# The Synthesis and Biological Evaluation of 2-(1H-Indol-3-yl)quinazolin-4(3H)-One Derivatives
## 2 Results and Discussion
### Chemistry
1 All reactions were performed at 1.3 mmol scale of aldehyde **1** and 1.3 mmol of amide **2**. Isolated yields. 2 The reaction was performed at 3 mmol of aldehyde **1** and 3 mmol of amide **2**. Isolated yield. 3 The 2-(1\(H\)-indol-3-yl)quinazolin-4(3\(H\))-one (**3a**) was isolated in 80-96% yield (n.d.--not detected). 3 The formation of indolylquinazolinones **3m**, **n** were detected using thin-layer chromatography (TLC) and gas chromatography-mass spectrometry (GC/MS). The quinazolinone **5a** was isolated in 37% and 59% yields. 4 The formation of indole (**4a**) was determined using TLC and GC/MS. 5 The corresponding \(N\),\(N\)-dimethyl-1\(H\)-indole-3-carbothioamide (**7a**) was also isolated in a 21-50% yield. 5 The reaction conditions: aldehyde **1** (0.76 mmol), amide **2** (0.69 mmol), DMSO (1 mL), 100 \({}^{\circ}\)C, 3.5 h. Isolated yield. 5 The reaction conditions: aldehyde **1** (0.25 mmol), amide **2** (0.25 mmol), TFA (0.25 mmol), toluene (2 mL), reflux, 40 h.  
Next, we expanded the scope of the developed protocol and used various carbo- and heteroaromatic aldehydes **1** as starting substrates. We found that, in all cases, the desired indolyquinazolinones **3** were isolated in high yields. The exception was the electron-deficient isonicotinaldehyde, for which the desired product **3y** was obtained in a low yield. It should be noted that the use of dimethyl sulfoxide without additional reagents in the reaction of 5-methylfurfural with anthranilamide (**2a**) resulted in the formation of the dihydroquinazolinone **6u** in a 62% yield. Product **6u**, in contrast to its indole analogue **6a**, was more stable and was not oxidized in the solution in air atmosphere. We tested a series of structural analogues of anthranilamide with 1\(H\)-indole-3-carboxaldehyde (**1a**). We found that the reaction of aldehyde **1a** with anthranilic acid hydrazide led to the corresponding product **3 ab** in a good yield. The reaction of salicylic amide with 1\(H\)-indole-3-carboxaldehyde (**1a**) unfortunately did not provide the desired product **3 ac** due to the predominant occurrence of the deformylation reaction. A similar result was also obtained in the case of [PERSON]'s thiophene. It is noteworthy that, when using thiophene-2-carbaldehyde, the product **3 ad** was isolated in a moderate yield. In the case of 2-aminobenzenesulfonamide and 2-amino-2-phenylacetamide, the thioamidation reaction predominated, while we did not observe the formation of the desired products **3 af** and **3 ag**. It should be noted that all the synthesized compounds were stable and fully characterized by NMR and HRMS. Finally, we studied some reactivity of the model 2-(1\(H\)-indol-3-yl)quinazolin-4(3\(H\))-one (**3a**) (Scheme 3). Initially, we checked the possibility of the functionalization of the nitrogen atom and synthesized various \(N\)-substituted indolyquinazolinones **3**. The problem of the hydrolysis of the protecting group at the nitrogen atom can be solved by changing the order of the reaction steps. The treatment of indolyquinazolinone **3a** with benzoyl chloride afforded 2-(1-benzoyl-1\(H\)-indol-3-yl)quinazolim-4(3\(H\))-one (**3i**) in a good yield. The sequential treatment of quinazolinone **3a** with NaH and methyl iodide afforded a mixture of three products in equal amounts. Along with the expected mono- 3b and disubstituted indolyquinazolinones **3 ah**, we observed the formation of 4-methoxy-2-(1-methyl-1\(H\)-indol-3-yl)quinazoline (**3 ai**). (Scheme 3). According to the literature data, it is known that some thioquinazolinones are characterized by increased antimyobacterial activity compared to that of quinazolinones [48]. To study the reactivity of the substrate **3a**, we developed a method of thionation with Lawesson's reagent (LR) and a subsequent alkylation affording the target 2-(1\(H\)-indol-3-yl)-4-(methylthio)quinazolinone (**3 ak**) in a moderate yield over two steps (Scheme 4).