N,N-dipropylpropan-1-amine

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

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

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

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

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

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

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

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

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

Procedure: To a suspension of 1-methyl-4-chloro-2(1H)quinazolinone (4 g), tri(n-propyl)amine (7.2 g) and dioxane (20 ml) was added 3-[4-(diphenylmethyl)piperazin-1-yl]propylamine (3.5 g) and the mixture was stirred for 1.5 hours at ambient temperature. The reaction mixture was concentrated in vacuo and to the residue was added water. After the aqueous layer was made basic with 1N potassium hydroxide aqueous solution, the mixture was extracted twice with chloroform. The chloroform layer was washed with 0.2N potassium hydroxide aqueous solution, with water and with saturated sodium chloride aqueous solution respectively, dried over anhydrous magnesium sulfate and then concentrated in vacuo. After the residue was dissolved in toluene, remaining tri(n-propyl)amine was removed by evaporation in vacuo. This procedure was carried out further twice and then the residual oil was purified by subjecting to a column chromatography on silica gel (70 g) using 2% methanol in chloroform for elution to give a crystal, which was recrystallized from a mixture of ethyl acetate and hexane to give 1-methyl-4-[ 3-{4-(diphenylmethyl)piperazin-1-yl}propylamino]-2(1H)-quinazolinone (2.4 g). The reaction mixture was concentrated in vacuo and to the residue was added water the mixture was extracted twice with chloroform The chloroform layer was washed with 0.2N potassium hydroxide aqueous solution, with water and with saturated sodium chloride aqueous solution respectively dried over anhydrous magnesium sulfate concentrated in vacuo After the residue was dissolved in toluene was removed by evaporation in vacuo the residual oil was purified for elution to give a crystal, which was recrystallized from a mixture of ethyl acetate and hexane

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

Procedure: A mixture of 4,6-diaminoquinazoline hydrochloride (10 g) and tripropylamine (26.4 g) in dry pyridine (100 ml) was stirred in an ice-bath for 20 minutes. To the mixture was added dropwise during 1.5 hours 3-cyclopentylpropionyl chloride (12.2 g). The mixture was stirred in an ice-bath for 1.5 hours. Crushed ice was added to the reaction mixture. The mixture was stirred for 5 minutes and concentrated under reduced pressure. After addition of water, sodium hydrogen carbonate was added in small portions to the mixture to give precipitates which were separated by filtration, washed with water and dried. The crude crystals were dissolved in a mixture of chloroform and methanol under heating. After the filtration of insoluble materials, the filtrate was treated with activated charcoal and concentrated under reduced pressure to give a residue. The residue was suspended in ethyl acetate. The suspension was stirred for 1 hour under heating and filtered to give crystalline 4-amino-6-(3-cyclopentylpropionamido)quinazoline (7.2 g). The mixture was stirred in an ice-bath for 1.5 hours Crushed ice was added to the reaction mixture The mixture was stirred for 5 minutes concentrated under reduced pressure After addition of water, sodium hydrogen carbonate was added in small portions to the mixture to give precipitates which were separated by filtration washed with water dried The crude crystals were dissolved in a mixture of chloroform and methanol under heating After the filtration of insoluble materials the filtrate was treated with activated charcoal concentrated under reduced pressure to give a residue The suspension was stirred for 1 hour under heating filtered

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

Procedure: A mixture of 4,6-diaminoquinazoline hydrochloride (12 g) and tripropylamine (31.7 g) in dry pyridine (120 ml) was stirred in an ice-bath for 1 hour. Cyclohexanecarbonyl chloride (12.1 g) was added dropwise during 4 hours and 20 minutes to the mixture at 70° C. The mixture was stirred for additional 1 hour at 5° C. Crushed ice was added to the reaction mixture. The mixture was stirred for 1 hour and concentrated under reduced pressure. After addition of water, the mixture was adjusted to pH 8 with sodium hydrogen carbonate to give precipitates which were separated by filtration, washed with water and dried. The precipitates were dissolved in a mixture of chloroform and methanol under heating. Insoluble materials were removed by filtration. The filtrate was concentrated under reduced pressure to give crystalline 4-amino-6-cyclohexanecarboxamidoquinazoline (9.25 g). The mixture was stirred for additional 1 hour at 5° C Crushed ice was added to the reaction mixture The mixture was stirred for 1 hour concentrated under reduced pressure After addition of water to give precipitates which were separated by filtration washed with water dried The precipitates were dissolved in a mixture of chloroform and methanol under heating Insoluble materials were removed by filtration The filtrate was concentrated under reduced pressure

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

Procedure: To a mixture of 4,6-diaminoquinazoline hydrochloride (1.97 g), tripropylamine (2.60 g) and dry pyridine (20 ml) in an ice-bath was added dropwise during 10 minutes 2-ethylbutyryl chloride (1.75 g). The mixture was stirred for 3 hours at the same temperature. Crushed ice was added to the reaction mixture. The mixture was stirred for 5 minutes and concentrated under reduced pressure. After the addition of water (50 ml), sodium hydrogen carbonate (3.36 g) was added in small portions to the residue to give precipitates which were separated by filtration, washed with water and dried. The crude crystals were dissolved in a mixture of chloroform and methanol under heating. After insoluble materials were removed by filtration, the filtrate was concentrated under reduced pressure to give a residue, which was suspended in ethyl acetate. After stirring under heating, the suspension was filtered to give crystalline 4-amino-6-(2-ethylbutyramido)quinazoline (1.20 g). Crushed ice was added to the reaction mixture The mixture was stirred for 5 minutes concentrated under reduced pressure After the addition of water (50 ml), sodium hydrogen carbonate (3.36 g) was added in small portions to the residue to give precipitates which were separated by filtration washed with water dried The crude crystals were dissolved in a mixture of chloroform and methanol under heating After insoluble materials were removed by filtration the filtrate was concentrated under reduced pressure to give a residue, which After stirring under heating the suspension was filtered