2-Bromo-4-methylthiazole-5-carboxamide
[CAS# 1254694-56-8]

Identification

• Classification: Organic raw materials >> Amino compound >> Amide compound
• Name: 2-Bromo-4-methylthiazole-5-carboxamide
• Molecular Formula: C₅H₅BrN₂OS
• Molecular Weight: 221.08
• CAS Registry Number: 1254694-56-8
• SMILES: CC1=C(SC(=N1)Br)C(=O)N

Properties

• Density: 1.8±0.1 g/cm³ Calc.^*
• Boiling point: 338.7±30.0 °C 760 mmHg (Calc.)^*
• Flash point: 158.7±24.6 °C (Calc.)^*
• Index of refraction: 1.636 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS06 Danger
• Risk Statements: H301-H311-H331
• Safety Statements: P261-P264-P270-P271-P280-P302+P352-P304+P340-P310-P330-P361-P403+P233-P405-P501
• Transport Information: UN 2811

Discovery and Applications

2-Bromo-4-methylthiazole-5-carboxamide is a heterocyclic compound featuring a thiazole ring substituted with a bromine atom at the 2-position, a methyl group at the 4-position, and a carboxamide at the 5-position. The combination of the electron-withdrawing bromine, the electron-donating methyl group, and the polar amide function gives the molecule distinctive chemical reactivity and makes it a versatile intermediate in organic synthesis.

The compound can be synthesized via bromination of the corresponding 4-methylthiazole-5-carboxamide or by condensation of suitable α-haloketones with thiourea derivatives under controlled conditions. Selective halogenation at the 2-position is crucial to preserve the integrity of the thiazole ring and avoid polyhalogenation. Careful control of temperature, solvent, and stoichiometry is necessary to achieve high yields and minimize side products.

2-Bromo-4-methylthiazole-5-carboxamide is primarily used as a building block in medicinal chemistry. The thiazole ring is a common pharmacophore in many bioactive molecules, and the 2-bromo substituent serves as a reactive handle for cross-coupling reactions such as Suzuki, Stille, or Negishi couplings. These reactions allow the introduction of diverse substituents at the 2-position, enabling the synthesis of structurally complex analogs for drug discovery programs.

The carboxamide at the 5-position is a versatile functional group for further derivatization. It can participate in hydrogen bonding and improve aqueous solubility, which is often important for biologically active compounds. The methyl group at the 4-position modulates the electronic properties of the thiazole ring and can influence the binding affinity and selectivity of derivatives toward biological targets.

In addition to medicinal applications, 2-Bromo-4-methylthiazole-5-carboxamide is used in agrochemical and material science research. It can serve as a precursor for the preparation of thiazole-containing ligands, fluorescent probes, or functionalized polymers. Its well-defined reactivity allows chemists to construct more complex molecular frameworks while maintaining stereochemical and regiochemical control.

Physically, the compound is generally obtained as a crystalline solid with moderate solubility in polar organic solvents such as dimethyl sulfoxide, dimethylformamide, and acetone. It is stable under normal laboratory conditions but should be protected from strong acids, bases, and reducing agents that could affect the bromide or amide functionality.

Overall, 2-Bromo-4-methylthiazole-5-carboxamide is a synthetically valuable heterocyclic building block. Its combination of a reactive halogen, a modulating methyl group, and a polar carboxamide enables diverse chemical transformations and applications in medicinal chemistry, agrochemicals, and materials science, making it a versatile intermediate in both academic and industrial research.

References

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URL: WO-2022042591-A1

2024. Nitrile derivative that acts as inhibitor of dipeptidyl peptidase 1 and use thereof. EP Patent.
URL: EP-4129989-A1

2024. Nitrile derivative that acts as inhibitor of dipeptidyl peptidase 1 and use thereof. AU Patent.
URL: AU-2021330865-B2