OpenSourceMalaria:GSK Amino-thienopyrimidine Series: Difference between revisions
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[[Image:4synthesis.png|thumb|center|450px|Proposed synthesis for the above compound]] | [[Image:4synthesis.png|thumb|center|450px|Proposed synthesis for the above compound]] | ||
====Alternatives==== | |||
The step that involves n-BuLi would best be avoided, and if a more direct route of arriving at the Suzuki coupling step could be discovered, that would take a potentially dangerous and difficult step out of the synthetic route. | |||
One possibility, involving NIS and an ionic liquid such as 1-Butyl-3-methylimidazolium tetrafluoroborate (which our lab doesn't have, but which is available from Aldrich in catalytic quality from $247/5g), is found below: | |||
[doi:10.1016/j.tetlet.2011.03.010 DOI] | |||
====Thiophene Starting Material Synthesis==== | |||
Additionally, the thiophene available from Sigma Aldrich for $159/10g can be made from the following synthesis. | Additionally, the thiophene available from Sigma Aldrich for $159/10g can be made from the following synthesis. |
Revision as of 03:20, 29 April 2012
GSK Thienopyrimidine Series
The first structure in this series, | TCMDC 135294, has the following structure:
| ChEMBL 581088 link.
| ChemSpider link.
SMILES: Nc1ncnc2cc(sc12)c3cccc(c3)S(=O)(=O)N
InChI=1S/C12H10N4O2S2/c13-12-11-9(15-6-16-12)5-10(19-11)7-2-1-3-8(4-7)20(14,17)18/h1-6H,(H2,13,15,16)(H2,14,17,18)
Synthesis
The proposed synthesis for this compound is below:
Alternatives
The step that involves n-BuLi would best be avoided, and if a more direct route of arriving at the Suzuki coupling step could be discovered, that would take a potentially dangerous and difficult step out of the synthetic route.
One possibility, involving NIS and an ionic liquid such as 1-Butyl-3-methylimidazolium tetrafluoroborate (which our lab doesn't have, but which is available from Aldrich in catalytic quality from $247/5g), is found below:
[doi:10.1016/j.tetlet.2011.03.010 DOI]
Thiophene Starting Material Synthesis
Additionally, the thiophene available from Sigma Aldrich for $159/10g can be made from the following synthesis.
Analogues
TCMDC 135294 is part of a series with one other member, | TCMDC 135255, shown below:
| ChEMBL639249 link.
| ChemSpider link.
SMILES: Nc1ncnc2cc(sc12)c3cccc(NC(=O)Nc4ccccc4)c3
InChI=1S/C19H15N5OS/c20-18-17-15(21-11-22-18)10-16(26-17)12-5-4-8-14(9-12)24-19(25)23-13-6-2-1-3-7-13/h1-11H,(H2,20,21,22)(H2,23,24,25)
Iain Wallace created a cytoscape file which details purchaseable compounds related to the two series that I am trying to make. The file can be found here, and Cytoscape can be downloaded for free here (one will need to activate the chemviz plugin, which can be activated from within Cytoscape). The results of this work, in the form of a list of purchaseable compounds, can be found here
A list of the above compounds in .csv format, with InChi, InChiKey, SMILES and eMolecules identifiers, can be found here
References
Brown, G. B.; Baker, B. R.; Bernstein, S.; Safir, S. R., BIOTIN. II. 3,4-trans-DIAMINOTHIOPHANE. The Journal of Organic Chemistry 1947, 12 (1), 155-159.
Castenado, G.; Dotson, J.; Goldsmith, R.; Gunzo, J.; Heffron, T.; Mathieu, S.; Oliveo, A.; Staben, S.; Sutherlin, D.P.; Tsui, V.; Wang, S.; Zhu, B.; Bayliss, T.; Chuckowree, I.; Folkes, A.; Wan, N.C. (Genentech, Inc., USA; Piramed Limited). Thienopyrimidine and furopyrimidine derivatives as phosphoinositide 3-kinase inhibitor and their preparation, pharmaceutical compositions and use in the treatment of cancer. World Intellectual Property Organisation 2008073785 A2, 2008; SciFinder Scholar AN 2008:735944 (accessed 2/2/2012).
Son, J.B.; Jung, S. H.; Choi, W.I.; Jung, Y.H.; Choi, J.Y.; Song, J.Y.; Lee, K.H.; Lee, J.C.; Kim, E.Y.; Ahn, Y.G.; Kim, M.S.; Choi, HG.; Sim, T.B.; Ham, Y.J.; Park, D.; Kim, H.; Kim, D. (Hanmi Holdings Co., Ltd., S. Korea; Korea Institute of Science and Technology; Catholic University Industry Academic Cooperation Foundation). Preparation of thienopyrimidine derivatives for use as protein kinase inhibitors. World Intellectual Property Organisation 2011093684 A2, 2011; SciFinder Scholar AN 2011:971406 (accessed 3/2/2012).
Woodward, R. B.; Eastman, R. H., Tetrahydrothiophene ("Thiophane") Derivatives. J. Am. Chem. Soc. 1946, 68 (11), 2229-2235.