4-chlorobutanamide

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 6.1 g (0.020 mole) of α,α-bis(4-fluorophenyl)-4-piperidinemethanol, 4.9 g (0.040 mole) of 4-chlorobutanamide, 8.5 g (0.080 mole) of anhydrous sodium carbonate and 0.4 g (0.002 mole) of potassium iodide in 100 mL of N,N-dimethylformamide was stirred at ambient temperature for 24 h. The mixture was poured into 1.5 L of water and extracted twice with 500 mL portions of ethyl acetate. The ethyl acetate fractions were combined, washed with water and brine, dried (MgSO4), and concentrated under reduced pressure to give a dark oil. The oil was purified by column chromatography using 250 g of silica gel on a 65 cm×4 cm column eluted with methanol-methylene chloride (1:2). The fractions containing the desired product were combined and concentrated under reduced pressure. The residue was partitioned between methylene chloride and water. The methylene chloride layer was washed with water and brine, dried (MgSO4) and concentrated under reduced pressure to give a glass. The glass was converted to the oxalic acid salt, and the solid was recrystallized from ethyl acetate/2-propanol to yield 0.7 g (9%) of the title compound as a white solid containing 0.25 mole H2O, mp 177°-179° C. extracted twice with 500 mL portions of ethyl acetate washed with water and brine dried (MgSO4) concentrated under reduced pressure to give a dark oil The oil was purified by column chromatography eluted with methanol-methylene chloride (1:2) The fractions containing the desired product concentrated under reduced pressure The residue was partitioned between methylene chloride and water The methylene chloride layer was washed with water and brine dried (MgSO4) concentrated under reduced pressure to give a glass the solid was recrystallized from ethyl acetate/2-propanol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Analogous reaction of 2-amino-6-aminomethylcarbonylamino-4-(2-hydroxyphenyl)quinazoline with 4-chlorobutyramide gives the compound 2-amino-6-aminomethylcarbonylamino-4-[2-(3-aminocarbonylpropoxy)phenyl]quinazoline (“A61”).

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Analogous reaction of 2-amino-6-aminomethylcarbonylamino-4-(2-hydroxyphenyl)quinazoline with 4-chlorobutyramide gives the compound 2-amino-6-aminomethylcarbonylamino-4-[2-(3-aminocarbonylpropoxy)phenyl]quinazoline (“A61”).

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 6.1 g (0.020 mole) of α,α-bis(4-fluorophenyl)-4-piperidinemethanol, 4.9 g (0.040 mole) of 4-chlorobutanamide, 8.5 g (0.080 mole) of anhydrous sodium carbonate and 0.4 g (0.002 mole) of potassium iodide in 100 mL of N,N-dimethylformamide was stirred at ambient temperature for 24 h. The mixture was poured into 1.5 L of water and extracted twice with 500 mL portions of ethyl acetate. The ethyl acetate fractions were combined, washed with water and brine, dried (MgSO4), and concentrated under reduced pressure to give a dark oil. The oil was purified by column chromatography using 250 g of silica gel on a 65 cm×4 cm column eluted with methanol-methylene chloride (1:2). The fractions containing the desired product were combined and concentrated under reduced pressure. The residue was partitioned between methylene chloride and water. The methylene chloride layer was washed with water and brine, dried (MgSO4) and concentrated under reduced pressure to give a glass. The glass was converted to the oxalic acid salt, and the solid was recrystallized from ethyl acetate/2-propanol to yield 0.7 g (9%) of the title compound as a white solid containing 0.25 mole H2O, mp 177°-179° C. extracted twice with 500 mL portions of ethyl acetate washed with water and brine dried (MgSO4) concentrated under reduced pressure to give a dark oil The oil was purified by column chromatography eluted with methanol-methylene chloride (1:2) The fractions containing the desired product concentrated under reduced pressure The residue was partitioned between methylene chloride and water The methylene chloride layer was washed with water and brine dried (MgSO4) concentrated under reduced pressure to give a glass the solid was recrystallized from ethyl acetate/2-propanol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 6.1 g (0.020 mole) of α,α-bis(4-fluorophenyl)-4-piperidinemethanol, 4.9 g (0.040 mole) of 4-chlorobutanamide, 8.5 g (0.080 mole) of anhydrous sodium carbonate and 0.4 g (0.002 mole) of potassium iodide in 100 mL of N,N-dimethylformamide was stirred at ambient temperature for 24 h. The mixture was poured into 1.5 L of water and extracted twice with 500 mL portions of ethyl acetate. The ethyl acetate fractions were combined, washed with water and brine, dried (MgSO4), and concentrated under reduced pressure to give a dark oil. The oil was purified by column chromatography using 250 g of silica gel on a 65 cm×4 cm column eluted with methanol-methylene chloride (1:2). The fractions containing the desired product were combined and concentrated under reduced pressure. The residue was partitioned between methylene chloride and water. The methylene chloride layer was washed with water and brine, dried (MgSO4) and concentrated under reduced pressure to give a glass. The glass was converted to the oxalic acid salt, and the solid was recrystallized from ethyl acetate/2-propanol to yield 0.7 g (9%) of the title compound as a white solid containing 0.25 mole H2O, mp 177°-179° C. extracted twice with 500 mL portions of ethyl acetate washed with water and brine dried (MgSO4) concentrated under reduced pressure to give a dark oil The oil was purified by column chromatography eluted with methanol-methylene chloride (1:2) The fractions containing the desired product concentrated under reduced pressure The residue was partitioned between methylene chloride and water The methylene chloride layer was washed with water and brine dried (MgSO4) concentrated under reduced pressure to give a glass the solid was recrystallized from ethyl acetate/2-propanol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Analogous reaction of 2-amino-6-aminomethylcarbonylamino-4-(2-hydroxyphenyl)quinazoline with 4-chlorobutyramide gives the compound 2-amino-6-aminomethylcarbonylamino-4-[2-(3-aminocarbonylpropoxy)phenyl]quinazoline (“A61”).

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 6.1 g (0.020 mole) of α,α-bis(4-fluorophenyl)-4-piperidinemethanol, 4.9 g (0.040 mole) of 4-chlorobutanamide, 8.5 g (0.080 mole) of anhydrous sodium carbonate and 0.4 g (0.002 mole) of potassium iodide in 100 mL of N,N-dimethylformamide was stirred at ambient temperature for 24 h. The mixture was poured into 1.5 L of water and extracted twice with 500 mL portions of ethyl acetate. The ethyl acetate fractions were combined, washed with water and brine, dried (MgSO4), and concentrated under reduced pressure to give a dark oil. The oil was purified by column chromatography using 250 g of silica gel on a 65 cm×4 cm column eluted with methanol-methylene chloride (1:2). The fractions containing the desired product were combined and concentrated under reduced pressure. The residue was partitioned between methylene chloride and water. The methylene chloride layer was washed with water and brine, dried (MgSO4) and concentrated under reduced pressure to give a glass. The glass was converted to the oxalic acid salt, and the solid was recrystallized from ethyl acetate/2-propanol to yield 0.7 g (9%) of the title compound as a white solid containing 0.25 mole H2O, mp 177°-179° C. extracted twice with 500 mL portions of ethyl acetate washed with water and brine dried (MgSO4) concentrated under reduced pressure to give a dark oil The oil was purified by column chromatography eluted with methanol-methylene chloride (1:2) The fractions containing the desired product concentrated under reduced pressure The residue was partitioned between methylene chloride and water The methylene chloride layer was washed with water and brine dried (MgSO4) concentrated under reduced pressure to give a glass the solid was recrystallized from ethyl acetate/2-propanol