N-乙基-2,2,2-三氟乙胺盐酸

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

实验步骤: To a cooled (0° C.) solution of N-ethyl-2,2,2-trifluoroethanamine hydrochloride, (0.45 g, 2.8 mmol) in DCM (10 mL) was added triethylamine (1.6 mL, 11.2 mmol) followed by 2-chloroacetyl chloride (0.22 mL, 2.8 mmol). The reaction was warmed to RT and stirred for 2 h. The reaction mixture was concentrated, redissolved in EtOAc (20 mL) and washed with brine (25 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated to yield 0.6 g of crude product which was further purified by flash column chromatography using 1:1 EtOAc:hexanes as the eluent. 0.5 g of 2-chloro-N-ethyl-N-(2,2,2-trifluoroethyl)acetamide, (yield: 88%) was isolated. The reaction mixture was concentrated redissolved in EtOAc (20 mL) washed with brine (25 mL) The organic layer was dried over anhydrous Na2SO4 concentrated to yield 0.6 g of crude product which was further purified by flash column chromatography

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 2,2,2-trifluoroethylamine hydrochloride (0.5 g, 3.7 mmol) in MeOH (5 mL) was added triethylamine (0.51 mL, 0.37 mmol) followed by acetaldehyde (1.0 mL, excess). The reaction mixture was then stirred at 0° C. for 3 h. Sodium borohydride (1 g, 5.9 mmol) was then added and the reaction mixture was stirred at 0° C. for 20 min. The reaction was quenched with 1M NaOH (10 mL) and the aqueous layer was extracted with DCM (25 mL). The organic layer was separated and to it was added 2M HCl in Et2O (10 mL). The resultant precipitate was filtered to give 0.45 g of N-ethyl-2,2,2-trifluoroethanamine hydrochloride, (yield: 75%). the reaction mixture was stirred at 0° C. for 20 min The reaction was quenched with 1M NaOH (10 mL) the aqueous layer was extracted with DCM (25 mL) The organic layer was separated and to it was added 2M HCl in Et2O (10 mL) The resultant precipitate was filtered

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 2,2,2-trifluoroethylamine hydrochloride (0.5 g, 3.7 mmol) in MeOH (5 mL) was added triethylamine (0.51 mL, 0.37 mmol) followed by acetaldehyde (1.0 mL, excess). The reaction mixture was then stirred at 0° C. for 3 h. Sodium borohydride (1 g, 5.9 mmol) was then added and the reaction mixture was stirred at 0° C. for 20 min. The reaction was quenched with 1M NaOH (10 mL) and the aqueous layer was extracted with DCM (25 mL). The organic layer was separated and to it was added 2M HCl in Et2O (10 mL). The resultant precipitate was filtered to give 0.45 g of N-ethyl-2,2,2-trifluoroethanamine hydrochloride, (yield: 75%). the reaction mixture was stirred at 0° C. for 20 min The reaction was quenched with 1M NaOH (10 mL) the aqueous layer was extracted with DCM (25 mL) The organic layer was separated and to it was added 2M HCl in Et2O (10 mL) The resultant precipitate was filtered

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

实验步骤: 133 mg (0.81 mmol) of N-ethyl-2,2,2-trifluoroethanamine hydrochloride were dissolved in 2 ml of DMF, 130 mg Amberlyst A-21 were added and the mixture was stirred at RT for 30 min. The mixture was filtered off and added to 100 mg (0.14 mmol, purity about 74%) of 2-chloro-6-({(2-(4-chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-4-(4-(2-hydroxyethoxy)phenyl)pyridine-3,5-dicarbonitrile (Example 2A), and the solution was stirred at RT overnight. The mixture was then warmed to 60° C. and stirred at this temperature overnight. In a separate flask, another 87 mg (0.54 mmol) of 2,2,2-trifluoro-N-methylethanamine hydrochloride were then dissolved in 0.5 ml of DMF, 88 mg of Amberlyst A-21 were added and the mixture was stirred at RT for 30 min. The mixture was filtered off and added to the first solution. The reaction mixture obtained was stirred at 100° C. for 4.5 h. The mixture was then diluted with a little water/THF and purified by preparative HPLC (acetonitrile/water+0.1% TFA). This gave 37 mg (41% of theory) of the target compound. 130 mg Amberlyst A-21 were added The mixture was filtered off the solution was stirred at RT overnight The mixture was then warmed to 60° C. stirred at this temperature overnight 88 mg of Amberlyst A-21 were added the mixture was stirred at RT for 30 min The mixture was filtered off added to the first solution The reaction mixture obtained was stirred at 100° C. for 4.5 h purified by preparative HPLC (acetonitrile/water+0.1% TFA)

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

实验步骤: 133 mg (0.81 mmol) of N-ethyl-2,2,2-trifluoroethanamine hydrochloride were dissolved in 2 ml of DMF, 130 mg Amberlyst A-21 were added and the mixture was stirred at RT for 30 min. The mixture was filtered off and added to 100 mg (0.14 mmol, purity about 74%) of 2-chloro-6-({(2-(4-chlorophenyl)-1,3-thiazol-4-ylmethyl}sulfanyl)-4-(4-(2-hydroxyethoxy)phenyl)pyridine-3,5-dicarbonitrile (Example 2A), and the solution was stirred at RT overnight. The mixture was then warmed to 60° C. and stirred at this temperature overnight. In a separate flask, another 87 mg (0.54 mmol) of 2,2,2-trifluoro-N-methylethanamine hydrochloride were then dissolved in 0.5 ml of DMF, 88 mg of Amberlyst A-21 were added and the mixture was stirred at RT for 30 min. The mixture was filtered off and added to the first solution. The reaction mixture obtained was stirred at 100° C. for 4.5 h. The mixture was then diluted with a little water/THF and purified by preparative HPLC (acetonitrile/water+0.1% TFA). This gave 37 mg (41% of theory) of the target compound. 130 mg Amberlyst A-21 were added The mixture was filtered off the solution was stirred at RT overnight The mixture was then warmed to 60° C. stirred at this temperature overnight 88 mg of Amberlyst A-21 were added the mixture was stirred at RT for 30 min The mixture was filtered off added to the first solution The reaction mixture obtained was stirred at 100° C. for 4.5 h purified by preparative HPLC (acetonitrile/water+0.1% TFA)

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

实验步骤: To a cooled (0° C.) solution of N-ethyl-2,2,2-trifluoroethanamine hydrochloride, (0.45 g, 2.8 mmol) in DCM (10 mL) was added triethylamine (1.6 mL, 11.2 mmol) followed by 2-chloroacetyl chloride (0.22 mL, 2.8 mmol). The reaction was warmed to RT and stirred for 2 h. The reaction mixture was concentrated, redissolved in EtOAc (20 mL) and washed with brine (25 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated to yield 0.6 g of crude product which was further purified by flash column chromatography using 1:1 EtOAc:hexanes as the eluent. 0.5 g of 2-chloro-N-ethyl-N-(2,2,2-trifluoroethyl)acetamide, (yield: 88%) was isolated. The reaction mixture was concentrated redissolved in EtOAc (20 mL) washed with brine (25 mL) The organic layer was dried over anhydrous Na2SO4 concentrated to yield 0.6 g of crude product which was further purified by flash column chromatography

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 2,2,2-trifluoroethylamine hydrochloride (0.5 g, 3.7 mmol) in MeOH (5 mL) was added triethylamine (0.51 mL, 0.37 mmol) followed by acetaldehyde (1.0 mL, excess). The reaction mixture was then stirred at 0° C. for 3 h. Sodium borohydride (1 g, 5.9 mmol) was then added and the reaction mixture was stirred at 0° C. for 20 min. The reaction was quenched with 1M NaOH (10 mL) and the aqueous layer was extracted with DCM (25 mL). The organic layer was separated and to it was added 2M HCl in Et2O (10 mL). The resultant precipitate was filtered to give 0.45 g of N-ethyl-2,2,2-trifluoroethanamine hydrochloride, (yield: 75%). the reaction mixture was stirred at 0° C. for 20 min The reaction was quenched with 1M NaOH (10 mL) the aqueous layer was extracted with DCM (25 mL) The organic layer was separated and to it was added 2M HCl in Et2O (10 mL) The resultant precipitate was filtered