74448-91-2

Upstream product

• 74448-90-1 4-tert-butylphenyl 4-methylphenyl ether 
• 98-54-4 para-tert-butylphenol 
• 623-00-7 4-bromobenzenecarbonitrile 
• 1194-02-1 4-fluorobenzonitrile 
• 25237-79-0 (4-tert-butylphenoxy)trimethylsilane 
• 459-57-4 4-fluorobenzaldehyde 
• 3058-39-7 4-iodobenzonitrile 
• 623-03-0 4-Cyanochlorobenzene 
• 3130-29-8 potassium 4-(tert-butyl)phenolate 

Downstream Products

• 108934-20-9 4-(4-tert-butylphenoxy)benzaldehyde 

Relevant academic research and scientific papers

Lipophilic tail modifications of 2-(hydroxymethyl)pyrrolidine scaffold reveal dual sphingosine kinase 1 and 2 inhibitors

The sphingosine 1-phosphate (S1P) signaling pathway is an attractive target for pharmacological manipulation due to its involvement in cancer progression and immune cell chemotaxis. The synthesis of S1P is catalyzed by the action of sphingosine kinase 1 or 2 (SphK1 or SphK2) on sphingosine and ATP. While potent and selective inhibitors of SphK1 or SphK2 have been reported, development of potent dual SphK1/SphK2 inhibitors are still needed. Towards this end, we report the structure–activity relationship profiling of 2-(hydroxymethyl)pyrrolidine-based inhibitors with 22d being the most potent dual SphK1/SphK2 inhibitor (SphK1 Ki = 0.679 μM, SphK2 Ki = 0.951 μM) reported in this series. 22d inhibited the growth of engineered Saccharomyces cerevisiae and decreased S1P levels in histiocytic lymphoma myeloid cell line (U937 cells), demonstrating inhibition of SphK1 and 2 in vitro. Molecular modeling studies of 22d docked inside the Sph binding pocket of both SphK1 and SphK2 indicate essential hydrogen bond between the 2-(hydroxymethyl)pyrrolidine head to interact with aspartic acid and serine residues near the ATP binding pocket, which provide the basis for dual inhibition. In addition, the dodecyl tail adopts a “J-shape” conformation found in crystal structure of sphingosine bound to SphK1. Collectively, these studies provide insight into the intermolecular interactions in the SphK1 and 2 active sites to achieve maximal dual inhibitory activity.

Design, synthesis, insecticidal, and acaricidal activities of novel pyrimidinamine derivatives containing a biphenyl ether

A series of original pyrimidinamine derivatives containing a biphenyl ether moiety were designed and synthesized. Their structures were confirmed by 1H NMR, MS, and elemental analyses. Their insecticidal activities against lepidopteran and hemiptera insects and acaricidal activities were tested. The results of bioassay demonstrated that 9k showed the best activity (LC50 = 2.08 mg/L) against Tetranychus urticae, which is comparable with the positive control, spirotetramat (LC50 = 2.27 mg/L), and 9g showed better activity (LC50 = 0.52 mg/L) against Aphis fabae than the positive control, imidacloprid (LC50 = 1.02 mg/L), and relatively good activity (LC50 = 2.49 mg/L) against T urticae. Their structure-activity relationships indicated that both an ethyl group on the 4-position of the pyrimidine ring and alkyl chain as a para-substituent group of the benzene ring showed good biological activity.

Simple N-Heterocyclic Carbenes as Ligands in Ullmann-Type Ether and Thioether Formations

A simple N-heterocyclic carbene (NHC) derived from 1-methyl-3-ethylimidazolium tetrafluoroborate was found to be an efficient ligand for a range of copper-catalyzed cross-coupling reactions, leading to the formation of aromatic ethers and thioethers. (Figure presented.) .

Design and Synthesis of a Focused Library of Diamino Triazines as Potential Mycobacterium tuberculosis DHFR Inhibitors

We report design of a series of 2,4-diamino triazines as Mycobacterium tuberculosis (Mtb) dihydrofolate reductase inhibitors. The synthesized compounds were evaluated against Mtb (H37Rv and Dormant stage H37Ra), their cytotoxicity was assessed (HepG2 and A549 cell lines), and selectivity toward Mtb was evaluated by testing against other bacterial strains. Some derivatives showed promising activity along with low cytotoxicity. The most potent compound in the whole cell assay (MIC 0.325 μM against H37Rv) showed selectivity in the enzyme assay and exhibited synergy with second line anti-TB agent p-amino salicylic acid. This study therefore provides promising molecules for further development as antituberculosis DHFR inhibitors.

Diaryl ether synthesis in supercritical carbon dioxide in batch and continuous flow modes

A high yielding, batch mode synthesis of diaryl ethers and sulfides by an SNAr fluoride-mediated process in scCO2 has been developed; the use of a polymer-supported imidazolium fluoride reagent in batch mode led to the development of

Efficient and versatile sol-gel immobilized copper catalyst for ullmann arylation of phenols

A new hybrid silica with urea-based bipyridyl bridging units has been synthesized by a solgel process. The copper-complexed hybrid silica is an efficient heterogeneous catalyst for the Ullmann coupling of aryl halides with phenols. It is easily withdrawn and recovered from the reaction media by filtration. It is also a versatile catalyst for subsequent reactions with several substrates yielding products with the same efficiency even after ten reuses and with minimal leaching. This is the first example of the use of a copper-complexed bridged silsesquioxane for the preparation of a recoverable catalyst in modern Ullmann chemistry. This may represent a promising route to the reduction of waste while maintaining economic viability.

Synthesis of diaryl ethers, diaryl sulfides, heteroaryl ethers and heteroaryl sulfides under microwave dielectric heating

This paper describes the synthesis of diaryl ethers and sulfides by utilizing microwave heating methodology. The methodology is shown to be rapid and efficient for the coupling of phenols or thiophenol with electron-deficient aryl halides through a SNAr reaction. The scope of the protocol can be expanded to six-membered heterocycles bearing a hydroxyl group as well as to the reaction of 2-pyrimidinethiol with mildly activated aryl halides, providing heteroaryl ethers and sulfides, respectively. The advantages of the present method include the wide substrate scope, the obviation of metal catalysts, ease of product isolation, and high purity of products. Georg Thieme Verlag Stuttgart.

CsF-Al2O3 mediated rapid condensation of phenols with aryl halides: Comparative study of conventional heating vs. microwave irradiation

Biaryl ethers and thio ethers are formed in high yields by the condensation of phenols and thiophenols with electron-deficient aryl halides using CsF supported on Al2O3 under microwave irradiation in solvent-free conditions.

SYNTHESIS OF MONOCYANODIPHENYL ETHERS

At 300-340 deg C, with a contact time of 0.4-0.5 sec., and with the initial compound, atmospheric oxygen, ammonia, and water in molar ratios of 1:12-23:8-23:40-60 2-cyano-, 4-cyano-, 4-cyano-4'-tert-butyl-, and 4-cyano-4'-chlorodiphenyl ethers are formed from the corresponding methyl derivatives with yields of 17-45percent and with 52-92percent selectivity.