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

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Hedidi, Madani | Maillard, Julien | Erb, William | Lassagne, Frédéric | Halauko, Yury | Ivashkevich, Oleg | Matulis, Vadim | Roisnel, Thierry | Dorcet, Vincent | Hamzé, Monzer | Fajloun, Ziad | Baratte, Blandine | Ruchaud, Sandrine | Bach, Stéphane | Bentabed-Ababsa, Ghenia | Mongin, Florence

Edité par CCSD ; Elsevier -

International audience. 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, K 3 PO 4 , DMF at 110 C) and above all protocol B (Cu 2 O, Cs 2 CO 3 , DMSO at 110 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 1 H 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.

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