3,4-dihydro-1H-quinazolin-2-one

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: An equimolar mixture of anthranilamide (136 mg, 1.0 mmole) and 2-ethoxybenzaldehyde (166 mg, 1.0 mmole) is suspended in methanol (30 mL) and heated to reflux for 3 hours. After cooling, the Schiff's base is isolated by vacuum filtration, suspended in ethanol (50 mL) containing p-toluenesulfonic acid (33 mg, 0.17 mmole), and heated to reflux for 1 hour. The resulting dihydroquinazolone is treated with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ, 227 mg, 1.0 mmole) and heating is continued as above for 1 hour. After cooling to room temperature, the precipitated solid is filtered and washed with methanol. The product is recrystallized from methanol to yield a colorless solid. 1H-NMR (CDCl3) δ:8.54 (d,1H);8.30 (d,1H); 7.77 (m,2H); 7.51-7.43 (m,2H); 7.15 (t,1H); 7.05 (d,1H); 4.30 (q,2H,-CH 2CH3); 1.60 (t,3H,-CH2CH3). heated to reflux for 1 hour heating is continued as above for 1 hour the precipitated solid is filtered washed with methanol The product is recrystallized from methanol to yield a colorless solid

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: An equimolar mixture of anthranilamide (136 mg, 1.0 mmole) and 2-ethoxybenzaldehyde (166 mg, 1.0 mmole) is suspended in methanol (30 mL) and heated to reflux for 3 hours. After cooling, the Schiff's base is isolated by vacuum filtration, suspended in ethanol (50 mL) containing p-toluenesulfonic acid (33 mg, 0.17 mmole), and heated to reflux for 1 hour. The resulting dihydroquinazolone is treated with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ, 227 mg, 1.0 mmole) and heating is continued as above for 1 hour. After cooling to room temperature, the precipitated solid is filtered and washed with methanol. The product is recrystallized from methanol to yield a colorless solid. 1H-NMR (CDCl3) δ:8.54 (d,1H);8.30 (d,1H); 7.77 (m,2H); 7.51-7.43 (m,2H); 7.15 (t,1H); 7.05 (d,1H); 4.30 (q,2H,-CH 2CH3); 1.60 (t,3H,-CH2CH3). heated to reflux for 1 hour heating is continued as above for 1 hour the precipitated solid is filtered washed with methanol The product is recrystallized from methanol to yield a colorless solid

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Bromopropionyl bromide (10.6 g) is added dropwise to a stirring mixture of 3,4-dihydro-2(1H)-quinazolinone (3.2 g) and anhydrous aluminum chloride (7.9 g) in carbon disulfide (60 ml). The reaction mixture is refluxed for four hours, the carbon disulfide decanted and the residue treated with aqueous hydrochloric acid (6N). The acidic residue is poured into ice water, and the precipitate filtered, washed with water and dried, affording the desired product as a solid, which is used in the next step without further purification. The reaction mixture is refluxed for four hours the carbon disulfide decanted the residue treated with aqueous hydrochloric acid (6N) The acidic residue is poured into ice water the precipitate filtered washed with water dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Bromoacetyl chloride (6.2 g) is added dropwise to a stirring mixture of 3,4-dihydro-2(1H)-quinazolinone (2.6 g) and anhydrous aluminum chloride (6.3 g) in carbon disulfide (60 ml). The reaction mixture is stirred under reflux for 4.5 hours, the carbon disulfide decanted, and the residue treated with HCl (6N). The resulting solid is poured into ice water, filtered, the filtered solid washed with water and dried in vacuo, affording the desired product, which is used in the next step without further purification. under reflux for 4.5 hours the carbon disulfide decanted the residue treated with HCl (6N) The resulting solid is poured into ice water filtered the filtered solid washed with water dried in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Bromoacetyl chloride (6.2 g) is added dropwise to a stirring mixture of 3,4-dihydro-2(1H)-quinazolinone (2.6 g) and anhydrous aluminum chloride (6.3 g) in carbon disulfide (60 ml). The reaction mixture is stirred under reflux for 4.5 hours, the carbon disulfide decanted, and the residue treated with HCl (6N). The resulting solid is poured into ice water, filtered, the filtered solid washed with water and dried in vacuo, affording the desired product, which is used in the next step without further purification. under reflux for 4.5 hours the carbon disulfide decanted the residue treated with HCl (6N) The resulting solid is poured into ice water filtered the filtered solid washed with water dried in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 144 mg (0.53 mmol) 1,1-bis-(4-methoxy-phenyl)-urea, 160 μl (1.06 mmol) cumic aldehyde and 16 μl (0.27 mmol) methane sulfonic acid in 1 ml diglyme is heated for 4 d at 100°. The reaction mixture is extracted with water/dichloromethane and the intermediate dihydro-quinazolinone is isolated by preparative HPLC. Oxidation with ruthenium trichloride and sodium periodate, as described above, furnishes 4-(4-isospropyl-phenyl)-6-methoxy-1-(4-methoxy-phenyl)-1.H.-quinazolin-2-one. The reaction mixture is extracted with water/dichloromethane

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a vigorously stirred amount of 45 parts of aluminum chloride were added dropwise 7.05 parts of N,N-dimethylformamide. After stirring for 5 min. at 70° C., there were added 5 parts of benzoyl chloride and, dropwise, 4.7 parts of 3,4-dihydro-2(1H)-quinazolinone. Stirring was continued for 2 hours at 70° C. The reaction mixture was poured into ice-water and there were added 63.5 parts of HCl. The precipitate was filtered off and recrystallized from 2-methoxyethanol, yielding 6.5 parts (76.4%) of 6-benzoyl-3,4-dihydro-2(1H)-quinazolinone; mp. 264.8° C. (interm. 1). Stirring was continued for 2 hours at 70° C The precipitate was filtered off recrystallized from 2-methoxyethanol

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a vigorously stirred amount of 45 parts of aluminum chloride were added dropwise 7.05 parts of N,N-dimethylformamide. After stirring for 5 min. at 70° C., there were added 5 parts of benzoyl chloride and, dropwise, 4.7 parts of 3,4-dihydro-2(1H)-quinazolinone. Stirring was continued for 2 hours at 70° C. The reaction mixture was poured into ice-water and there were added 63.5 parts of HCl. The precipitate was filtered off and recrystallized from 2-methoxyethanol, yielding 6.5 parts (76.4%) of 6-benzoyl-3,4-dihydro-2(1H)-quinazolinone; mp. 264.8° C. (interm. 1). Stirring was continued for 2 hours at 70° C The precipitate was filtered off recrystallized from 2-methoxyethanol

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a vigorously stirred amount of 45 parts of aluminum chloride were added dropwise 7.05 parts of N,N-dimethylformamide. After stirring for 5 min. at 70° C., there were added 5 parts of benzoyl chloride and, dropwise, 4.7 parts of 3,4-dihydro-2(1H)-quinazolinone. Stirring was continued for 2 hours at 70° C. The reaction mixture was poured into ice-water and there were added 63.5 parts of HCl. The precipitate was filtered off and recrystallized from 2-methoxyethanol, yielding 6.5 parts (76.4%) of 6-benzoyl-3,4-dihydro-2(1H)-quinazolinone; mp. 264.8° C. (interm. 1). Stirring was continued for 2 hours at 70° C The precipitate was filtered off recrystallized from 2-methoxyethanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3,4-Dihydro-2(1H)-quinazolinone (3.6 g) is added to a stirred suspension of anhydrous aluminum chloride (16.5 g) in carbon disulfide (120 ml) under nitrogen. 3-Carbomethoxy-2-methyl-propionyl chloride (4 g) is added dropwise to the stirred suspension, and the reaction mixture refluxed for about 18 hours, cooled to RT and further cooled to 0° C. in an ice bath. The liquid phase is decanted and ice and cold water slowly added to the residue. The aqueous mixture is filtered and the filtered solid suspended and stirred in the anhydrous diethyl ether overnight. The suspension is filtered and the filtered solid used in the next step without further purification. the reaction mixture refluxed for about 18 hours further cooled to 0° C. in an ice bath The liquid phase is decanted ice and cold water slowly added to the residue The aqueous mixture is filtered The suspension is filtered the filtered solid used in the next step without further purification