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CAS No. : | 7012-88-6 | MDL No. : | MFCD11048436 |
Formula : | C9H7ClN2O | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | HSXQJNOGRWBTBQ-UHFFFAOYSA-N |
M.W : | 194.62 | Pubchem ID : | 135462579 |
Synonyms : |
|
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P305+P351+P338-P280 | UN#: | N/A |
Hazard Statements: | H317-H319 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
3.6 g | With ammonium hydroxide; at 25℃; | General procedure: The benzoxazin-4-one intermediates (1 mmol) were suspended in concentrated ammonium hydroxide (1 ml) and were stirred at room temperature overnight. 10% sodium hydoxide solution was added to the reaction mixtures until the results of transparent solutions. The pH was adjusted to 7 with acetic acid. The products precipitated from the solution were filtered out and were washed with water. The solid compounds were dried under vacuum overnight. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ammonium hydroxide; at 20℃; | General procedure: 6-chloro-2-methylquinazolin-4(3H)-one 10 g (58 mmol) 2-amino-5-chlorobenzoic acid was solved in 35 ml acetic anhydride and was stirred at reflux temperature for 4 hours. The reaction mixture was cooled down to room temperature and the solvent was rotary evaporated. The crude product was washed with hexane/ether 2:1 and than filtered. The solid 6-chloro-2-methyl-4H-3,1-benzoxazin-4-one (58 mmol) was suspended in 80 ml concentrated ammonium hydroxide and stirred at room temperature overnight. 10 % sodium hydoxide solution was given to the reaction mixture resulting a transparent solution. The pH was adjusted to 7 with acetic acid. The product, which was precipitated from the solution, was filtered, washed with water and dried under vacuum overnight. Preparation of other 2-methylquinazolin-4(3H)-one derivatives were carried out with the same method. Yield: 8.76 g (77 %) 1H NMR (300 MHz, DMSO-d6) delta ppm 7.98 (s, 1H); 7,76 (6Hz, d, 1H); 7.57 (9 Hz, d, 1H); 2.34 (s, 3H). LC-MS (ESI): m z (M+H)+ 195, Rt: 2.43 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.73 g (73%) | With sodium hydroxide; lithium hydroxide monohydrate; In tetrahydrofuran; water; | EXAMPLE 5 7-Chloro-2,3-dimethyl-4(3H)-quinazolinone A mixture of 0.96 g (5.0 mmol) of <strong>[7012-88-6]7-chloro-2-methyl-4(3H)-quinazolinone</strong> and 0.20 g (4.8 mmol) of lithium hydroxide monohydrate in 25 ml of tetrahydrofuran is heated at reflux with stirring for 0.5 h. After cooling to room temperature, 0.89 g (4.8 mmol) of methyl p-toluene sulfonate is added and the reaction mixture heated at reflux for 4 hours. The reaction mixture is neutralized with con. HCl and the solvent removed in vacuo to give a residue. The residue is slurried with 50 ml of water, filtered, washed with 50 ml of 0.5M sodium hydroxide, followed by (3*50 ml) of water. The solid is dried to give 0.73 g (73%) of the desired product, m.p. 162-165 C. None of the isomeric O-alkylated product is detected by HPLC. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.8 g | With acetic acid; at 120℃; for 8h;Sealed tube; | (E)-7-Chloro-2-(3,4-dichlorostyryl)quinazolin-4(3H)-one 7-Chloro-2-methylquinazolin-4(3H)-one (1.0 g, 5.14 mmol, 1 eq) was placed in a 40 ml screw-top vial with a stir bar. Added 3,4-dichlorobenzaldehyde (1.0 g, 5.71 mmol) was added and acetic acid (15 ml) was added to the mixture. The mixture was placed on a pre-heated hotplate-stirrer (120 C.) for 8 hrs. The reaction was cooled and the precipitate was vacuum filtered, washed with water, sat'd NaHCO3 solution, water and a small amount of diethyl ether to remove the excess aldehyde. The solid was dried in a vacuum desiccator to give 1.80 grams of 411. (E)-7-chloro-2-(3,4-dichlorostyryl)quinazolin-4(3H)-one. 1H NMR (400 MHz, DMSO-d6): delta 12.4 (bs, 1H), 8.1 (d, 1H), 7.86-7.96 (m, 2H), 7.64-7.76 (m, 3H), 7.50-7.55 (m, 1H), 7.65 (d, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
10 mg | 7-Chloro-2-methylquinazolin-4(3H)-one (1230) (1231) Placed 2-amino-4-chlorobenzoic acid (10.0 g, 58.28 mmol, 1 eq) in a 1000 ml round bottom flask with a stir bar. Added acetic anhydride (21.6 g, 20 ml, 211.5 mmol, 3.6 eq) and placed on a pre-heated oil bath at 120 C. for 3 h with stirring. This mixture was then placed on a rotary evaporator (50 C.) to remove excess acetic anhydride which gave a dry solid. To this was added 100 ml of ammonium hydroxide (28% NH3) and heated to 95 C. for 4 h. Cooled, vacuum filtered and washed the solid with water (500 ml), then Et2O (100 ml), and dried in vacuo to give 10 grams of 410. 1H NMR (400 MHz, DMSO-d6), S 12.3 (bs, 1H), 8.0-8.1 (m, 1H), 7.61 (s, 1H), 7.4-7.5 (m, 1H), 2.35 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With acetic acid; In water; for 24h;Reflux; Green chemistry; | General procedure: A mixture of 2-methylquinazolin-4(3H)-ones 1 (2 mmol), aryl amines 2 (2 mmol), and 2-formylbenzoic acids 3 (2 mmol), and acetic acid (40 mol) in H2O (6 mL) were refluxed for 24 hours. After reaction completion (TLC), the reaction mixture was cooled to room temperature. Then the obtained solid was filtered off, washed with cold water (20 mL) and recrystallized from aqueous EtOH to afford the pure product 4a-n. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With acetic acid; In water; for 24h;Reflux; Green chemistry; | General procedure: A mixture of 2-methylquinazolin-4(3H)-ones 1 (2 mmol), aryl amines 2 (2 mmol), and 2-formylbenzoic acids 3 (2 mmol), and acetic acid (40 mol) in H2O (6 mL) were refluxed for 24 hours. After reaction completion (TLC), the reaction mixture was cooled to room temperature. Then the obtained solid was filtered off, washed with cold water (20 mL) and recrystallized from aqueous EtOH to afford the pure product 4a-n. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With acetic acid; In water; for 24h;Reflux; Green chemistry; | General procedure: A mixture of 2-methylquinazolin-4(3H)-ones 1 (2 mmol), aryl amines 2 (2 mmol), and 2-formylbenzoic acids 3 (2 mmol), and acetic acid (40 mol) in H2O (6 mL) were refluxed for 24 hours. After reaction completion (TLC), the reaction mixture was cooled to room temperature. Then the obtained solid was filtered off, washed with cold water (20 mL) and recrystallized from aqueous EtOH to afford the pure product 4a-n. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With acetic acid; In water; for 24h;Reflux; Green chemistry; | General procedure: A mixture of 2-methylquinazolin-4(3H)-ones 1 (2 mmol), aryl amines 2 (2 mmol), and 2-formylbenzoic acids 3 (2 mmol), and acetic acid (40 mol) in H2O (6 mL) were refluxed for 24 hours. After reaction completion (TLC), the reaction mixture was cooled to room temperature. Then the obtained solid was filtered off, washed with cold water (20 mL) and recrystallized from aqueous EtOH to afford the pure product 4a-n. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With acetic acid; In water; for 24h;Reflux; Green chemistry; | General procedure: A mixture of 2-methylquinazolin-4(3H)-ones 1 (2 mmol), aryl amines 2 (2 mmol), and 2-formylbenzoic acids 3 (2 mmol), and acetic acid (40 mol) in H2O (6 mL) were refluxed for 24 hours. After reaction completion (TLC), the reaction mixture was cooled to room temperature. Then the obtained solid was filtered off, washed with cold water (20 mL) and recrystallized from aqueous EtOH to afford the pure product 4a-n. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With acetic acid; In water; for 24h;Reflux; Green chemistry; | General procedure: A mixture of 2-methylquinazolin-4(3H)-ones 1 (2 mmol), aryl amines 2 (2 mmol), and 2-formylbenzoic acids 3 (2 mmol), and acetic acid (40 mol) in H2O (6 mL) were refluxed for 24 hours. After reaction completion (TLC), the reaction mixture was cooled to room temperature. Then the obtained solid was filtered off, washed with cold water (20 mL) and recrystallized from aqueous EtOH to afford the pure product 4a-n. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With acetic acid; In water; for 24h;Reflux; Green chemistry; | General procedure: A mixture of 2-methylquinazolin-4(3H)-ones 1 (2 mmol), aryl amines 2 (2 mmol), and 2-formylbenzoic acids 3 (2 mmol), and acetic acid (40 mol) in H2O (6 mL) were refluxed for 24 hours. After reaction completion (TLC), the reaction mixture was cooled to room temperature. Then the obtained solid was filtered off, washed with cold water (20 mL) and recrystallized from aqueous EtOH to afford the pure product 4a-n. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With acetic acid; In water; for 24h;Reflux; Green chemistry; | General procedure: A mixture of 2-methylquinazolin-4(3H)-ones 1 (2 mmol), aryl amines 2 (2 mmol), and 2-formylbenzoic acids 3 (2 mmol), and acetic acid (40 mol) in H2O (6 mL) were refluxed for 24 hours. After reaction completion (TLC), the reaction mixture was cooled to room temperature. Then the obtained solid was filtered off, washed with cold water (20 mL) and recrystallized from aqueous EtOH to afford the pure product 4a-n. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With acetic acid; In ethanol; at 110℃; for 24h;Inert atmosphere; Sealed tube; | General procedure: The 2-aminobenzamide (1 equiv), the orthoester (2?3 equiv) and absolute ethanol (2?3 mL) wereplaced in a 15-mL Chemglass screw-cap pressure tube (No. CG-1880-01, Chemglass, Vineland, NJ,USA). Glacial acetic acid (3 equiv) was added, N2 was introduced to the vessel and the cap wastightened. The vessel was heated at 110 °C for 12?72 h, then cooled and concentrated to give thequinazolinone, which was purified by crystallization from absolute ethanol or trituration from 5percentether in pentane. The following compounds were prepared: |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With sulfuric acid; at 190℃; under 750.075 - 5250.53 Torr; for 1.5h;Microwave irradiation; | General procedure: The 2-methylquinazolin-4(3H)-ones (1 mmol) were mixed with benzaldehydes (1.5 mmol) and 1 drop concentrated sulphuric acid was added to the mixtures. The reaction was carried out in microwave set (Personal Chemistry, Emrys Creator, heating power: 150 W, measured pressure 1-7 bar, reaction time: 1.5 hours) at 190 C. The crude product was washed with 5% sodium hydrogen carbonate and filtered out. The products were crystallized from dimethyl formamide and dried under vacuum. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With sulfuric acid; at 190℃; under 750.075 - 5250.53 Torr; for 1.5h;Microwave irradiation; | General procedure: The 2-methylquinazolin-4(3H)-ones (1 mmol) were mixed with benzaldehydes (1.5 mmol) and 1 drop concentrated sulphuric acid was added to the mixtures. The reaction was carried out in microwave set (Personal Chemistry, Emrys Creator, heating power: 150 W, measured pressure 1-7 bar, reaction time: 1.5 hours) at 190 C. The crude product was washed with 5% sodium hydrogen carbonate and filtered out. The products were crystallized from dimethyl formamide and dried under vacuum. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With ammonium acetate; In 1,4-dioxane;Reflux; | General procedure: N -(2-aminobenzoyl)benzotriazoles (0.25 mmol) 1 previously synthesized by our group were reacted with orthoester (0.50 mmol) 2 and ammonium acetate (1.0 mmol) in dioxane for 6-10 h. After completion of the reaction, the solvent was evaporated under reduced pressure. The reaction mixture was purified by column chromatography over silica gel with a EtOAc/n-hexane mixture (from 1:2 or 1:1) to obtain white crystals (62%-95%). |
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