## 3 Materials and Methods
### Preparation of Ethyl 2-[(2-(4-antipyrinylthiazol-2-yl)amino)-2-oxoethyl)-thio]acetate (**2**)  
A suspension of chloroacetamido derivative **1** (2 mmol, 0.72 g) and ethyl thioglycolate (2 mmol, 0.24 mL) in 15 mL ethyl alcohol containing CH\({}_{3}\)COONa (0.2 g) was heated under reflux for 3 h. The resulting precipitate upon cooling was filtered, dried, and recrystallized from EtOH to furnish the sulfide compound **2**. White solid, yield = 84%, m.p. = 161-163 \({}^{\circ}\)C. IR (\(\overline{v}\)/cm\({}^{-1}\)): 3195 (N-H), 1723 (C=O), 1682 (C=O). \({}^{1}\)H-NMR (CDCl\({}_{3}\)): \(\delta\) 1.22 (t, J = 7.15 Hz, 3H, CH\({}_{3}\)), 2.66 (s, 3H, CH\({}_{3}\)), 3.16 (s, 3H, CH\({}_{3}\)), 3.32 (s, 2H, CH\({}_{2}\)), 3.64 (s, 2H, CH\({}_{2}\)), 4.12 (q, J = 7.15 Hz, 2H, CH\({}_{2}\)), 7.08 (s, 1H, thiazole-H5), 7.26-7.52 (m, 5H, Ar-H), 11.24 (s, 1H, NH). \({}^{13}\)C-NMR (CDCl\({}_{3}\)): \(\delta\) 12.48, 14.02, 34.28, 35.16, 36.37, 61.68, 104.23, 109.18, 124.44 (2C), 126.87, 129.31 (2C), 135.08, 142.67, 151.92, 156.41, 163.85, 164.91, 170.67. Analysis for C\({}_{20}\)H\({}_{22}\)N\({}_{4}\)O\({}_{4}\)S\({}_{2}\) (446): Calcd. : C, 53.80; H, 4.97; N, 12.55%. Found: C, 53.89; H, 4.94; N, 12.50%. \begin{table}
\begin{tabular}{c c c} \hline \hline
**Compound Number** & **Absorbance** & **ABTS Inhibition (\%)** \\ \hline
**Control of ABTS** & 0.540 & 0 \\ L-Ascorbic acid** & 0.060 & 88.88 \\
**2** & 0.306 & 43.33 \\
**4** & 0.274 & 49.25 \\
**5** & 0.219 & 59.44 \\
**6** & 0.144 & 73.33 \\
**7a** & 0.118 & 78.14 \\
**7b** & 0.223 & 58.70 \\
**9** & 0.211 & 60.92 \\
**10a** & 0.182 & 66.29 \\
**10b** & 0.077 & 85.74 \\
**10c** & 0.089 & 83.51 \\
**12** & 0.347 & 35.74 \\
**14** & 0.212 & 60.74 \\ \hline \hline \end{tabular}
\end{table} 
Table 2: ABTS scavenging activity of the synthesized 4-antipyrinylthiazole scaffolds. Preparation of N-(4-antiyyrinylthiazol-2-yl)-2-((3-cyano-4,6-dimethyllypyridin-2-yl))thio-acetamide (4)  
To a stirred suspension of 3-cyano-4,6-dimethyllypyridine-2-thiol (0.82 g, 0.005 mol) and anhydrous K\({}_{2}\)CO\({}_{3}\) (0.70 g, 0.005 mol) in 40 mL acetone, 4-antiyyrinyl-2-chloroacetamidothiazole (1.81 g, 0.005 mol) was added. The reaction suspension was heated under reflux for two h and then cooled to 25 \({}^{\circ}\)C. The solid, obtained after dilution by 20 mL cold water, was filtered and dried. Recrystallization was achieved by heating in ethanol. Yellow crystals, yield = 80%, m.p. 178-180 \({}^{\circ}\)C. IR (\(\overline{v}\)/cm\({}^{-1}\)): 3371 (N-H), 2219 (C\(\equiv\)N), 1688 (C=O). \({}^{1}\)H-NMR (CDCl\({}_{3}\)): \(\delta\) 2.41 (s, 6H, 2 CH\({}_{3}\)), 2.64 (s, 3H, CH\({}_{3}\)), 3.33 (s, 3H, CH\({}_{3}\)), 4.05 (s, 2H, CH\({}_{2}\)), 7.05 (s, 1H, pyridine-H\({}_{5}\)), 7.21 (s, 1H, thiazole-H\({}_{5}\)), 7.31-7.55 (m, 5H, Ar-H), 12.14 (s, 1H, CONH). \({}^{13}\)C-NMR (CDCl\({}_{3}\)): \(\delta\) 12.44, 20.00, 24.53, 34.49, 40.26, 104.70, 105.81, 112.31, 119.78, 124.23, 126.16 (2C), 127.74, 129.51 (2C), 133.81, 142.42, 151.68, 155.62, 157.47, 158.26, 160.37, 163.38, 164.91. Analysis for C\({}_{24}\)H\({}_{22}\)N\({}_{6}\)O\({}_{2}\)S\({}_{2}\) (490): Calcd. : C, 58.76; H, 4.52; N, 17.13%. Found: C, 58.82; H, 4.50; N, 17.06%. Synthesis of 3-amino-N-(4-antiyyrinylthiazol-2-yl)-4,6-dimethylthieno[2,3-blpyridine-2-carboxylate (5)  
The sulfide derivative **4** (0.98 g, 0.002 mol) was heated under reflux in sodium ethoxide solution (prepared by stirring small parts of 0.08 g sodium metal in 20 mL dry ethyl alcohol) for 2 h. The reaction mixture was cooled, then poured into ice-cold water and neutralized with 0.1 N HCl. The obtained solid was filtered and recrystallized from ethyl alcohol. Yellow crystals, yield = 54%, m.p. = 271-273 \({}^{\circ}\)C. IR (\(\overline{v}\)/cm\({}^{-1}\)): 3412, 3353, 3184 (N-H and NH\({}_{2}\)), 1658 (C=O).