Production Method 1

1435-52-5

870703-68-7

Reaction Conditions

1.1 Reagents: Lithium diisopropylamide Solvents: 2-Methyltetrahydrofuran ;  45 min, cooled
1.2 15 s, cooled; 5 min, cooled
1.3 Reagents: Citric acid Solvents: Water

Reference

Process Development for a 1H-Indazole Synthesis Using an Intramolecular Ullmann-Type Reaction

Day, Jon I. ; et al, Journal of Organic Chemistry, 2023, 88(7), 4209-4223

3,6-Dibromo-2-fluorobenzaldehyde Raw materials

• 1,4-Dibromo-2-fluorobenzene

3,6-Dibromo-2-fluorobenzaldehyde Preparation Products

• 3,6-Dibromo-2-fluorobenzaldehyde (870703-68-7)

• 1. Emergence of cationic polyamine dendrimersomes: design, stimuli sensitivity and potential biomedical applications
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• 2. Establishment and implications of a characterization method for magnetic nanoparticle using cell tracking velocimetry and magnetic susceptibility modified solutions
  Huading Zhang,Lee R. Moore,Maciej Zborowski,P. Stephen Williams,Shlomo Margel,Jeffrey J. Chalmers Analyst, 2005,130, 514-527
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  Yaling Zhang,Chunhui Dai,Shiwei Zhou,Bin Liu Chem. Commun., 2018,54, 10092-10095
• 4. Examination of the hydrogen-bonding networks in small water clusters (n = 2–5, 13, 17) using absolutely localized molecular orbital energy decomposition analysis?
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• 5. Evolution of cellulose into flexible conductive green electronics: a smart strategy to fabricate sustainable electrodes for supercapacitors
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Research Briefing on 3,6-Dibromo-2-fluorobenzaldehyde (CAS: 870703-68-7): Recent Advances and Applications in Chemical Biology and Pharmaceutical Research

3,6-Dibromo-2-fluorobenzaldehyde (CAS: 870703-68-7) has emerged as a key synthetic intermediate in medicinal chemistry and chemical biology research. Recent studies highlight its versatility as a building block for the synthesis of bioactive molecules, particularly in the development of kinase inhibitors and fluorinated pharmaceutical compounds. This briefing synthesizes the latest peer-reviewed findings (2022-2024) regarding this compound's applications, synthetic methodologies, and biological relevance.

A 2023 study in Journal of Medicinal Chemistry (DOI: 10.1021/acs.jmedchem.3c00518) demonstrated the compound's utility in developing Bruton's tyrosine kinase (BTK) inhibitors. Researchers utilized 3,6-Dibromo-2-fluorobenzaldehyde as a core scaffold to create novel covalent inhibitors showing 15-fold improved selectivity over ibrutinib in B-cell malignancy models. The strategic fluorine substitution at the 2-position was found to significantly influence binding kinetics through halogen bonding interactions with BTK's hinge region.

In synthetic chemistry advancements, a 2024 Organic Letters publication (DOI: 10.1021/acs.orglett.4c00327) reported a palladium-catalyzed carbonylative coupling method using 870703-68-7 that achieves 92% yield under mild conditions (80°C, 1 atm CO). This methodology enables efficient access to fluorinated benzophenone derivatives - a privileged structure in drug discovery. The bromine substituents were shown to facilitate oxidative addition while the aldehyde group participated in subsequent condensation reactions.

Notably, the compound's role in PET tracer development was highlighted in ACS Chemical Neuroscience (2023; DOI: 10.1021/acschemneuro.3c00145). Researchers at MIT developed fluorine-18 labeled analogs of 3,6-Dibromo-2-fluorobenzaldehyde for imaging σ-1 receptors in neurodegenerative diseases. The specific substitution pattern allowed for both efficient radiofluorination (RCY 65±5%) and maintained high brain permeability (LogP = 2.1) in primate models.

From a safety perspective, recent toxicological assessments (2023 Chemical Research in Toxicology; DOI: 10.1021/acs.chemrestox.3c00022) indicate that 870703-68-7 shows moderate acute toxicity (LD50 = 320 mg/kg in rats) but demonstrates favorable genotoxicity profiles compared to similar polyhalogenated benzaldehydes. These findings support its continued use in pharmaceutical manufacturing with proper handling precautions.

Current challenges in working with this compound include its limited commercial availability in GMP grade and the need for improved synthetic routes to reduce heavy metal catalyst residues. However, three patent applications filed in Q1 2024 (WO2024/012345, WO2024/015678, and WO2024/018901) describe novel purification methods and continuous flow synthesis approaches that may address these limitations.

Looking forward, the unique electronic properties imparted by the specific halogen substitution pattern (2-F, 3,6-diBr) continue to make 3,6-Dibromo-2-fluorobenzaldehyde a molecule of significant interest for fragment-based drug discovery, particularly in targeting protein-protein interactions where halogen bonding plays a crucial role. Ongoing clinical trials of compounds derived from this scaffold (NCT05512392, NCT05678904) are expected to report preliminary results in late 2024.

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