2-bromo-1-(1-methyl-1H-pyrazol-4-yl)ethan-1-one
[CAS# 706819-66-1]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyrimidine compound >> Ketones
• Name: 2-bromo-1-(1-methyl-1H-pyrazol-4-yl)ethan-1-one
• Molecular Formula: C₆H₇BrN₂O
• Molecular Weight: 203.04
• CAS Registry Number: 706819-66-1
• EC Number: 893-492-9
• SMILES: CN1C=C(C=N1)C(=O)CBr

Properties

• Density: 1.6±0.1 g/cm³ Calc.^*
• Boiling point: 276.0±15.0 ºC 760 mmHg (Calc.)^*
• Flash point: 120.7±20.4 ºC (Calc.)^*
• Index of refraction: 1.602 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS05;GHS07 Danger
• Hazard Statements: H302-H315-H318-H335
• Precautionary Statements: P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P304+P340-P305+P354+P338-P317-P319-P321-P330-P332+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
Serious eye damage	Eye Dam.	1	H318

Discovory and Applicatios

2-Bromo-1-(1-methyl-1H-pyrazol-4-yl)ethan-1-one is a synthetic organic compound belonging to the class of halogenated α-bromo ketones featuring a substituted pyrazole ring. The structure comprises a 1-methyl-1H-pyrazole moiety substituted at the 4-position with an ethanone group, which in turn is brominated at the α-position. This structural arrangement imparts significant electrophilicity to the molecule, especially at the brominated carbon, rendering it highly reactive toward nucleophilic substitution reactions.

The 1-methyl-1H-pyrazole core is a well-established heteroaromatic structure widely used in medicinal and agrochemical chemistry. Pyrazole derivatives have been explored since the late 19th century, with systematic synthetic methodologies emerging prominently during the mid-20th century. The inclusion of a methyl group at the nitrogen atom (N1) enhances the lipophilicity and stability of the heterocycle, contributing to its compatibility with biological targets and synthetic intermediates.

2-Bromo-1-(1-methyl-1H-pyrazol-4-yl)ethan-1-one is primarily used as a synthetic intermediate in the preparation of more complex heterocyclic and peptidomimetic compounds. The α-bromo ketone functionality acts as a versatile electrophile in C–C and C–N bond-forming reactions. It undergoes facile nucleophilic substitution with a wide range of amines, thiols, and heterocycles, leading to the formation of substituted pyrazole-based amides, thioethers, and other functional motifs. Such transformations are commonly utilized in the development of small molecule libraries for structure–activity relationship studies in pharmaceutical research.

In medicinal chemistry, compounds bearing substituted pyrazole rings have demonstrated a broad spectrum of biological activities, including anti-inflammatory, analgesic, antipyretic, and anticancer effects. The functionalized pyrazole scaffold is found in various clinically relevant drugs, and the bromoketone intermediate plays a role in accessing these derivatives via modular and divergent synthesis pathways. The ketone moiety can also be transformed via further functionalization such as reduction to alcohols, condensation with hydrazines or amines, and cyclization with nucleophiles to generate five- or six-membered ring systems fused to the pyrazole nucleus.

In chemical biology and enzyme inhibition studies, α-bromo ketones are recognized for their capacity to act as covalent inhibitors due to their reactivity with thiol groups of cysteine residues in active sites. Although such usage demands careful optimization to control selectivity and avoid nonspecific alkylation, this property provides a strategic avenue for designing irreversible enzyme inhibitors based on the 1-methylpyrazole framework.

Synthetically, 2-bromo-1-(1-methyl-1H-pyrazol-4-yl)ethan-1-one is typically prepared via halogenation of the corresponding methyl ketone using N-bromosuccinimide (NBS) or elemental bromine in the presence of acid or light. This approach ensures selective bromination at the α-position without altering the integrity of the pyrazole ring, which is generally stable under such conditions.

The combination of the reactive bromoacetyl group with a bioactive heterocycle makes this compound a valuable tool in both synthetic organic chemistry and medicinal research. Its well-established reactivity and predictable behavior have led to its integration in various synthetic routes aimed at the exploration of novel therapeutic agents.

References

2021. Synthesis of Quinoxaline Derivatives as Intermediates to Obtain Erdafitinib. Pharmaceutical Chemistry Journal, 55(9).
DOI: 10.1007/s11094-021-02521-x

2021. Synthesis of PF-06826647. Synfacts, 17(2).
DOI: 10.1055/s-0040-1719324