Synthesis of C,N′-linked bis-heterocycles using a deprotometalation–iodination–N-arylation sequence and evaluation of their antiproliferative activity in melanoma cells
作者:Madani Hedidi、Ghenia Bentabed-Ababsa、Aïcha Derdour、Thierry Roisnel、Vincent Dorcet、Floris Chevallier、Laurent Picot、Valérie Thiéry、Florence Mongin
DOI:10.1016/j.bmc.2014.04.028
日期:2014.7
crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2 equiv) and Cs2CO3 (2 equiv), and using acetonitrile as solvent (no other ligand) to provide after 24 h reflux the expected N-arylated azoles in yields ranging from 33% to 81%. Using benzotriazole also led to N-arylation products, but in lower 34%, 39%
苯并噻吩,苯并呋喃,苯并噻唑和苯并恶唑是使用由ZnCl 2 ·TMEDA(TMEDA = N,N,N ',N'-四甲基乙二胺,1当量)和2,2,6,6-四甲基哌啶锂制备的锂-锌组合脱金属金属盐的。(LiTMP,3当量)。随后使用碘作为亲电试剂拦截2-金属化衍生物,碘化物的收率分别为81%,82%,67%和42%。与使用ZnCl 2获得的产率相比,这些产率更高(提高了10%)·TMEDA(0.5当量)和LiTMP(1.5当量),但苯并恶唑(少10%)的情况除外。在Cu(0.2当量)和Cs 2 CO 3存在下,粗碘化物参与吡咯,吲哚,咔唑,吡唑,吲唑,咪唑和苯并咪唑的N-芳基化反应(2当量),并使用乙腈作为溶剂(无其他配体),在回流24小时后提供预期的N-芳基化吡咯,产率为33%至81%。使用苯并三唑还可以产生N-芳基化产物,但产率分别较低,分别为34%,39%,36%和6%。对该唑的进一步研究证明了2