# The Synthesis and Biological Evaluation of 2-(1H-Indol-3-yl)quinazolin-4(3H)-One Derivatives
## 3 Materials and Methods
### Synthesis
#### 3.3.8 Synthesis of Quinazolin-4(3\(H\))-Ones **3b**, **3 ah**, **3 ai**  
To a stirred solution of 2-(1\(H\)-indole-3-yl)quinazolin-4(3\(H\))-one (3a) (0.9 mmol, 0.235 g) in dry DMF (1 mL), sodium hydride (2.7 mmol, 60% dispersion in mineral oil, 0.108 g) was added portion wise. The reaction mixture was stirred at room temperature for 5 min, followed by the addition of a methyl iodide (1.8 mmol, 112 \(\mu\)L). The reaction mixture was stirred for 48 h at ambient temperature (TLC control). The reaction mixture was poured into H\({}_{2}\)O (30 mL). The formed precipitate was filtered. The products were purified using column chromatography on silica gel using the mixture of petroleum ether/EtOAc (3:1) as an eluent and recrystallized from a suitable solvent. 2-(1-Methyl-1H-indol-3-yl)quinazolin-4(3H)-one (**3b**) [83]. A yield of 0.067 g (27%), white solid. Mp. \(\geq\) 324 \({}^{\circ}\)C, decomposition (EtOH, lit. [83] 290-295 \({}^{\circ}\)C). All the spectral data of 2-(1-methyl-1\(H\)-indol-3-yl)quinazolin-4(3\(H\))-one (**3b**) were consistent with those described above. 3-Methyl-2-(1-methyl-1H-indol-2-yl)quinazolin-4(3H)-one (**3 ah**) [90]. A yield of 0.057 g (22%), white solid. Mp. = 192-193 \({}^{\circ}\)C (EtOH, lit. [90] 194-196 \({}^{\circ}\)C). \({}^{1}\)H NMR (400 MHz, DMSO-\(d_{6}\)) \(\delta\) = 8.16 (dd, \(J\) = 8.0, 1.2 Hz, 1H), 8.06-8.04 (m, 2H), 7.82-7.78 (m, 1H), 7.66 (d, \(J\) = 8.0 Hz, 1H), 7.57 (d, \(J\) = 8.0 Hz, 1H), 7.50-7.46 (m, 1H), 7.32-7.28 (m, 1H), 7.23-7.20 (m, 1H), 3.92 (s, 3H), and 3.69 (s, 3H) ppm; \({}^{13}\)C{\({}^{1}\)H} NMR (100 MHz, DMSO-\(d_{6}\)) \(\delta\) = 162.1, 151.8, 147.6, 136.3, 134.0, 132.7, 126.7, 126.6, 126.0, 125.7, 122.2, 121.2, 120.6, 119.2, 110.2, 108.7, 33.6, and 32.8 ppm. 4-Methoxy-2-(1-methyl-1H-indol-3-yl)quinazoline (**3 ai**). A yield of 0.052 g (20%), yellow solid. Mp. = 160 \({}^{\circ}\)C, decomposition (EtOAc). \({}^{1}\)H NMR (400 MHz, DMSO-\(d_{6}\)) \(\delta\) = 8.76-8.74 (m, 1H), 8.36 (s, 1H), 8.09-8.06 (m, 1H), 7.89-7.84 (m, 2H), 7.55-7.48 (m, 2H), 7.30-7.24 (m, 2H), 4.27 (s, 3H), and 3.92 (s, 3H) ppm; \({}^{13}\)C{\({}^{1}\)H} NMR (100 MHz, DMSO-\(d_{6}\)) \(\delta\) = 165.7, 158.7, 151.4, 137.7, 134.0, 133.7, 126.7, 126.1, 125.2, 123.0, 122.2, 121.9, 120.7, 113.9, 113.7, 110.2, 53.9, and 32.8 ppm. HRMS (ESI) Calcd for C\({}_{18}\)H\({}_{16}\)N\({}_{3}\)O [M + H]\({}^{+}\) 290.1288; Found 290.1279. 3.3.9. Synthesis of 2-(1\(H\)-indol-3-yl)-4-(methylthio)quinazoline (**3 ak**)  
To a solution of 2-(1\(H\)-indol-3-yl)quinazoline-4(3\(H\))-one (**3a**) (0.5 mmol, 131 mg) in toluene (5 mL), [PERSON]'s reagent (1.5 mmol, 606 mg) was added. The reaction mixture was refluxed for 4 h (TLC control) and cooled to room temperature. The mixture was treated with 1N sodium hydroxide (5 mL) and extracted with EtOAc (3 \(\times\) 10 mL). The combined organic layers were washed with brine (3 \(\times\) 10 mL), dried with anhydrous Na\({}_{2}\)SO\({}_{4}\), and concentrated to dryness. To a solution of 2-(1\(H\)-indol-3-yl)quinazoline-4(3\(H\))-thione (**3 aj**) in acetone (2 mL), K\({}_{2}\)CO\({}_{3}\) (0.6 mmol, 0.083 g) and MeI (0.6 mmol, 37 \(\mu\)L) were added. The reaction mixture was stirred for 2 h at room temperature (TLC control). The reaction was poured into H\({}_{2}\)O (100 mL) and extracted with EtOAc (3 \(\times\) 20 mL). To the reaction, H\({}_{2}\)O (2 mL) was added and extracted with EtOAc (3 \(\times\) 20 mL). The combined organic layers were washed with brine (3 \(\times\) 10 mL), dried with anhydrous Na\({}_{2}\)SO\({}_{4}\), and concentrated to dryness. The product was purified using column chromatography on silica gel using the mixture of petroleum ether/EtOAc (19:1) as an eluent and recrystallized from a mixture of petroleum ether/EtOAc. A yield of 0.076 g (52%), yellow solid. Mp. = 182-184 \({}^{\circ}\)C (petroleum ether/EtOAc).