2-AMINO-4,6-DICHLOROBENZOIC ACID

At room temperature, to a solution of the intermediate I-2 (5.0 g, 23.1 mmol) prepared by the above peparation example I(2) in 75 mL 1N NaOH (aq) was added portionwise hydrogen peroxide (28percent v/v, 10 mL). The reaction mixture was filtered after stirring for 2 hours to remove insoluble dark brown solid. The filterate was then carefully acidified to pH 2 by conc. hydrochloric acid. The formed yellow precipitates were collected, washed with water, and dried in vacuo. The objective compound (3.90 g, 82percent) was obtained as ivory-colored solid by recrystalization from benzene: TLC R3) Intermediate I-3; 2-amino-4, 6-dichloro benzoic acid; At room temperature, to a solution of the intermediate I-2 (5.0 g, 23.1 mmol) prepared by the above peparation example I(2) in 75 mL 1N NaOH (aq) was added portionwise hydrogen peroxide (28 percent v/v, 10 mL). The reaction mixture was filtered after stirring for 2 hours to remove insoluble dark brown solid. The filterate was then carefully acidified to pH 2 by conc. hydrochloric acid. The formed yellow precipitates were collected, washed with water, and dried in vacuo. The objective compound (3.90 g, 82 percent) was obtained as ivory-colored solid by recrystalization from benzene: TLC RStep 3: Preparation of 2-amino-4, 6-dichlorobenzoic acidTo a solution of 4, 6-dihloro-lH-indole-2, 3-dione (5.0 g, 23.1 mmol) in 75 ml of 1 N Step 3 In a pressure vessel, a mixture of (S)-2-((tert-butoxycarbonyl)ammo)-3-(3, 5- difluorophenyl)propanoic acid (84 mg, 0.28 mmol) and General procedure: We run multicomponent reaction between antranilic acids, acetic anhydride and primary amines in the present of MNPTA for synthesis of 3-substituted 2-methylquinazoline-4-(3H)-one derivatives (Scheme 1).Into a canonical flask (25 ml), a mixture of anthranilic acid (1 mmol), acetic anhydride (1.2 mmol) with selected aromatic amines (1 mmol) and MNP-TA (0.058 g, 5 mol%) was heated at 80 C for 4-12 h. After completion the reaction, monitored by TLC, the catalyst was separated by external magnet. The precipitated solid was filtered. Then, the pure product was obtained by its recrystallization in dichloromethane/petroleum ether solvent system and compounds that did not reach this level were purified by column chromatography on silica gel using petroleum ether/ethyl acetate aselution afforded the pure 3-substituted 2-methylquinazoline-4(3H)-one derivatives (Fig. 3).General procedure: We run multicomponent reaction between antranilic acids, acetic anhydride and primary amines in the present of MNPTA for synthesis of 3-substituted 2-methylquinazoline-4-(3H)-one derivatives (Scheme 1).Into a canonical flask (25 ml), a mixture of anthranilic acid (1 mmol), acetic anhydride (1.2 mmol) with selected aromatic amines (1 mmol) and MNP-TA (0.058 g, 5 mol%) was heated at 80 C for 4-12 h. After completion the reaction, monitored by TLC, the catalyst was separated by external magnet. The precipitated solid was filtered. Then, the pure product was obtained by its recrystallization in dichloromethane/petroleum ether solvent system and compounds that did not reach this level were purified by column chromatography on silica gel using petroleum ether/ethyl acetate aselution afforded the pure 3-substituted 2-methylquinazoline-4(3H)-one derivatives (Fig. 3).General procedure: We run multicomponent reaction between antranilic acids, acetic anhydride and primary amines in the present of MNPTA for synthesis of 3-substituted 2-methylquinazoline-4-(3H)-one derivatives (Scheme 1).Into a canonical flask (25 ml), a mixture of anthranilic acid (1 mmol), acetic anhydride (1.2 mmol) with selected aromatic amines (1 mmol) and MNP-TA (0.058 g, 5 mol%) was heated at 80 C for 4-12 h. After completion the reaction, monitored by TLC, the catalyst was separated by external magnet. The precipitated solid was filtered. Then, the pure product was obtained by its recrystallization in dichloromethane/petroleum ether solvent system and compounds that did not reach this level were purified by column chromatography on silica gel using petroleum ether/ethyl acetate aselution afforded the pure 3-substituted 2-methylquinazoline-4(3H)-one derivatives (Fig. 3).General procedure: We run multicomponent reaction between antranilic acids, acetic anhydride and primary amines in the present of MNPTA for synthesis of 3-substituted 2-methylquinazoline-4-(3H)-one derivatives (Scheme 1).Into a canonical flask (25 ml), a mixture of anthranilic acid (1 mmol), acetic anhydride (1.2 mmol) with selected aromatic amines (1 mmol) and MNP-TA (0.058 g, 5 mol%) was heated at 80 C for 4-12 h. After completion the reaction, monitored by TLC, the catalyst was separated by external magnet. The precipitated solid was filtered. Then, the pure product was obtained by its recrystallization in dichloromethane/petroleum ether solvent system and compounds that did not reach this level were purified by column chromatography on silica gel using petroleum ether/ethyl acetate aselution afforded the pure 3-substituted 2-methylquinazoline-4(3H)-one derivatives (Fig. 3).General procedure: We run multicomponent reaction between antranilic acids, acetic anhydride and primary amines in the present of MNPTA for synthesis of 3-substituted 2-methylquinazoline-4-(3H)-one derivatives (Scheme 1).Into a canonical flask (25 ml), a mixture of anthranilic acid (1 mmol), acetic anhydride (1.2 mmol) with selected aromatic amines (1 mmol) and MNP-TA (0.058 g, 5 mol%) was heated at 80 C for 4-12 h. After completion the reaction, monitored by TLC, the catalyst was separated by external magnet. The precipitated solid was filtered. Then, the pure product was obtained by its recrystallization in dichloromethane/petroleum ether solvent system and compounds that did not reach this level were purified by column chromatography on silica gel using petroleum ether/ethyl acetate aselution afforded the pure 3-substituted 2-methylquinazoline-4(3H)-one derivatives (Fig. 3).General procedure: We run multicomponent reaction between antranilic acids, acetic anhydride and primary amines in the present of MNPTA for synthesis of 3-substituted 2-methylquinazoline-4-(3H)-one derivatives (Scheme 1).Into a canonical flask (25 ml), a mixture of anthranilic acid (1 mmol), acetic anhydride (1.2 mmol) with selected aromatic amines (1 mmol) and MNP-TA (0.058 g, 5 mol%) was heated at 80 C for 4-12 h. After completion the reaction, monitored by TLC, the catalyst was separated by external magnet. The precipitated solid was filtered. Then, the pure product was obtained by its recrystallization in dichloromethane/petroleum ether solvent system and compounds that did not reach this level were purified by column chromatography on silica gel using petroleum ether/ethyl acetate aselution afforded the pure 3-substituted 2-methylquinazoline-4(3H)-one derivatives (Fig. 3).General procedure: 1 eq. anthranilic acid analog was dissolved in 12.4 eq. pyridine, followed by addition of 4 eq. chloroformate in a dropwise manner over 15 min. 30min later, the excess pyridine was removed under vacuum. Silica column chromatography(5-20% ethyl acetate in petroleum ether) gave final compound. For compounds 1d, 2d, 3d, 4, 5, 6 and 8, this was followed by a recrystallization from MeOH. 7 was recrystallized from ethyl acetateand 9 from ethyl acetate/petrolium ether.

Molecular Weight:206.02
XLogP3:2.6
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:204.9697338
Monoisotopic Mass:204.9697338
Topological Polar Surface Area:63.3
Heavy Atom Count:12
Complexity:188
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes