methyl N-(4-aminophenyl)sulfonylcarbamate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: A solution of methyl 4-aminophenylsulfonylcarbamate (50 mg, 0.2 mmol), N,N-diisopropylethylamine (35 L, 0.2 mmol), 3,4-dichlorobenzylisocyanate (30 L, 0.2 mmol) in acetonitrile was stirred under an N2 atmosphere for 19 h. The mixture was concentrated and the residue purified by reverse phase HPLC using 10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA) to give methyl 4-(3-(3,4-dichlorobenzyl)ureido)phenylsulfonylcarbamate. LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=431.01; tR=2.9 min. The mixture was concentrated the residue purified by reverse phase

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

実験手順: To a stirring suspension of the methyl 4-aminophenylsulfonylcarbamate (111 mg, 0.48 mmol) and CH2Cl2 (1 mL) under N2, at 0° C., was added trimethylaluminum (0.24 mL, 0.48 mmol) dropwise over 20 minutes. The solution was stirred at ambient temperature for 30 minutes. The solution was cooled to 0° C. followed by the dropwise addition of (S)-3-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)dihydrofuran-2(3H)-one (100 mg, 0.40 mmol) in CH2Cl2 (1.0 mL) over 30 minutes. The solution was stirred at ambient temperature for 19 h. The solution was cooled to 0° C. and quenched by slow addition of aqueous 1.0 M HCl. The organic portion was washed with 1.0 N aqueous HCl (2×1.0 mL) and evaporated to dryness under reduced pressure. The crude product of (R)-methyl 4-(2-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)-4-hydroxybutanamido)phenylsulfonylcarbamate was used without purification in the next step. The solution was cooled to 0° C. The solution was stirred at ambient temperature for 19 h The solution was cooled to 0° C. quenched by slow addition of aqueous 1.0 M HCl The organic portion was washed with 1.0 N aqueous HCl (2×1.0 mL) evaporated to dryness under reduced pressure The crude product of (R)-methyl 4-(2-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)-4-hydroxybutanamido)phenylsulfonylcarbamate was used without purification in the next step

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: A solution of methyl 4-aminophenylsulfonylcarbamate (50 mg, 0.2 mmol), N,N-diisopropylethylamine (35 L, 0.2 mmol), 3,4-dichlorobenzylisocyanate (30 L, 0.2 mmol) in acetonitrile was stirred under an N2 atmosphere for 19 h. The mixture was concentrated and the residue purified by reverse phase HPLC using 10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA) to give methyl 4-(3-(3,4-dichlorobenzyl)ureido)phenylsulfonylcarbamate. LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=431.01; tR=2.9 min. The mixture was concentrated the residue purified by reverse phase

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

実験手順: A solution of methyl 4-aminophenylsulfonylcarbamate (50 mg, 0.2 mmol), N,N-diisopropylethylamine (35 L, 0.2 mmol), 3,4-dichlorobenzylisocyanate (30 L, 0.2 mmol) in acetonitrile was stirred under an N2 atmosphere for 19 h. The mixture was concentrated and the residue purified by reverse phase HPLC using 10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA) to give methyl 4-(3-(3,4-dichlorobenzyl)ureido)phenylsulfonylcarbamate. LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=431.01; tR=2.9 min. The mixture was concentrated the residue purified by reverse phase

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

実験手順: To a stirring suspension of the methyl 4-aminophenylsulfonylcarbamate (111 mg, 0.48 mmol) and CH2Cl2 (1 mL) under N2, at 0° C., was added trimethylaluminum (0.24 mL, 0.48 mmol) dropwise over 20 minutes. The solution was stirred at ambient temperature for 30 minutes. The solution was cooled to 0° C. followed by the dropwise addition of (S)-3-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)dihydrofuran-2(3H)-one (100 mg, 0.40 mmol) in CH2Cl2 (1.0 mL) over 30 minutes. The solution was stirred at ambient temperature for 19 h. The solution was cooled to 0° C. and quenched by slow addition of aqueous 1.0 M HCl. The organic portion was washed with 1.0 N aqueous HCl (2×1.0 mL) and evaporated to dryness under reduced pressure. The crude product of (R)-methyl 4-(2-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)-4-hydroxybutanamido)phenylsulfonylcarbamate was used without purification in the next step. The solution was cooled to 0° C. The solution was stirred at ambient temperature for 19 h The solution was cooled to 0° C. quenched by slow addition of aqueous 1.0 M HCl The organic portion was washed with 1.0 N aqueous HCl (2×1.0 mL) evaporated to dryness under reduced pressure The crude product of (R)-methyl 4-(2-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)-4-hydroxybutanamido)phenylsulfonylcarbamate was used without purification in the next step

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

実験手順: To a stirring suspension of the methyl 4-aminophenylsulfonylcarbamate (111 mg, 0.48 mmol) and CH2Cl2 (1 mL) under N2, at 0° C., was added trimethylaluminum (0.24 mL, 0.48 mmol) dropwise over 20 minutes. The solution was stirred at ambient temperature for 30 minutes. The solution was cooled to 0° C. followed by the dropwise addition of (S)-3-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)dihydrofuran-2(3H)-one (100 mg, 0.40 mmol) in CH2Cl2 (1.0 mL) over 30 minutes. The solution was stirred at ambient temperature for 19 h. The solution was cooled to 0° C. and quenched by slow addition of aqueous 1.0 M HCl. The organic portion was washed with 1.0 N aqueous HCl (2×1.0 mL) and evaporated to dryness under reduced pressure. The crude product of (R)-methyl 4-(2-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)-4-hydroxybutanamido)phenylsulfonylcarbamate was used without purification in the next step. The solution was cooled to 0° C. The solution was stirred at ambient temperature for 19 h The solution was cooled to 0° C. quenched by slow addition of aqueous 1.0 M HCl The organic portion was washed with 1.0 N aqueous HCl (2×1.0 mL) evaporated to dryness under reduced pressure The crude product of (R)-methyl 4-(2-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)-4-hydroxybutanamido)phenylsulfonylcarbamate was used without purification in the next step

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

実験手順: A solution of methyl 4-aminophenylsulfonylcarbamate (50 mg, 0.2 mmol), N,N-diisopropylethylamine (35 L, 0.2 mmol), 3,4-dichlorobenzylisocyanate (30 L, 0.2 mmol) in acetonitrile was stirred under an N2 atmosphere for 19 h. The mixture was concentrated and the residue purified by reverse phase HPLC using 10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA) to give methyl 4-(3-(3,4-dichlorobenzyl)ureido)phenylsulfonylcarbamate. LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=431.01; tR=2.9 min. The mixture was concentrated the residue purified by reverse phase

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

実験手順: To a stirring suspension of the methyl 4-aminophenylsulfonylcarbamate (111 mg, 0.48 mmol) and CH2Cl2 (1 mL) under N2, at 0° C., was added trimethylaluminum (0.24 mL, 0.48 mmol) dropwise over 20 minutes. The solution was stirred at ambient temperature for 30 minutes. The solution was cooled to 0° C. followed by the dropwise addition of (S)-3-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)dihydrofuran-2(3H)-one (100 mg, 0.40 mmol) in CH2Cl2 (1.0 mL) over 30 minutes. The solution was stirred at ambient temperature for 19 h. The solution was cooled to 0° C. and quenched by slow addition of aqueous 1.0 M HCl. The organic portion was washed with 1.0 N aqueous HCl (2×1.0 mL) and evaporated to dryness under reduced pressure. The crude product of (R)-methyl 4-(2-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)-4-hydroxybutanamido)phenylsulfonylcarbamate was used without purification in the next step. The solution was cooled to 0° C. The solution was stirred at ambient temperature for 19 h The solution was cooled to 0° C. quenched by slow addition of aqueous 1.0 M HCl The organic portion was washed with 1.0 N aqueous HCl (2×1.0 mL) evaporated to dryness under reduced pressure The crude product of (R)-methyl 4-(2-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)-4-hydroxybutanamido)phenylsulfonylcarbamate was used without purification in the next step