阿普唑仑杂质4

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A stirred solution of acetic anhydride (25.3 ml) and 97% formic acid (10.6 ml) is kep at ambient temperature (25°) for 30 minutes, cooled in an ice bath and treated with 3-amino-6-chloro-3,4-dihydro-4-hydroxy-4-phenylquinazoline (12.24 g, 0.0447 mole). The solution is kept at ambient temperature for 18 hours, diluted with acetic acid (25 ml), warmed to the reflux temperature during 1 hour and refluxed for 1.5 hours. The solution is concentrated in vacuo, and the residue is mixed with cold water, made alkaline with sodium hydroxide and extracted with chloroform. The extract is washed with brine, dried over anhydrous sodium sulfate and concentrated. The residue is crystallized from ethylacetate to give 7.76 g of 5-chloro-2-(4H-1,2,4-triazol-4-yl)-benzophenone of melting point 184°-186° C., 0.971 g of melting point 182.5°-184° C., and 0.144 of melting point 181°-182° C. is kep at ambient temperature (25°) for 30 minutes cooled in an ice bath warmed to the reflux temperature during 1 hour refluxed for 1.5 hours The solution is concentrated in vacuo the residue is mixed with cold water extracted with chloroform The extract is washed with brine dried over anhydrous sodium sulfate concentrated The residue is crystallized from ethylacetate

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A stirred solution of acetic anhydride (25.3 ml) and 97% formic acid (10.6 ml) is kep at ambient temperature (25°) for 30 minutes, cooled in an ice bath and treated with 3-amino-6-chloro-3,4-dihydro-4-hydroxy-4-phenylquinazoline (12.24 g, 0.0447 mole). The solution is kept at ambient temperature for 18 hours, diluted with acetic acid (25 ml), warmed to the reflux temperature during 1 hour and refluxed for 1.5 hours. The solution is concentrated in vacuo, and the residue is mixed with cold water, made alkaline with sodium hydroxide and extracted with chloroform. The extract is washed with brine, dried over anhydrous sodium sulfate and concentrated. The residue is crystallized from ethylacetate to give 7.76 g of 5-chloro-2-(4H-1,2,4-triazol-4-yl)-benzophenone of melting point 184°-186° C., 0.971 g of melting point 182.5°-184° C., and 0.144 of melting point 181°-182° C. is kep at ambient temperature (25°) for 30 minutes cooled in an ice bath warmed to the reflux temperature during 1 hour refluxed for 1.5 hours The solution is concentrated in vacuo the residue is mixed with cold water extracted with chloroform The extract is washed with brine dried over anhydrous sodium sulfate concentrated The residue is crystallized from ethylacetate

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 0.1 mole of 2'-benzoyl-4'-chloroformanilide and 0.15 mole of hydrazine are stirred at room temperature in ethanol. Stirring is continued for 20 hours. The reaction mixture is chilled, and the precipitate filtered. The solid is washed and recrystallized from dimethylformamide to give 3-amino-6-chloro-3,4-dihydro-4-hydroxy-4-phenylquinazoline. The reaction mixture is chilled the precipitate filtered The solid is washed recrystallized from dimethylformamide

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 0.1 mole of 2'-benzoyl-4'-chloroformanilide and 0.15 mole of hydrazine are stirred at room temperature in ethanol. Stirring is continued for 20 hours. The reaction mixture is chilled, and the precipitate filtered. The solid is washed and recrystallized from dimethylformamide to give 3-amino-6-chloro-3,4-dihydro-4-hydroxy-4-phenylquinazoline. The reaction mixture is chilled the precipitate filtered The solid is washed recrystallized from dimethylformamide

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A stirred solution of acetic anhydride (25.3 ml) and 97% formic acid (10.6 ml) is kep at ambient temperature (25°) for 30 minutes, cooled in an ice bath and treated with 3-amino-6-chloro-3,4-dihydro-4-hydroxy-4-phenylquinazoline (12.24 g, 0.0447 mole). The solution is kept at ambient temperature for 18 hours, diluted with acetic acid (25 ml), warmed to the reflux temperature during 1 hour and refluxed for 1.5 hours. The solution is concentrated in vacuo, and the residue is mixed with cold water, made alkaline with sodium hydroxide and extracted with chloroform. The extract is washed with brine, dried over anhydrous sodium sulfate and concentrated. The residue is crystallized from ethylacetate to give 7.76 g of 5-chloro-2-(4H-1,2,4-triazol-4-yl)-benzophenone of melting point 184°-186° C., 0.971 g of melting point 182.5°-184° C., and 0.144 of melting point 181°-182° C. is kep at ambient temperature (25°) for 30 minutes cooled in an ice bath warmed to the reflux temperature during 1 hour refluxed for 1.5 hours The solution is concentrated in vacuo the residue is mixed with cold water extracted with chloroform The extract is washed with brine dried over anhydrous sodium sulfate concentrated The residue is crystallized from ethylacetate

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 0.1 mole of 2'-benzoyl-4'-chloroformanilide and 0.15 mole of hydrazine are stirred at room temperature in ethanol. Stirring is continued for 20 hours. The reaction mixture is chilled, and the precipitate filtered. The solid is washed and recrystallized from dimethylformamide to give 3-amino-6-chloro-3,4-dihydro-4-hydroxy-4-phenylquinazoline. The reaction mixture is chilled the precipitate filtered The solid is washed recrystallized from dimethylformamide

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 0.1 mole of 2'-benzoyl-4'-chloroformanilide and 0.15 mole of hydrazine are stirred at room temperature in ethanol. Stirring is continued for 20 hours. The reaction mixture is chilled, and the precipitate filtered. The solid is washed and recrystallized from dimethylformamide to give 3-amino-6-chloro-3,4-dihydro-4-hydroxy-4-phenylquinazoline. The reaction mixture is chilled the precipitate filtered The solid is washed recrystallized from dimethylformamide

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 0.29 part of 5-chloro-2-dimethylaminomethyleneaminobenzophenone in 4 volume parts of ethanol are added 0.2 volume part of hydrazine hydrate and 0.06 volume part of glacial acetic acid. The mixture is shaken and kept standing at room temperature for about 30 minutes. The resulting crystals are recovered by filtration and washed with ethanol and then dried, whereby 3-amino-6-chloro-3,4-dihydro-4-hydroxy-4-phenylquinazoline is obtained as colorless needles melting at 185° (softening) to 192° C. This compound is identical with the product obtained in Example 1. Yield: 95%. The resulting crystals are recovered by filtration washed with ethanol dried

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 2.7 parts of 5-chloro-2-formamidobenzophenone in 40 volume parts of ethanol is added 2.5 volume parts of hydrazine hydrate, followed by refluxing for 20 minutes. After cooling, the resulting crystals are recovered by filtration and washed with ethanol and ether and then dried. This procedure gives 3-amino-6-chloro-3,4-dihydro-4-hydroxy-4-phenylquinazoline as crystals melting at 189° to 192° C. Yield: 95%. by refluxing for 20 minutes After cooling the resulting crystals are recovered by filtration washed with ethanol and ether dried

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A stirred mixture of 3-amino-6-chloro-3,4-dihydro-4-hydroxy-4-phenylquinazoline (2.74 g. 0.01 mole) in dry tetrahydrofuran (150 ml.) is cooled in an ice bath, under nitrogen, and treated with dry pyridine (1.77 ml., 0.022 mole). This mixture is then treated dropwise, during 1 hour with a solution of β-phthalimidopropionyl chloride (5.23 g., 0.022 mole) in tetrahydrofuran (25 ml.). The mixture is kept in the ice bath for 1 hour and at ambient temperature for 4 hours. It is then poured into cold, dilute aqueous sodium bicarbonate and extracted with chloroform. The extract is washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue is mixed with toluene (165 ml.), treated with trifluoroacetic acid (0.732 ml.) and warmed, under nitrogen at 100°-110° C. for 1.5 hours. The mixture is concentrated in vacuo and the residue mixed with cold water and extracted with chloroform. The extract is washed with brine, dried over anhydrous sodium sulfate and concentrated. The residue is chromatographed on silica gel (300 g) with 1.5% methanol-98.5% chloroform. The product thus obtained is crystallized to give 5-chloro-2-[3-(2-phthalimidoethyl)-4H-1,2,4-triazol-4-yl]benzophenone. is cooled in an ice bath, under nitrogen extracted with chloroform The extract is washed with brine dried over anhydrous sodium sulfate concentrated in vacuo The residue is mixed with toluene (165 ml.) treated with trifluoroacetic acid (0.732 ml.) warmed, under nitrogen at 100°-110° C. for 1.5 hours The mixture is concentrated in vacuo the residue mixed with cold water extracted with chloroform The extract is washed with brine dried over anhydrous sodium sulfate concentrated The residue is chromatographed on silica gel (300 g) with 1.5% methanol-98.5% chloroform The product thus obtained is crystallized

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A stirred solution of acetic anhydride (25.3 ml) and 97% formic acid (10.6 ml) is kep at ambient temperature (25°) for 30 minutes, cooled in an ice bath and treated with 3-amino-6-chloro-3,4-dihydro-4-hydroxy-4-phenylquinazoline (12.24 g, 0.0447 mole). The solution is kept at ambient temperature for 18 hours, diluted with acetic acid (25 ml), warmed to the reflux temperature during 1 hour and refluxed for 1.5 hours. The solution is concentrated in vacuo, and the residue is mixed with cold water, made alkaline with sodium hydroxide and extracted with chloroform. The extract is washed with brine, dried over anhydrous sodium sulfate and concentrated. The residue is crystallized from ethylacetate to give 7.76 g of 5-chloro-2-(4H-1,2,4-triazol-4-yl)-benzophenone of melting point 184°-186° C., 0.971 g of melting point 182.5°-184° C., and 0.144 of melting point 181°-182° C. is kep at ambient temperature (25°) for 30 minutes cooled in an ice bath warmed to the reflux temperature during 1 hour refluxed for 1.5 hours The solution is concentrated in vacuo the residue is mixed with cold water extracted with chloroform The extract is washed with brine dried over anhydrous sodium sulfate concentrated The residue is crystallized from ethylacetate

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 0.1 mole of 2'-benzoyl-4'-chloroformanilide and 0.15 mole of hydrazine are stirred at room temperature in ethanol. Stirring is continued for 20 hours. The reaction mixture is chilled, and the precipitate filtered. The solid is washed and recrystallized from dimethylformamide to give 3-amino-6-chloro-3,4-dihydro-4-hydroxy-4-phenylquinazoline. The reaction mixture is chilled the precipitate filtered The solid is washed recrystallized from dimethylformamide