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Synthesis 2009(14): 2379-2284  
DOI: 10.1055/s-0029-1216854
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Efficient Synthesis of 2-Substituted Pyrido[3,2-d]pyrimidines Involving SNAr and Palladium-Catalyzed Cross-Coupling Reactions

Abdellatif Tikada,b, Sylvain Routier*a, Mohamed Akssirab, Jean-Michel Légerc, Christian Jarryc, Gérald Guillaumeta
a Institut de Chimie Organique et Analytique, Université d’Orléans, UMR CNRS 6005, rue de Chartres, BP 6759, 45067 Orléans Cedex 2, France
Fax: +33(2)38417281; e-Mail: sylvain.routier@univ-orleans.fr;
b Laboratoire de Chimie Bioorganique et Analytique, Université Hassan II-Mohammedia, BP 146, 20650 Mohammedia, Morocco
c EA 2962, Pharmacochimie, Université Victor Segalen Bordeaux II, 33076 Bordeaux, France
Further Information

Publication History

Received 4 February 2009
Publication Date:
02 June 2009 (online)

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Abstract

The efficient and original synthesis of various 2-substituted pyrido[3,2-d]pyrimidines is reported. Starting from 2,4-dichloropyrido[3,2-d]pyrimidine, a regioselective pallado-dehalogenation led to 2-chloropyrido[3,2-d]pyrimidine, which was used in SNAr and palladium-catalyzed cross-coupling reactions in order to afford highly functionalized products in very good yields.

Key words

arylations - amination - palladium

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12

Crystallographic study: The structure of compound 2 has been established by X-ray crystallography (Figure  [¹] ). Colorless single crystals of 2 were obtained by slow evaporation from MeOH-CHCl3 (20:80). The unit cell dimensions were determined using the least-squares fit from 25 reflections (25˚ < θ < 35˚). Intensities were collected with an Enraf-Nonius CAD-4 diffractometer using the CuKα radiation and a graphite monochromator up to θ = 45˚. The data were collected to relatively low resolution, i.e. no reflections were observed for θ > 45˚ with λCu. The data were corrected for Lorentz and polarization effects and for empirical absorption correction.¹4a The structure was solved by direct methods SHELX 86² and refined using SHELX 97² suite of programs.¹4b,c Crystallographic data for the structure 2 in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication (CCDC 718788): Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; E-mail: deposit@ccdc.cam.ac.uk.