4-pyrrolidin-1-yloxan-3-amine;dihydrochloride

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

実験手順: 2-Cyclopropyl-4-trifluoromethyl-benzoic acid (intermediate J, 118 mg, 0.513 mmol) was dissolved in 2.5 mL dimethylformamide. N,N-Diisopropyl ethyl amine (338 mg, 2.62 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (195 mg, 0.513 mmol) were added. After 10 minutes of stirring at room temperature trans-(4-pyrrolidin-1-yl-tetrahydro-pyran-3-ylamine dihydrochloride (intermediate 1,187 mg, 0.769 mmol) was added. The reaction mixture was stirred at room temperature overnight. The solvent was evaporated off. The residue was taken up in 2N sodium carbonate solution and ethyl acetate and was extracted three times with ethyl acetate. The combined organic phases were dried on sodium sulfate, filtered and evaporated. Purification of the residue by flash chromatography on silica gel (heptane/ethyl acetate/triethylamine 1:0:0→10:10:1) yielded the title compound as a white solid (121 mg, 62%), MS: m/e=383.3 [(M+H)+]. was added The solvent was evaporated off ethyl acetate and was extracted three times with ethyl acetate The combined organic phases were dried on sodium sulfate filtered evaporated Purification of the residue by flash chromatography on silica gel (heptane/ethyl acetate/triethylamine 1:0:0→10:10:1)

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

実験手順: trans-(4-Pyrrolidin-1-yl-tetrahydro-pyran-3-yl)-carbamic acid tert-butyl ester (intermediate H, 345 mg, 1.28 mmol) was dissolved in 6.4 mL dioxane. Hydrochloric acid (4N in dioxan, 3.2 mL, 13 mmol) was added. The reaction mixture was stirred at room temperature for 3 h. The solvent was evaporated off. The crude material, light brown solid (378 mg, >100%), MS: m/e=171.2 [(M+H)+] was used without further purification. The solvent was evaporated off The crude material, light brown solid (378 mg, >100%), MS: m/e=171.2 [(M+H)+] was used without further purification

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

実験手順: 2-Cyclopropyl-4-trifluoromethyl-benzoic acid (intermediate J, 118 mg, 0.513 mmol) was dissolved in 2.5 mL dimethylformamide. N,N-Diisopropyl ethyl amine (338 mg, 2.62 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (195 mg, 0.513 mmol) were added. After 10 minutes of stirring at room temperature trans-(4-pyrrolidin-1-yl-tetrahydro-pyran-3-ylamine dihydrochloride (intermediate 1,187 mg, 0.769 mmol) was added. The reaction mixture was stirred at room temperature overnight. The solvent was evaporated off. The residue was taken up in 2N sodium carbonate solution and ethyl acetate and was extracted three times with ethyl acetate. The combined organic phases were dried on sodium sulfate, filtered and evaporated. Purification of the residue by flash chromatography on silica gel (heptane/ethyl acetate/triethylamine 1:0:0→10:10:1) yielded the title compound as a white solid (121 mg, 62%), MS: m/e=383.3 [(M+H)+]. was added The solvent was evaporated off ethyl acetate and was extracted three times with ethyl acetate The combined organic phases were dried on sodium sulfate filtered evaporated Purification of the residue by flash chromatography on silica gel (heptane/ethyl acetate/triethylamine 1:0:0→10:10:1)

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

実験手順: trans-(4-Pyrrolidin-1-yl-tetrahydro-pyran-3-yl)-carbamic acid tert-butyl ester (intermediate H, 345 mg, 1.28 mmol) was dissolved in 6.4 mL dioxane. Hydrochloric acid (4N in dioxan, 3.2 mL, 13 mmol) was added. The reaction mixture was stirred at room temperature for 3 h. The solvent was evaporated off. The crude material, light brown solid (378 mg, >100%), MS: m/e=171.2 [(M+H)+] was used without further purification. The solvent was evaporated off The crude material, light brown solid (378 mg, >100%), MS: m/e=171.2 [(M+H)+] was used without further purification

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

実験手順: 2-Cyclopropyl-4-trifluoromethyl-benzoic acid (intermediate J, 118 mg, 0.513 mmol) was dissolved in 2.5 mL dimethylformamide. N,N-Diisopropyl ethyl amine (338 mg, 2.62 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (195 mg, 0.513 mmol) were added. After 10 minutes of stirring at room temperature trans-(4-pyrrolidin-1-yl-tetrahydro-pyran-3-ylamine dihydrochloride (intermediate 1,187 mg, 0.769 mmol) was added. The reaction mixture was stirred at room temperature overnight. The solvent was evaporated off. The residue was taken up in 2N sodium carbonate solution and ethyl acetate and was extracted three times with ethyl acetate. The combined organic phases were dried on sodium sulfate, filtered and evaporated. Purification of the residue by flash chromatography on silica gel (heptane/ethyl acetate/triethylamine 1:0:0→10:10:1) yielded the title compound as a white solid (121 mg, 62%), MS: m/e=383.3 [(M+H)+]. was added The solvent was evaporated off ethyl acetate and was extracted three times with ethyl acetate The combined organic phases were dried on sodium sulfate filtered evaporated Purification of the residue by flash chromatography on silica gel (heptane/ethyl acetate/triethylamine 1:0:0→10:10:1)

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

実験手順: trans-(4-Pyrrolidin-1-yl-tetrahydro-pyran-3-yl)-carbamic acid tert-butyl ester (intermediate H, 345 mg, 1.28 mmol) was dissolved in 6.4 mL dioxane. Hydrochloric acid (4N in dioxan, 3.2 mL, 13 mmol) was added. The reaction mixture was stirred at room temperature for 3 h. The solvent was evaporated off. The crude material, light brown solid (378 mg, >100%), MS: m/e=171.2 [(M+H)+] was used without further purification. The solvent was evaporated off The crude material, light brown solid (378 mg, >100%), MS: m/e=171.2 [(M+H)+] was used without further purification