propan-2-yl 4-aminopiperidine-1-carboxylate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 18b (1.1 g, 5.9 mmol), 6a (1.5 g, 4.84 mmol) and diisopropylethylamine (3 mL, 18.1 mmol) in 15 mL of DMF was heated at 80° C. for 17 h and at 90° C. for 24 h. The mixture was diluted with 100 mL of DCM, washed with brine (3×50 mL) and the extracts were dried, filtered and concentrated under vacuum. The residue was purified by flash chromatography (elution with 50-100% ethyl acetate and 0.1% TEA in hexanes) and finally purified on preparative HPLC to afford 0.3 g (14%) of 18-1. tR=5.21 (Method 5). EC50: 611 nM. washed with brine (3×50 mL) the extracts were dried filtered concentrated under vacuum The residue was purified by flash chromatography (elution with 50-100% ethyl acetate and 0.1% TEA in hexanes) finally purified on preparative HPLC

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

実験手順: To a solution of 18a (3.26 g, 11.37 mmol) in 10 mL of DCM, was added TFA (5 mL, 64.9 mmol). The mixture was stirred at room temperature for 2 h and the solvent were evaporated. The residue was dissolved in DCM and a saturated solution of NaHCO3 and 1N NaOH were added until pH was 8. The layers were separated and the aqueous layer was extracted with 3:1 DCM:IPA (3×40 mL). The organic extracts were combined, dried, filtered and evaporated to afford 1.89 g (89%) of 18b. the solvent were evaporated The residue was dissolved in DCM a saturated solution of NaHCO3 and 1N NaOH were added until pH was 8 The layers were separated the aqueous layer was extracted with 3:1 DCM dried filtered evaporated

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 18b (1.1 g, 5.9 mmol), 6a (1.5 g, 4.84 mmol) and diisopropylethylamine (3 mL, 18.1 mmol) in 15 mL of DMF was heated at 80° C. for 17 h and at 90° C. for 24 h. The mixture was diluted with 100 mL of DCM, washed with brine (3×50 mL) and the extracts were dried, filtered and concentrated under vacuum. The residue was purified by flash chromatography (elution with 50-100% ethyl acetate and 0.1% TEA in hexanes) and finally purified on preparative HPLC to afford 0.3 g (14%) of 18-1. tR=5.21 (Method 5). EC50: 611 nM. washed with brine (3×50 mL) the extracts were dried filtered concentrated under vacuum The residue was purified by flash chromatography (elution with 50-100% ethyl acetate and 0.1% TEA in hexanes) finally purified on preparative HPLC

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

実験手順: To a solution of 18a (3.26 g, 11.37 mmol) in 10 mL of DCM, was added TFA (5 mL, 64.9 mmol). The mixture was stirred at room temperature for 2 h and the solvent were evaporated. The residue was dissolved in DCM and a saturated solution of NaHCO3 and 1N NaOH were added until pH was 8. The layers were separated and the aqueous layer was extracted with 3:1 DCM:IPA (3×40 mL). The organic extracts were combined, dried, filtered and evaporated to afford 1.89 g (89%) of 18b. the solvent were evaporated The residue was dissolved in DCM a saturated solution of NaHCO3 and 1N NaOH were added until pH was 8 The layers were separated the aqueous layer was extracted with 3:1 DCM dried filtered evaporated