N-(3-hydroxyphenyl)methanesulfonamide

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 0.094 g (0.352 mmol) of 2-(chloromethyl)-3-(phenylethynyl)imidazo[1,2-a]pyridine were dissolved in 2 ml of dimethylformamide with magnetic stirring, 121 mg (0.529 mmol) of N-(3-hydroxyphenyl)methanesulfonamide and 0.172 g (0.529 mmol) of cesium carbonate were added. The mixture was stirred at 60° C. for 3 h before being poured onto 15 ml of a saturated NaCl aqueous solution. The aqueous phase was extracted with 2×20 ml of ethyl acetate. The combined organic phases were dried on Na2SO4 which was then removed by filtration. The obtained filtrate was concentrated in vacuo. The crude residue was purified by preparative HPLC and 0.028 g (yield=18%) of N-(3-((3-(phenylethynyl)imidazo[1,2-a]pyridin-2-yl)-methoxy)phenyl)methane sulfonamide were obtained as a white solid. LC-MS: m/z=418 (MH+); UV purity at 254 nm=95%. 1H NMR (300 MHz, DMSO) δ 9.53 (s, 1H), 8.55 (d, J=6.8 Hz, 1H), 7.76-7.57 (m, 3H), 7.54-7.33 (m, 4H), 7.17-7.02 (m, 2H), 6.89 (dd, J=8.0, 1.1 Hz, 1H), 6.79 (t, J=2.1 Hz, 1H), 6.69-6.54 (m, 1H), 5.07 (s, 2H), 3.14 (s, 3H). were added The aqueous phase was extracted with 2×20 ml of ethyl acetate The combined organic phases were dried on Na2SO4 which was then removed by filtration The obtained filtrate was concentrated in vacuo The crude residue was purified by preparative HPLC

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 0.094 g (0.352 mmol) of 2-(chloromethyl)-3-(phenylethynyl)imidazo[1,2-a]pyridine were dissolved in 2 ml of dimethylformamide with magnetic stirring, 121 mg (0.529 mmol) of N-(3-hydroxyphenyl)methanesulfonamide and 0.172 g (0.529 mmol) of cesium carbonate were added. The mixture was stirred at 60° C. for 3 h before being poured onto 15 ml of a saturated NaCl aqueous solution. The aqueous phase was extracted with 2×20 ml of ethyl acetate. The combined organic phases were dried on Na2SO4 which was then removed by filtration. The obtained filtrate was concentrated in vacuo. The crude residue was purified by preparative HPLC and 0.028 g (yield=18%) of N-(3-((3-(phenylethynyl)imidazo[1,2-a]pyridin-2-yl)-methoxy)phenyl)methane sulfonamide were obtained as a white solid. LC-MS: m/z=418 (MH+); UV purity at 254 nm=95%. 1H NMR (300 MHz, DMSO) δ 9.53 (s, 1H), 8.55 (d, J=6.8 Hz, 1H), 7.76-7.57 (m, 3H), 7.54-7.33 (m, 4H), 7.17-7.02 (m, 2H), 6.89 (dd, J=8.0, 1.1 Hz, 1H), 6.79 (t, J=2.1 Hz, 1H), 6.69-6.54 (m, 1H), 5.07 (s, 2H), 3.14 (s, 3H). were added The aqueous phase was extracted with 2×20 ml of ethyl acetate The combined organic phases were dried on Na2SO4 which was then removed by filtration The obtained filtrate was concentrated in vacuo The crude residue was purified by preparative HPLC

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2 g (18.33 mmol) of 3-aminophenol were dissolved in 6 ml of pyridine with magnetic stirring, the mixture was cooled to 10° C. and then 1.8 ml (23.26 mmol) of methanesulfonyl chloride were added. The cold bath was withdrawn and the mixture was stirred at r.t. for 18 h before being diluted with 100 ml of a saturated NaCl aqueous solution. The aqueous phase was extracted with 100 ml of ethyl acetate. The organic phase was washed with 50 ml of a saturated NaHCO3 aqueous solution, extracted with 50 ml of an aqueous solution of NaOH (0.5 N). The basic aqueous phase was washed with 2×100 ml of ethyl acetate and then acidified down to pH 2-3 by adding a 1N HCl aqueous solution. The acidified aqueous phase was extracted with 2×100 ml of ethyl acetate. The combined organic phases were washed with 100 ml of a saturated NaCl aqueous solution and then dried on Na2SO4 which was then removed by filtration. The obtained filtrate was concentrated in vacuo. 3.3 g (yield=80%) of N-(3-hydroxyphenyl)methanesulfonamide were obtained as an oil. LC-MS: m/z=186 (M-H+); UV purity at 254 nm=81%. The cold bath was withdrawn before being diluted with 100 ml of a saturated NaCl aqueous solution The aqueous phase was extracted with 100 ml of ethyl acetate The organic phase was washed with 50 ml of a saturated NaHCO3 aqueous solution extracted with 50 ml of an aqueous solution of NaOH (0.5 N) The basic aqueous phase was washed with 2×100 ml of ethyl acetate by adding a 1N HCl aqueous solution The acidified aqueous phase was extracted with 2×100 ml of ethyl acetate The combined organic phases were washed with 100 ml of a saturated NaCl aqueous solution dried on Na2SO4 which was then removed by filtration The obtained filtrate was concentrated in vacuo

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 0.094 g (0.352 mmol) of 2-(chloromethyl)-3-(phenylethynyl)imidazo[1,2-a]pyridine were dissolved in 2 ml of dimethylformamide with magnetic stirring, 121 mg (0.529 mmol) of N-(3-hydroxyphenyl)methanesulfonamide and 0.172 g (0.529 mmol) of cesium carbonate were added. The mixture was stirred at 60° C. for 3 h before being poured onto 15 ml of a saturated NaCl aqueous solution. The aqueous phase was extracted with 2×20 ml of ethyl acetate. The combined organic phases were dried on Na2SO4 which was then removed by filtration. The obtained filtrate was concentrated in vacuo. The crude residue was purified by preparative HPLC and 0.028 g (yield=18%) of N-(3-((3-(phenylethynyl)imidazo[1,2-a]pyridin-2-yl)-methoxy)phenyl)methane sulfonamide were obtained as a white solid. LC-MS: m/z=418 (MH+); UV purity at 254 nm=95%. 1H NMR (300 MHz, DMSO) δ 9.53 (s, 1H), 8.55 (d, J=6.8 Hz, 1H), 7.76-7.57 (m, 3H), 7.54-7.33 (m, 4H), 7.17-7.02 (m, 2H), 6.89 (dd, J=8.0, 1.1 Hz, 1H), 6.79 (t, J=2.1 Hz, 1H), 6.69-6.54 (m, 1H), 5.07 (s, 2H), 3.14 (s, 3H). were added The aqueous phase was extracted with 2×20 ml of ethyl acetate The combined organic phases were dried on Na2SO4 which was then removed by filtration The obtained filtrate was concentrated in vacuo The crude residue was purified by preparative HPLC

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2 g (18.33 mmol) of 3-aminophenol were dissolved in 6 ml of pyridine with magnetic stirring, the mixture was cooled to 10° C. and then 1.8 ml (23.26 mmol) of methanesulfonyl chloride were added. The cold bath was withdrawn and the mixture was stirred at r.t. for 18 h before being diluted with 100 ml of a saturated NaCl aqueous solution. The aqueous phase was extracted with 100 ml of ethyl acetate. The organic phase was washed with 50 ml of a saturated NaHCO3 aqueous solution, extracted with 50 ml of an aqueous solution of NaOH (0.5 N). The basic aqueous phase was washed with 2×100 ml of ethyl acetate and then acidified down to pH 2-3 by adding a 1N HCl aqueous solution. The acidified aqueous phase was extracted with 2×100 ml of ethyl acetate. The combined organic phases were washed with 100 ml of a saturated NaCl aqueous solution and then dried on Na2SO4 which was then removed by filtration. The obtained filtrate was concentrated in vacuo. 3.3 g (yield=80%) of N-(3-hydroxyphenyl)methanesulfonamide were obtained as an oil. LC-MS: m/z=186 (M-H+); UV purity at 254 nm=81%. The cold bath was withdrawn before being diluted with 100 ml of a saturated NaCl aqueous solution The aqueous phase was extracted with 100 ml of ethyl acetate The organic phase was washed with 50 ml of a saturated NaHCO3 aqueous solution extracted with 50 ml of an aqueous solution of NaOH (0.5 N) The basic aqueous phase was washed with 2×100 ml of ethyl acetate by adding a 1N HCl aqueous solution The acidified aqueous phase was extracted with 2×100 ml of ethyl acetate The combined organic phases were washed with 100 ml of a saturated NaCl aqueous solution dried on Na2SO4 which was then removed by filtration The obtained filtrate was concentrated in vacuo