1-哌啶-4-基-3,4-二氢喹唑啉-2-one

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In this reference example, 16.0 g of 1-benzyl-4-[3,5-dihydro-2(1H)-quinazolinon-1-yl]-piperidine, 4.0 g of 10% Pd-C, 50 ml of 1 N hydrochloric acid, 150 ml of water and 300 ml of methanol are mixed and stirred at 40° C. Hydrogen gas is introduced to the mixture for 5 hours with stirring. Then, the Pd-C is removed by filtration and the filtrate is concentrated. The white crystalline residue is dissolved in 50 ml of water. The solution is adjusted to pH 10 with aqueous 5 N sodium hydroxide and extracted with chloroform. The extract is washed with water, dried and thereafter concentrated. Then, 50 ml of a mixture of ethyl acetate and n-hexane (1:1 by volume) is added to the residue. After trituration, the solid is separated by filtration, washed with the same mixed solvent to obtain 9.9 g of a crude product. The crude product is recrystallized from water-ethanol to obtain 5.1 g of the desired product. with stirring Then, the Pd-C is removed by filtration the filtrate is concentrated The white crystalline residue is dissolved in 50 ml of water extracted with chloroform The extract is washed with water dried concentrated Then, 50 ml of a mixture of ethyl acetate and n-hexane (1:1 by volume) is added to the residue After trituration, the solid is separated by filtration washed with the same mixed solvent to obtain 9.9 g of a crude product The crude product is recrystallized from water-ethanol

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In this reference example, 16.0 g of 1-benzyl-4-[3,5-dihydro-2(1H)-quinazolinon-1-yl]-piperidine, 4.0 g of 10% Pd-C, 50 ml of 1 N hydrochloric acid, 150 ml of water and 300 ml of methanol are mixed and stirred at 40° C. Hydrogen gas is introduced to the mixture for 5 hours with stirring. Then, the Pd-C is removed by filtration and the filtrate is concentrated. The white crystalline residue is dissolved in 50 ml of water. The solution is adjusted to pH 10 with aqueous 5 N sodium hydroxide and extracted with chloroform. The extract is washed with water, dried and thereafter concentrated. Then, 50 ml of a mixture of ethyl acetate and n-hexane (1:1 by volume) is added to the residue. After trituration, the solid is separated by filtration, washed with the same mixed solvent to obtain 9.9 g of a crude product. The crude product is recrystallized from water-ethanol to obtain 5.1 g of the desired product. with stirring Then, the Pd-C is removed by filtration the filtrate is concentrated The white crystalline residue is dissolved in 50 ml of water extracted with chloroform The extract is washed with water dried concentrated Then, 50 ml of a mixture of ethyl acetate and n-hexane (1:1 by volume) is added to the residue After trituration, the solid is separated by filtration washed with the same mixed solvent to obtain 9.9 g of a crude product The crude product is recrystallized from water-ethanol

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

实验步骤: To a solution of 1-(4-piperidinyl)-3,4-dihydroquinazolin-2(1H)-one (680 mg, 1.40 mmol) from Step 5 in DCM (15 mL) was added DIEA (0.366 mL, 2.1 mmol) followed by 2,4-dimethoxybenzoyl chloride (309 mg, 1.54 mmol). The reaction was stirred for 2 h and the solvent was removed under reduced pressure. The residue was dissolved in EtOAc (100 mL) and washed with 5% aqueous citric acid (50 mL) and saturated aqueous NaHCO3 (2×50 mL). The EtOAc layer was dried (MgSO4), filtered, and the solvent was removed under reduced pressure. The residue was purified by pressurized silica gel column chromatography eluting first with 95:5 EtOAc:CHCl3 and then with 95:3:2 EtOAc:CHCl3 :MeOH. The title compound was obtained as a white solid (77% yield). the solvent was removed under reduced pressure The residue was dissolved in EtOAc (100 mL) washed with 5% aqueous citric acid (50 mL) and saturated aqueous NaHCO3 (2×50 mL) The EtOAc layer was dried (MgSO4) filtered the solvent was removed under reduced pressure The residue was purified by pressurized silica gel column chromatography eluting first with 95:5 EtOAc

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

实验步骤: To a solution of 1-(1-benzyl-4-piperidinyl)-3,4-dihydroquinazolin-2(1H)-one (947 g, 295 mmol) from Step 4 in dry dichloroethane (20 mL) was added 1-chloroethyl chloroformate (0.35 mL, 3.2 mmol). The reaction was refluxed for 3 h. The solvent was rmoved under reduced pressure and the residue was dissolved in MeOH (50 mL) and the solution was refluxed for 1 h. The reaction was cooled to ambient temperature, conc. NH4OH (1 mL) was added, and the solvent was removed under reduced pressure. The residue was purified by pressurized silica gel column chromatography using 90:10:1 CHCl3 :MeOH:NH4OH as eluant. 1-(4-Piperidinyl)-3,4-dihydroquinazolin-2(1H)-one was obtained as an oil (48% yield). The reaction was refluxed for 3 h the solution was refluxed for 1 h the solvent was removed under reduced pressure The residue was purified by pressurized silica gel column chromatography

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In this reference example, 16.0 g of 1-benzyl-4-[3,5-dihydro-2(1H)-quinazolinon-1-yl]-piperidine, 4.0 g of 10% Pd-C, 50 ml of 1 N hydrochloric acid, 150 ml of water and 300 ml of methanol are mixed and stirred at 40° C. Hydrogen gas is introduced to the mixture for 5 hours with stirring. Then, the Pd-C is removed by filtration and the filtrate is concentrated. The white crystalline residue is dissolved in 50 ml of water. The solution is adjusted to pH 10 with aqueous 5 N sodium hydroxide and extracted with chloroform. The extract is washed with water, dried and thereafter concentrated. Then, 50 ml of a mixture of ethyl acetate and n-hexane (1:1 by volume) is added to the residue. After trituration, the solid is separated by filtration, washed with the same mixed solvent to obtain 9.9 g of a crude product. The crude product is recrystallized from water-ethanol to obtain 5.1 g of the desired product. with stirring Then, the Pd-C is removed by filtration the filtrate is concentrated The white crystalline residue is dissolved in 50 ml of water extracted with chloroform The extract is washed with water dried concentrated Then, 50 ml of a mixture of ethyl acetate and n-hexane (1:1 by volume) is added to the residue After trituration, the solid is separated by filtration washed with the same mixed solvent to obtain 9.9 g of a crude product The crude product is recrystallized from water-ethanol