Doctor of Philosophy
School of Chemistry
Rashad Ahmed, Adel Ahmed, The medicinal chemistry development for new antimicrobial chemotherapeutics, Doctor of Philosophy thesis, School of Chemistry, University of Wollongong, 2014. http://ro.uow.edu.au/theses/4132
Chapter 2 discusses the synthesis of the arenearylpyrimidylmethanes (AAPMs) series was investigated to further develop the structure activity relationships (SAR) of these compounds as potential anti-chikungunya virus agents. 1-(4,6-Dichloropyrimidin-5-yl)- 2-methyl-1-(3-nitrophenyl)propan-1-ol was prepared in 50% yield. Subsequent dehydration and amination gave the intermediate 4-amino-6-chloro-5-(2-methyl-1-(3- nitrophenyl)prop-1-en-1-yl)pyrimidine in 90% yield, over two steps. Final amination using either 1-amino-3-(diethylamino)propan-2-ol or N1,N1-diethylpentane-1,4-diamine was attempted using several conditions, however, the desired final AAPM derivatives were not obtained.
Further modification of the synthetic protocol was achieved through the replacement of the 4,6-dichloropyrimidine with the less hindered 4-chloropyridine. The 4- chloropyridin-3-yl alcohols were prepared in 42-52% yield. Subsequent dehydration afforded the 4-chloropyridine alkenes in 62-85% yield. Final replacement of the chlorine atom with the amine N1,N1-diethylpentane-1,4-diamine was attempted under different conditions, however, the desired products were not obtained. Instead the 3- (cyclobutylidene(4-phenoxypyridin-3-yl)methyl)aniline was isolated when using phenol as a solvent for the amination reaction. Replacement of the N1,N1-diethylpentane-1,4- diamine with the secondary amine morpholine gave 4-(3-(cyclopropylidene(3- nitrophenyl)methyl)pyridin-4-yl)morpholine in 65% yield.