2,2,2-三氟-N-[2-(甲氨基)乙基]乙酰胺

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

实验步骤: N-Methyl ethylenediamine (15 g, 202.3 mmol) was added dropwise to a stirred solution of ethyl trifluoroacetate (28.7 g, 204.34 mmol) in dry Et2O (50 mL) at 0° C. The resulting solution was stirred at room temperature for 2 hours. Hexane (75 mL) was added and the solution was left at −20° C. for 16 hours to produce a white precipitate which was removed by filtration, washed with Et2O (100 mL) and dried in vacuo for 3 hours to afford the title compound (29.4 g, 85%). 1H NMR (300 MHz, CDCl3) δ 3.42 (t, J=5.8 Hz, 2H), 2.80 (t, J=5.9 Hz, 2H), 2.43 (s, 3H); mass spectrum (API-TIS) 171 (M+H). the solution was left at −20° C. for 16 hours to produce a white precipitate which was removed by filtration washed with Et2O (100 mL) dried in vacuo for 3 hours

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

实验步骤: A solution of N-methylethylenediamine (27.0 g, 364 mmol) and ethyl trifluoroacetate (96.6 mL, 812 mmol) in a mixture of ACN (350 mL) and water (7.8 mL, 436 mmol) was refluxed with stiffing overnight. Solvents were evaporated in vacuo. The residue was re-evaporated with i-PrOH (3×100 mL), followed by heat-cool crystallization from DCM (500 mL). Formed crystals were filtered, washed with DCM and dried in vacuo to provide compound AA (88.3 g, 85%) as white solid powder. was refluxed Solvents were evaporated in vacuo The residue was re-evaporated with i-PrOH (3×100 mL) by heat-cool crystallization from DCM (500 mL) Formed crystals were filtered washed with DCM dried in vacuo to provide compound AA (88.3 g, 85%) as white solid powder

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

实验步骤: A solution of compound A (88.2 g, 311 mmol) and DIEA (54.1 mL, 311 mmol) in THF (350 mL) was cooled in an ice bath, followed by the addition of a solution of N-(benzyloxycarbonyl)succinimide (76.6 g, 307 mmol) in THF (150 mL) drop wise over the period of 20 min. The temperature of the reaction mixture was raised to ambient temperature and stirring was continued for an additional 30 min. Solvents were then evaporated and the resulting residue was dissolved in EtOAc (600 mL). The organic layer was extracted with 5% aq. NaHCO3 (2×150 mL) and brine (150 mL). The organic layer was evaporated to provide compound B as yellowish oil. LC-MS [M+H] 305.1 (C13H15F3N2O3+H, calc: 305.3). Compound B was used directly in the next reaction without purification as a MeOH solution. Solvents were then evaporated the resulting residue was dissolved in EtOAc (600 mL) The organic layer was extracted with 5% aq. NaHCO3 (2×150 mL) and brine (150 mL) The organic layer was evaporated

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

实验步骤: A solution of N-methylethylenediamine (27.0 g, 364 mmol) and ethyl trifluoroacetate (96.6 mL, 812 mmol) in a mixture of ACN (350 mL) and water (7.8 mL, 436 mmol) was refluxed with stirring overnight. Solvents were evaporated in vacuo. The residue was re-evaporated with i-PrOH (3×100 mL), followed by heat-cool crystallization from DCM (500 mL). Formed crystals were filtered, washed with DCM and dried in vacuo to provide compound A (88.3 g, 85%) as white solid powder. was refluxed Solvents were evaporated in vacuo The residue was re-evaporated with i-PrOH (3×100 mL) by heat-cool crystallization from DCM (500 mL) Formed crystals were filtered washed with DCM dried in vacuo

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

实验步骤: A solution of N-methylethylenediamine (27.0 g, 364 mmol) and ethyl trifluoroacetate (96.6 mL, 812 mmol) in a mixture of ACN (350 mL) and water (7.8 mL, 436 mmol) was refluxed with stirring overnight. Solvents were evaporated in vacuo. The residue was re-evaporated with i-PrOH (3×100 mL), followed by heat-cool crystallization from DCM (500 mL). Formed crystals were filtered, washed with DCM and dried in vacuo to provide compound A (88.3 g, 85%) as white solid powder. was refluxed Solvents were evaporated in vacuo The residue was re-evaporated with i-PrOH (3×100 mL) by heat-cool crystallization from DCM (500 mL) Formed crystals were filtered washed with DCM dried in vacuo

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

实验步骤: N-Methyl ethylenediamine (15 g, 202.3 mmol) was added dropwise to a stirred solution of ethyl trifluoroacetate (28.7 g, 204.34 mmol) in dry Et2O (50 mL) at 0° C. The resulting solution was stirred at room temperature for 2 hours. Hexane (75 mL) was added and the solution was left at −20° C. for 16 hours to produce a white precipitate which was removed by filtration, washed with Et2O (100 mL) and dried in vacuo for 3 hours to afford the title compound (29.4 g, 85%). 1H NMR (300 MHz, CDCl3) δ 3.42 (t, J=5.8 Hz, 2H), 2.80 (t, J=5.9 Hz, 2H), 2.43 (s, 3H); mass spectrum (API-TIS) 171 (M+H). the solution was left at −20° C. for 16 hours to produce a white precipitate which was removed by filtration washed with Et2O (100 mL) dried in vacuo for 3 hours

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

实验步骤: A solution of compound A (96.8 g, 340.7 mmol) and DIEA (59.3 ml, 340.7 mmol) in THF (350 ml) was cooled to ˜5° C., followed by addition of a solution of N-(benzyloxycarbonyl)succinimide (84.0 g, 337.3 mmol) in THF (150 ml) dropwise over the period of 20 min The temperature of reaction mixture was raised to room temperature and stirring was continued for an additional 30 min, followed by the solvents being evaporated. The resultant residue was dissolved in EtOAc (600 ml). EtOAc was extracted with 5% aq. NaHCO3 (2×150 ml) and brine (150 ml). The organic layer was separated and evaporated to provide compound B as yellowish oil (103.0 g, 340.7 mmol). LC-MS [M+H] 305.3 (C13H15F3N2O3+H, calc: 305.3). Compound B was used without further purification. The temperature of reaction mixture being evaporated The resultant residue was dissolved in EtOAc (600 ml) EtOAc was extracted with 5% aq. NaHCO3 (2×150 ml) and brine (150 ml) The organic layer was separated evaporated

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

实验步骤: A solution of N-methylethylenediamine (27.0 g, 364.0 mmol) and ethyl trifluoroacetate (96.6 ml, 838.0 mmol) in a mixture of acetonitrile (350 ml) and water (7.8 ml, 436 mmol) was refluxed overnight with stirring. Next the solvents were evaporated in vacuo. Residue was re-evaporated with isopropanol (3×100 ml). Residue was dissolved in dichloromethane (500 ml) and left overnight at room temperature. The formed crystals were filtered, washed with dichloromethane and dried in vacuo to provide compound A (96.8 g, 94%) as white solid powder. was refluxed overnight Next the solvents were evaporated in vacuo Residue was re-evaporated with isopropanol (3×100 ml) Residue was dissolved in dichloromethane (500 ml) The formed crystals were filtered washed with dichloromethane dried in vacuo

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

实验步骤: To a round bottom flask was added N-methylethylenediamine (1.9 ml, 21.79 mmol), water (0.43 mL), acetonitrile (33 mL) and ethyl trifluoroacetate (6.5 ml, 54.62 mmol). The mixture was stirred at reflux for 18 hours. The mixture was concentrated in vacuo. Dichloromethane was added to the residue and the solid filtered off to give 3.71 g of crude 2,2,2-trifluoro-N-(2-methylamino-ethyl)-acetamide, which was used in step 2 without further purification. MS: m/z 171.1 (M+H+). at reflux for 18 hours The mixture was concentrated in vacuo Dichloromethane was added to the residue the solid filtered off

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

实验步骤: To a round bottom flask was added N-methylethylenediamine (1.9 ml, 21.79 mmol), water (0.43 mL), acetonitrile (33 mL) and ethyl trifluoroacetate (6.5 ml, 54.62 mmol). The mixture was stirred at reflux for 18 hours. The mixture was concentrated in vacuo. Dichloromethane was added to the residue and the solid filtered off to give 3.71 g of crude 2,2,2-trifluoro-N-(2-methylamino-ethyl)-acetamide, which was used in step 2 without further purification. MS: m/z 171.1 (M+H+). at reflux for 18 hours The mixture was concentrated in vacuo Dichloromethane was added to the residue the solid filtered off

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

实验步骤: N-Methyl ethylenediamine (15 g, 202.3 mmol) was added dropwise to a stirred solution of ethyl trifluoroacetate (28.7 g, 204.34 mmol) in dry Et2O (50 mL) at 0° C. The resulting solution was stirred at room temperature for 2 hours. Hexane (75 mL) was added and the solution was left at −20° C. for 16 hours to produce a white precipitate which was removed by filtration, washed with Et2O (100 mL) and dried in vacuo for 3 hours to afford the title compound (29.4 g, 85%). 1H NMR (300 MHz, CDCl3) δ 3.42 (t, J=5.8 Hz, 2H), 2.80 (t, J=5.9 Hz, 2H), 2.43 (s, 3H); mass spectrum (API-TIS) 171 (M+H). the solution was left at −20° C. for 16 hours to produce a white precipitate which was removed by filtration washed with Et2O (100 mL) dried in vacuo for 3 hours

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

实验步骤: To a solution of 2,2,2-trifluoro-N-[2-(methylamino)ethyl]acetamide (5 g) in DMF (50 ml) were added ethyl 7-bromoheptanoate (3.6 ml) and potassium carbonate (7.7 g) and stirring was continued at room temperature for 18 hr. Potassium carbonate was removed by filtration and saturated aqueous sodium bicarbonate and water was added to the filtrate, which was extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride sequentially, dried with sodium sulfate, and concentrated. The residue was dissolved in toluene and purified by passing through the silica gel column (eluent; hexane to hexane-ethyl acetate (4:1) to ethyl acetate) to obtain the titled compound as a crude material (7 g). Potassium carbonate was removed by filtration and saturated aqueous sodium bicarbonate and water was added to the filtrate, which was extracted with ethyl acetate The organic layer was washed with water and saturated aqueous sodium chloride sequentially dried with sodium sulfate concentrated The residue was dissolved in toluene purified