# Synthesis and Anticancer Activity of Novel Thiazole-5-Carboux Derivatives
## 3 Experimental Section
### Synthesis
#### 3.2.7 Synthesis of Target Compounds (**8a-g**)  
To a suspension of **6** (1 mmol) and oxalyl chloride (3 mmol) in CH\({}_{2}\)Cl\({}_{2}\) was added two drops of DMF and stirred at room temperature for 6 h. After the reaction was complete, the solution was evaporated _in vacuo_ to get the crude residue. The crude residue was dissolved in CH\({}_{2}\)Cl\({}_{2}\), then was slowly added into a solution of o-amino-benzamide (1.2 mmol) in CH\({}_{2}\)Cl\({}_{2}\). After stirring for 20 min, the acid binding agent (_i_-Pr)\({}_{2}\)EtN (1 mmol) was added and kept stirring in room temperature for 12 h.  
After the reaction was complete, the solution was added 20 mL CH\({}_{2}\)Cl\({}_{2}\). Combined organic layers were washed with dilute hydrochloric acid (20 mL), saturated Na\({}_{2}\)CO\({}_{3}\) solution (20 mL) and saturated NaCl solution (20 mL) respectively, dried with anhydrous Na\({}_{2}\)SO\({}_{4}\). The mixture was filtered under reduced pressure, the filtrate was evaporated under vacuo. The crude residue was purified by column chromatography to get compounds **8** (Scheme 5). _N-(4-chloro-2-methylphenyl)-2-(2-fluorophenyl)-4-(trifluoromethylomethyl) thiazole-5-carboxamide_ (**8a**) White solid (69%); m.p. 226-227 \({}^{\circ}\)C; \({}^{1}\)H NMR (400 MHz, DMSO-\(d_{6}\)) 8: 2.24 (s, 3H, CH\({}_{3}\)), 7.29-7.32 (m, 1H, Ar-H), 7.39-7.56 (m, 4H, Ar-H), 7.65-7.69 (m, 1H, Ar-H), 8.23-8.27 (m, 1H, Ar-H), 10.55 (br, 1H, NH). Anal. Calculated for C\({}_{18}\)H\({}_{11}\)ClF\({}_{4}\)N\({}_{2}\)OS: C 51.61, H 3.21, N 6.79; found: C 52.12, H 2.67, N 6.75. IR (KBr, \(v_{\rm max}\)) cm\({}^{-1}\): 3249 (N-H stretch); 3026-3121 (aliphatic C-H stretch); 1633 (C=O stretch); 1436-1548(aromatic and thiazole C=C stretch); 1126(C-S stretch). _N-(2,4-dichlorophenyl)-2-(2-fluorophenyl)-4-(trifluoromethyl) thiazole-5-carboxamide_ (**8b**) White solid (58%); m.p. 195-196 \({}^{\circ}\)C; \({}^{1}\)H NMR (400 MHz, DMSO-\(d_{6}\)) 8: 7.43-7.56 (m, 3H, Ar-H), 7.65-7.76 (m, 3H, Ar-H), 8.24-8.28 (m, 1H, Ar-H), 10.87 (br, 1H, NH). Anal. Calculated for C\({}_{17}\)H\({}_{8}\)C\({}_{12}\)F\({}_{4}\)N\({}_{2}\)OS: C 46.85, H 2.36, N 6.21; found: C 46.91, H 1.85, N 6.44. _N-(4-chloro-2-methylphenyl)-2-(2-chlorophenyl)-4-(trifluoromethyl) thiazole-5-carboxamide_ (**8c**) Yellow solid (44%); m.p. 228-229 \({}^{\circ}\)C; \({}^{1}\)H NMR (400 MHz, DMSO-\(d_{6}\)) 8: 2.25 (s, 3H, CH\({}_{3}\)), 7.30-7.49 (m, 3H, Ar-H), 7.59-7.65 (m, 2H, Ar-H), 7.73-7.75 (m, 1H, Ar-H), 8.25-8.27 (m, 1H, Ar-H), 10.59 (br, 1H, NH). Anal. Calculated for C\({}_{18}\)H\({}_{11}\)C\({}_{12}\)F\({}_{3}\)N\({}_{2}\)OS: C 49.91, H 2.87, N 6.59; found: C 50.13, H 2.57, N 6.50. _2-(2-Chlorophenyl)-N-(2,4-dichlorophenyl)-4-(trifluoromethyl)thiazole-5-carboxamide_ (**8d**) White solid (65%); m.p. 204-205 \({}^{\circ}\)C; \({}^{1}\)H NMR (400 MHz, DMSO-\(d_{6}\)) 8: 7.493-7.52 (m, 1H, Ar-H), 7.56-7.64 (m, 2H, Ar-H), 7.69-7.76 (m, 3H, Ar-H), 8.25-8.27 (m, 1H, Ar-H), 10.90 (br, 1H, NH). Anal. Calculated for C\({}_{17}\)H\({}_{8}\)Cl\({}_{3}\)F\({}_{3}\)N\({}_{2}\)OS: C 45.02, H 2.09, N 6.29; found: C 45.21, H 1.79, N 6.20. _2-(2-Chlorophenyl)-4-(trifluoromethylomethyl)-N-(2-(trifluoromethyl)phenyl)thiazole-5-carboxamide_ (**8e**) White solid (68%); m.p. 158-160 \({}^{\circ}\)C; \({}^{1}\)H NMR (400 MHz, DMSO-\(d_{6}\)) 8: 7.56-7.65 (m, 4H, Ar-H), 7.73-7.83 (m, 4H, Ar-H), 10.92 (br, 1H, NH). Anal. Calculated for C\({}_{18}\)H\({}_{9}\)ClF\({}_{6}\)N\({}_{2}\)OS: C 47.67, H 2.51, N 6.39; found: C 47.96, H 2.01, N 6.21. _2-(2-Chlorophenyl)-N-(2,4,6-tichlorophenyl)-4-(trifluoromethyl)thiazole-5-carboxamide_ (**8f**) White solid (58%); m.p. 120-122 \({}^{\circ}\)C; \({}^{1}\)H NMR (400 MHz, DMSO-\(d_{6}\)) 8: 7.56-7.66 (m, 2H, Ar-H), 7.88 (s, 2H, Ar-H), 7.75-7.77 (m, 1H, Ar-H), 8.29-8.31 (m, 1H, Ar-H), 11.18 (br, 1H, NH). Anal. Calculated for C\({}_{17}\)H\({}_{7}\)Cl\({}_{4}\)F\({}_{3}\)N\({}_{2}\)OS: C 42.19, H 1.78, N 5.49; found: C 42.00, H 1.45, N 5.76. _N-(2-bromo-4,6-dichlorophenyl)-2-(2-chlorophenyl)-4-(trifluoromethyl)thiazole-5-carboxamide_ (**8g**) White solid (60%); m.p.