Synthesis of N-pyridyl azoles using a deprotometalation-iodolysis-N-arylation sequence and evaluation of their antiproliferative activity in melanoma cells

TETRAHEDRON

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Article

Hedidi, Madani^1,2,6  Erb, William¹  Bentabed-Ababsa, Ghenia²  Chevallier, Floris¹  Picot, Laurent³  Thiery, Valerie³  Bach, Stephane⁴  Ruchaud, Sandrine⁴  Roisnel, Thierry⁵  Dorcet, Vincent⁵  Mongin, Florence¹ 

[1] Univ Rennes 1, Inst Sci Chim Rennes, Chim & Photon Mol, CNRS,UMR 6226, 1,Batiment 10A,Case 1003,Campus Beaulieu, F-35042 Rennes, France

[2] Univ Oran, Fac Sci, Lab Synth Organ Appl, 1 Ahmed Ben Bella,BP 1524 El MNaouer, Oran 31000, Algeria

[3] Univ La Rochelle, Lab Littoral Environm & Soc, CNRS, UMRi 7266, F-17042 La Rochelle, France

[4] Univ Paris 06, Prot Phosphorylat & Human Dis Unit, Plateforme Criblage KISSf, Sorbonne Univ,Stn Biol Roscoff,CNRS,USR3151, Pl Georges Teissier, F-29688 Roscoff, France

[5] Univ Rennes 1, Inst Sci Chim Rennes, Ctr Diffractometrie 10, CNRS,UMR 6226, Batiment 10B,Campus Beaulieu, F-35042 Rennes, France

[6] Univ Hassiba Benbouali Chief, Dept Chim, Fac Sci Exactes & Informat, RN 19, Hay Es Salem 02000, Chief, Algeria

关键词: Pyridine;    Azole;    N-Arylation;    Copper;    Antiproliferative activity;   

DOI  :  10.1016/j.tet.2016.08.056

来源: Elsevier

【 摘 要 】

N-Arylation of pyrrole with 3-iodo-4-methoxypyridine was investigated by copper catalysis under different conditions. The best conditions, that proved to be protocol A (CuI, DMEDA or TMEDA, K3PO4, DMF at 110 degrees C) and above all protocol B (Cu2O, Cs2CO3, DMSO at 110 degrees C), were applied to the synthesis of various N-(methoxypyridyl) pyrroles, indoles and benzimidazoles. The behavior of the different iodinated methoxypyridines was rationalized by evaluating the partial positive charge on the carbon bearing iodine from the H-1 NMR chemical shift of the corresponding deiodinated substrates. The reaction was next connected with the deprotometalation-iodolysis step generating iodinated methoxypyridines: straight involvement of the crude iodo intermediates in pyrrole N-arylation afforded the expected N-(methoxypyridyl) pyrroles in good yields. Several synthesized N-(methoxypyridyl) azoles exerted low to moderate antiproliferative activity in A2058 melanoma cells. (C) 2016 Elsevier Ltd. All rights reserved.

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