6-chloro-3-iodo-1H-indazole
[CAS# 503045-59-8]

Identification

• Classification: Organic raw materials >> Heterocyclic compound >> Indazoles
• Name: 6-chloro-3-iodo-1H-indazole
• Molecular Formula: C₇H₄ClIN₂
• Molecular Weight: 278.48
• CAS Registry Number: 503045-59-8
• EC Number: 821-990-8
• SMILES: C1=CC2=C(NN=C2C=C1Cl)I

Properties

• Density: 2.2±0.1 g/cm³ Calc.^*
• Boiling point: 391.5±22.0 ºC 760 mmHg (Calc.)^*
• Flash point: 190.6±22.3 ºC (Calc.)^*
• Index of refraction: 1.785 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319-H335
• Precautionary Statements: P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Eye irritation	Eye Irrit.	2A	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335
Acute toxicity	Acute Tox.	4	H302
Skin irritation	Skin Irrit.	2	H315

Discovory and Applicatios

6-chloro-3-iodo-1H-indazole is a halogenated heterocyclic compound derived from the indazole scaffold, in which a chlorine atom is substituted at the 6-position and an iodine atom at the 3-position of the bicyclic 1H-indazole ring. The indazole core is a fused bicyclic system consisting of a benzene ring fused to a pyrazole ring, known for its aromaticity and ability to participate in hydrogen bonding and π–π interactions. The introduction of halogen atoms enhances the compound’s reactivity for further functionalization and can influence electronic and steric properties.

The synthesis of 6-chloro-3-iodo-1H-indazole generally begins with a suitably substituted indazole precursor, followed by regioselective halogenation reactions. Chlorination at the 6-position and iodination at the 3-position are typically achieved using electrophilic halogenating agents under controlled conditions to avoid over-substitution. Reaction parameters such as temperature, solvent, and stoichiometry are optimized to preserve the indazole core and ensure selective mono-halogenation at the desired positions. The product is usually purified by recrystallization or chromatography to obtain a crystalline solid suitable for synthetic applications.

In organic synthesis, 6-chloro-3-iodo-1H-indazole is a versatile intermediate for the preparation of substituted indazoles and heterocyclic derivatives. The iodine atom at the 3-position provides a reactive site for cross-coupling reactions, including Suzuki, Sonogashira, or Buchwald–Hartwig couplings, enabling the introduction of diverse aryl, alkyl, or heteroaryl groups. The chlorine atom can also serve as a site for nucleophilic aromatic substitution or further cross-coupling reactions, allowing stepwise functionalization to construct complex molecules.

In medicinal chemistry, derivatives of halogenated indazoles are explored for their bioactivity, including potential kinase inhibitors, receptor modulators, and enzyme inhibitors. The indazole nitrogen atoms can participate in hydrogen bonding and metal coordination, while halogen substituents influence binding affinity, metabolic stability, and lipophilicity. By modifying the halogen pattern, chemists can tune the pharmacokinetic and pharmacodynamic properties of target molecules for drug discovery.

The compound is also relevant in methodology research and chemical development. Its dual halogenation pattern allows the study of selective halogen–metal exchange reactions, cross-coupling strategies, and the development of regioselective functionalization techniques for nitrogen-containing heterocycles. It serves as a model substrate for designing synthetic routes to complex indazole-based architectures with potential applications in medicinal and materials chemistry.

Physically, 6-chloro-3-iodo-1H-indazole is generally obtained as a crystalline solid with moderate solubility in polar organic solvents such as dimethylformamide, dichloromethane, and ethanol. It is stable under standard laboratory conditions but should be protected from strong acids, bases, and oxidizing agents that could alter the indazole ring or the halogen substituents. Proper storage ensures chemical integrity for synthetic and research applications.

Overall, 6-chloro-3-iodo-1H-indazole is a multifunctional halogenated indazole featuring a chlorine atom at the 6-position and an iodine atom at the 3-position. Its structural features enable selective chemical transformations and derivatization, making it a valuable intermediate for the synthesis of heterocyclic derivatives, bioactive molecules, and complex organic targets in medicinal and synthetic chemistry.

References

2021. A compound as a PAK4 kinase inhibitor and its preparation method and application. CN Patent, 114507215.

2018. Mitogen-activated protein kinase kinase 7 inhibitors. WO Patent, 2018021445.