Indian Journal of Chemistry Vol. 50B, March 2011, pp. 284-289 Synthesis and biological evaluation of pyrido(2, 3-d)pyrimidine-carboxylate derivatives P Shanmugasundaram*, N Harikrishnan, M Vijey Aanandini, M Sathish Kumar & J N Sateesh Department of Pharmaceutical Chemistry, Vels College of Pharmacy, Chennai 600 117, India E-mail: samsimahe@yahoo.com Received 26 February 2008; accepted (revised) 25 November 2010 Ethyl-5-amino-8-(4-halophenyl)-2-methyl-4,7-dioxo-3,4,5,6,7,8-hexahydro pyrido(2,3-d) pyrimidine-6-carboxylate and ethyl-5-amino-8-(4-halophenyl)-2-amino-4,7 dioxo-3,4,5,6,7,8 hexahydropyrido(2,3-d)pyrimidine-6-carboxylate derivatives have been synthesized through nucleophilic substitution reactions with the use of amidines, followed by 4- haloanilines and malonic acid. These synthesized novel derivatives have been confirmed by elemental analysis, IR, 1 H NMR and mass spectra. These novel derivatives have also been screened for antibacterial, antifungal and antitumor activity. Keywords: Pyrido(2,3-d)pyrimidnes, CS 2, amidines, 4-haloanilines, malonic acid, antibacterial, antifungal, antitumor activity From the past few decades research on pyrido(2,3-d) pyrimidne derivatives revealed that derivatives had wide range of therapeutic applications such as antibacterial 1-3 , antifungal 4-7 , anti-inflammatory 8 , anti- allergic 9 , antidiabetic 10 , antiviral 11,12 and antitumor 13-16 , antiherpes 17 and calcium channel blocking acti- vity 18,19 . The versatile applications of pyrido(2,3-d) pyrimidnes have given zeal to design and synthesize the novel derivatives with an aim to achieve antitumor and antimicrobial activity. Ethyl cyanoacetate 1 was converted to ethyl 3,3 bis (methyl thio)-2-cyano acrylate 3 with the help of carbon disulphide 2. This was substituted with respective amidines to produce 2-methyl-4-(methyl- thio)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile 4 and 2-amino-4-(methyl thio)-6-oxo-1,6-dihydropyri- midine-5-carbonitrile 5. Further condensation with aromatic 4-haloanilines to produce 4-(4-halo phenyl- amino)-2-methyl-6-oxo-1,6 dihydro pyrimidine-5- carbonitrile 6a-c and 4-(4-halo phenylamino)-2- amino-6-oxo-1,6 dihydro pyrimidine-5-carbonitrile 7a-c. Further treatment with malonic acid gave ethyl-5-amino-8-(4-halophenyl)-2-methyl-4,7 dioxo- 3,4,5,6,7,8 hexahydro pyrido(2,3-d)pyrimidine-6- carboxylate 8a-c and ethyl-2,5 diamino-8-(4-halo- phenyl)-4,7 dioxo-3,4,5,6,7,8 hexahydropyrido(2,3- d)pyrimidine-6-carboxylate 9a-c derivatives, res- pectively (Scheme I). The synthesized compounds were purified by pre-coated TLC plates using solvent methanol:hexane (1:1 ratio). Thus, synthesized novel derivatives were characterized by elemental analysis, IR, 1 H NMR and MS. All these elemental and 1 H NMR data have been summarized in Table I. Compounds 3, 4, 5, 6a-c and 7a-c showed sharp bands between the regions of 2250 to 2210 cm -1 due to the presence of -C≡N group. The -C=O group showed strong absorption band in the region of 1680 to 1640 cm -1 in 3, 4, 5, 6a-c, 7a-c, 8a-c and 9a-c compounds. The -C≡N group absorption found in 3, 4, 5, 6a-c and 7a-c compounds disappeared in 8a-c and 9a-c compounds which indicates the confirmation of final products. The compounds 5, 7a-c and 9a-c showed strong absorption in the region of 3450 to 3350 cm -1 due to –NH 2 group. The -C=C- and -C-H of aromatic showed absorption bands between 1600 to 1470 cm -1 and 3050 to 3010 cm -1 respectively by 4, 5, 6a-c, 7a-c, 8a-c and 9a-c compounds. The aryl -C-F, - C-Cl and -C-Br groups showed strong absorption in the regions 1250 to 1180, 1150 to 1040 and 1080 to 1030 cm -1 respectively by the compounds 8a and 9a, 8b and 9b and, 8c and 9c. 1 H NMR spectra of synthesized novel derivatives 8a-c and 9a-c showed multiplet of aromatic protons in the region of δ 6.5 to 7.6. In all the derivatives a singlet is observed at δ 2 which indicates the presence of -NH 2 . A triplet at δ 1.30 reveals the presence of -CH 3 attached to -CH 2 in ethoxy group. And in the compounds 8a-c the -CH 3 group showed singlet at δ 0.9.