Synthesis 2014; 46(12): 1613-1620
DOI: 10.1055/s-0033-1341105
paper
© Georg Thieme Verlag Stuttgart · New York

One-Pot Chemoselective Synthesis of 2,4,6,8-Tetrasubstituted Quinazolines via Microwave-Assisted Consecutive Bis-SNAr/Bis-Suzuki–Miyaura Cross-Coupling Reactions

Youssef Kabri
Aix-Marseille Université, Institut de Chimie Radicalaire ICR, UMR CNRS 7273, Laboratoire de Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin – CS 30064, 13385 Marseille Cedex 05, France   Fax: +33(4)91794677   Email: patrice.vanelle@univ-amu.fr
,
Maxime D. Crozet
Aix-Marseille Université, Institut de Chimie Radicalaire ICR, UMR CNRS 7273, Laboratoire de Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin – CS 30064, 13385 Marseille Cedex 05, France   Fax: +33(4)91794677   Email: patrice.vanelle@univ-amu.fr
,
Sébastien Redon
Aix-Marseille Université, Institut de Chimie Radicalaire ICR, UMR CNRS 7273, Laboratoire de Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin – CS 30064, 13385 Marseille Cedex 05, France   Fax: +33(4)91794677   Email: patrice.vanelle@univ-amu.fr
,
Patrice Vanelle*
Aix-Marseille Université, Institut de Chimie Radicalaire ICR, UMR CNRS 7273, Laboratoire de Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin – CS 30064, 13385 Marseille Cedex 05, France   Fax: +33(4)91794677   Email: patrice.vanelle@univ-amu.fr
› Author Affiliations
Further Information

Publication History

Received: 14 January 2014

Accepted after revision: 13 March 2014

Publication Date:
02 April 2014 (online)


Abstract

A practical and efficient synthesis of 2,4,6,8-tetrasubstituted quinazolines through one-pot chemoselective sequential bis-SNAr/bis-Suzuki–Miyaura reactions under microwave irradiation is presented. The bis-SNAr reaction occurs selectively at the C-2 and C-4 positions of 6,8-dibromo-2,4-dichloroquinazoline and the bis-Suzuki–Miyaura cross-coupling at C-6 and C-8. This procedure affords convergent synthesis of polysubstituted quinazoline derivatives in high yields in very few steps and tolerates a wide range of boronic acids and amines.