A facile synthetic route for antineoplastic drug GDC-0449
-
Meng Cao
,
Hua-You Hu
Abstract
In the current study a facile synthetic route for preparing antineoplastic drug GDC-0449 is investigated. Starting with pyridine-1-oxide and 1-iodo-3-nitrobenzene, the intermediate product 2-(2-chloro-5-nitrophenyl) pyridine was prepared by cross-coupling, deoxidation and halogenation. The final compound was then synthesised by reduction of the nitro group followed by amidation. This synthetic route avoids the use of unstable organometallic or organic boride compounds; it employs relatively inexpensive and bench-stable reagents, involves readily controllable reaction conditions, and achieves a relatively high yield.
[1] Abramovitch, R. A., Kato, S., & Singer, G. M. (1971). N-aryloxypyridinium salts and their base-catalyzed rearrangement. Journal of the American Chemical Society, 93, 3074–3075. DOI: 10.1021/ja00741a059. http://dx.doi.org/10.1021/ja00741a05910.1021/ja00741a059Suche in Google Scholar
[2] Abramovitch, R. A., Inbasekaran, M. N., Kato, S., & Singer, G. M. (1976). Reaction of pyridine 1-oxides and N-iminopyridinium ylides with diazonium salts N-aryloxypyridinium salts and their base-catalyzed rearrangement. Journal of Organic Chemistry, 41, 1717–1724. DOI: 10.1021/jo00872a011. http://dx.doi.org/10.1021/jo00872a01110.1021/jo00872a011Suche in Google Scholar
[3] Berman, D. M., Karhadkar, S. S., Maitra, A., Montes de Oca, R., Gerstenblith, M. R., Briggs, K., Parker, A. R., Shimada, Y., Eshleman, J. R., Watkins, D. N., & Beachy, P. A. (2003). Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours. Nature, 425, 846–851. DOI: 10.1038/nature01972. http://dx.doi.org/10.1038/nature0197210.1038/nature01972Suche in Google Scholar PubMed
[4] Campeau, L. C., Rousseaux, S., & Fagnou, K. (2005). A solution to the 2-pyridyl organometallic cross-coupling problem: Regioselective catalytic direct arylation of pyridine N-oxides. Journal of the American Chemical Society, 127, 18020–18021. DOI: 10.1021/ja056800x. http://dx.doi.org/10.1021/ja056800x10.1021/ja056800xSuche in Google Scholar PubMed
[5] Campeau, L. C., Schipper, D. J., & Fagnou, K. (2008a). Siteselective sp2 and benzylic sp3 palladium-catalyzed direct arylation. Journal of the American Chemical Society, 130, 3266–3267. DOI: 10.1021/ja710451s. http://dx.doi.org/10.1021/ja710451s10.1021/ja710451sSuche in Google Scholar PubMed
[6] Campeau, L. C., Bertrand-Laperle, M., Leclerc, J. P., Villemure, E., Gorelsky, S., & Fagnou, K. (2008b). C2, C5, and C4 azole N-oxide direct arylation including room-temperature reactions. Journal of the American Chemical Society, 130, 3276–3277. DOI: 10.1021/ja7107068. http://dx.doi.org/10.1021/ja710706810.1021/ja7107068Suche in Google Scholar PubMed
[7] Dick, A. R., Hull, K. L., & Sanford, M. S. (2004). A highly selective catalytic method for the oxidative functionalization of C—H bonds. Journal of the American Chemical Society, 126, 2300–2301. DOI: 10.1021/ja031543m. http://dx.doi.org/10.1021/ja031543m10.1021/ja031543mSuche in Google Scholar PubMed
[8] Dick, G. R., Knapp, D. M., Gillis, E. P., & Burke, M. D. (2010). General method for synthesis of 2-heterocyclic N-methyliminodiacetic acid boronates. Organic Letters, 12, 2314–2317. DOI: 10.1021/ol100671v. http://dx.doi.org/10.1021/ol100671v10.1021/ol100671vSuche in Google Scholar PubMed PubMed Central
[9] Epstein, E. H. (2008). Basal cell carcinomas: attack of the hedgehog. Nature Reviews Cancer, 8, 743–754. DOI: 10.1038/nrc2503. http://dx.doi.org/10.1038/nrc250310.1038/nrc2503Suche in Google Scholar PubMed PubMed Central
[10] Gavryushin, A., Kofink, C., Manolikakes, G., & Knochel, P. (2005). Efficient cross-coupling of functionalized arylzinc halides catalyzed by a nickel chloride-diethyl phosphite system. Organic Letters, 7, 4871–4874. DOI: 10.1021/ol051615+. http://dx.doi.org/10.1021/ol051615+10.1021/ol051615+Suche in Google Scholar PubMed
[11] Gunzner, J. L., Sutherlin, D., Stanley, M. S., Bao, L., Castanedo, G. M., Lalonde, R. L., Wang, S., Reynolds, M. E., Savage, S. J., Malesky, K., & Dina, M. S. (2011). U.S. Patent No. 07888364. Washington, D.C., USA: U.S. Patent and Trademark Office. Suche in Google Scholar
[12] Hull, K. L., Anani, W. Q., & Sanford, M. S. (2006). Palladiumcatalyzed fluorination of carbon-hydrogen bonds. Journal of the American Chemical Society, 128, 7134–7135. DOI: 10.1021/ja061943k. http://dx.doi.org/10.1021/ja061943k10.1021/ja061943kSuche in Google Scholar PubMed
[13] Kalyani, D., Deprez, N. R., Desai, L. V., & Sanford, M. S. (2005). Oxidative C—H activation/C—C bond forming reactions: Synthetic scope and mechanistic insights. Journal of the American Chemical Society, 127, 7330–7331. DOI: 10.1021/ja051402f. http://dx.doi.org/10.1021/ja051402f10.1021/ja051402fSuche in Google Scholar PubMed
[14] Kalyani, D., Dick, A. R., Anani, W. Q., & Sanford, M. S. (2006a). Scope and selectivity in palladium-catalyzed directed C—H bond halogenation reactions. Tetrahedron, 62, 11483–11498. DOI: 10.1016/j.tet.2006.06.075. http://dx.doi.org/10.1016/j.tet.2006.06.07510.1016/j.tet.2006.06.075Suche in Google Scholar
[15] Kalyani, D., Dick, A. R., Anani, W. Q., & Sanford, M. S. (2006b). A simple catalytic method for the regioselective halogenation of arenes. Organic Letters, 8, 2523–2526. DOI: 10.1021/ol060747f. http://dx.doi.org/10.1021/ol060747f10.1021/ol060747fSuche in Google Scholar PubMed
[16] Knapp, D. M., Gillis, E. P., & Burke, M. D. (2009). A general solution for unstable boronic acids: Slow-release cross-coupling from air-stable MIDA boronates. Journal of the American Chemical Society, 131, 6961–6963. DOI: 10.1021/ja901416p. http://dx.doi.org/10.1021/ja901416p10.1021/ja901416pSuche in Google Scholar PubMed PubMed Central
[17] Leclerc, J. P., & Fagnou, K. (2006). Palladium-catalyzed crosscoupling reactions of diazine N-oxides with aryl chlorides, bromides, and iodides. Angewandte Chemie International Edition, 45, 7781–7786. DOI: 10.1002/anie.200602773. http://dx.doi.org/10.1002/anie.20060277310.1002/anie.200602773Suche in Google Scholar PubMed
[18] Lyons, T. W., & Sanford, M. S. (2010). Palladium-catalyzed ligand-directed C—H functionalization reactions. Chemical Reviews, 110, 1147–1169. DOI: 10.1021/cr900184e. http://dx.doi.org/10.1021/cr900184e10.1021/cr900184eSuche in Google Scholar PubMed PubMed Central
[19] Matondo, H., Souirti, S., & Baboul`ene, M. (2003). Improved synthesis of azaheteroarylboronic acids using tris-trimethylsilylborate under mild conditions. Synthetic Communications, 33, 795–800. DOI: 10.1081/scc-120016325. http://dx.doi.org/10.1081/SCC-12001632510.1081/SCC-120016325Suche in Google Scholar
[20] Miyaura, N., & Suzuki, A. (1979). Stereoselective synthesis of arylated (E)-alkenes by the reaction of alk-1-enylboranes with aryl halides in the presence of palladium catalyst. Journal of the Chemical Society, Chemical Communications, 1979, 866–867. DOI: 10.1039/c39790000866. http://dx.doi.org/10.1039/c3979000086610.1039/c39790000866Suche in Google Scholar
[21] Robarge, K. D., Brunton, S. A., Castanedo, G. M., Cui, Y., Dina, M. S., Goldsmith, R., Gould, S. E., Guichert, O., Gunzner, J. L., Halladay, J., Jia, W., Khojasteh, C., Koehler, M. F. T., Kotkow, T., La, H., LaLonde, L. R., Lau, K., Lee, L., Marshall, D., Marsters, J. C., Jr., Murray, L. J., Quian, C. G., Rubin, L. L., Salphati, L., Stanley, M. S., Stibbard, J. H. A., Sutherlind, D. P., Unhayaker, S., Wang, S. M., Wong, S., & Xie, M. (2009). GDC-0449-a potent inhibitor of the hedgehog pathway. Bioorganic & Medicinal Chemistry Letters, 19, 5576–5581. DOI: 10.1016/j.bmcl.2009.08.049. http://dx.doi.org/10.1016/j.bmcl.2009.08.04910.1016/j.bmcl.2009.08.049Suche in Google Scholar PubMed
[22] Su, Z. M., Yeagley, A. A., Su, R., Peng, L. L., & Melander, C. (2012). Structural studies on 4,5-disubstituted 2- aminoimidazole-based biofilm modulators that suppress bacterial resistance to β-lactams. ChemMedChem, 7, 2030–2039. DOI: 10.1002/cmdc.201200350. http://dx.doi.org/10.1002/cmdc.20120035010.1002/cmdc.201200350Suche in Google Scholar PubMed
[23] Taipale, J., & Beachy, P. A. (2001). Progress the hedgehog and wnt signalling pathways in cancer. Nature, 411, 349–354. DOI: 10.1038/35077219. http://dx.doi.org/10.1038/3507721910.1038/35077219Suche in Google Scholar PubMed
[24] US Food and Drug Administration (2012). FDA approves new treatment for most common type of skin cancer. FDA News Release. News & Events. Retrieved June 7, 2013, from www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm289545.htm Suche in Google Scholar
[25] Varjosalo, M., & Taipale, J. (2008). Hedgehog: functions and mechanisms. Genes & Development, 22, 2454–2472. DOI: 10.1101/gad.1693608. http://dx.doi.org/10.1101/gad.169360810.1101/gad.1693608Suche in Google Scholar PubMed
[26] Wang, C., Tobrman, T., Xu, Z. Q., & Negishi, E. I. (2009). Highly regio- and stereoselective synthesis of (Z)-trisubstituted alkenes via propyne bromoboration and tandem Pdcatalyzed cross-coupling. Organic Letters, 11, 4092–4095. DOI: 10.1021/ol901566e. http://dx.doi.org/10.1021/ol901566e10.1021/ol901566eSuche in Google Scholar PubMed PubMed Central
[27] Watkins, D. N., Berman, D. M., Burkholder, S. G., Wang, B., Beachy, P. A., & Baylin, S. B. (2003). Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer. Nature, 422, 313–317. DOI: 10.1038/nature01493. http://dx.doi.org/10.1038/nature0149310.1038/nature01493Suche in Google Scholar PubMed
[28] Wenkert, D., & Woodward, R. B. (1983). Studies of 2,2′-bipyridyl N,N′-dioxides. Journal of Organic Chemistry, 48, 283–289. DOI: 10.1021/jo00151a001. http://dx.doi.org/10.1021/jo00151a00110.1021/jo00151a001Suche in Google Scholar
[29] Zhao, D. B., Wang, W. H., Yang, F., Lan, J. B., Yang, L., Gao, G., & You, J. S. (2009). Copper-catalyzed direct C arylation of heterocycles with aryl bromides: discovery of fluorescent core frameworks. Angewandte Chemie International Edition, 48, 3296–3300. DOI: 10.1002/anie.200900413. http://dx.doi.org/10.1002/anie.20090041310.1002/anie.200900413Suche in Google Scholar PubMed
© 2014 Institute of Chemistry, Slovak Academy of Sciences
Artikel in diesem Heft
- Chemical preparation and applications of silver dendrites
- Evaluation of antioxidant activity and DNA cleavage protection effect of naphthyl hydroxamic acid derivatives through conventional and fluorescence microscopic methods
- Modelling of ORL1 receptor-ligand interactions
- Kinetics of enantioselective liquid-liquid extraction of phenylglycine enantiomers using a BINAP-copper complex as chiral selector
- Diffusive transport of Cu(II) ions through thin ion imprinted polymeric membranes
- Magnetic mixed matrix membranes in air separation
- The use of impregnated perlite as a heterogeneous catalyst for biodiesel production from marula oil
- Nitrobenzene degradation by micro-sized iron and electron efficiency evaluation
- RP-HPLC-UV-ESI-MS phytochemical analysis of fruits of Conocarpus erectus L.
- Residue analysis of fosthiazate in cucumber and soil by QuEChERS and GC-MS
- Degradation of polylactide using basic ionic liquid imidazolium acetates
- Ring-opening polymerisation of ɛ-caprolactone catalysed by Brønsted acids
- Click synthesis by Diels-Alder reaction and characterisation of hydroxypropyl methylcellulose-based hydrogels
- Preparation and physical properties of chitosan-coated calcium sulphate whiskers
- A facile synthetic route for antineoplastic drug GDC-0449
- Two new frameworks for biphenyl-3,3′,5,5′-tetracarboxylic acid and nitrogen-containing organics
- Antioxidant and binding properties of methanol extracts from indigo plant leaves
- Dithiols as more effective than monothiols in protecting biomacromolecules from free-radical-mediated damage: in vitro oxidative degradation of high-molar-mass hyaluronan
Artikel in diesem Heft
- Chemical preparation and applications of silver dendrites
- Evaluation of antioxidant activity and DNA cleavage protection effect of naphthyl hydroxamic acid derivatives through conventional and fluorescence microscopic methods
- Modelling of ORL1 receptor-ligand interactions
- Kinetics of enantioselective liquid-liquid extraction of phenylglycine enantiomers using a BINAP-copper complex as chiral selector
- Diffusive transport of Cu(II) ions through thin ion imprinted polymeric membranes
- Magnetic mixed matrix membranes in air separation
- The use of impregnated perlite as a heterogeneous catalyst for biodiesel production from marula oil
- Nitrobenzene degradation by micro-sized iron and electron efficiency evaluation
- RP-HPLC-UV-ESI-MS phytochemical analysis of fruits of Conocarpus erectus L.
- Residue analysis of fosthiazate in cucumber and soil by QuEChERS and GC-MS
- Degradation of polylactide using basic ionic liquid imidazolium acetates
- Ring-opening polymerisation of ɛ-caprolactone catalysed by Brønsted acids
- Click synthesis by Diels-Alder reaction and characterisation of hydroxypropyl methylcellulose-based hydrogels
- Preparation and physical properties of chitosan-coated calcium sulphate whiskers
- A facile synthetic route for antineoplastic drug GDC-0449
- Two new frameworks for biphenyl-3,3′,5,5′-tetracarboxylic acid and nitrogen-containing organics
- Antioxidant and binding properties of methanol extracts from indigo plant leaves
- Dithiols as more effective than monothiols in protecting biomacromolecules from free-radical-mediated damage: in vitro oxidative degradation of high-molar-mass hyaluronan
