7-Iodopyrrolo[2,1-f][1,2,4]triazin-4-amine
[CAS# 1770840-43-1]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyrimidine compound >> Amine
• Name: 7-Iodopyrrolo[2,1-f][1,2,4]triazin-4-amine
• Molecular Formula: C₆H₅IN₄
• Molecular Weight: 260.04
• CAS Registry Number: 1770840-43-1
• EC Number: 855-636-9
• SMILES: C1=C2C(=NC=NN2C(=C1)I)N

Properties

• Density: 2.4±0.1 g/cm³ Calc.^*
• Solubility: water: Slightly soluble (1.2 g/L) (25 ºC), Calc.
• Index of refraction: 1.903 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS06;GHS07 Danger
• Hazard Statements: H301-H302-H312-H315-H317-H319-H332-H335
• Precautionary Statements: P261-P264-P264+P265-P270-P271-P272-P280-P301+P316-P301+P317-P302+P352-P304+P340-P305+P351+P338-P317-P319-P321-P330-P332+P317-P333+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Eye irritation	Eye Irrit.	2A	H319
Acute toxicity	Acute Tox.	4	H332
Acute toxicity	Acute Tox.	4	H312
Skin sensitization	Skin Sens.	1	H317
Specific target organ toxicity - single exposure	STOT SE	3	H335

Discovory and Applicatios

The compound 7-iodopyrrolo[2,1-f][1,2,4]triazin-4-amine is a fused heterocyclic system consisting of a pyrrole ring fused to a 1,2,4-triazine ring. The nitrogen at position 4 bears an amino substituent, and the iodine atom is attached at position 7 of the bicyclic system. Its molecular formula is C₅H₄IN₅, with a molecular weight of approximately 259.02 g/mol. The presence of the electron-rich amino group and the halogen substituent gives the molecule distinct chemical reactivity suitable for further functionalization.

Synthesis of 7-iodopyrrolo[2,1-f][1,2,4]triazin-4-amine typically starts from a pyrrolo[2,1-f][1,2,4]triazine core. Halogenation at position 7 can be achieved using electrophilic iodination reagents under controlled conditions, taking advantage of the electron density on the fused bicyclic system. The amino group is usually introduced prior to or during cyclization to ensure regioselective substitution and to avoid overreaction of sensitive positions. Protective groups may be employed to control reactivity and ensure high selectivity during the iodination process.

The iodine atom at position 7 serves both as a steric modifier and as a synthetic handle. It can participate in palladium-catalyzed cross-coupling reactions, including Suzuki, Sonogashira, or Buchwald–Hartwig reactions, enabling the introduction of various aryl, alkynyl, or amine substituents at the 7-position. This allows chemists to rapidly diversify the heterocyclic scaffold for structure–activity relationship studies in medicinal chemistry or for constructing more complex heterocyclic systems.

The amino group at position 4 enhances solubility in polar solvents and enables hydrogen bonding interactions. It also serves as a nucleophilic site for acylation, sulfonylation, or other derivatization reactions. The combination of a halogenated position and a free amino group makes the compound a versatile intermediate for the synthesis of analogs designed to interact with biological targets, particularly in antiviral, anticancer, or kinase inhibition research, where pyrrolo[2,1-f][1,2,4]triazin-4-amine derivatives are commonly explored.

In terms of chemical properties, 7-iodopyrrolo[2,1-f][1,2,4]triazin-4-amine is generally a solid at room temperature, with moderate solubility in polar aprotic solvents such as dimethylformamide or dimethyl sulfoxide. It is stable under ambient conditions but should be protected from strong nucleophiles and bases that could displace the iodine atom or decompose the fused heterocycle. Its fused planar bicyclic structure contributes to rigidity and planarity, features that can enhance π–π stacking interactions in crystal structures or biological binding sites.

In practical application, this compound serves as a key building block for medicinal chemistry programs. The combination of a reactive halogen and an amino group allows rapid diversification, while the fused heterocyclic core maintains structural integrity and electronic properties relevant to biological recognition. The molecule can be employed in the design of small molecule inhibitors, fluorescent probes, or other functionalized derivatives where selective modification at the 7-position is desirable.

References

2020. Methods of Synthesis of Remdesivir, Favipiravir, Hydroxychloroquine, and Chloroquine: Four Small Molecules Repurposed for Clinical Trials during the Covid-19 Pandemic. Synthesis.
DOI: 10.1055/s-0040-1707386

2020. Synthesis of Remdesivir (GS-5734) � A Candidate for the Treatment of Ebola and COVID-19 Infections. Synfacts.
DOI: 10.1055/s-0040-1707019