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Pharmacologically Relevant Bifunctional Compounds Containing Chloroquinoline and Dihydropyrimidone Moieties: Syntheses and Crystal Structures of a Target Molecule and Selected Intermediates

Research paper by Nicholas D. Watermeyer, Kelly Chibale, Mino R. Caira

Indexed on: 03 Apr '09Published on: 03 Apr '09Published in: Journal of chemical crystallography



Abstract

We report the regioselective synthesis and X-ray structure of the pharmacologically relevant 3-[2-(7-chloro-quinolin-4-ylamino)-ethylcarbamoyl]-4-(4-methoxy-phenyl)-1,6-dimethyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid methyl ester (3) (triclinic, space group \( P\bar{1} \), a = 11.1775 (3), b = 13.6470 (4), c = 16.3680 (6) Å, α = 82.645 (1), β = 86.423 (1), γ = 88.415 (2)°, V = 2470.9 (1) Å3, Z = 4). Further support for the regioselectivity is provided by the X-ray structures of two intermediates, namely 4-(4-methoxy-phenyl)-1,6-dimethyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid methyl ester, 8 (monoclinic, space group P21/c, a = 11.7710 (2), b = 5.5290 (1), c = 22.9500 (5) Å, β = 104.342 (1)°, V = 1447.08 (5) Å3, Z = 4), and 4-(4-methoxy-phenyl)-1,3,6-trimethyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid methyl ester, 9 (monoclinic, space group P21/c, a = 16.6529 (7), b = 10.9426 (4), c = 8.2819 (3) Å, β = 91.395 (2)°, V = 1508.7 (1) Å3, Z = 4), which are also reported. The three compounds display significant differences in the conformations of their DHPM rings as well as a variety of hydrogen bonding arrangements in their crystals.

Graphical abstract 10.1007/s10870-009-9568-2.gif