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Current Organic Synthesis

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ISSN (Print): 1570-1794
ISSN (Online): 1875-6271

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Letter Article

Facile Synthetic Protocols for the Preparation of New Impurities in Pemetrexed Disodium Heptahydrate as an Anti-cancer Drug

Author(s): Rama Mohana Reddy Jaggavarapu, Venkatanarayana Muvvala*, Venkatareddy Ghojala, H. Sharath Babu and Ravi Kumar Cheedarala*

Volume 19, Issue 1, 2022

Published on: 14 January, 2021

Page: [2 - 9] Pages: 8

DOI: 10.2174/1570179418666210114145914

Price: $65

Abstract

A facile synthetic protocol was employed to prepare process-related impurities associated with the synthesis of pemetrexed disodium heptahydrate, Alimta. The research work is described for the development of the novel synthetic methods and their structure elucidation of Pemetrexed glutamide, N-methyl pemetrexed, and N-methyl pemetrexed glutamide impurities. The listed impurities were deduced through spectral analysis, such as 1H-NMR, 13CNMR, and HRMS. The target compounds can be used as the reference substances for quality control.

Keywords: Pemetrexed disodium, pemetrexed glutamide impurity, multi-targeted antifolate, N-methyl pemetrexed glutamide, L-Glutamic acid, alimta.

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[1]
Aydın, M.; Kartal, Z.; Osmanoğlu, Ş.; Başkan, M.H.; Topkaya, R. EPR and FT-IR spectroscopic studies of l-lysine monohydrochloride and l-glutamic acid hydrochloride powders. J. Mol. Struct., 2011, 994, 150-154.
[http://dx.doi.org/10.1016/j.molstruc.2011.03.010]
[2]
Başkan, M. H.; Aydın, M. Spectrochimica Acta Part A: Molecular and biomolecular spectroscopy. Spectrochimica Acta, 2013, 112(A), 280-282.
[3]
Sayin, U.; Dereli, Ö.; Türkkan, E.; Yüksel, H.; Birey, M. EPR study of gamma irradiated 2,5-di-tert-butyl-hydroquinone single crystals. Radiat. Phys. Chem., 2011, 80, 38.
[http://dx.doi.org/10.1016/j.radphyschem.2010.08.017]
[4]
Başkan, M.H.; Aydın, M.; Çanakçı, D.; Osmanoğlu, Ş. Electron paramagnetic resonance and FT-IR spectroscopic studies of DL-2-aminoadipic acid and ammonium acetate powders. Radiat. Eff. Defects Solids, 2014, 169, 226.
[http://dx.doi.org/10.1080/10420150.2013.860977]
[5]
Şimşek, M.G.; Gündüz, C.; Şafak, Ö. Kökpınar .; M. Aydın. Free radicals properties of some gamma-irradiated organic compounds 2017, 49(1), 82-86.
[6]
Osmanoğlu, Ş.; Aydın, M.; Başkan, M.H. Zeitschrift fur Naturforschung Section A-A. J. Physiol. Sci., 2005, 60a, 549-553.
[7]
Aydın, M. EPR investigation of gamma-irradiated iminodiacetic and amino acid derivatives. Bulg. Chem. Commun., 2010, 42(3), 232-235.
[8]
Aydın, M. EPR study of free radicals in amino acid derivatives gamma-irradiated at 300 K. Indian J. Pure Appl. Phy., 2010, 48, 611-614.
[9]
Roche, M.; Parisi, L.; Li, L.; Knehans, A.; Phaeton, R.; Kesterson, J.P. The role of pemetrexed in recurrent epithelial ovarian cancer: A scoping review. Oncol. Rev., 2018, 12(1), 346.
[http://dx.doi.org/10.4081/oncol.2018.346] [PMID: 29983902]
[10]
Manohar, S.; Leung, N. Cisplatin nephrotoxicity: A review of the literature. J. Nephrol., 2018, 31(1), 15-25.
[http://dx.doi.org/10.1007/s40620-017-0392-z] [PMID: 28382507]
[11]
Kjell, D. P.; Hallberg, D. W.; Kalbfleisch, J. M.; McCurry, C. K.; Semo, M. J.; Sheldon, E. M.; Spitler, J. T.; Wang, M. Determination of the Source of the N-Methyl impurity in the synthesis of pemetrexed disodium heptahydrate. Org. Process Res. Dev., 2005, 9(6), 738-742.
[http://dx.doi.org/10.1021/op0498013]
[12]
Cronin, J.S.; Ginah, F.O.; Murray, A.R.; Copp, J.D. An improved procedure for the large scale preparation of 2-Chloro-4,6-dimethoxy-1,3,5-triazine. Synth. Commun., 1996, 26, 3491-3494.
[http://dx.doi.org/10.1080/00397919608003754]
[13]
Michalak, O.; Gruza, M.M.; Witkowska, A.; Bujak, I.; Cmoch, P. Synthesis and physicochemical characterization of the impurities of pemetrexed disodium, an anticancer drug. Molecules, 2015, 20(6), 10004-10031.
[http://dx.doi.org/10.3390/molecules200610004] [PMID: 26035100]
[14]
Albert, R.; Danklmaier, J.; Hönig, H.; Kandolf, H. A simple and convenient synthesis of β-aspartates and γ-glutamates. Synthesis, 1987, 1987(07), 635-637.
[http://dx.doi.org/10.1055/s-1987-28030]
[15]
Perron, V.; Abbott, S.; Moreau, N.; Lee, D.; Penney, C.; Zacharie, B. A METHOD FOR THE SELECTIVE PROTECTION OF AROMATIC AMINES IN THE PRESENCE OF ALIPHATIC AMINES. Synthesis, 2009, 283-289.
[16]
Avila-Zárraga, J.G.; Martínez, R. Efficient methylation of carboxylic acids with potassium hydroxide/methyl sulfoxide and iodomethane. Synth. Commun., 2011, 31(14), 2177-2183.
[http://dx.doi.org/10.1081/SCC-100104469]
[17]
Li, Y.; Manickam, G.; Ghoshal, A.; Subramaniam, P. Hydrogenolysis without hydrogen gas: hydrogen loaded palladiumelectrodes by electrolysis of H[NTf2] in a room temperature ionic liquid. Green Chem., 2006, 36(7), 925-928.
[18]
Kaminski, Z.J. 2-Chloro-4,6-dimethoxy-1,3,5-triazine. A new coupling reagent for peptide synthesis. Synthesis, 1987, 10, 917-920.
[http://dx.doi.org/10.1055/s-1987-28122]
[19]
Lee, H-W.; Kang, T.W.; Cha, K.H.; Kim, E-N.; Choi, N-H.; Kim, J-W.; Hong, C.I. Synthesis and characterization of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride. Tetrahedron Lett., 1998, 28(8), 1339-1349.
[20]
Han, G.; Tamaki, M.; Hruby, V.J. Fast, efficient and selective deprotection of the tert-butoxycarbonyl (Boc) group using HCl/dioxane (4 m). J. Pept. Res., 2001, 58(4), 338-341.
[http://dx.doi.org/10.1034/j.1399-3011.2001.00935.x] [PMID: 11606219]
[21]
Robert, K. Boeckman, Jr., Pengcheng, S.; Joseph J. Mullins. The dess-martin periodinane: 1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1h)-one[1,2- benziodoxol-3(1h)-one, 1,1,1-tris(acetyloxy)-1,1-dihydro- Organic Syntheses. Coll., 2004, 77, 141.
[22]
Qi, H.; Wen, J.; Li, L.; Bai, R.; Chen, L.; Wang, D. An efficient synthesis of pemetrexed disodium. J. Hetero. Chem., 2014, 52(5), 1565-1569.
[23]
E.R., Blout R. H. Karlson. Peptides. V. J. Chem. Soc., 1956, 371-380.
[24]
Nakamura, H.; Watanabe, M.; Ban, H.S.; Nabeyama, W.; Asai, A. Synthesis and biological evaluation of boron peptide analogues of Belactosin C as proteasome inhibitors. Bioorg. Med. Chem. Lett., 2009, 19(12), 3220-3224.
[http://dx.doi.org/10.1016/j.bmcl.2009.04.103] [PMID: 19428245]
[25]
Cheedrala, R.K.; Rachna, S.; Palakodety, P. K/Lipase mediated kinetic resolution of benzimidazolyl ethanols. Tetrahedron Asymmetry, 2008, 19, 901-905.
[26]
Cheedrala, R.K.; Vijay, S.; Park, J.W. Facile synthesis of second-generation dendrons with an orthogonal functional group at the focal point. Synth. Commun., 2009, 39, 1966-1980.
[27]
Cheedrala, R.K.; Kim, G.H.; Cho, S.; Lee, J.H.; Kim, J.; Song, H.K.; Kim, J.Y.; Yang, C. Polymorphic and mechanochromic luminescence modulation in the highly emissive dicyanodistyrylbenzene crystal: secondary bonding interaction in molecular stacking assembly. J. Mater. Chem., 2011, 21, 843-850.
[28]
Park, E.J.; Kong, K.; Park, Y.B.; Park, H.W. Experimental study on critical heat flux of highly efficient soft hydrophilic CuO–chitosan nanofluid templates. Int. J. Heat Mass Trasfer, 2016, 100, 396-406.
[29]
Cheedarala, R.K.; Duy, L.C.; Ahn, K.K. Double characteristic BNO-SPI-TENGs for robust contact electrification by vertical contact separation mode through ion and electron charge transfer. Nano Energy, 2018, 44, 430-437.
[30]
Cheedarala, R.K.; Parvez, A.N.; Ahn, K.K. Electric impulse spring-assisted contact separation mode triboelectric nanogenerator fabricated from polyaniline emeraldine salt and woven carbon fibers. Nano Energy, 2018, 53, 362-372.
[http://dx.doi.org/10.1016/j.nanoen.2018.08.066]
[31]
Cheedarala, R.K.; Shahriar, M.; Ahn, J.H.; Hwang, J.Y.; Ahn, K.K. Electric impulse spring-assisted contact separation mode triboelectric nanogenerator fabricated from polyaniline emeraldine salt and woven carbon fibers. Nano Energy, 2019, 65104017
[http://dx.doi.org/10.1016/j.nanoen.2019.104017]
[32]
Cheedarala, R.K.; Song, J.L. In situ generated hydrophobic micro ripples via π–π stacked pop-up reduced graphene oxide nanoflakes for extended critical heat flux and thermal conductivities. RSC Advances, 2019, 9, 31735-31746.
[http://dx.doi.org/10.1039/C9RA04563E]
[33]
Cheedarala, R.K.; Kee, C.D.; Oh, I.K. Dry‐type artificial muscles based on pendent sulfonated chitosan and functionalized graphene oxide for greatly enhanced ionic interactions and mechanical stiffness. Adv. Funct. Mater., 2013, 23, 6007-6018.
[http://dx.doi.org/10.1002/adfm.201203550]
[34]
Cheedarala, R.K.; Jeon, J.J.; Kee, C.D.; Oh, I.K. Bio‐inspired all‐organic soft actuator based on a π–π stacked 3d ionic network membrane and ultra‐fast solution processing. Adv. Funct. Mater., 2014, 24, 6005-6015.
[http://dx.doi.org/10.1002/adfm.201401136]
[35]
Rao, T.N.; Cheedarala, R.K. Multilingual denoising pre-training for neural machine translation. TACL, 2019, 9(6), 845-852.
[36]
Cheedarala, R.K.; Park, E.J.; Park, Y.B.; Park, H.W. Highly wettable CuO: Graphene oxide core–shell porous nanocomposites for enhanced critical heat flux. PSS, 2015, 212, 1756-1766.

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