Journal
TETRAHEDRON
Volume 64, Issue 9, Pages 2035-2041Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tet.2007.12.056
Keywords
dihydropyrimidines; multicomponent reaction; design of experiments; microwave irradiation; heterocycles
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The rapid preparation of the mitotic kinesin Eg5 inhibitor monastrol has been performed using multicomponent chemistry and combining microwave-assisted synthesis and a statistical design of experiments (DoEs) approach. By variation of the solvent, catalyst type and concentration, reaction time, and temperature a matrix of experiments for the DoE method was derived. As a result of 29 experiments with reaction times ranging from 10 to 30 min, an optimized procedure was derived that allowed the preparation of monastrol in 82%. (c) 2008 Elsevier Ltd. All rights reserved.
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