503627-65-4

Upstream product

• 4926-28-7 2-Bromo-4-picoline 
• 667-27-6 Ethyl bromodifluoroacetate 

Relevant academic research and scientific papers

Synthetic method of aromatic ring group or aromatic heterocyclic tetrazole

The synthetic method comprises the following steps: (1) reacting 1.0 eq of ArI or HArI with 1.2 eq of ethyl 2, 2-difluoroacetate in the presence of DMSO as a solvent and 4.0 eq of Cu under the protection of nitrogen at 30 DEG C and 50 DEG C, and purifying to obtain a first intermediate compound; (2) dissolving 1.0 eq of the first intermediate compound in a mixed solvent of THF and water, adding 2.0 eq of LiOH, reacting at room temperature for 2 hours, spin-drying the solvent, adding HCl until the pH value is equal to 3, and filtering to obtain a second intermediate compound; and (3) reacting 1.0 eq of the second intermediate compound with 2.0 eq of diphenyl azide phosphate in the presence of 2.5 eq of triethylamine by taking tert-butyl alcohol as a solvent to generate aromatic ring group or aromatic heterocyclic tetrazole. The invention provides a novel synthetic method of aromatic ring group or aromatic heterocyclic tetrazole, wherein a target compound can be more conveniently obtained, and reagents participating in the reaction are low in toxicity, mild in reaction condition, simple and safe in aftertreatment, good in product quality and suitable for large-scale production.

Safety Evaluation of the Copper-Mediated Cross-Coupling of 2-Bromopyridines with Ethyl Bromodifluoroacetate

The potential safety hazards associated with the copper-mediated cross-coupling of 2-bromopyridines with ethyl bromodifluoroacetate were evaluated. Thermal stability evaluation of the postreaction mixture of 50.6 mmol of 2-bromopyridine with 1.3 equiv of ethyl bromodifluoroacetate in the presence of 2.1 equiv of copper in 40 mL of dimethyl sulfoxide (DMSO) indicated a significant decomposition event with an onset temperature of 115.5 °C by accelerating rate calorimetry, which was significantly lower than that of neat DMSO. In contrast, the reaction mixture in N,N-dimethylformamide did not show any exothermic decomposition up to 400 °C by differential scanning calorimetry. Reaction calorimetry evaluation of this reaction in DMSO revealed a heat output (ΔH) of -13.5 kJ and an adiabatic temperature rise (ΔTad) of 129.5 °C, resulting in a maximum temperature of a synthesis reaction (MTSR) of 189.5 °C. The predicted heat of reaction using density functional theory with the BLYP functional was in good agreement with the experimental data. The scope studies with a variety of substituted 2-bromopyridines revealed similar magnitudes of ΔH and ΔTad compared to 2-bromopyridine when reacted at the same concentration. In all of the studied cases, the MTSR was significantly higher than the onset temperature of reaction mixture decomposition, indicating that in the absence of active cooling the system could quickly trigger the decomposition of the reaction mixture, resulting in a runaway reaction.

Orally efficacious thrombin inhibitors with cyanofluorophenylacetamide as the P2 motif

2-Cyano-6-fluorophenylacetamide was explored as a novel P2 scaffold in the design of thrombin inhibitors. Optimization around this structural motif culminated in 14, which is a potent thrombin inhibitor (Ki = 1.2 nM) that exhibits robust effica

Copper-mediated reaction of 2-halopyridines with ethyl bromodifluoroacetate

A facile process for the preparation of substituted ethyl 2′-pyridyldifluoroacetates 3 is described starting from readily available ethyl bromodifluoroacetate 2 and substituted 2-bromo or 2-chloropyridines 1. This process features a copper-mediated cross-coupling reaction in DMSO and is the first to utilise pyridylbromides or chlorides with ethyl bromodifluoroacetate 2 in this reaction.