) wherein X, Y, R1, R2, R3, R4 and R5 and defined herein.

  这项发明通常涉及使用式I的有机化合物治疗细菌感染。在某些方面，该发明涉及治疗由革兰氏阴性细菌引起的感染。其中X、Y、R1、R2、R3、R4和R5在此定义。