SYNYHESIS AND REACTION MECHANISM OF SOME COMPOUNDS RELATED TO FURO[2,3-D][PYRIMIDINES AND PYRIMIDO[4\,5\ ; 4,5 ]FURO[2,3-D][PYRIMIDINES]
Keywords:
Synthesis, reaction mechanism, furo[2,3-d]pyrimidine, pyrimido[4\,5\:4,5]furo[2,3-d]pyrimidine, Spectral characteristicsAbstract
Ethyl 5-amino-4-methyl-2-phenylfuro[2,3-d]pyrimidine–6-carboxylate (1) was used as precursor for the synthesis of pyrimidofuroppyrimidines 2 , 3 and furopyrimidine derivative4 by reaction withphenyl isothiocyanate , formamide and hydrazine hydrate respectively .AlsoSaponification of compound 1 followed by treatment with orthophosphoric acid afforded compound6 which underwent condensation with 4-methoxybenzaldehyde to give 6-arylidene-4-methyl-2-phenylfuro[2,3-d]pyrimidin-5-one(7) . On the other handrefluxing of compound 5 with acetic anhydride gave 5-(N,N-diacetylamino)-4-methyl-2-phenylfuro[2,3-d]pyrimidine (9), which on treatment with hydrazine hydrate afforded N-acetylamino derivative 10 .Chlorination of compound 3 with phosphorus oxychloride gave 8-Chloro-4-methyl-2-phenylpyrimido[4\,5\:4,5]furo[2,3-d]pyrimidine (11),which up on treatment with hydrazine hydrate gave the corresponding hydrazine derivatives 12. Condensation of compound 4 with 4-nitrobenzaldehydes gave 5-Amino-6-(4-nitrobenzylidene)-4-methyl-2-phenylfuro[2,3-d]pyrimidine-6-carbohydrazone (13).On the other hand refluxing of carbohydrazide 4 with formic acid and acetic anhydride led to the formation of compounds 14 and 15 respectively. Also 3,5-dimethyl parazolyl derivative 16 was prepared from the reaction of compound 4 with acetyl acetone . Treatment of compound1with 2,5-dimethoxytetrahydrofuran produced the compound17,which reacted with hydrazine hydrate to give carbohydrazide derivative18. The reaction of 18 with CS2followed by methyl iodide gave the 6-(2-methylthio-1,3,4-oxadiazol-5-yl)-4-methyl-5-(1-pyrrolyl)-2-phenylfuro[2,3-d]pyrimidine ( 20 ). On the other handcompounds21 and 22 were obtained by the condensation of compound 20 with morpholine and 1,2,3,4-tetrahydroquinoline respectively
References
Sambaverkar, P. P., Aitawade, M. M., Kolekar, G. B., Deshmuka, M. B. and Anbhnle, P. V. " Uncatalized Synthesis of furo[2,3-d]pyrimidine -2,4-(1H,3H)-diones in water and their anti-microbial activity ″. Indian Journal of Chemistry. (2014), 53B, p.p. 1454.
Xin , Zhang et al "Synthesis and biological evalution of Conformationally restricted 4-substituted -2,6-dimethylfuro[2,3-d]pyrtimidine as multitargeted receptor tyrosine kinase and microtubule inhibitors as potential antitumor agents ″ Biorg. Med. Chem. (2015), 23, pp 2408.
Devambatla R. K. et al "Design, Synthesis preclinical evaluation of 4-substituted -5-methylfuro[2,3-d]pyrimidines as microtubule targeting agent that are effective against multidrug resistant cancer cells ″ J. Med. Chem. (2016) doi : 1021/acs. Jmedchem. 6b00237.
Gangjee, A., Yu, J., Mcguire, J. J., Cody, V., C., Galitsky, N., Kisliuk, R. L. and Queener, S. F. 2000 "Design, Synthesis and X-ray Crystal Structure of an Potent Dual Inhibitors of Thymidylate Synthase and Dihydrofolate Reductase as an Antitumor Agent″ J. Med. Chem. (2000), 43(21) , p.p. 3837-3851.
Rochdi, A., Taourirte, M., Lazrek, H. B., BarascutJ. L. and Imbach, J. L. "Synthesis of New Bis-Alkylated Phosphono Alkenyl Acylonucleosides : (Z) and (E)-Diethyl –2-(3-alkyl Pyrimidin-1-Yl Phosphonate. ″ Molecules., (2000), 3(5) p.p. 1139-1145.
Goebel, R. J., Adams, A. D., McKernan, P. A., Murray, B. K.,Robins, R. K., Revankar, G. R. and Canonico, P. G. "Synthesis and Antiviral Activity of Certain Carbamoylpyrrolopyrimidine and Pyrazolopyrimidine Nucleosides″ J. Med. Chem. (1982), 25(11), p.p. 1334-1338.
Marwa, A. Aziz, Rabah, A. T. Serya. Deena, S. Lasheen and Kahled, A. Abouzid. " furo[2,3-d]pyrimidine based derivatives as kinase inhibitors and anticancer agents.″ future J. pharm. Sci. (2016), 2, pp 1-8. ( http// dx.doi.org/10.1016/j.fips2015 ) .
Rakesh S. and Anuja C. "An over view of biological importance of pyrimidines ″ World J. pharm. Pharm. Sci. (2014) 3 , (12), P.p.574-597 .
Kamal El-Dean, Adel M. "Synthesis of Some Pyrimidothienopyrimidine Derivatives″ Monatshefte für Chemie, 129, Faculty of Science, Assiut University, Egypt, (1998) 523-533.
Mussa S. M. "Synthesis of Some New Fused Pyrimidothienopyrimidines Derivatives″ Al-Satil, Jouranal, Misurata University, 2007, 1, pp 53.
Mussa S. M, Salem El-T. Ashoor and Lamia A. Albahi "Synthesis and Computional Studies of Some Pyrimido[4,5:4,5] thieno[2,3-d]pyrimidine Compounds″ Ind. J. Het. Chem. 2016 , 25, (3&4) p.p. 251-261
J. A. Joule and G. F. Smith, Heterocyclic Chemistry, Second edition (1978).
[ 13] W. Mc Crae, Basic organic reactions book,. Translated by Dr. K. M. Dwod (1984) .
] Peter Sykes , A guide book to mechanism in organic chemistry . Fourth edition.
Downloads
Published
Issue
Section
License
Copyright (c) 2016 Journal of Basic Sciences
This work is licensed under a Creative Commons Attribution 4.0 International License.
