# Synthesis and Anticancer Activity of Novel Thiazole-5-Carboux Derivatives
## 3 Experimental Section
### Synthesis
#### 3.2.6 Synthesis of Target Compounds (**7a-f**)  
To a suspension of **6** (1 mmol) and oxalyl chloride (3 mmol) in CH\({}_{2}\)Cl\({}_{2}\) (20 mL) was added two drops of DMF and stirred at room temperature for 6 h. After the reaction was complete by TLC, 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\({}_{2}\) (20 mL). After stirring for 20 min, the solution was neutralized using (\(i\)-Pr)\({}_{2}\)EtN (1 mmol). After the reaction was complete, a great quantity of white solid was precipitated and 20 mL distilled water was added. After thorough stirring, the mixture was filtered to get the white solid, which was washed with CH\({}_{2}\)Cl\({}_{2}\) (10 mL) and distilled water (10 mL) to obtain **7** (Scheme 4). _N-(4-chloro-2-methyl-6-(methylcarbamoyl)phenyl)-2-(2-fluoromethyl)-4-(trifluoromethylomethyl)thiazole-5-carboxamide_ (**7a**) White solid (48%); m.p. 256-259 \({}^{\circ}\)C; \({}^{1}\)H NMR (400 MHz, DMSO-\(d_{6}\)) \(\delta\): 2.26 (s, 3H, CH\({}_{3}\)), 2.73 (d, J = 4.4 Hz, 3H, CH\({}_{3}\)NH), 7.41-7.71 (m, 5H, Ar-H), 8.25-8.29 (m, 1H, Ar-H), 8.40 (br, 1H, NHCH\({}_{3}\)), 10.55 (br, 1H, NH). Anal. Calculated for C\({}_{20}\)H\({}_{14}\)C\({}_{4}\)N\({}_{3}\)O\({}_{2}\)S: C 50.72, H 3.47, N 8.90; found: C 50.91, H 2.99, N 8.91. _N-(4-chloro-2-(iso-propyl-)-6-methylphenyl)-2-(2-fluoromethyl)-4-(trifluoromethyl)thiazole-5-carboxamide_ (**7b**) White solid (38%); m.p. 280-284 \({}^{\circ}\)C; \({}^{1}\)H NMR (400 MHz, DMSO-\(d_{6}\)) \(\delta\): 1.12 (d, J = 6.4 Hz, 6H, CH(CH\({}_{3}\))\({}_{2}\)), 2.24 (s, 3H, CH\({}_{3}\)), 3.94-4.01 (m, 1H, CH(CH\({}_{3}\))\({}_{2}\)), 7.34-7.55 (m, 4H, Ar-H), 7.64-7.69 (m, 1H, Ar-H), 8.23-8.27 (m, 1H, Ar-H), 8.31-8.33 (m, 1H, NHCH(CH\({}_{3}\))\({}_{2}\)), 10.53 (br, 1H, NH). Anal. Calculated for C\({}_{22}\)H\({}_{18}\)C\({}_{4}\)N\({}_{3}\)O\({}_{2}\)S: C 53.37, H 4.10, N 8.60; found: C 52.86, H 3.63, N 8.41. _N-(4-chloro-2-(cyclohex)carbamoyl)-6-methylphenyl)-2-(2-fluoromethyl)-4-(trifluoromethyl)thiazole-5-carboxamide_ (**7c**) White solid (68%); m.p. 157-159 \({}^{\circ}\)C; \({}^{1}\)H NMR (400 MHz, DMSO-\(d_{6}\)) \(\delta\): 1.21-1.84 (m, 10H, cyclohexyl-H), 2.24 (s, 3H, CH\({}_{3}\)), 3.62-3.67 (m, 1H, CH), 7.32-7.33 (m, 1H, Ar-H), 7.42-7.56 (m, 3H, Ar-H), 7.64-7.69 (m, 1H, Ar-H), 8.23-8.27 (m, 1H, Ar-H), 8.31 (d, J = 7.6 Hz, 1H, NHCH), 10.53 (br, 1H, NH). Anal. Calculated for C\({}_{25}\)H\({}_{22}\)CIF\({}_{4}\)N\({}_{3}\)O\({}_{2}\)S: C 55.44, H 3.86, N 7.93; found: C 55.61, H 4.11, N 7.78. _N-(4-chloro-2-methyl-6-(methylcarbamoyl)phenyl)-2-(2-chlorophenyl)-4-(trifluoromethyl)thiazole-5-carboxamide_ (**7d**) White solid (81%); m.p. 247-249 \({}^{\circ}\)C; \({}^{1}\)H NMR (400 MHz, DMSO-\(d_{6}\)) \(\delta\): 2.24 (s, 3H, CH\({}_{3}\)), 2.71 (d, J = 4.4 Hz, 3H, NHCH\({}_{3}\)), 7.37-7.75 (m, SH, Ar-H), 8.23-8.36 (m, 2H, Ar-H), 8.24 (br, 1H, NHCH), 10.58 (br, 1H, NH). Anal. Calculated for C\({}_{20}\)H\({}_{14}\)Cl\({}_{2}\)F\({}_{3}\)N\({}_{3}\)O\({}_{2}\)S: C 49.05, H 3.39, N 8.59; found: C 49.19, H 2.89, N 8.61. _N-(4-chloro-2-(iso-propyl-)-6-methylphenyl)-2-(2-chlorophenyl)-4-(trifluoromethyl)thiazole-5-carboxamide_ (**7e**) White solid (91%); m.p. 277-280 \({}^{\circ}\)C; \({}^{1}\)H NMR (400 MHz, DMSO-\(d_{6}\)) \(\delta\): 1.12 (d, J = 6.4 Hz, 6H, CH(CH\({}_{3}\))\({}_{2}\)), 2.24 (s, 3H, CH\({}_{3}\)), 3.92-4.01 (m, 1H, CH(CH\({}_{3}\))\({}_{2}\)), 7.33-7.34 (m, 1H, Ar-H), 7.51-7.62 (m, 3H, Ar-H), 7.72-7.74 (m, 1H, Ar-H), 8.23-8.26 (m, 1H, Ar-H), 8.31 (br, 1H, NHCH), 10.56 (br, 1H, NH). Anal. Calculated for C\({}_{22}\)H\({}_{18}\)Cl\({}_{2}\)F\({}_{3}\)N\({}_{3}\)O\({}_{2}\)S: C 50.92, H 3.90, N 7.98; found: C 51.17, H 3.51, N 8.14. _N-(4-chloro-2-(cyclohexyl)carbamoyl)-6-methylphenyl)-2-(2-chlorophenyl)-4-(trifluoromethyl)thiazole-5-carboxamide_ (**7f**) White solid (67%); m.p.