2,2,2-trifluoro-N-methylacetamide

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium hydride (60% dispersion in mineral oil, 31.5 g, 1.28 eq.) was slowly added under nitrogen atmosphere to a solution of N-methyl-2,2,2-trifluoroacetamide (100 g, 1.28 eq.) in DMF (500 mL) at 0° C. The reaction mixture was stirred for 90 min at 0° C., and then 6-bromo-1-hexene (100 g, 1 eq.) was added dropwise over 45 min. The reaction mixture was allowed to warm up to room temperature, and stirred for 3 days at room temperature. The reaction mixture was then poured into water and extracted tree time with EtOAc. The combined organics layers were dried over anhydrous sodium sulphate and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel to produce compound 31a as colorless oil in 56% yield. to warm up to room temperature stirred for 3 days at room temperature extracted tree time with EtOAc The combined organics layers were dried over anhydrous sodium sulphate concentrated under reduced pressure The residue was purified by flash chromatography on silica gel

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: At 0° C. and under nitrogen atmosphere, sodium hydride (60% dispersion in mineral oil, 31.5 g, 1.28 eq.) was slowly added to a cooled solution of N-methyl-2,2,2-trifluoroacetamide (100 g, 1.28 eq.) in DMF (500 mL). The reaction mixture was stirred for 2 hrs at 0° C. and 6-bromo-1-hexene (100 g, 1 eq.) was added dropwise for 45 min. The reaction mixture was allowed to warm up to room temperature and was stirred for 3 days. The reaction mixture was poured into water and extracted three times with EtOAc. The combined organic layers were dried over anhydrous sodium sulphate, and evaporated under reduced pressure. The resulting residue was purified by chromatography on silica gel (petroleum ether/EtOAc) to yield compound 1a as colourless oil in 56% yield. 1H NMR (DMSO-d6, 400 MHz) δ (ppm) 1.27-1.38 (m, 2H), 1.48-1.60 (m, 2H), 2-2.06 (m, 2H), 2.93 (m, 3H), 3.35-3.40 (m, 2H), 4.92-5.04 (m, 2H), 5.73-5.83 (m, 1H). to warm up to room temperature was stirred for 3 days extracted three times with EtOAc The combined organic layers were dried over anhydrous sodium sulphate evaporated under reduced pressure The resulting residue was purified by chromatography on silica gel (petroleum ether/EtOAc)

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

実験手順: To 800 ml of dry benzene:acetonitrile (v/v, 1:1) was added 127 g (1.0 mole) of N-methyl-trifluoroacetamide. To this solution, while stirring and maintaining the temperature at 0 degress C., was slowly added 23.5 g (0.98 mole) of sodium hydride. The solution was then stirred for 4 hours at 4 degrees C. At this time, 173.34 g (1.15 mole) of t-butyldimethylsilyl chloride was added in four equal aliquots over a period of 80 minutes. After the last addition the solution was stirred for 2 hours at 4 degrees C. The precipitate of sodium chloride was then removed from the reaction mixture by filtration under dry nitrogen and the resulting filter cake washed twice with 100 ml each of dry benzene. Washings and filtrate were combined and concentrated. The remaining yellow solution was fractionally distilled with the distillate at 158-172 degrees C. being collected. Redistillation of this fraction gave the desired product. maintaining the temperature at 0 degress C The solution was then stirred for 4 hours at 4 degrees C After the last addition the solution was stirred for 2 hours at 4 degrees C The precipitate of sodium chloride was then removed from the reaction mixture by filtration under dry nitrogen the resulting filter cake washed twice with 100 ml each of dry benzene concentrated The remaining yellow solution was fractionally distilled with the distillate at 158-172 degrees C being collected Redistillation of this fraction

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium hydride (60% dispersion in mineral oil, 31.5 g, 1.28 eq.) was slowly added under nitrogen atmosphere to a solution of N-methyl-2,2,2-trifluoroacetamide (100 g, 1.28 eq.) in DMF (500 mL) at 0° C. The reaction mixture was stirred for 90 min at 0° C., and then 6-bromo-1-hexene (100 g, 1 eq.) was added dropwise over 45 min. The reaction mixture was allowed to warm up to room temperature, and stirred for 3 days at room temperature. The reaction mixture was then poured into water and extracted tree time with EtOAc. The combined organics layers were dried over anhydrous sodium sulphate and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel to produce compound 31A as colorless oil in 56% yield. 1H NMR (DMSO-d6, 400 MHz) δ 1.27-1.38 (m, 2H), 1.48-1.60 (m, 2H), 2.00-2.06 (m, 2H), 2.93-3.07 (2m, 3H), 3.35-3.40 (m, 2H), 4.92-5.04 (m, 2H), 5.73-5.83 (m, 1H). to warm up to room temperature stirred for 3 days at room temperature extracted tree time with EtOAc The combined organics layers were dried over anhydrous sodium sulphate concentrated under reduced pressure The residue was purified by flash chromatography on silica gel

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: At 0° C. and under nitrogen atmosphere, sodium hydride (60% dispersion in mineral oil, 31.5 g, 1.28 eq.) was slowly added to a cooled solution of N-methyl-2,2,2-trifluoroacetamide (100 g, 1.28 eq.) in DMF (500 mL). The reaction mixture was stirred for 2 hrs at 0° C. and 6-bromo-1-hexene (100 g, 1 eq.) was added dropwise for 45 min. The reaction mixture was allowed to warm up to room temperature and was stirred for 3 days. The reaction mixture was poured into water and extracted three times with EtOAc. The combined organic layers were dried over anhydrous sodium sulphate, and evaporated under reduced pressure. The resulting residue was purified by chromatography on silica gel (petroleum ether/EtOAc) to yield compound 1a as colourless oil in 56% yield. 1H NMR (DMSO-d6, 400 MHz) δ (ppm) 1.27-1.38 (m, 2H), 1.48-1.60 (m, 2H), 2-2.06 (m, 2H), 2.93 (m, 3H), 3.35-3.40 (m, 2H), 4.92-5.04 (m, 2H), 5.73-5.83 (m, 1H). to warm up to room temperature was stirred for 3 days extracted three times with EtOAc The combined organic layers were dried over anhydrous sodium sulphate evaporated under reduced pressure The resulting residue was purified by chromatography on silica gel (petroleum ether/EtOAc)

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

実験手順: A solution of N-methyl-2,2,2-trifluoroacetamide (197 mg, 1.55 mmol) in DMF (5 mL) at 0° C. was treated with sodium hydride (60% dispersion in mineral oil; 62 mg, 1.55 mmol), stirred for 15 min, treated with 3-(6-bromomethyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (120 mg, 0.310 mmol), stirred at 50° C. for 1 h, cooled to room temperature, poured into water (20 mL), extracted with EtOAc (3×10 mL) and the combined organic phase dried (MgSO4) and concentrated in vacuo to give N-(6-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-2-pyridylmethyl)-N-methyltrifluoroacetamide. A solution of this product in MeOH (20 mL) was treated with a solution of sodium (71 mg, 3.10 mmol) in MeOH (10 mL), stirred for 16 h, concentrated in vacuo, treated with EtOAc (20 mL), filtered through Celite and concentrated in vacuo. The resulting solid was suspended in MeOH (2 mL), treated with HCl (4-M in dioxane, 1.0 mL), stirred for 10 min, concentrated in vacuo and triturated with Et2O to give the title compound (80 mg, 58%) as a yellow solid. stirred at 50° C. for 1 h extracted with EtOAc (3×10 mL) the combined organic phase dried (MgSO4) concentrated in vacuo

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

実験手順: A solution of N-methyl-2,2,2-trifluoroacetamide (197 mg, 1.55 mmol) in DMF (5 mL) at 0° C. was treated with sodium hydride (60% dispersion in mineral oil; 62 mg, 1.55 mmol), stirred for 15 min, treated with 3-(6-bromomethyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (120 mg, 0.310 mmol), stirred at 50° C. for 1 h, cooled to room temperature, poured into water (20 mL), extracted with EtOAc (3×10 mL) and the combined organic phase dried (MgSO4) and concentrated in vacuo to give N-(6-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-2-pyridylmethyl)-N-methyltrifluoroacetamide. A solution of this product in MeOH (20 mL) was treated with a solution of sodium (71 mg, 3.10 mmol) in MeOH (10 mL), stirred for 16 h, concentrated in vacuo, treated with EtOAc (20 mL), filtered through Celite and concentrated in vacuo. The resulting solid was suspended in MeOH (2 mL), treated with HCl (4-M in dioxane, 1.0 mL), stirred for 10 min, concentrated in vacuo and triturated with Et2O to give the title compound (80 mg, 58%) as a yellow solid. stirred at 50° C. for 1 h extracted with EtOAc (3×10 mL) the combined organic phase dried (MgSO4) concentrated in vacuo

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

実験手順: A solution of N-methyl-2,2,2-trifluoroacetamide (197 mg, 1.55 mmol) in DMF (5 mL) at 0° C. was treated with sodium hydride (60% dispersion in mineral oil; 62 mg, 1.55 mmol), stirred for 15 min, treated with 3-(6-bromomethyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (120 mg, 0.310 mmol), stirred at 50° C. for 1 h, cooled to room temperature, poured into water (20 mL), extracted with EtOAc (3×10 mL) and the combined organic phase dried (MgSO4) and concentrated in vacuo to give N-(6-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-2-pyridylmethyl)-N-methyltrifluoroacetamide. A solution of this product in MeOH (20 mL) was treated with a solution of sodium (71 mg, 3.10 mmol) in MeOH (10 mL), stirred for 16 h, concentrated in vacuo, treated with EtOAc (20 mL), filtered through Celite and concentrated in vacuo. The resulting solid was suspended in MeOH (2 mL), treated with HCl (4-M in dioxane, 1.0 mL), stirred for 10 min, concentrated in vacuo and triturated with Et2O to give the title compound (80 mg, 58%) as a yellow solid. stirred at 50° C. for 1 h extracted with EtOAc (3×10 mL) the combined organic phase dried (MgSO4) concentrated in vacuo

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium hydride (60% dispersion in mineral oil, 31.5 g, 1.28 eq.) was slowly added under nitrogen atmosphere to a solution of N-methyl-2,2,2-trifluoroacetamide (100 g, 1.28 eq.) in DMF (500 mL) at 0° C. The reaction mixture was stirred for 90 min at 0° C., and then 6-bromo-1-hexene (100 g, 1 eq.) was added dropwise over 45 min. The reaction mixture was allowed to warm up to room temperature, and stirred for 3 days at room temperature. The reaction mixture was then poured into water and extracted tree time with EtOAc. The combined organics layers were dried over anhydrous sodium sulphate and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel to produce compound 31a as colorless oil in 56% yield. 1H NMR (DMSO-d6, 400 MHz) δ (ppm) 1.27-1.38 (m, 2H), 1.48-1.60 (m, 2H), 2.00-2.06 (m, 2H), 2.93-3.07 (2m, 3H), 3.35-3.40 (m, 2H), 4.92-5.04 (m, 2H), 5.73-5.83 (m, 1H). to warm up to room temperature stirred for 3 days at room temperature extracted tree time with EtOAc The combined organics layers were dried over anhydrous sodium sulphate concentrated under reduced pressure The residue was purified by flash chromatography on silica gel

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium hydride (60% dispersion in mineral oil, 31.5 g, 1.28 eq.) was slowly added under nitrogen atmosphere to a solution of N-methyl-2,2,2-trifluoroacetamide (100 g, 1.28 eq.) in DMF (500 mL) at 0° C. The reaction mixture was stirred for 90 min at 0° C., and then 6-bromo-1-hexene (100 g, 1 eq.) was added dropwise over 45 min. The reaction mixture was allowed to warm up to room temperature, and stirred for 3 days at room temperature. The reaction mixture was then poured into water and extracted tree time with EtOAc. The combined organics layers were dried over anhydrous sodium sulphate and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel to produce compound 31a as colorless oil in 56% yield. 1H NMR (DMSO-d6, 400 MHz) δ (ppm) 1.27-1.38 (m, 2H), 1.48-1.60 (m, 2H), 2.00-2.06 (m, 2H), 2.93-3.07 (2m, 3H), 3.35-3.40 (m, 2H), 4.92-5.04 (m, 2H), 5.73-5.83 (m, 1H). to warm up to room temperature stirred for 3 days at room temperature extracted tree time with EtOAc The combined organics layers were dried over anhydrous sodium sulphate concentrated under reduced pressure The residue was purified by flash chromatography on silica gel

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium hydride (60% dispersion in mineral oil, 31.5 g, 1.28 eq.) was slowly added under nitrogen atmosphere to a solution of N-methyl-2,2,2-trifluoroacetamide (100 g, 1.28 eq.) in DMF (500 mL) at 0° C. The reaction mixture was stirred for 90 min at 0° C., and then 6-bromo-1-hexene (100 g, 1 eq.) was added dropwise over 45 min. The reaction mixture was allowed to warm up to room temperature, and stirred for 3 days at room temperature. The reaction mixture was then poured into water and extracted tree time with EtOAc. The combined organics layers were dried over anhydrous sodium sulphate and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel to produce compound 31a as colorless oil in 56% yield. 1H NMR (DMSO-d6, 400 MHz) δ (ppm) 1.27-1.38 (m, 2H), 1.48-1.60 (m, 2H), 2.00-2.06 (m, 2H), 2.93-3.07 (2m, 3H), 3.35-3.40 (m, 2H), 4.92-5.04 (m, 2H), 5.73-5.83 (m, 1H). to warm up to room temperature stirred for 3 days at room temperature extracted tree time with EtOAc The combined organics layers were dried over anhydrous sodium sulphate concentrated under reduced pressure The residue was purified by flash chromatography on silica gel

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium hydride (60% dispersion in mineral oil, 31.5 g, 1.28 eq.) was slowly added under nitrogen atmosphere to a solution of N-methyl-2,2,2-trifluoroacetamide (100 g, 1.28 eq.) in DMF (500 mL) at 0° C. The reaction mixture was stirred for 90 min at 0° C., and then 6-bromo-1-hexene (100 g, 1 eq.) was added dropwise over 45 min. The reaction mixture was allowed to warm up to room temperature, and stirred for 3 days at room temperature. The reaction mixture was then poured into water and extracted tree time with EtOAc. The combined organics layers were dried over anhydrous sodium sulphate and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel to produce compound 31a as colorless oil in 56% yield. to warm up to room temperature stirred for 3 days at room temperature extracted tree time with EtOAc The combined organics layers were dried over anhydrous sodium sulphate concentrated under reduced pressure The residue was purified by flash chromatography on silica gel