N-benzyl-3-chloropropane-1-sulfonamide

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

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Benzylamine (1 eq.) was dissolved in anhydrous DCM (0.5 M) and Et3N (1.1 eq.) was added; after cooling at 0° C., 1-chloro-3-propanesulfonyl chloride was slowly added and the mixture was stirred at RT for 20 h. All volatiles were evaporated in vacuo and the residue taken up with Et2O; the precipitate was filtered off and the filtrate was concentrated; addition of PE afforded N-benzyl-3-chloropropane-1-sulfonamide as a white solid (87%). (ES+) m/z 248 (M+H+). Di-tert-butyl dicarbonate (1.5 eq.) was slowly added to an ice-cooled 0.45 M THF solution of N-benzyl-3-chloropropane-1-sulfonamide. DMAP (0.1 eq.) was then added and the reaction stirred overnight at RT. All volatiles were removed in vacuo and the crude diluted with EtOAc, washed with HCl, sat. aq. NaHCO3 and brine. After drying over Na2SO4, all volatiles were evaporated in vacuo and the residual material used in the next step without purification. (ES+) m/z 348, 350 (M+H+). All volatiles were evaporated in vacuo the precipitate was filtered off the filtrate was concentrated addition of PE

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

Procedure: 3-chloro-propylsulfonyl chloride was added dropwise to a stirred solution of benzylamine (1 eq) and triethylamine (1.1 eq) in DCM (0.6 M) at 0° C. The solution was stirred at RT overnight. The solvent was then removed in vacuo, Et2O was added to get a precipitate that was eliminated by filtration, while the filtrate was concentrated in vacuo. Subsequent addition of PE resulted in the formation of a white precipitate that was collected by filtration to afford the title compound (86%). 1H NMR (400 MHz, DMSO-d6, 300 K) δ 2.02-2.09 (m, 2H), 3.03-3.07 (m, 2H), 3.67 (t, J 6.6, 2H), 4.14 (d, J6.1, 2H), 7.25-7.30 (m, 1H), 7.32-7.36 (m, 4H), 7.73 (t, J 6.1, 1H). The solvent was then removed in vacuo, Et2O was added to get a precipitate that was eliminated by filtration, while the filtrate was concentrated in vacuo Subsequent addition of PE resulted in the formation of a white precipitate that was collected by filtration

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Benzylamine (1 eq.) was dissolved in anhydrous DCM (0.5M) and Et3N (1.1 eq.) was added; after cooling at 0° C., 1-chloro-3-propanesulfonyl chloride was slowly added and the mixture was stirred at RT for 20 h. All volatiles were evaporated in vacuo and the residue taken up with Et2O; the precipitate was filtered off and the filtrate was concentrated; addition of PE afforded N-benzyl-3-chloropropane-1-sulfonamide as a white solid (87%). MS (ES+): 248 (M+H+). Di-tert-butyl dicarbonate (1.5 eq.) was slowly added to an ice-cooled 0.45 M THF solution of N-benzyl-3-chloropropane-1-sulfonamide. DMAP (0.1 eq.) was then added and the reaction stirred overnight at RT. All volatiles were removed in vacuo and the crude diluted with EtOAc, washed with HCl, sat. aq. NaHCO3 and brine. After drying over Na2SO4, all volatiles were evaporated in vacuo and the residual material used in the next step without purification. (ES+) m/z 348, 350 (M+H+). All volatiles were evaporated in vacuo the precipitate was filtered off the filtrate was concentrated addition of PE

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Benzylamine (1 eq.) was dissolved in anhydrous DCM (0.5 M) and Et3N (1.1 eq.) was added; after cooling at 0° C., 1-chloro-3-propanesulfonyl chloride was slowly added and the mixture was stirred at RT for 20 h. All volatiles were evaporated in vacuo and the residue taken up with Et2O; the precipitate was filtered off and the filtrate was concentrated; addition of PE afforded N-benzyl-3-chloropropane-1-sulfonamide as a white solid (87%). (ES+) m/z 248 (M+H+). Di-tert-butyl dicarbonate (1.5 eq.) was slowly added to an ice-cooled 0.45 M THF solution of N-benzyl-3-chloropropane-1-sulfonamide. DMAP (0.1 eq.) was then added and the reaction stirred overnight at RT. All volatiles were removed in vacuo and the crude diluted with EtOAc, washed with HCl, sat. aq. NaHCO3 and brine. After drying over Na2SO4, all volatiles were evaporated in vacuo and the residual material used in the next step without purification. (ES+) m/z 348, 350 (M+H+). All volatiles were evaporated in vacuo the precipitate was filtered off the filtrate was concentrated addition of PE

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

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

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of the crude 1-{2-[{2-[(tert-butoxycarbonyl)(methyl)amino]ethyl}(methyl)amino]-2-oxoethyl}-3-cyclohexyl-2-phenyl-1H-indole-6-carboxylic acid in DCM (0.04 M) was treated with DMAP (2.5 eq), N-benzyl-3-chloropropane-1-sulfonamide (1.5 eq) and EDAC.HCl (1.5 eq). The reaction was left stirring at 40° C. overnight. Further DMAP (2.5 eq), N-benzyl-3-chloropropane-1-sulfonamide (1.5 eq) and EDAC.HCl (1.5 eq) were added and the reaction left to stir at 40° C. for another night. The mixture was diluted with DCM and washed with an aqueous solution of HCl (1N), a saturated aqueous solution of NaHCO3 and brine before being dried over Na2SO4, filtered and concentrated in vacuo. The crude was then used in the next step without any further purification. (ES+) m/z 777 (M+H)+ The reaction was left the reaction left to stir at 40° C. for another night washed with an aqueous solution of HCl (1N) a saturated aqueous solution of NaHCO3 and brine before being dried over Na2SO4 filtered concentrated in vacuo The crude was then used in the next step without any further purification

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

Procedure: 3-chloro-propylsulfonyl chloride was added dropwise to a stirred solution of benzylamine (1 eq) and triethylamine (1.1 eq) in DCM (0.6 M) at 0° C. The solution was stirred at RT overnight. The solvent was then removed in vacuo, Et2O was added to get a precipitate that was eliminated by filtration, while the filtrate was concentrated in vacuo. Subsequent addition of PE resulted in the formation of a white precipitate that was collected by filtration to afford the title compound (86%). 1H NMR (400 MHz, DMSO-d6, 300 K) δ 2.02-2.09 (m, 2H), 3.03-3.07 (m, 2H), 3.67 (t, J 6.6, 2H), 4.14 (d, J 6.1, 2H), 7.25-7.30 (m, 1H), 7.32-7.36 (m, 4H), 7.73 (t, J 6.1, 1H). The solvent was then removed in vacuo, Et2O was added to get a precipitate that was eliminated by filtration, while the filtrate was concentrated in vacuo Subsequent addition of PE resulted in the formation of a white precipitate that was collected by filtration

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Benzylamine (1 eq.) was dissolved in anhydrous DCM (0.5 M) and Et3N (1.1 eq.) was added; after cooling at 0° C., 1-chloro-3-propanesulfonyl chloride was slowly added and the mixture was stirred at RT for 20 h. All volatiles were evaporated in vacuo and the residue taken up with Et2O; the precipitate was filtered off and the filtrate was concentrated; addition of PE afforded N-benzyl-3-chloropropane-1-sulfonamide as a white solid (87%). (ES+) m/z 248 (M+H+). Di-tert-butyl dicarbonate (1.5 eq.) was slowly added to an ice-cooled 0.45 M THF solution of N-benzyl-3-chloropropane-1-sulfonamide. DMAP (0.1 eq.) was then added and the reaction stirred overnight at RT. All volatiles were removed in vacuo and the crude diluted with EtOAc, washed with HCl, sat. aq. NaHCO3 and brine. After drying over Na2SO4, all volatiles were evaporated in vacuo and the residual material used in the next step without purification. (ES+) m/z 348, 350 (M+H+). All volatiles were evaporated in vacuo the precipitate was filtered off the filtrate was concentrated addition of PE

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Benzylamine (1 eq.) was dissolved in anhydrous DCM (0.5 M) and Et3N (1.1 eq.) was added; after cooling at 0° C., 1-chloro-3-propanesulfonyl chloride was slowly added and the mixture was stirred at RT for 20 h. All volatiles were evaporated in vacuo and the residue taken up with Et2O; the precipitate was filtered off and the filtrate was concentrated; addition of PE afforded N-benzyl-3-chloropropane-1-sulfonamide as a white solid (87%). (ES+) m/z 248 (M+H+). Di-tert-butyl dicarbonate (1.5 eq.) was slowly added to an ice-cooled 0.45 M THF solution of N-benzyl-3-chloropropane-1-sulfonamide. DMAP (0.1 eq.) was then added and the reaction stirred overnight at RT. All volatiles were removed in vacuo and the crude diluted with EtOAc, washed with HCl, sat. aq. NaHCO3 and brine. After drying over Na2SO4, all volatiles were evaporated in vacuo and the residual material used in the next step without purification. (ES+) m/z 348, 350 (M+H+). All volatiles were evaporated in vacuo the precipitate was filtered off the filtrate was concentrated addition of PE

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

Procedure: 3-chloro-propylsulfonyl chloride was added dropwise to a stirred solution of benzylamine (1 eq) and triethylamine (1.1 eq) in DCM (0.6 M) at 0° C. The solution was stirred at RT overnight. The solvent was then removed in vacuo, Et2O was added to get a precipitate that was eliminated by filtration, while the filtrate was concentrated in vacuo. Subsequent addition of PE resulted in the formation of a white precipitate that was collected by filtration to afford the title compound (86%). 1H NMR (400 MHz, DMSO-d6, 300 K) δ 2.02-2.09 (m, 2H), 3.03-3.07 (m, 2H), 3.67 (t, J 6.6, 2H), 4.14 (d, J6.1, 2H), 7.25-7.30 (m, 1H), 7.32-7.36 (m, 4H), 7.73 (t, J 6.1, 1H). The solvent was then removed in vacuo, Et2O was added to get a precipitate that was eliminated by filtration, while the filtrate was concentrated in vacuo Subsequent addition of PE resulted in the formation of a white precipitate that was collected by filtration