butane-1-sulfonamide

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: To a solution of 6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinic acid (100 mg, 0.32 mmol) in dichloromethane (5 mL) was added butane-1-sulfonic acid amide (44.2 mg, 0.32 mmol), N,N-dicyclohexylcarbodiimide (67.1 mg, 322 mmol) and 4-dimethylaminopyridine (40.1 mg, 0.32 mmol). The resulting mixture was stirred at room temperature overnight. The mixture was then filtered and the filtrate was concentrated and purified by chromatography (SiO2, heptane:ethyl acetate 100:0 to 0:100) to give the title compound (17 mg, 12%) as a white solid. MS: m/e=428.1 [M−H]−. The mixture was then filtered the filtrate was concentrated purified by chromatography (SiO2, heptane:ethyl acetate 100:0 to 0:100)

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

実験手順: To a solution of 6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinic acid (100 mg, 0.32 mmol) in dichloromethane (5 mL) was added butane-1-sulfonic acid amide (44.2 mg, 0.32 mmol), N,N-dicyclohexylcarbodiimide (67.1 mg, 322 mmol) and 4-dimethylaminopyridine (40.1 mg, 0.32 mmol). The resulting mixture was stirred at room temperature overnight. The mixture was then filtered and the filtrate was concentrated and purified by chromatography (SiO2, heptane:ethyl acetate 100:0 to 0:100) to give the title compound (17 mg, 12%) as a white solid. MS: m/e=428.1 [M−H]−. The mixture was then filtered the filtrate was concentrated purified by chromatography (SiO2, heptane:ethyl acetate 100:0 to 0:100)

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

実験手順: In the same manner as in Example 1, N,N′-carbonyldiimidazole (0.290 g) was added to a mixture of 6-carboxy-1-(2,4-dichlorobenzyl)-3-methyl-2-benzimidazolone (0.314 g) and N,N-dimethylformamide (9 ml), and the mixture was stirred at room temperature for 1 hr. 1-n-Butanesulfonamide (0.246 g) and DBU (0.273 g) were added and the mixture was stirred at 100° C. for 16 hr. The solvent was evaporated and the resulting mixture was extracted with chloroform and water. The organic layer was concentrated and the residue was purified by preparative thin layer chromatography to give 6-(1-n-butanesulfonylcarbamoyl)-1-(2,4-dichlorobenzyl)-3-methyl-2-benzimidazolone (0.123 g). the mixture was stirred at 100° C. for 16 hr The solvent was evaporated the resulting mixture was extracted with chloroform and water The organic layer was concentrated the residue was purified by preparative thin layer chromatography

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of n-butylsulphonamide (500 mg) in DMF (5 ml) was added dropwise to a suspension of sodium hydride (150 mg, 60% dispersion in mineral oil) in DMF (10 ml) and the mixture was stirred for 10 minutes. 4-Methanesulphonyloxymethyl-N-benzyloxycarbonylpiperidine (1.09 g) was added and the mixture heated at 80° C. for 16 hours. The mixture was cooled, poured into water (100 ml) and extracted with ethyl acetate (3×50 ml). The combined organic extracts were washed with water (3×50 ml) and saturated aqueous sodium chloride (50 ml), dried (MgSO4) and concentrated. The residual oil was purified by flash column chromatography, eluting with methanol/dichloromethane (1:99) to give a colourless semi-solid. This mixture was dissolved in warm tetrachloromethane (6 ml) and cooled to give 4-n-butylsulphonylaminomethyl-N-benzyloxycarbonylpiperidine (230 mg) as colourless prisms, mp 83°-85° C. NMR (d6DMSO): δ0.9(3H,t); 0.9-1.1(2H,m); 1.3-1.5(2H,m); 1.5-1.8(5H,m); 2.7-2.9(4H,m); 2.95(2H,m); 4.0(2H,d); 5.1(2H,s); 7.0(1H t); 7.3(5H m). m/e 369(M+H)+ ; 391(M+Na)+ ; calculated for C18H28N2SO4 : C, 58.7; H, 7.7; N, 7.6; found: C, 58.5; H, 7.8; N, 7.6%. The mixture was cooled extracted with ethyl acetate (3×50 ml) The combined organic extracts were washed with water (3×50 ml) and saturated aqueous sodium chloride (50 ml) dried (MgSO4) concentrated The residual oil was purified by flash column chromatography eluting with methanol/dichloromethane (1:99) to give a colourless semi-solid cooled

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of n-butylsulphonamide (500 mg) in DMF (5 ml) was added dropwise to a suspension of sodium hydride (150 mg, 60% dispersion in mineral oil) in DMF (10 ml) and the mixture was stirred for 10 minutes. 4-Methanesulphonyloxymethyl-N-benzyloxycarbonylpiperidine (1.09 g) was added and the mixture heated at 80° C. for 16 hours. The mixture was cooled, poured into water (100 ml) and extracted with ethyl acetate (3×50 ml). The combined organic extracts were washed with water (3×50 ml) and saturated aqueous sodium chloride (50 ml), dried (MgSO4) and concentrated. The residual oil was purified by flash column chromatography, eluting with methanol/dichloromethane (1:99) to give a colourless semi-solid. This mixture was dissolved in warm tetrachloromethane (6 ml) and cooled to give 4-n-butylsulphonylaminomethyl-N-benzyloxycarbonylpiperidine (230 mg) as colourless prisms, mp 83°-85° C. NMR (d6DMSO): δ0.9(3H,t); 0.9-1.1(2H,m); 1.3-1.5(2H,m); 1.5-1.8(5H,m); 2.7-2.9(4H,m); 2.95(2H,m); 4.0(2H,d); 5.1(2H,s); 7.0(1H t); 7.3(5H m). m/e 369(M+H)+ ; 391(M+Na)+ ; calculated for C18H28N2SO4 : C, 58.7; H, 7.7; N, 7.6; found: C, 58.5; H, 7.8; N, 7.6%. The mixture was cooled extracted with ethyl acetate (3×50 ml) The combined organic extracts were washed with water (3×50 ml) and saturated aqueous sodium chloride (50 ml) dried (MgSO4) concentrated The residual oil was purified by flash column chromatography eluting with methanol/dichloromethane (1:99) to give a colourless semi-solid cooled

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

実験手順: To a solution of 6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinic acid (100 mg, 0.32 mmol) in dichloromethane (5 mL) was added butane-1-sulfonic acid amide (44.2 mg, 0.32 mmol), N,N-dicyclohexylcarbodiimide (67.1 mg, 322 mmol) and 4-dimethylaminopyridine (40.1 mg, 0.32 mmol). The resulting mixture was stirred at room temperature overnight. The mixture was then filtered and the filtrate was concentrated and purified by chromatography (SiO2, heptane:ethyl acetate 100:0 to 0:100) to give the title compound (17 mg, 12%) as a white solid. MS: m/e=428.1 [M−H]−. The mixture was then filtered the filtrate was concentrated purified by chromatography (SiO2, heptane:ethyl acetate 100:0 to 0:100)

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

実験手順: To a solution of 6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinic acid (100 mg, 0.32 mmol) in dichloromethane (5 mL) was added butane-1-sulfonic acid amide (44.2 mg, 0.32 mmol), N,N-dicyclohexylcarbodiimide (67.1 mg, 322 mmol) and 4-dimethylaminopyridine (40.1 mg, 0.32 mmol). The resulting mixture was stirred at room temperature overnight. The mixture was then filtered and the filtrate was concentrated and purified by chromatography (SiO2, heptane:ethyl acetate 100:0 to 0:100) to give the title compound (17 mg, 12%) as a white solid. MS: m/e=428.1 [M−H]−. The mixture was then filtered the filtrate was concentrated purified by chromatography (SiO2, heptane:ethyl acetate 100:0 to 0:100)

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

実験手順: To a solution of 6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinic acid (100 mg, 0.32 mmol) in dichloromethane (5 mL) was added butane-1-sulfonic acid amide (44.2 mg, 0.32 mmol), N,N-dicyclohexylcarbodiimide (67.1 mg, 322 mmol) and 4-dimethylaminopyridine (40.1 mg, 0.32 mmol). The resulting mixture was stirred at room temperature overnight. The mixture was then filtered and the filtrate was concentrated and purified by chromatography (SiO2, heptane:ethyl acetate 100:0 to 0:100) to give the title compound (17 mg, 12%) as a white solid. MS: m/e=428.1 [M−H]−. The mixture was then filtered the filtrate was concentrated purified by chromatography (SiO2, heptane:ethyl acetate 100:0 to 0:100)

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

実験手順: To a solution of 6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinic acid (100 mg, 0.32 mmol) in dichloromethane (5 mL) was added butane-1-sulfonic acid amide (44.2 mg, 0.32 mmol), N,N-dicyclohexylcarbodiimide (67.1 mg, 322 mmol) and 4-dimethylaminopyridine (40.1 mg, 0.32 mmol). The resulting mixture was stirred at room temperature overnight. The mixture was then filtered and the filtrate was concentrated and purified by chromatography (SiO2, heptane:ethyl acetate 100:0 to 0:100) to give the title compound (17 mg, 12%) as a white solid. MS: m/e=428.1 [M−H]−. The mixture was then filtered the filtrate was concentrated purified by chromatography (SiO2, heptane:ethyl acetate 100:0 to 0:100)

反応条件: temp:0.00; pressure:0.00; stir: