3-(2-Chloro-4-pyrimidinyl)-1-methyl-1H-indole
[CAS# 1032452-86-0]

Identification

• Classification: Organic raw materials >> Heterocyclic compound
• Name: 3-(2-Chloro-4-pyrimidinyl)-1-methyl-1H-indole
• Molecular Formula: C₁₃H₁₀ClN₃
• Molecular Weight: 243.69
• CAS Registry Number: 1032452-86-0
• EC Number: 806-155-8
• SMILES: CN1C=C(C2=CC=CC=C21)C3=NC(=NC=C3)Cl

Properties

• Solubility: Practically insoluble (0.095 g/L) (25 °C), Calc.^*
• Density: 1.31±0.1 g/cm³ (20 °C 760 Torr), Calc.^*
• Boiling point: 486.3±28.0 °C 760 mmHg (Calc.)^*
• Flash point: 247.9±24.0 °C (Calc.)^*
• Index of refraction: 1.672 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335
• Safety 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
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335
Acute toxicity	Acute Tox.	4	H302
Eye irritation	Eye Irrit.	2	H319

Discovery and Applications

3-(2-Chloro-4-pyrimidinyl)-1-methyl-1H-indole is a synthetic heterocyclic compound that integrates two pharmacologically significant moieties: the indole ring and the pyrimidine ring. The discovery of this compound is part of a broader exploration into indole-based molecules, which have a long-standing reputation for their diverse biological activities. Researchers have historically combined the indole core with various heterocyclic systems, including pyrimidines, to create novel frameworks for drug development. The specific coupling of a 2-chloro-4-pyrimidinyl group at the 3-position of a 1-methylindole scaffold was pursued to enhance the compound's chemical reactivity and biological potential.

The synthesis of 3-(2-chloro-4-pyrimidinyl)-1-methyl-1H-indole typically begins with the preparation of 1-methylindole, which is then subjected to selective functionalization at the 3-position. Using methods such as lithiation or palladium-catalyzed cross-coupling, the indole ring can be coupled with a chloropyrimidine derivative. In this case, 2,4-dichloropyrimidine is a common starting material, wherein selective substitution at the 2-position facilitates the attachment of the indole. Reaction conditions are carefully controlled to favor mono-substitution and to prevent overreaction or degradation of the indole moiety. Purification methods such as chromatography are employed to isolate the final product, which is then characterized using techniques like nuclear magnetic resonance spectroscopy and mass spectrometry to confirm the molecular structure.

Applications of 3-(2-chloro-4-pyrimidinyl)-1-methyl-1H-indole are predominantly in the field of medicinal chemistry. The compound serves as a valuable intermediate for further structural elaboration, particularly in the synthesis of kinase inhibitors. The presence of the chloro group on the pyrimidine ring allows for additional modifications through nucleophilic aromatic substitution, enabling the attachment of various amines or other nucleophiles. Such modifications are crucial in the development of compound libraries for biological screening, aiming to identify molecules with high affinity and selectivity for therapeutic targets such as protein kinases, which play pivotal roles in cell signaling pathways associated with cancer and inflammatory diseases.

Additionally, the indole framework of 3-(2-chloro-4-pyrimidinyl)-1-methyl-1H-indole is recognized for its ability to participate in hydrogen bonding and π-π stacking interactions, which are critical for binding to biological macromolecules. These properties make the compound a promising starting point for the design of inhibitors against a wide range of enzymes and receptors. Studies have indicated that compounds containing similar indole-pyrimidine hybrids exhibit potent biological activities, including antiproliferative, antiviral, and anti-inflammatory effects.

Moreover, the modular nature of 3-(2-chloro-4-pyrimidinyl)-1-methyl-1H-indole allows medicinal chemists to quickly generate analogs by modifying the pyrimidine or indole portions independently. This adaptability facilitates the optimization of pharmacokinetic and pharmacodynamic properties during the drug development process. The compound's chemical stability and ease of further derivatization also make it suitable for high-throughput synthesis techniques employed in early-stage drug discovery projects.

Overall, 3-(2-chloro-4-pyrimidinyl)-1-methyl-1H-indole represents an important synthetic intermediate that supports the generation of diverse, biologically active molecules. Its design reflects strategic considerations in modern medicinal chemistry aimed at maximizing chemical diversity and biological relevance, underscoring its significance in ongoing pharmaceutical research efforts.

References

2023. Insights of Indole: A Novel Target in Medicinal Chemistry (A Review). Russian Journal of General Chemistry, 93(7).
DOI: 10.1134/s1070363223070216