282543-44-6Relevant articles and documents
Structural studies on bioactive compounds. Part 29: Palladium catalysed arylations and alkynylations of sterically hindered immunomodulatory 2-amino- 5-halo-4,6-(disubstituted)pyrimidines
Hannah, Duncan R.,Sherer, Edward C.,Davies, Roy V.,Titman, Roger B.,Laughton, Charles A.,Stevens, Malcolm F. G.
, p. 739 - 750 (2007/10/03)
The immunological agent bropirimine 5 is a tetra-substituted pyrimidine with anticancer and interferon-inducing properties. Synthetic routes to novel 5-aryl analogues of bropirimine have been developed and their potential molecular recognition properties analysed by molecular modelling methods. Sterically challenged 2-amino-5-halo-6-phenylpyrimidin-4-ones (halo=Br or I) are poor substrates for palladium catalysed Suzuki cross-coupling reactions with benzeneboronic acid because the basic conditions of the reaction converts the amphoteric pyrimidinones to their unreactive enolic forms. Palladium-mediated reductive dehalogenation of the pyrimidinone substrates effectively competes with cross-coupling. 2-Amino-5-halo-4-methoxy-6- phenylpyrimidines can be converted to a range of 5-aryl derivatives with the 5-iodopyrimidines being the most efficient substrates. Hydrolysis of the 2- amino-5-aryl-4-methoxy-6-phenylpyrimidines affords the required pyrimidin-4- ones in high yields. Semi-empirical quantum mechanical calculations show how the nature of the 5-substituent influences the equilibrium between the 1H- and 3H-tautomeric forms, and the rotational freedom about the bond connecting the 6-phenyl group and the pyrimidine ring. Both of these factors may influence the biological properties of these compounds. (C) 2000 Elsevier Science Ltd.
