Sonogashira cross-coupling reaction in 4-chloro-2-trichloromethylquinazoline series is possible despite a side dimerization reaction

被引:22
作者
Kieffer, Charline [1 ]
Verhaeghe, Pierre [1 ]
Primas, Nicolas [1 ]
Castera-Ducros, Caroline [1 ]
Gellis, Armand [1 ]
Rosas, Roselyne [2 ]
Rault, Sylvain [3 ]
Rathelot, Pascal [1 ]
Vanelle, Patrice [1 ]
机构
[1] Aix Marseille Univ, Lab Pharmacochimie Radicalaire, Fac Pharm, CNRS,ICR,UMR 7273, F-13385 Marseille 05, France
[2] Aix Marseille Univ, Fac Sci St Jerome, FR Federat Sci Chim Marseille 1739, F-13397 Marseille 20, France
[3] Univ Caen Basse Normandie, Ctr Etud & Rech Medicament Normandie, UFR Sci Pharmaceut, UPRES,EA 4258,CNRS,FR 3038,INC3M, F-14032 Caen, France
关键词
Quinazoline ring; Sonogashira cross-coupling reaction; Trichloromethyl group; Reductive homocoupling reaction; ANTIPLASMODIAL ACTIVITY; DERIVATIVES; ALKYNES; IDENTIFICATION; ACETYLENES;
D O I
10.1016/j.tet.2013.01.094
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
We studied the Sonogashira coupling reaction between 4-chloro-2-trichloromethylquinazoline and various terminal alkynes, mainly in phenylacetylene series. A brief review of the literature shows that mono- or polybromo/chloromethylated substrates, especially in aromatic series, are very rarely compatible with the achievement of Sonogashira reactions. Thus, although the 4-chloroquinazoline scaffold is a very good substrate for this palladium-catalyzed reaction, the typical behavior of the trichloromethyl group in reductive media leads to the competitive formation of undesirable reduced homodimers in high yields. However, by closely examining all the Sonogashira reaction parameters, we developed a specific operating procedure, using Pd(OAc)(2), Cs2CO3, and DMF, which resulted in the synthesis of 14 original coupling products in 10-70% yield, depending on the alkyne used. (C) 2013 Elsevier Ltd. All rights reserved.
引用
收藏
页码:2987 / 2995
页数:9
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