7-羧基-1H-吲唑 | 677304-69-7

• 物质功能分类: 医药中间体
• 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: 7-羧基-1H-吲唑
• 中文别名: 1H-吲唑-7-羧酸；吲唑-7-羧酸；吲唑-7-甲酸
• 英文名称: 1H-indazole-7-carboxylic acid
• CAS: 677304-69-7
• 化学式: C₈H₆N₂O₂
• mdl: MFCD06804572
• 分子量: 162.148
• InChiKey: WBCWIQCXHSXMDH-UHFFFAOYSA-N

物化性质

• 熔点：
  ca 240℃
• 沸点：
  443.7±18.0 °C(Predicted)
• 密度：
  1.506±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  66
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090
• WGK Germany：
  3
• 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

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
1H-indazole-7-carboxylic acid
Product Name:
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H315: Causes skin irritation
H319: Causes serious eye irritation
H335: May cause respiratory irritation
P261: Avoid breathing dust/fume/gas/mist/vapours/spray
Wear protective gloves/protective clothing/eye protection/face protection
P280:
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing
P304+P340: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing
P405: Store locked up

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Section 3. Composition/information on ingredients.
1H-indazole-7-carboxylic acid
Ingredient name:
CAS number: 677304-69-7

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Section 4. First aid measures
Immediately wash skin with copious amounts of water for at least 15 minutes while removing
Skin contact:
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.
Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.
Ingestion:

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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, refrigerated.

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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
Not specified
Appearance:
Boiling point: No data
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C8H6N2O2
Molecular weight: 162.1

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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

应用

7-羧基-1H-吲唑作为众多医药和农药的中间体时，表现出了强大的生物活性和潜在的药理学特性。

制备过程

步骤1：将酯（106 mmol）溶解于氯仿（300 mL）中，然后在温度低于40°C的情况下逐滴加入乙酸酐（239 mmol）。随后，添加乙酸钾（30.6 mmol）和亚硝酸异戊酯（228 mmol），并在室温下搅拌1小时。将反应混合物加热回流24小时后冷却至室温，用饱和碳酸氢钠水溶液洗涤，然后使用硫酸钠干燥并浓缩。向残余物中加入甲醇（100 mL）和6 N盐酸（100 mL），在室温下搅拌18小时。通过减压蒸馏除去挥发性物质，并用乙酸乙酯（100 mL）研磨残余物。产物通过过滤分离，再用乙酸乙酯（20 mL）洗涤并干燥，最终以68%的产率得到1H-吲唑-7-甲酸甲酯盐酸盐。

步骤2：在0°C下，将吲唑（33.0 mmol）溶解于甲醇（100 mL）中，并用29%氢氧化钾水溶液（20 mL）处理。反应混合物升温至室温并搅拌18小时后，通过加入浓盐酸调节pH值至5.5，并减压除去挥发性物质。残余物在盐水（100 mL）和乙酸乙酯（200 mL）之间分配，水层用温热的乙酸乙酯（200 mL）萃取。合并的有机提取物使用无水硫酸钠干燥并浓缩。最后，残余物用乙酸乙酯（30 mL）研磨，通过过滤分离固体，得到7-羧基-1H-吲唑，产率为94%。

反应信息

• 作为反应物：
  描述：

  7-羧基-1H-吲唑 在 8-羟基喹啉 、 甲烷磺酸 、 (1R,2R)-(-)-N,N'-二甲基-1,2-环己二胺 、 potassium carbonate 、 N,N'-羰基二咪唑 、 copper(I) bromide 作用下， 以 N,N-二甲基乙酰胺 、 邻二甲苯 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.5h， 生成 尼拉帕尼
  参考文献：
  名称：

  一种尼拉帕尼及其中间体的制备方法以及中 间体化合物

  摘要：

  本发明公开了一种尼拉帕尼的中间体的制备方法，如下式所示，其包含下列步骤：以(S)‑恶唑烷酮与对溴苯乙酸为起始原料，进行酰胺缩合，迈克尔加成，脂和酰胺的还原，磺酰脂的合成，氨化成环，与有机酸成盐的反应，即可。本发明还公开了尼拉帕尼的制备方法及其中间体化合物。本发明的制备方法成本低，原料易得，产率较高，适于工业化生产。

  公开号：

  CN107663190B
• 作为产物：
  描述：

  2-氨基-3-甲基苯甲酸甲酯 在 叔丁基硫醇 、 sodium nitrite 、 potassium tert-butylate 、 盐酸 作用下， 以 乙醇 、 二氯甲烷 、 水 、 溶剂黄146 、 二甲基亚砜 为溶剂， 反应 2.0h， 生成 7-羧基-1H-吲唑
  参考文献：
  名称：

  Compounds

  摘要：

  这项发明涉及一般式(I)的烟酰胺衍生物： 其中R1、Z和R2具有本文所定义的含义，并涉及用于制备、用于制备的中间体、含有和使用这种衍生物的组合物的过程。

  公开号：

  US20050020611A1

文献信息

• [EN] INDAZOLE COMPOUNDS AS 5-HT4 RECEPTOR AGONISTS<br/>[FR] COMPOSÉS D'INDAZOLE EN TANT QU'AGONISTES DE RÉCEPTEUR DE 5-HT4
  申请人：SUVEN LIFE SCIENCES LTD

  公开号：WO2015092804A1

  公开（公告）日：2015-06-25

  The present invention relates to novel indazole compounds of the Formula (I), wherein, R1 is alkyl or cycloalkyl; (Formula II) including their stereoisomers and their pharmaceutically acceptable salts. This invention also relates to methods of making such compounds and pharmaceutical compositions comprising such compounds. The compounds of this invention are useful in the treatment of various disorders that are related to 5-Hydroxytryptamine 4 (5-HT4) receptor agonists

  本发明涉及一种新型吲唑化合物，其化学式为（I），其中R1为烷基或环烷基；（化学式II），包括其立体异构体和药学上可接受的盐。本发明还涉及制备这种化合物的方法和包含这种化合物的药物组合物。本发明的化合物在治疗与5-羟色胺4（5-HT4）受体激动剂相关的各种疾病中是有用的。
• [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] MODULATORS OF INDOLEAMINE 2,3-DIOXYGENASE<br/>[FR] MODULATEURS D'INDOLAMINE 2,3-DIOXYGÉNASE
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2019003148A1

  公开（公告）日：2019-01-03

  Provided are IDO inhibitor compounds of Formula I and pharmaceutically acceptable salts thereof, their pharmaceutical compositions, their methods of preparation, and methods for their use in the prevention and/or treatment of diseases. Formula (I):

  提供了公式I的IDO抑制剂化合物及其药用盐，它们的药物组合物，它们的制备方法，以及它们在预防和/或治疗疾病中的使用方法。公式（I）:
• [EN] PROCESS FOR LARGE SCALE PRODUCTION OF 1-ISOPROPYL-3-{5- [1-(3-METHOXYPROPYL) PIPERIDIN-4-YL]-[1,3,4]OXADIAZOL-2-YL}- 1H-INDAZOLE OXALATE<br/>[FR] PROCÉDÉ DE PRODUCTION À GRANDE ÉCHELLE D'OXALATE DE 1-ISOPROPYL-3-{5-[1-(3-MÉTHOXYPROPYL)PIPÉRIDIN-4-YL]-[1,3,4]-OXADIAZOL-2-YL}-1H-INDAZOLE
  申请人：SUVEN LIFE SCIENCES LTD

  公开号：WO2016027277A1

  公开（公告）日：2016-02-25

  The present invention relates to a process suitable for adoption to large scale manufacture of l-IsopropyI-3-5-[l1-(3-methoxypropyl) piperidin-4-yl]-[ 1,3,4] oxadiazol-2-yl}- 1H-indazole oxalate of formula (I), which is a selective 5-HT4 receptor ligand intended for the symptomatic treatment of Alzheimer's disease and other disorders of memory and cognition like Attention deficient hyperactivity, Parkinson's and Schizophrenia.

  本发明涉及一种适用于大规模生产 l-异丙基-3-5-[11-(3-甲氧基丙基)哌啶-4-基]-[1,3,4]噁二唑-2-基}-1H-吲唑草酸盐（I）的工艺，该药物是一种选择性5-HT4受体配体，用于治疗阿尔茨海默病和其他记忆和认知障碍，如注意力不足过动症、帕金森病和精神分裂症。
• Monoacylglycerol Lipase Modulators
  申请人：Janssen Pharmaceutica NV

  公开号：US20200102303A1

  公开（公告）日：2020-04-02

  Fused compounds of Formula (I) and Formula (II), pharmaceutical compositions containing them, methods of making them, and methods of using them including methods for treating disease states, disorders, and conditions associated with MGL modulation, such as those associated with pain, psychiatric disorders, neurological disorders (including, but not limited to major depressive disorder, treatment resistant depression, anxious depression, bipolar disorder), cancers and eye conditions. Wherein R 1 , R 2 , R 2a , R 3 , R 3a , R 4 , and R 4a are defined herein.

  化合物的结构式（I）和结构式（II），含有它们的药物组合物，制备它们的方法，以及使用它们的方法，包括用于治疗与MGL调节相关的疾病状态、紊乱和病况的方法，例如与疼痛、精神障碍、神经障碍（包括但不限于重性抑郁障碍、治疗抵抗性抑郁症、焦虑性抑郁症、躁郁症）、癌症和眼部疾病相关的方法。 其中R1、R2、R2a、R3、R3a、R4和R4a在此处定义。