# The Synthesis and Biological Evaluation of 2-(1H-Indol-3-yl)quinazolin-4(3H)-One Derivatives
## 3 Materials and Methods
#### Synthesis of 2-(1\(H\)-indol-3-yl)quinazolin-4(3\(h\))-one (**3a**) [80]  
To a solution of 1\(H\)-indole-3-carboxaldehyde (**1a**) (1.3 mmol, 0.189 g) and anthranilamide (**2a**) (1.3 mmol, 0.177 g) in dry acetonitrile (2.5 mL), \(p\)-TSA (0.5 mmol, 0.095 g) was added. The reaction mixture was refluxed for 4 h (TLC control). Then, the reaction mixture was poured into H\({}_{2}\)O (50 mL). The formed precipitate was filtered. The products were purified using column chromatography on silica gel using the mixture of petroleum ether/EtOAc (1:1) as an eluent and recrystallized from ethanol. There was a yield of 0.112 g (33%) and it was a colorless oil. \({}^{1}\)H NMR (400 MHz, DMSO-\(d_{6}\)) \(\delta\) = 12.08 (br.s, 1H), 11.81 (br.s, 1H), 8.72--8.70 (m, 1H), 8.55 (d, \(J\) = 2.8 Hz, 1H), 8.13--8.11 (m, 1H), 7.81--7.72 (m, 2H), 7.50--7.48 (m, 1H), 7.43--7.39 (m, 1H), and 7.27--7.20 (m, 2H) ppm; \({}^{13}\)C[\({}^{1}\)H] NMR (100 MHz, DMSO-\(d_{6}\)) \(\delta\) = 162.0, 150.2, 149.7, 136.8, 134.2, 129.0, 126.9, 125.7, 125.5, 125.0, 122.5, 122.3, 120.8, 120.4, 111.9, and 108.6 ppm. Indole (**4a**) and quinazolin-4(3\(H\))-one (**5a**) were isolated as by-products in the synthesis of 2-(1\(H\)-indol-3-yl)quinazolin-4(3\(H\))-one (**3a**). The spectral data of the indole (**4a**) were identical to the commercially available ones. Quinazolin-4(3\(H\))-one (**5a**) [81]. There was a yield of 0.023 g (12%) and it was a white solid. Mp. = 215--216 \({}^{\circ}\)C (EtOH, lit. [81] 213--214 \({}^{\circ}\)C). \({}^{1}\)H NMR (400 MHz, DMSO-\(d_{6}\)) \(\delta\) = 12.16 (br.s, 1H), 8.12 (br.d, \(J\) = 8.0 Hz, 1H), 8.08 (s, 1H), 7.82--7.78 (m, 1H), 7.66 (d, \(J\) = 8.0 Hz, 1H), and 7.53--7.49 (m, 1H) ppm; \({}^{13}\)C[\({}^{1}\)H] NMR (100 MHz, DMSO-\(d_{6}\)) \(\delta\) = 160.6, 148.7, 145.2, 134.2, 127.1, 126.6, 125.7, and 122.6 ppm. 3.3.3. Synthesis of 2-(1\(H\)-indol-3-yl)-2,3-dihydroquinazolin-4(1\(H\))-one (6**a**) [82]  
To a suspension of 1\(H\)-indole-3-carboxaldehyde (**1a**) (1.3 mmol, 0.189 g) and Al\({}_{2}\)O\({}_{3}\) (acidic) (2.3 mmol, 0.235 g) in dry acetonitrile (2.5 mL), anthranilamide (**2a**) (1.3 mmol, 0.177 g) was added. The reaction mixture was refluxed for 55 h (TLC control). Then, the Al\({}_{2}\)O\({}_{3}\) was filtered off and washed with hot EtOAc (3 \(\times\) 5 mL). The combined organic fractions were concentrated to dryness under reduced pressure. The product was purified using column chromatography on silica gel using the mixture of petroleum ether/EtOAc (1:1) as an eluent. There was a yield of 0.154 g (45%) and it was a colorless oil. 1\({}^{1}\)H NMR (400 MHz, DMSO-\(d_{6}\)) \(\delta\) = 11.09 (br.s, 1H), 8.08 (br.s, 1H), 7.80-7.78 (m, 1H), 7.70-7.68 (m, 1H), 7.43-7.41 (m, 2H), 7.27-7.23 (m, 1H), 7.15-7.11 (m, 1H), 7.04-7.01 (m, 1H), 6.92 (br.s, 1H), 6.79-6.77 (m, 1H), 6.73-6.69 (m, 1H), and 6.07 (s, 1H) ppm; \({}^{13}\)C[\({}^{1}\)H] NMR (100 MHz, DMSO-\(d_{6}\)) \(\delta\) = 164.2, 148.8, 136.6, 133.0, 127.5, 125.4, 124.6, 121.4, 120.0, 118.7, 117.0, 115.3, 114.43, 114.38, 111.6, and 61.7 ppm. Indole (**4a**) was isolated as by-product in the synthesis of 2-(1\(H\)-indol-3-yl)-2,3-dihydroquinazolin-4(1\(H\))-one (**6a**). The spectral data of the indole (**4a**) were identical to the commercially available ones. 3.3.4. General Procedure for the Synthesis of Quinazolin-4(3\(H\))-Ones **3a-3g, 3k-3 ab**  
To a suspension of aldehyde **1** (1.3 mmol) and Na\({}_{2}\)S\({}_{2}\)O\({}_{5}\) (4.5 mmol, 0.855 g) in \(N\)-dimethylacetamide (2.5 mL), amide **2** (1.3 mmol) and H\({}_{2}\)O (4.5 mmol, 81 \(\mu\)L) were added. The reaction mixture was heated at 150 \({}^{\circ}\)C for 6.5-55 h (TLC control). Then, the reaction mixture was poured into H\({}_{2}\)O (50 mL). The formed precipitate was filtered. The products **3a,d,f,g,k,l,o-r,t,w,x,ab** were purified using column chromatography on silica gel using the mixture of petroleum ether/EtOAc (1:1) as an eluent and recrystallized from a suitable solvent.