4-(2-胺乙基)硫代吗啉

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Place 5-(2-fluoro-4-formylphenoxy)pyridine-2-carboxamide (Example 403, Part B) (0.650 g, 2.50 mmol), 2-thiomorpholin-4-ylethylamine (0.402 g, 2.75 mmol) and 3 Å molecular sieves in a vial. Add methanol (12 mL), cap and stir overnight. Add NaBH4 (slight excess) and stir until the gasses stop evolving. Load the reaction mixture directly onto a 25 g ISCO® pre-load column. Dry the column in a vacuum oven at room temperature. Purify by eluting through a 40 g ISCO® column with 0% to 30% (2.0 M NH3 in methanol) in ethyl acetate to give the title compound (0.792 g, 81%): TOF MS ES+ 391.2 (M+H)+, HRMS calcd for C19H24N4O2FS 391.1604 (M+H)+, found 391.1594, time 0.48 min; HPLC [YMC-Pro pack C-18 (150×4.6 mm, S-5 microm), 0.05% TFA/acetonitrile in 0.05% TFA/water at 1.0 mL/min, 10-20% over 5 min, 20-95% over 18], tR=6.7 min, 100% purity. Dry the column in a vacuum oven at room temperature Purify by eluting through a 40 g ISCO® column with 0% to 30% (2.0 M NH3 in methanol) in ethyl acetate

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To 150 ml of methylene chloride under nitrogen atmosphere add 3.1 g (14.3 mmole) of 4-thiomorpholinethanamine and 4.42 g (43.6 mmole) of triethylamine. Stir the mixture at ambient temperature for 1 hour, then cool the mixture to -10° C. To the cooled mixture add slowly 3.67 g (15.1 mmole) of 4-[(methylsulfonyl)amino]benzoyl chloride, keeping the temperature below 5° C. When the addition is complete, allow the reaction mixture to stir at ambient temperature. Monitor the progress of the reaction by thin layer chromatography on silica gel (acetonitrile:ammonium hydroxide, 9:1). Upon completion of the reaction, remove the solvent in vacuo. To the resulting solid add 50 ml of water. To the mixture add 50% sodium hydroxide until pH of 14 is reached. Wash the aqueous layer with 3×50 ml of diethyl ether. Add concentrated hydrochloric acid until a white precipitate forms (pH=8.5). Filter the solid and recrystallize from methanol/ethanol to yield the title compound. cool the mixture to -10° C the temperature below 5° C When the addition to stir at ambient temperature Monitor the progress of the reaction by thin layer chromatography on silica gel (acetonitrile:ammonium hydroxide, 9:1) Upon completion of the reaction remove the solvent in vacuo To the resulting solid add 50 ml of water To the mixture add 50% sodium hydroxide until pH of 14 Wash the aqueous layer with 3×50 ml of diethyl ether Add concentrated hydrochloric acid until a white precipitate forms (pH=8.5) Filter the solid recrystallize from methanol/ethanol

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To 150 ml of methylene chloride under nitrogen atmosphere add 3.1 g (14.3 mmole) of 4-thiomorpholinethanamine and 4.42 g (43.6 mmole) of triethylamine. Stir the mixture at ambient temperature for 1 hour, then cool the mixture to -10° C. To the cooled mixture add slowly 3.67 g (15.1 mmole) of 4-[(methylsulfonyl)amino]benzoyl chloride, keeping the temperature below 5° C. When the addition is complete, allow the reaction mixture to stir at ambient temperature. Monitor the progress of the reaction by thin layer chromatography on silica gel (acetonitrile:ammonium hydroxide, 9:1). Upon completion of the reaction, remove the solvent in vacuo. To the resulting solid add 50 ml of water. To the mixture add 50% sodium hydroxide until pH of 14 is reached. Wash the aqueous layer with 3×50 ml of diethyl ether. Add concentrated hydrochloric acid until a white precipitate forms (pH=8.5). Filter the solid and recrystallize from methanol/ethanol to yield the title compound. cool the mixture to -10° C the temperature below 5° C When the addition to stir at ambient temperature Monitor the progress of the reaction by thin layer chromatography on silica gel (acetonitrile:ammonium hydroxide, 9:1) Upon completion of the reaction remove the solvent in vacuo To the resulting solid add 50 ml of water To the mixture add 50% sodium hydroxide until pH of 14 Wash the aqueous layer with 3×50 ml of diethyl ether Add concentrated hydrochloric acid until a white precipitate forms (pH=8.5) Filter the solid recrystallize from methanol/ethanol

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Place 5-(2-fluoro-4-formylphenoxy)pyridine-2-carboxamide (Example 403, Part B) (0.650 g, 2.50 mmol), 2-thiomorpholin-4-ylethylamine (0.402 g, 2.75 mmol) and 3 Å molecular sieves in a vial. Add methanol (12 mL), cap and stir overnight. Add NaBH4 (slight excess) and stir until the gasses stop evolving. Load the reaction mixture directly onto a 25 g ISCO® pre-load column. Dry the column in a vacuum oven at room temperature. Purify by eluting through a 40 g ISCO® column with 0% to 30% (2.0 M NH3 in methanol) in ethyl acetate to give the title compound (0.792 g, 81%): TOF MS ES+ 391.2 (M+H)+, HRMS calcd for C19H24N4O2FS 391.1604 (M+H)+, found 391.1594, time 0.48 min; HPLC [YMC-Pro pack C-18 (150×4.6 mm, S-5 microm), 0.05% TFA/acetonitrile in 0.05% TFA/water at 1.0 mL/min, 10-20% over 5 min, 20-95% over 18], tR=6.7 min, 100% purity. Dry the column in a vacuum oven at room temperature Purify by eluting through a 40 g ISCO® column with 0% to 30% (2.0 M NH3 in methanol) in ethyl acetate

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Place 5-(2-fluoro-4-formylphenoxy)pyridine-2-carboxamide (Example 403, Part B) (0.650 g, 2.50 mmol), 2-thiomorpholin-4-ylethylamine (0.402 g, 2.75 mmol) and 3 {acute over (Å)} molecular sieves in a vial. Add methanol (12 mL), cap and stir overnight. Add NaBH4 (slight excess) and stir until the gasses stop evolving. Load the reaction mixture directly onto a 25 g ISCO® pre-load column. Dry the column in a vacuum oven at room temperature. Purify by eluting through a 40 g ISCO® column with 0% to 30% (2.0 M NH3 in methanol) in ethyl acetate to give the title compound (0.792 g, 81%): TOF MS ES+ 391.2 (M+H)+, HRMS calcd for C19H24N4O2FS 391.1604 (M+H)+, found 391.1594, time 0.48 min; HPLC [YMC-Pro pack C-18 (150×4.6 mm, S-5 microm), 0.05% TFA/acetonitrile in 0.05% TFA/water at 1.0 mL/min, 10-20% over 5 min, 20-95% over 18], tR=6.7 min, 100% purity. Dry the column in a vacuum oven at room temperature Purify by eluting through a 40 g ISCO® column with 0% to 30% (2.0 M NH3 in methanol) in ethyl acetate

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Place 5-(2-fluoro-4-formylphenoxy)pyridine-2-carboxamide (Example 403, Part B) (0.650 g, 2.50 mmol), 2-thiomorpholin-4-ylethylamine (0.402 g, 2.75 mmol) and 3 Å molecular sieves in a vial. Add methanol (12 mL), cap and stir overnight. Add NaBH4 (slight excess) and stir until the gasses stop evolving. Load the reaction mixture directly onto a 25 g ISCO® pre-load column. Dry the column in a vacuum oven at room temperature. Purify by eluting through a 40 g ISCO® column with 0% to 30% (2.0 M NH3 in methanol) in ethyl acetate to give the title compound (0.792 g, 81%): TOF MS ES+ 391.2 (M+H)+, HRMS calcd for C19H24N4O2FS 391.1604 (M+H)+, found 391.1594, time 0.48 min; HPLC [YMC-Pro pack C-18 (150×4.6 mm, S-5 microm), 0.05% TFA/acetonitrile in 0.05% TFA/water at 1.0 mL/min, 10-20% over 5 min, 20-95% over 18], tR=6.7 min, 100% purity. Dry the column in a vacuum oven at room temperature Purify by eluting through a 40 g ISCO® column with 0% to 30% (2.0 M NH3 in methanol) in ethyl acetate

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Place 5-(2-fluoro-4-formylphenoxy)pyridine-2-carboxamide (Example 403, Part B) (0.650 g, 2.50 mmol), 2-thiomorpholin-4-ylethylamine (0.402 g, 2.75 mmol) and 3 {acute over (Å)} molecular sieves in a vial. Add methanol (12 mL), cap and stir overnight. Add NaBH4 (slight excess) and stir until the gasses stop evolving. Load the reaction mixture directly onto a 25 g ISCO® pre-load column. Dry the column in a vacuum oven at room temperature. Purify by eluting through a 40 g ISCO® column with 0% to 30% (2.0 M NH3 in methanol) in ethyl acetate to give the title compound (0.792 g, 81%): TOF MS ES+ 391.2 (M+H)+, HRMS calcd for C19H24N4O2FS 391.1604 (M+H)+, found 391.1594, time 0.48 min; HPLC [YMC-Pro pack C-18 (150×4.6 mm, S-5 microm), 0.05% TFA/acetonitrile in 0.05% TFA/water at 1.0 mL/min, 10-20% over 5 min, 20-95% over 18], tR=6.7 min, 100% purity. Dry the column in a vacuum oven at room temperature Purify by eluting through a 40 g ISCO® column with 0% to 30% (2.0 M NH3 in methanol) in ethyl acetate

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To 150 ml of methylene chloride under nitrogen atmosphere add 3.1g (14.3 mmole) of 4-thiomorpholinethanamine and 4.42 g (43.6 mmole) of triethylamine. Stir the mixture at ambient temperature for 1 hour, then cool the mixture to -10° C. To the cooled mixture add slowly 3.67 g (15.1 mmole) of 4-[(methylsulfonyl)amino]benzoyl chloride, keeping the temperature below 5° C. When the addition is complete, allow the reaction mixture to stir at ambient temperature. Monitor the progress of the reaction by thin layer chromatography on silica gel (acetonitrile:ammonium hydroxide, 9:1). Upon completion of the reaction, remove the solvent in vacuo. To the resulting solid add 50 ml of water. To the mixture add 50% sodium hydroxide until pH of 14 is reached. Wash the aqueous layer with 3×50 ml of diethyl ether. Add concentrated hydrochloric acid until a white precipitate forms (pH=8.5). Filter the solid and recrystallize from methanol/ethanol to yield the title compound. cool the mixture to -10° C the temperature below 5° C When the addition to stir at ambient temperature Monitor the progress of the reaction by thin layer chromatography on silica gel (acetonitrile:ammonium hydroxide, 9:1) Upon completion of the reaction remove the solvent in vacuo To the resulting solid add 50 ml of water To the mixture add 50% sodium hydroxide until pH of 14 Wash the aqueous layer with 3×50 ml of diethyl ether Add concentrated hydrochloric acid until a white precipitate forms (pH=8.5) Filter the solid recrystallize from methanol/ethanol

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Place 5-(2-fluoro-4-formylphenoxy)pyridine-2-carboxamide (Example 403, Part B) (0.650 g, 2.50 mmol), 2-thiomorpholin-4-ylethylamine (0.402 g, 2.75 mmol) and 3 Å molecular sieves in a vial. Add methanol (12 mL), cap and stir overnight. Add NaBH4 (slight excess) and stir until the gasses stop evolving. Load the reaction mixture directly onto a 25 g ISCO® pre-load column. Dry the column in a vacuum oven at room temperature. Purify by eluting through a 40 g ISCO® column with 0% to 30% (2.0 M NH3 in methanol) in ethyl acetate to give the title compound (0.792 g, 81%): TOF MS ES+ 391.2 (M+H)+, HRMS calcd for C19H24N4O2FS 391.1604 (M+H)+, found 391.1594, time 0.48 min; HPLC [YMC-Pro pack C-18 (150×4.6 mm, S-5 microm), 0.05% TFA/acetonitrile in 0.05% TFA/water at 1.0 mL/min, 10-20% over 5 min, 20-95% over 18], tR=6.7 min, 100% purity. Dry the column in a vacuum oven at room temperature Purify by eluting through a 40 g ISCO® column with 0% to 30% (2.0 M NH3 in methanol) in ethyl acetate

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To 150 ml of methylene chloride under nitrogen atmosphere add 3.1 g (14.3 mmole) of 4-thiomorpholinethanamine and 4.42 g (43.6 mmole) of triethylamine. Stir the mixture at ambient temperature for 1 hour, then cool the mixture to -10° C. To the cooled mixture add slowly 3.67 g (15.1 mmole) of 4-[(methylsulfonyl)amino]benzoyl chloride, keeping the temperature below 5° C. When the addition is complete, allow the reaction mixture to stir at ambient temperature. Monitor the progress of the reaction by thin layer chromatography on silica gel (acetonitrile:ammonium hydroxide, 9:1). Upon completion of the reaction, remove the solvent in vacuo. To the resulting solid add 50 ml of water. To the mixture add 50% sodium hydroxide until pH of 14 is reached. Wash the aqueous layer with 3×50 ml of diethyl ether. Add concentrated hydrochloric acid until a white precipitate forms (pH=8.5). Filter the solid and recrystallize from methanol/ethanol to yield the title compound. cool the mixture to -10° C the temperature below 5° C When the addition to stir at ambient temperature Monitor the progress of the reaction by thin layer chromatography on silica gel (acetonitrile:ammonium hydroxide, 9:1) Upon completion of the reaction remove the solvent in vacuo To the resulting solid add 50 ml of water To the mixture add 50% sodium hydroxide until pH of 14 Wash the aqueous layer with 3×50 ml of diethyl ether Add concentrated hydrochloric acid until a white precipitate forms (pH=8.5) Filter the solid recrystallize from methanol/ethanol

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Place 5-(2-fluoro-4-formylphenoxy)pyridine-2-carboxamide (Example 403, Part B) (0.650 g, 2.50 mmol), 2-thiomorpholin-4-ylethylamine (0.402 g, 2.75 mmol) and 3 {acute over (Å)} molecular sieves in a vial. Add methanol (12 mL), cap and stir overnight. Add NaBH4 (slight excess) and stir until the gasses stop evolving. Load the reaction mixture directly onto a 25 g ISCO® pre-load column. Dry the column in a vacuum oven at room temperature. Purify by eluting through a 40 g ISCO® column with 0% to 30% (2.0 M NH3 in methanol) in ethyl acetate to give the title compound (0.792 g, 81%): TOF MS ES+ 391.2 (M+H)+, HRMS calcd for C19H24N4O2FS 391.1604 (M+H)+, found 391.1594, time 0.48 min; HPLC [YMC-Pro pack C-18 (150×4.6 mm, S-5 microm), 0.05% TFA/acetonitrile in 0.05% TFA/water at 1.0 mL/min, 10-20% over 5 min, 20-95% over 18], tR=6.7 min, 100% purity. Dry the column in a vacuum oven at room temperature Purify by eluting through a 40 g ISCO® column with 0% to 30% (2.0 M NH3 in methanol) in ethyl acetate

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Place 5-(2-fluoro-4-formylphenoxy)pyridine-2-carboxamide (Example 403, Part B) (0.650 g, 2.50 mmol), 2-thiomorpholin-4-ylethylamine (0.402 g, 2.75 mmol) and 3 Å molecular sieves in a vial. Add methanol (12 mL), cap and stir overnight. Add NaBH4 (slight excess) and stir until the gasses stop evolving. Load the reaction mixture directly onto a 25 g ISCO® pre-load column. Dry the column in a vacuum oven at room temperature. Purify by eluting through a 40 g ISCO® column with 0% to 30% (2.0 M NH3 in methanol) in ethyl acetate to give the title compound (0.792 g, 81%): TOF MS ES+ 391.2 (M+H)+, HRMS calcd for C19H24N4O2FS 391.1604 (M+H)+, found 391.1594, time 0.48 min; HPLC [YMC-Pro pack C-18 (150×4.6 mm, S-5 microm), 0.05% TFA/acetonitrile in 0.05% TFA/water at 1.0 mL/min, 10-20% over 5 min, 20-95% over 18], tR=6.7 min, 100% purity. Dry the column in a vacuum oven at room temperature Purify by eluting through a 40 g ISCO® column with 0% to 30% (2.0 M NH3 in methanol) in ethyl acetate