A Simple Synthesis of the Anticancer Drug Altretamine

Author(s): Vu Binh Duong, Pham Van Hien, Tran Thai Ngoc, Phan Dinh Chau, Tran Khac Vu*

Journal Name: Letters in Organic Chemistry

Volume 17 , Issue 8 , 2020

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Abstract:

A simple and practical method for the synthesis on a large scale of altretamine (1), a wellknown antitumor drug, has been successfully developed. The synthesis method involves the conversion of cyanuric chloride (2) into altretamine (1) by dimethylamination of 2 with an aqueous solution of 40% dimethylamine and potassium hydroxide in 1, -dioxan 4in one step to give altretamine (1) in high yield.

Keywords: Altretamine, hexamethylmelamine, cyanuric chloride, dimethylamine, antitumor, potassium hydroxide, sodium hydroxide.

[1]
Manetta, A.; MacNeill, C.; Lyter, J.A.; Scheffler, B.; Podczaski, E.S.; Larson, J.E.; Schein, P. Gynecol. Oncol., 1990, 36(1), 93-96.
[http://dx.doi.org/10.1016/0090-8258(90)90115-2] [PMID: 2104819]
[2]
Van der Hoop, R.G.; van der Burg, M.E.L.; ten Bokkel Huinink, W.W.; van Houwelingen, C.; Neijt, J.P. Cancer, 1990, 66(8), 1697-1702.
[http://dx.doi.org/10.1002/1097-0142(19901015)66:8<1697::AIDCNCR2820660808>3.0.CO;2-G] [PMID: 2119878]
[3]
D’Incalci, M.; Farina, P.; Sessa, C.; Mangioni, C.; Garattini, S. Cancer Treat. Rep., 1982, 66(2), 231-235.
[PMID: 6799199]
[4]
Groszkowski, S. J. Pharm. Sci., 1985, 74, 44-46.
[http://dx.doi.org/10.1002/jps.2600740112] [PMID: 3981416]
[5]
Kallmayer, H.J.; Bender, R. Pharmazie, 2000, 55(4), 320-321.
[PMID: 10798250]
[6]
Brachel, H.V.; Main, O.A.; Kinler, H 1969.
[7]
Dicke, R.; Endesfelder, A.; Burger, M.; Hahn, C.; Schwarzinger, C.; Gabriel, H.; Schmidt, H. DE 102008016966A1,, 2009.
[8]
Kaiser, D.W.; Thurston, J.T.; Dudley, J.R.; Schaefer, F.C.; Hechenbleikner, I.; Dagfrid, H-H. J. Am. Chem. Soc., 1951, 73, 2984-2986.
[http://dx.doi.org/10.1021/ja01151a002]
[9]
Reddy, N.D.; Elias, A.J.; Vij, A. J. Chem. Res., 1998, 9, 504-505, 2033-2055.
[http://dx.doi.org/10.1039/a801596a]
[10]
Arya, K.; Dandia, A. Bioorg. Med. Chem. Lett., 2007, 17(12), 3298-3304.
[http://dx.doi.org/10.1016/j.bmcl.2007.04.007] [PMID: 17449247]
[11]
Kolesinska, B.; Kaminski, Z.J. Tetrahedron, 2009, 65, 3573-3576.
[http://dx.doi.org/10.1016/j.tet.2009.03.017]
[12]
List, M.; Puchinger, H.; Gabriel, H.; Monkowius, U.; Schwarzinger, C. J. Org. Chem., 2016, 81(10), 4066-4075.
[http://dx.doi.org/10.1021/acs.joc.6b00355] [PMID: 27100712]
[13]
Shimada, K.; Hikage, S.; Takeishi, Y.; Takikawa, Y. Chem. Lett., 1990, 8, 1403-1406.
[http://dx.doi.org/10.1246/cl.1990.1403]
[14]
Chen, X.; Du, C.; Guo, J-P.; Wei, X-H.; Liu, D-S. J. Organomet. Chem., 2002, 655, 89-95.
[http://dx.doi.org/10.1016/S0022-328X(02)01422-5]
[15]
Chen, X.; Bai, S.; Liu, D. CN 1396159A, 2003.
[16]
Antonio, H.; Roberto, M.A.; Pedro, R.; Mourad, C.; Rachid, C. Synthesis, 2004, 4, 503-505.
[17]
Von Angerer, S. Science of Synthesis., 2004, 17, 449-583.
[18]
Chen, X.; Bai, S-D.; Wang, L.; Liu, D-S. Heterocycles, 2005, 65, 1425-1430.
[http://dx.doi.org/10.3987/COM-05-10357]
[19]
Dornan, P.; Rowley, C.N.; Priem, J.; Barry, S.T.; Burchell, T.J.; Woo, T.K.; Richeson, D.S. Chem. Commun. (Camb.), 2008, 44(31), 3645-3647.
[http://dx.doi.org/10.1039/b803732a] [PMID: 18665286]
[20]
Spahn, N.A.; Nguyen, M.H.; Renner, J.; Lane, T.K.; Louie, J. J. Org. Chem., 2017, 82(1), 234-242.
[http://dx.doi.org/10.1021/acs.joc.6b02374] [PMID: 27957836]
[21]
Baudgar, B. Synth. Commun., 2006, 37, 859-864.
[http://dx.doi.org/10.1080/00397910500464848]
[22]
Sanders, M.E.; Ames, M.M. Tetrahedron Lett., 1985, 26, 5247-5250.
[http://dx.doi.org/10.1016/S0040-4039(00)95006-8]
[23]
Kingston, M.; Chen, S-J.; Lork, E.; Mews, R. Dalton Trans., 2004, 9(9), 1400-1404.
[http://dx.doi.org/10.1039/B402527J] [PMID: 15252633]


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Article Details

VOLUME: 17
ISSUE: 8
Year: 2020
Page: [628 - 630]
Pages: 3
DOI: 10.2174/1570178617666200210111041
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