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

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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

The synthetic strategy for deriving pharmacologically-relevant bifunctional compounds based on linked dihydropyrimidone and chloroquinoline moieties is reported, together with supporting X-ray structures of two synthetic intermediates and a representative target compound.

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Acknowledgment

We thank the University of Cape Town and the NRF (Pretoria) for research support.

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Authors and Affiliations

  1. Department of Chemistry, University of Cape Town, Rondebosch, 7701, South Africa

    Nicholas D. Watermeyer, Kelly Chibale & Mino R. Caira

  2. Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch, 7701, South Africa

    Kelly Chibale

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  1. Nicholas D. Watermeyer
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  2. Kelly Chibale
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  3. Mino R. Caira
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Correspondence to Kelly Chibale or Mino R. Caira.

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Watermeyer, N.D., Chibale, K. & Caira, M.R. Pharmacologically Relevant Bifunctional Compounds Containing Chloroquinoline and Dihydropyrimidone Moieties: Syntheses and Crystal Structures of a Target Molecule and Selected Intermediates. J Chem Crystallogr 39, 753–760 (2009). https://doi.org/10.1007/s10870-009-9568-2

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