2166-27-0

Upstream product

• 2166-14-5 1,2,4,5-tetrazine-3,6-dicarboxylic acid dimethyl ester 
• 66324-10-5 tert-butyldimethyl(1-phenylvinyloxy)silane 
• 98-86-2 acetophenone 
• 122-78-1 phenylacetaldehyde 
• 536-74-3 phenylacetylene 
• 7196-01-2 4-(1-phenylvinyl)morpholine 
• 3433-56-5 1-(1-phenylvinyl)pyrrolidine 
• 13735-81-4 1-styrenyloxytrimethylsilane 

Downstream Products

• 92144-12-2 3-phenyl-1H-pyrrole-2,5-dicarboxylic acid dimethyl ester 
• 2166-18-9 4-phenyl-1,4-dihydropyridazine-3,6-dicarboxylic acid dimethyl ester 
• 1396424-56-8 4,4′-(1E,1′E)-2,2′-(4-phenylpyridazine-3,6-diyl)bis(ethene-2,1-diyl)bis(N,N-dimethylaniline) 
• 1396424-63-7 4,4′-(4,4′-(1E,1′E)-2,2′-(4-phenylpyridazine-3,6-diyl)bis(ethene-2,1-diyl)bis(4,1-phenylene))dimorpholine 
• 1396423-98-5 (4-phenylpyridazine-3,6-diyl)dimethanol 
• 1396424-17-1 3,6-bis(chloromethyl)-4-phenylpyridazine 
• 1396424-36-4 tetraethyl (4-phenylpyridazine-3,6-diyl)bis(methylene)-diphosphonate 
• 27649-43-0 3-phenyl-1H-pyrrole 
• 92184-43-5 4-phenylpyridazine 

Relevant academic research and scientific papers

Boron Trifluoride-Mediated Cycloaddition of 3-Bromotetrazine and Silyl Enol Ethers: Synthesis of 3-Bromo-pyridazines

Pyridazines are important scaffolds for medicinal chemistry or crop protection agents, yet the selective preparation of 3-bromo-pyridazines with high regiocontrol remains difficult. We achieved the Lewis acid-mediated inverse electron demand Diels-Alder reaction between 3-monosubstituted s-tetrazine and silyl enol ethers and obtained functionalized pyridazines. In the case of 1-monosubstituted silyl enol ethers, exclusive regioselectivity was observed. Downstream functionalization of the resulting 3-bromo-pyridazines was demonstrated utilizing several cross-coupling protocols to synthesize 3,4-disubstituted pyridazines with excellent control over the substitution pattern.

Selective N1/N4 1,4-Cycloaddition of 1,2,4,5-Tetrazines Enabled by Solvent Hydrogen Bonding

An unprecedented 1,4-cycloaddition (vs 3,6-cycloaddition) of 1,2,4,5-tetrazines is described with preformed or in situ generated aryl-conjugated enamines promoted by the solvent hydrogen bonding of hexafluoroisopropanol (HFIP) that is conducted under mild reaction conditions (0.1 M HFIP, 25 °C, 12 h). The reaction constitutes a formal [4 + 2] cycloaddition across the two nitrogen atoms (N1/N4) of the 1,2,4,5-tetrazine followed by a formal retro [4 + 2] cycloaddition loss of a nitrile and aromatization to generate a 1,2,4-triazine derivative. The factors that impact the remarkable change in the reaction mode, optimization of reaction parameters, the scope and simplification of its implementation through in situ enamine generation from aldehydes and ketones, the reaction scope for 3,6-bis(thiomethyl)-1,2,4,5-tetrazine, a survey of participating 1,2,4,5-tetrazines, and key mechanistic insights into this reaction are detailed. Given its simplicity and breath, the study establishes a novel method for the simple and efficient one-step synthesis of 1,2,4-triazines under mild conditions from readily accessible starting materials. Whereas alternative protic solvents (e.g., MeOH vs HFIP) provide products of the conventional 3,6-cycoladdition, the enhanced hydrogen bonding capability of HFIP uniquely results in promotion of the unprecedented formal 1,4-cycloaddition. As such, the studies represent an example of not just an enhancement in the rate or efficiency of a heterocyclic azadiene cycloaddition by hydrogen bonding catalysis but also the first to alter the mode (N1/N4 vs C3/C6) of cycloaddition.

Bis(arylvinyl)pyrazines, -pyrimidines, and -pyridazines As imaging agents for tau fibrils and β-Amyloid plaques in alzheimers disease models

The in vivo diagnosis of Alzheimers disease (AD) is of high socioeconomic interest and remains a demanding field of research. The biopathological hallmarks of the disease are extracellular plaques consisting of aggregated β-amyloid peptides (Aβ) and tau protein derived intracellular tangles. Here we report the synthesis and evaluation of fluorescent pyrazine, pyrimidine,and pyridazine derivatives in vitro and in vivo aiming at a tau-based diagnosis of AD. The probes were pre-evaluated on human brain tissue by fluorescence microscopy and were found to label all known disease-related alterations at high contrast and specificity. To quantify the binding affinity, a new thiazine red displacement assay was developed and selected candidates were toxicologically profiled. The application in transgenic mouse models demonstrated bioavailability and brain permeability for one compound. In the course of histological testing, we discovered an AD-related deposition of tau aggregates in the Bowmans glands of the olfactory epithelium, which holds potential for an endoscopic diagnosis of AD in the olfactory system.

Thermal Cycloaddition of Dimethyl 1,2,4,5-Tetrazine-3,6-dicarboxylate with Electron-Rich Olefins: 1,2-Diazine and Pyrrole Introduction. Preparation of Octamethylporphin (OMP)

An investigation of the inverse electron demand Diels-Alder reactions of dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate with electron-rich olefins for the introduction of 1,2-diazines and pyrroles is described.A short synthesis of 2,3,7,8,12,13,17,18-octamethylporphin (OMP) is detailed.