15905-18-7Relevant articles and documents
Identification of N- or O-Alkylation of Aromatic Nitrogen Heterocycles and N-Oxides Using 1H–15N HMBC NMR Spectroscopy
Bateman, Lorraine M.,Breugst, Martin,Byrne, Peter A.,Flosbach, Niko T.,Sheehy, Kevin J.
, (2020)
A series of representative diazines and pyridine N-oxides were subjected to alkylation using several different alkylating agents. The 15N NMR chemical shifts (δN values) of the diazines, pyridine N-oxides and derived alkylation products were determined using 1H-15N HMBC NMR spectroscopy at natural 15N abundance. The changes in the 15N NMR chemical shifts (Δ(δN) values) that occurred on going from starting materials to products in these reactions were analyzed. N-alkylation of diazines resulted in large upfield shifts of the δN values of the alkylated nitrogen (of the order of 100 ppm or greater). While O-alkylation of pyridine N-oxides resulted in upfield shifts of the δN values of the N-(alkoxy)pyridinium nitrogen, the Δ(δN) values were of a much smaller magnitude (ca. –42 ppm) than those observed for N-alkylations of diazines. Nitrogen NMR spectroscopic data from the literature of relevance to alkylation of azines, diazines, azine N-oxides and diazine N-oxides was gathered together, and using this in tandem with our 15N NMR spectroscopic data, we have been able to corroborate our observations on the trends observed in the Δ(δN) values associated with N- and O-alkylation reactions of aromatic N-heterocycles and N-oxides. An analysis protocol that relies on synergistic evaluation of 1H-15N HMBC and 1H-13C HMBC NMR spectra has been developed that enables unambiguous diagnosis of the occurrence of N-alkylation of aromatic N-heterocycles and O-alkylation of aromatic N-oxides.
Visible-Light-Induced ortho-Selective Migration on Pyridyl Ring: Trifluoromethylative Pyridylation of Unactivated Alkenes
Jeon, Jinwon,He, Yu-Tao,Shin, Sanghoon,Hong, Sungwoo
supporting information, p. 281 - 285 (2019/11/26)
The photocatalyzed ortho-selective migration on a pyridyl ring has been achieved for the site-selective trifluoromethylative pyridylation of unactivated alkenes. The overall process is initiated by the selective addition of a CF3 radical to the alkene to provide a nucleophilic alkyl radical intermediate, which enables an intramolecular endo addition exclusively to the ortho-position of the pyridinium salt. Both secondary and tertiary alkyl radicals are well-suited for addition to the C2-position of pyridinium salts to ultimately provide synthetically valuable C2-fluoroalkyl functionalized pyridines. Moreover, the method was successfully applied to the reaction with P-centered radicals. The utility of this transformation was further demonstrated by the late-stage functionalization of complex bioactive molecules.
Photoredox generation of the trifluoromethyl radical from borate complexes: Via single electron reduction
Smirnov, Vladimir O.,Maslov, Anton S.,Kokorekin, Vladimir A.,Korlyukov, Alexander A.,Dilman, Alexander D.
supporting information, p. 2236 - 2239 (2018/03/06)
A method for the generation of the CF3 radical from CF3-substituted borate complexes bearing a pyridine-N-oxide ligand is described. Cleavage of the C-B bond occurs via single electron reduction by a Cu(i) photocatalyst activated by visible light.
INHIBITORS OF COLLAGEN PROLYL 4-HYDROXYLASE
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Paragraph 0187; 0188; 0189, (2016/10/17)
Biheteroaryl dicarboxylates and esters, and salts thereof which are useful as modulators of CP4H activity and more particularly as inhibitors of CP4H. Compounds of formula: and salts thereof where: X is S, O, NH, or NR, where R is an alkyl group having 1-3 carbon atoms; R1 and R2 independently are —OR7, or —NHSO2R8, where R7 is selected from: hydrogen, alkyl, alkenyl, alkoxyalkyl, —R′—CO—R″, —R′—CO—O—R″, —CO—R″, —R′—O—CO—R″, —R′—CO—NR″, —CO—NR″, or —R′—O—CO—NR″, and R8 is selected from hydrogen, alkyl, aryl, arylalkyl; R3, R4 and R6 independently are hydrogen, alkyl, alkoxy, alkenyl, alkenoxy, halo alkyl, haloalkenyl, halogen, hydroxyl, hydroxyalkyl, hydroxyalkenyl, aryl, aryloxy, arylalkyl or arylalkyloxy; R5 is hydrogen, halogen, alkyl having 1-3 carbon atoms, or alkoxy having 1-3 carbon atoms; —R′— is a divalent straight chain or branched alkylene, and —R″ is an alkyl, alkenyl, arylalkyl, or aryl group. Methods for inhibition of CP4H in vivo and in vitro.
Selective inhibition of prolyl 4-hydroxylases by bipyridinedicarboxylates
Vasta, James D.,Raines, Ronald T.
, p. 3081 - 3090 (2015/08/03)
Abstract Collagen is the most abundant protein in animals. A variety of indications are associated with the overproduction of collagen, including fibrotic diseases and cancer metastasis. The stability of collagen relies on the posttranslational modification of proline residues to form (2S,4R)-4-hydroxyproline. This modification is catalyzed by collagen prolyl 4-hydroxylases (CP4Hs), which are Fe(II)- and α-ketoglutarate (AKG)-dependent dioxygenases located in the lumen of the endoplasmic reticulum. Human CP4Hs are validated targets for treatment of both fibrotic diseases and metastatic breast cancer. Herein, we report on 2,2′-bipyridinedicarboxylates as inhibitors of a human CP4H. Although most 2,2′-bipyridinedicarboxylates are capable of inhibition via iron sequestration, the 4,5′- and 5,5′-dicarboxylates were found to be potent competitive inhibitors of CP4H, and the 5,5′-dicarboxylate was selective in its inhibitory activity. Our findings clarify a strategy for developing CP4H inhibitors of clinical utility.
A general synthesis of bis(o-azaheteroaryl)methane derivatives from N-oxides of azines and azoles
Szpunar, Magdalena,Loska, Rafa?
supporting information, p. 2133 - 2137 (2015/03/31)
A general method of preparation of derivatives of bis(o-azaheteroaryl)methanes from aromatic N-oxides is reported, the key step of which is a 1,3-dipolar cycloaddition between N-oxides of azines or azoles and in situ generated terminal difluoroalkenes containing an o-azaheteroaryl substituent at the double bond. Selected products were applied for the preparation of two novel unsymmetrical analogues of BODIPY fluorescent dyes, containing both an imidazole and a quinoline or isoquinoline unit.
BIOREVERSABLE PROMOIETIES FOR NITROGEN-CONTAINING AND HYDROXYL-CONTAINING DRUGS
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Page/Page column 130; 131, (2015/06/18)
Disclosed are promoieties of the following formula which can be used to form prodrugs of nitrogen-containing or hydroxyl-containing drug or a pharmaceutically active agent: (I) and pharmaceutical compositions comprising the prodrugs.
Synthesis of unsymmetrically substituted bipyridines by palladium-catalyzed direct C-H arylation of pyridine N -oxides
Duric, Sasa,Tzschucke, C. Christoph
supporting information; experimental part, p. 2310 - 2313 (2011/06/28)
Chemical equations presented. Substituted bipyridines were efficiently prepared by direct coupling between pyridine N-oxides and halopyridines using a palladium catalyst. Pyridine N-oxides with electron-withdrawing substitutents gave the best yields. This method allows the convenient preparation of 2,2′-, 2,3′-, and 2,4′-bipyridines which are useful as functionalized ligands for metal complexes or as building blocks for supramolecular architectures.
A simple and efficient method for the preparation of N- heteroaromatic N-oxides
Balicki, Roman,Golinski, Jerzy
, p. 1529 - 1534 (2007/10/03)
Urea-hydrogen peroxide/formic acid system has shown utility for mild and safe N-oxidation of N-heteroaromatic compounds.
